The Pre-Travel Consultation

THE PRE-TRAVEL CONSULTATION

Rebecca W. Acosta

The pre-travel consultation is a risk-based assessment process that provides a guide to prioritizing and customizing pre-travel health care to the traveler's itinerary, risks, and needs. The goal of the pre-travel consultation is the effective and efficient preparation of travelers with the appropriate counseling, vaccinations, and medications to help reduce their risk of illness and injury during travel.

To conduct a risk-based assessment, health-care providers involved in preparing travelers must—

• •Have a working knowledge of destination-specific disease and health risks and standard recommendations to promote health and prevent illness among travelers. The information and recommendations presented in this publication, the Body of Knowledge in Travel Medicine (as published by the International Society of Travel Medicine [ISTM]), and other authoritative sources (see Appendix B) form the basis for this knowledge.
• •
  Understand the standard for and expectations of conducting a pre-travel consultation and gain expertise in the process. The well-organized and well-executed pre-travel consultation supports consistent, appropriate, and efficient pre-travel health preparation with the following three essential elements:

  • 1.
    Risk Assessment
  • 2.
    Risk Communication
  • 3.
    Risk Management

Risk Assessment

The risk assessment provides the foundation for the recommendations given during the consultation. A risk assessment involves gathering pertinent information about the itinerary (“where and when”) and traveler (“who, why, what, and how”) to highlight the traveler's risks and alert the provider to any contraindications and precautions to vaccinations or medications that may be indicated. A questionnaire designed to collect and organize the itinerary and traveler data is an essential tool to help support the risk assessment process and facilitate consistent practice (see Box 1-1).

The most important information to gather includes the following:

• •
  Itinerary data

  • ○
    Countries and regions to be visited; urban versus rural
  • ○
    Dates and length of travel
  • ○
    Purpose of travel (e.g., business, vacation, visiting friends and relatives)
  • ○
    Mode(s) of transportation
  • ○
    Planned and possible activities
  • ○
    Types of accommodations
• •
  Traveler demographic and health/medical history

  • ○
    Age, sex
  • ○
    Vaccination history, including prior adverse events
  • ○
    Medical and psychiatric history (past and current)
  • ○
    Medications
  • ○
    Allergies
  • ○
    Pregnancy and breastfeeding status (current status and plans)

A basic example of using the itinerary and traveler data includes determining if there will be a risk of yellow fever disease or a requirement for yellow fever vaccination based on the itinerary, and if there is a contraindication (e.g., egg allergy) or a precaution (e.g., >60 years of age) to the traveler's receiving the vaccine. Malaria risk is another important consideration. Will the traveler be going to a region endemic for malaria, and what are the appropriate measures to help prevent malaria based on the details of the itinerary and traveler's medical history?

During the risk assessment, the provider must remain alert to other factors about “who” will be traveling. Such factors include the traveler's previous travel experience, perception of risk, cultural background, peer group(s), and possible barriers to care, such as economic issues, attitudes regarding vaccine safety, and fear of vaccines. These factors may greatly affect the traveler's ability and willingness to accept and adhere to the recommendations, and therefore affect the pre-travel consultation.

Anticipating the unique needs of high-risk travelers and preparing them for healthy travel will help prevent illness and injury. The following travelers may be considered high risk:

• •Travelers visiting friends and relatives (VFRs). These individuals have typically migrated from a less-developed area to a developed area and are now returning to the region of their birth. This is especially important when these individuals are traveling with new family members or children. The traveler returning to his or her country of origin may not understand the dynamics of risk and waning immunity (see the VFR section in Chapter 8).
• •The elderly
• •Families with young children
• •Persons traveling to adopt children abroad
• •Persons with weakened immune systems
• •Women who are pregnant or breastfeeding

Risk Communication

The next phase of the consultation process is focused on risk communication and includes the presentation of reliable, evidence-based information in a context appropriate for the individual traveler. Time should be allocated for discussion of the risks with the traveler to promote informed decision making about risk avoidance and prevention measures, such as vaccinations and malaria chemoprophylaxis. Risk communication depends heavily upon the risk assessment for the individual traveler, as well as that traveler's perception of risk. For example, three travelers may be going to the same country: one for a week-long, urban-based, business visit; the next on an adventure-seeking, backpack trip to rural areas over several months; and the third is a pregnant VFR traveler. The recommendations and preparation for each of these travelers will vary, even though the destination country is the same.

It is important to give both verbal and written information to the traveler to help guide and focus the discussion and reinforce important issues based on his or her risk assessment. Examples include information pamphlets, malaria risk maps, and vaccine information statements (VISs). Through careful risk assessment and thoughtful risk communication, a risk management plan (i.e., vaccinations, medications, and targeted risk-avoidance education) takes shape.

Risk Management

The essential elements of risk management include the following:

• •
  Selection, administration, and documentation of vaccinations

  • ○
    Required, recommended, and routine vaccinations should all be considered (see below)
  • ○
    Providers should consider indications, contraindications, precautions, and timing of dosages
• •
  Prescribing and advising about preventive medications

  • ○
    Where appropriate according to risk, antimalarial chemoprophylaxis and medications for travelers' diarrhea, motion sickness, and altitude sickness
• •Education related to malaria prevention and adherence to chemoprophylaxis (if indicated by the risk assessment)
• •Information on risk and prevention of other insect-borne diseases
• •Instruction on methods to reduce foodborne and waterborne illness and the self-management of travelers' diarrhea
• •Instruction about animal avoidance and rabies
• •
  Information to help reduce the negative effect of

  • ○
    Other itinerary risks (e.g., altitude, pollution)
  • ○
    Activity-specific risks (e.g., diving, rafting, rural road travel)
  • ○
    Personal behavior risks (e.g., sexually transmitted diseases)
• •
  General guidance on

  • ○
    Symptoms (e.g., fever, gastrointestinal or dermatologic symptoms) that may require medical attention during or after travel
  • ○
    Preparing a travel health kit (see the Travel Health Kits section later in this chapter)
  • ○
    Accessing medical care abroad and obtaining medical/evacuation insurance

When considering vaccinations, common terms used include “required,” “recommended,” and “routine.” Required vaccines are those needed when a destination country requires documentation of vaccine administration or some sort of medical waiver. Recommended vaccines are those vaccines that are considered based on the actual disease risk the traveler may encounter during travel. Routine vaccines refer to those vaccines that are recommended in the United States, regardless of travel. These routine vaccines are an important part of pre-travel care because many of the diseases they protect against are more common in countries outside the United States.

Careful documentation of all vaccinations, medications, and specific recommendations given to the traveler helps to complete the care plan record. Providers who are registered to give yellow fever vaccine should be familiar with properly completing the International Certificate of Vaccination or Prophylaxis (ICVP) to ensure that this documentation will be accepted at the borders of destination countries (see the Yellow Fever section later in this chapter). Using an electronic record or standardized form facilitates documentation and helps ensure consistency of practice.

Providers should plan to spend an average of 30–45 minutes conducting a complete pre-travel consultation, based on the risk assessment, given the potential complexities in preparing the traveler. Providers with limited knowledge and expertise in travel medicine and the pre-travel consultation should consider referring travelers with complex itineraries or special needs (see Chapters 7 and 8) to a travel medicine clinic or travel medicine specialist through CDC's Travelers' Health website at www.cdc.gov/travel. References 1–4 can assist those providers interested in gaining a more in-depth perspective on the expectations for providing pre-travel health care and the pre-travel consultation process.

GENERAL RECOMMENDATIONS FOR VACCINATION AND IMMUNOPROPHYLAXIS

William Atkinson, Andrew Kroger

Recommendations for the use of vaccines and other biologic products (e.g., immune globulin products) in the United States are developed by the Advisory Committee on Immunization Practices (ACIP) and other groups, such as the American Academy of Pediatrics. These recommendations are based on scientific evidence of benefits (immunity to the disease) and risks (vaccine adverse reactions) and, where few or no data are available, on expert opinion. The recommendations include information on general immunization issues and the use of specific vaccines. When these recommendations are issued or revised, they are published in CDC's Morbidity and Mortality Weekly Report (MMWR) (www.cdc.gov/mmwr). This section is based primarily on the ACIP General Recommendations on Immunization.

Vaccinations against diphtheria, tetanus, pertussis, measles, mumps, rubella, varicella, poliomyelitis, hepatitis A, hepatitis B, Haemophilus influenzae type b, rotavirus, influenza, human papillomavirus, and pneumococcal and meningococcal invasive disease are routinely administered in the United States, usually in childhood or adolescence. If persons do not have a history of adequate protection against these diseases, immunizations appropriate to their age and previous immunization status should be obtained, whether or not international travel is planned. A visit to a provider for immunizations for travel should be seen as an opportunity to bring an incompletely vaccinated person up-to-date on his or her routine vaccinations.

Both the child and adolescent vaccination schedule and an adult vaccination schedule are published annually in the MMWR. Vaccine providers should obtain the most current schedules from the CDC Vaccines and Immunization website at www.cdc.gov/vaccines/. The text and Table 2-1, Table 2-2, Table 2-3, Table 2-4, Table 2-5, Table 2-6, Table 2-7 , 2-9 –2-10 , 2-18 –2-19 , 2-21 , 5-2, 7-2,7-3,7-4,7-5, 8-1, 8-7 and 8-8 of this publication present recommendations for the use, number of doses, dose intervals, adverse reactions, precautions, and contraindications for vaccines and toxoids that may be indicated for travelers. For specific vaccines and toxoids, additional details on background, adverse reactions, precautions, and contraindications are found in the respective ACIP statements.

Table 2-1.

Revaccination (booster) schedules

Vaccine	Recommendation
Japanese encephalitis	Full duration of protection unknown. Neutralizing antibodies may persist at least 2 years after primary immunization.
Hepatitis A (HAV)	Booster doses not recommended for adults and children who have completed the primary series (2 doses) according to the routine schedule
Hepatitis B (HBV)	Booster doses not recommended for adults and children who have completed the primary series (3 doses) according to the routine schedule1
Influenza	1 annual dose (children 6 months to 9 years of age and certain incompletely vaccinated children should receive 2 doses separated by at least 4 weeks the first time that influenza vaccine is administered). Live attenuated influenza vaccine is approved only for healthy nonpregnant persons 2–49 years of age.
Measles–mumps–rubella (MMR)	2 doses of MMR vaccine separated by at least 4 weeks or other evidence of immunity (e.g., serologic testing) is recommended for persons born after 1956 who travel outside the United States. Revaccination is not recommended.
Meningococcal Quadrivalent A,C,Y, W-135	Revaccination after 5 years is recommended for persons who received meningococcal polysaccharide vaccine and who remain at increased risk for meningococcal disease (including some international travelers). Revaccination is not recommended after receipt of meningococcal conjugate vaccine.
Pneumococcal (polysaccharide)	One-time revaccination 5 years after original dose for persons with certain underlying medical conditions (e.g., asplenia) or persons who were first vaccinated at younger than 65 years of age
Rotavirus	Booster doses not recommended
Polio (IPV)	A single lifetime booster dose is recommended for adults who have written documentation of having completed a primary series.
Rabies pre-exposure vaccine	No serologic testing or boosters recommended for travelers. For persons in higher risk groups (e.g., rabies laboratory workers) serologic testing and booster doses are recommended. See Table 2-17.
Tetanus/diphtheria, and acellular pertussis (Tdap)	Tetanus and diphtheria booster dose is recommended every 10 years. A single dose of adolescent/adult formulation Td that includes acellular pertussis vaccine (Tdap) is recommended to replace one Td booster dose for persons 11–64 years of age. See ACIP statement for details.
Typhoid oral	Repeat series every 5 years.
Typhoid IM	Booster dose every 2 years
Varicella	Revaccination is not recommended.
Yellow fever	Repeat vaccination every 10 years.

¹Booster dosing may be appropriate for certain populations, such as hemodialysis patients.

Table 2-2.

Recommended intervals between administration of antibody-containing products and measles-containing vaccine or varicella-containing vaccine¹

Indication	Dose	Recommended Interval Before Measles or Varicella Vaccination
Tetanus (TIG)	250 units (10 mg IgG/kg) IM2	3 months
Hepatitis A (IG), duration of international travel <3-month stay >3-month stay	0.02 mL/kg (3.3 mg IgG/kg) IM 0.06 mL/kg (10 mg IgG/kg) IM	3 months 3 months
Hepatitis B prophylaxis (HBIG)	0.06 mL/kg (10 mg IgG/kg) IM	3 months
Rabies prophylaxis (HRIG)	20 IU/kg (22 mg IgG/kg) IM	4 months
Varicella prophylaxis (VZIG)	125 units/10 kg (20–40 mg IgG/kg) IM (maximum 625 units)	5 months
Measles prophylaxis (IG) Immunocompetent contact Immunocompromised contact	0.25 mL/kg (40 mg IgG/kg) IM 0.50 mL/kg (80 mg IgG/kg) IM	5 months 6 months
Blood transfusion   Red blood cells (RBCs), washed RBCs, adenine-saline added Packed RBCs (Hct 65%)3 Plasma/platelet products	10 mL/kg (negligible IgG/kg) IV 10 mL/kg (10 mg IgG/kg) IV 10 mL/kg (60 mg IgG/kg) IV 10 mL/kg (160 mg IgG/kg) IV	None 3 months 6 months 7 months
Cytomegalovirus prophylaxis (CMV IGIV)	150 mg/kg maximum	6 months
Respiratory syncytial virus (RSV) monoclonal antibody (Synagis)4	15 mg/kg IM	None
Intravenous immune globulin (IGIV) Replacement therapy Immune thrombocytopenic purpura (ITP) ITP ITP or Kawasaki disease	300–400 mg/kg IV 400 mg/kg IV 1 gm/kg IV 1.6–2 gm/kg IV	8 months 8 months 10 months 11 months

¹Adapted from General Recommendations on Immunization, MMWR, 2006. This table is not intended for determining the correct indications and dosage for the use of IG preparations. Unvaccinated people may not be fully protected against measles during the entire recommended interval, and additional doses of immune globulin (IG) or measles vaccine may be indicated after measles exposure. Concentrations of measles antibody in an IG preparation can vary by manufacturer's lot. For example, fourfold or greater variation in the amount of measles antibody titers has been demonstrated in different IG preparations. Rates of antibody clearance after receipt of an IG preparation can also vary. Recommended intervals are extrapolated from an estimated half-life of 30 days for passively acquired antibody and an observed interference with the immune response to measles vaccine for 5 months after a dose of 80 mg IgG/kg.

²IG, immune globulin; IM, intramuscular; IV, intravenous.

³Assumes a serum IgG concentration of 16 mg/mL.

⁴Contains only antibody to respiratory syncytial virus.

Table 2-3.

Recommended and minimum ages and intervals between vaccine doses¹

Vaccine and Dose Number	Recommended Age for this Dose	Minimum Age for this Dose	Recommended Interval to Next Dose	Minimum Interval to Next Dose
Hepatitis B (HepB)-12	Birth	Birth	1–4 months	4 weeks
Hep B-2	1–2 months	4 weeks	2–17 months	8 weeks
Hep B-33	6–18 months	24 weeks	NA	NA
Diphtheria–tetanus–acellular pertussis (DTaP)-12	2 months	6 weeks	2 months	4 weeks
DTaP-2	4 months	10 weeks	2 months	4 weeks
DTaP-3	6 months	14 weeks	6–12 months	6 months4,5
DTaP-4	15–18 months	12 months	3 years	6 months4
DTaP-5	4–6 years	4 years	NA	NA
Haemophilus influenzae type b (Hib)-12,6	2 months	6 weeks	2 months	4 weeks
Hib-2	4 months	10 weeks	2 months	4 weeks
Hib-37	6 months	14 weeks	6–9 months	8 weeks
Hib-4	12–15 months	12 months	NA	NA
Inactivated poliovirus (IPV)-12	2 months	6 weeks	2 months	4 weeks
IPV-2	4 months	10 weeks	2–14 months	4 weeks
IPV-3	6–18 months	14 weeks	3–5 years	4 weeks
IPV-4	4–6 years	18 weeks	NA	NA
Pneumococcal conjugate (PCV)-16	2 months	6 weeks	2 months	4 weeks
PCV-2	4 months	10 weeks	2 months	4 weeks
PCV-3	6 months	14 weeks	6 months	8 weeks
PCV-4	12–15 months	12 months	NA	NA
Measles–mumps–rubella (MMR)-18	12–15 months	12 months	3–5 years	4 weeks
MMR-28	4–6 years	13 months	NA	NA
Varicella (Var)-1	12–15 months	12 months	3–5 years	12 weeks9
Var-2	4–6 years	15 months	NA	NA
Hepatitis A (HepA)-1	12–23 months	12 months	6–18 months4	6 months4
HepA-2	18–41 months	18 months	NA	NA
Influenza, inactivated10	6–18 years	6 months	4 weeks	4 weeks
Influenza, live attenuated10	NA	2 years	4 weeks	4weeks
Meningococcal conjugate (MCV)	11–12 years	11 years	NA	NA
Meningococcal polysaccharide (MPSV)-1	NA	2 years	5 years11	5 years11
MPSV-212	NA	7 years	NA	NA
Td	11–12 years	7 years	10 years	5 years
Tdap13	≥11 years	10 years	NA	NA
Pneumococcal polysaccharide (PPV)-1	NA	2 years	5 years	5 years
PPV-214	NA	7 years	NA	NA
Human papillomavirus (HPV)-115	11–12 years	9 years	2 months	4 weeks
HPV-2	2 months after dose 1	9 years, 4 weeks	4 months	12 weeks15
HPV-3	6 months after dose 1	9 years, 24 weeks	NA	NA
Rotavirus (RV)-116	2 months	6 weeks	2 months	4 weeks
RV-2	4 months	10 weeks	2 months	4 weeks
RV-316	6 months	14 weeks	NA	NA
Herpes zoster17	60 years	60 years	NA	NA
Typhoid, inactivated (ViCPS)	≥2 years	≥2 years	NA	NA
Typhoid, live attenuated (Ty21a)	≥6 years	≥6 years	See footnote 18	See footnote 18
Yellow Fever	>9 months19	>9 months19	10 years	10 years
Japanese encephalitis (JE)-1	≥1 year	1 year	7 days	7 days
JE-2	7 days after dose 1	1 year, 7 days	30 days	14 days
JE-3	30 days after dose 1	1 year, 21 days	NA	NA
Rabies-1 (pre-exposure)	See footnote 20	See footnote 20	7 days	7 days
Rabies-2	7 days after dose 1	7 days after dose 1	21 days	14 days
Rabies-3	21 days after dose 1	21 days after dose 1	NA	NA

DtaP, diphtheria and tetanus toxoids and acellular pertussis vaccine, pediatric (6 weeks through 6 years); MMR, measles, mumps and rubella; TIV, trivalent (inactivated) influenza vaccine; LAIV, live, attenuated (intranasal) influenza vaccine; Td, tetanus and reduced diphtheria toxoids, Tdap, tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis vaccine.

¹Combination vaccines are available. Use of licensed combination vaccines is generally preferred over separate injections of their equivalent component vaccines (CDC. Combination vaccines for childhood immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). MMWR Recomm Rep. 1999;48(RR-5):5). When administering combination vaccines, the minimum age for administration is the oldest age for any of the individual components; the minimum interval between doses is equal to the greatest interval of any of the individual components.

²Combination vaccines containing the HepB component are available (HepB-Hib, DTaP-HepB-IPV, HepA-HepB). These vaccines should not be administered to infants younger than 6 weeks of age because of the other components (i.e., Hib, DTaP, IPV). HepA-HepB is not licensed for persons <18 years of age in the United States.

³HepB-3 should be administered at least 8 weeks after Hep B-2 and at least 16 weeks after Hep B-1; it should not be administered before age 24 weeks.

⁴Calendar months.

⁵The minimum recommended interval between DTaP-3 and DTaP-4 is 6 months. However, DTaP-4 need not be repeated if administered at least 4 months after DTaP-3. Adapted from Table 1, CDC. General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1–48.

⁶For Hib and PCV, children receiving the first dose of vaccine at ≥7 months of age require fewer doses to complete the series (see the current childhood and adolescent immunization schedule at www.cdc.gov/vaccines/).

⁷If PRP-OMP (Pedvax-Hib, Merck Vaccine Division) was administered at 2 and 4 months of age, a dose at 6 months of age is not indicated. Adapted from Table 1, CDC. General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1–48.

⁸Combination MMR-varicella can be used for children 12 months through 12 years of age. Also see footnote ⁹.

⁹The minimum interval from VAR-1 to VAR-2 for persons beginning the series at ≥13 years of age is 4 weeks.

¹⁰Two doses of influenza vaccine are recommended only for children <9 years of age who are receiving the vaccine for the first time and for certain incompletely vaccinated children. See reference 5.

¹¹Some experts recommend that a second dose of MPSV be given 3 years after the first dose for persons at increased risk for meningococcal disease.

¹²A second dose of meningococcal vaccine is recommended for persons previously vaccinated with MPSV who remain at high risk for meningococcal disease. MCV is preferred when revaccinating persons 2–55 years of age (CDC. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005;54(RR07);1–21.) Adapted from Table 1, CDC. General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1–48.

¹³Only one dose of Tdap is recommended. Subsequent doses should be given as Td. If vaccination to prevent tetanus and/or diphtheria disease is required for children 7–9 years of age, Td should be given (minimum age for Td is 7 years). For one brand of Tdap, the minimum age is 11 years. The preferred interval between Tdap and a previous dose of Td is 5 years, but Tdap may be administered earlier if pertussis immunity is needed. For management of a tetanus-prone wound, the minimum interval after a previous dose of any tetanus-containing vaccine is 5 years.

¹⁴A second dose of PPV is recommended for persons at highest risk for serious pneumococcal infection and those who are likely to have a rapid decline in pneumococcal antibody concentration. (CDC. Prevention of pneumococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1997; 46(RR-8):1–24.)

¹⁵HPV is approved only for females 9–26 years of age. HPV-3 should be administered at least 12 weeks after HPV-2 and at least 24 weeks after HPV-1.

¹⁶The first dose of RV must be administered by 14 weeks and 6 days of age. The vaccine series should not be started at 15 weeks of age or older. The final dose in the series should be administered by age 8 months 0 days. If Rotarix rotavirus vaccine is administered at 2 and 4 months of age, a dose at 6 months of age is not indicated.

¹⁷Herpes zoster vaccine is approved as a single dose for persons 60 years of age and older.

¹⁸Oral typhoid vaccine is recommended to be administered 1 hour before a meal with a cold or lukewarm drink (temperature not to exceed body temperature) (i.e., 98.6° F (37° C)) on alternate days, for a total of 4 doses.

¹⁹Yellow fever vaccine may be administered to children younger than 9 months of age in certain situations. (CDC. Yellow Fever Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002. MMWR Recomm Rep. 2002;51(RR-17):6–7.)

²⁰There is no minimum age for pre-exposure immunization for rabies. (CDC. Human rabies prevention—United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008; 57(RR-3):1–28.)

Adapted from Table 1, CDC. General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1–48.

Table 2-4.

Licensed schedule for HAVRIX¹

Age Group (YRS)	Dose (EL.U.)2	Volume	No. of Doses	Schedule (Months)
1–18	720	0.5 mL	2	0, 6–2
≥19	1440	1.0 mL	2	0, 6–12

¹Hepatitis A vaccine, inactivated, GlaxoSmithKline.

²EL.U., enzyme-linked immunosorbent assay (ELISA) units of inactivated hepatitis A virus.

Table 2-5.

Licensed schedule for VAQTA¹

Age Group (YRS)	Dose (U.)2	Volume	No. of Doses	Schedule (Months)
1–18	25	0.5 mL	2	0, 6–18
≥19	50	1.0 mL	2	0, 6–18

¹Hepatitis A vaccine, inactivated, Merck & Co., Inc.

²U., units of hepatitis A virus antigen.

Table 2-6.

Licensed schedule for TWINRIX¹

Age Group (YRS)	Dose (EL.U./20 mg)2	Volume	No. of Doses	Schedule (Months)
≥18	720	1.0 mL	3	0, 1, 6 months
≥18	720	1.0 mL	4	0, 7, 21 days +1 year

¹Combined hepatitis A and hepatitis B vaccine, GlaxoSmithKline.

²EL.U., enzyme-linked immunosorbent assay (ELISA) units of inactivated hepatitis A virus/micrograms hepatitis B surface antigen.

Table 2-7.

Recommended doses of immune globulin (IG) for protection against hepatitis A

Setting	Duration of Coverage	Dose (Ml/Kg)1
Pre-exposure	Short-term (1–2 months)	0.02
	Long-term (3–5 months)	0.062
Postexposure	NA	0.02

¹IG should be administered by intramuscular injection into either the deltoid or gluteal muscle. For children <12 months of age, IG can be administered in the anterolateral thigh muscle.

²Repeat every 5 months if continued exposure to hepatitis A virus occurs.

Table 2-9.

Recommended doses of currently licensed formulations of hepatitis B vaccine

Group	Single-Antigen Vaccine				Combination Vaccine
	RECOMBIVAX HB		ENGERIX-B		COMVAX1		PEDIARIX2		TWINRIX3
	Dose (μg)4	Volume (ml)	Dose (μg)4	Volume (ml)	Dose (μg)4	Volume (ml)	Dose (μg)4	Volume (ml)	Dose (μg)4	Volume (ml)
Infants (<1 year)	57	0.5	107	0.5	5	0.5	10	0.5	NA5	NA
Children (1–10 years)	5	0.5	10	0.5	5	0.5	10	0.5	NA	NA
Adolescents
11–15 years	106	1.0	NA	NA	NA	NA	NA	NA	NA	NA
11–19 years	5	0.5	10	0.5	NA	NA	NA	NA	203	1.03
Adults (>20 years)	10	1.0	20	1.0	NA	NA	NA	NA	20	1.0
Hemodialysis patients and other immunocompromised persons7
<20 years7	5	0.5	10	0.5	NA	NA	NA	NA	NA	NA
≥20 years	408	10	409	2.0	NA	NA	NA	NA	NA	NA

¹Combined hepatitis B–Haemophilus influenzae type b conjugate vaccine. This vaccine cannot be administered before age 6 weeks or after age 71 months.

²Combined hepatitis B–diphtheria, tetanus, pertussis-inactivated poliovirus vaccine. This vaccine cannot be administered at birth, before age 6 weeks, or after age 7 years.

³Combined hepatitis A and hepatitis B vaccine. This vaccine is recommended for persons ≥18 years who are at increased risk for both hepatitis A virus and hepatitis B virus infections.

⁴Recombinant hepatitis B surface antigen dose.

⁵Not applicable.

⁶Adult formulation administered on a 2-dose schedule.

⁷Higher doses might be more immunogenic, but no specific recommendations have been made.

⁸Dialysis formulation administered on a 3-dose schedule at 0, 1, and 6 months.

⁹Two 1.0-mL doses administered at one site, on a 4-dose schedule at 0, 1, 2, and 6 months.

Table 2-10.

Dosage and schedule for typhoid fever vaccination

Vaccination	Age (Years)	Dose/Mode of Administration	No. of Doses	Dosing Interval	Boosting Interval
Oral, live, attenuated Ty21a vaccine (Vivotif)
Primary series	≥6	1 capsule,1 oral	4	48 hours	Not applicable
Booster	≥6	1 capsule,1 oral	4	48 hours	Every 5 years
Vi Capsular polysaccharide vaccine (Typhim Vi)
Primary series	≥2	0.50 mL, intramuscular	1	Not applicable	Not applicable
Booster	≥2	0.50 mL, intramuscular	1	Not applicable	Every 2 years

¹Administer with cool liquid no warmer than 98.6° F (37° C).

Table 2-18.

Pre-exposure immunization for rabies¹

Vaccine	Dose (Ml)	No. of Doses	Schedule (Days)	Route
HDCV	1.0	3	0, 7, and 21 or 28	Intramuscular
PCEC	1.0	3	0, 7, and 21 or 28	Intramuscular

¹HDCV, human diploid cell vaccine; PCEC, purified chick embryo cell. Patients who are immunosuppressed by disease or medications should postpone pre-exposure vaccinations and consider avoiding activities for which rabies pre-exposure prophylaxis is indicated. When this course is not possible, immunosuppressed persons who are at risk for rabies should have their antibody titers checked after vaccination.

Table 2-19.

Postexposure immunization for rabies¹

Immunization Status	Vaccine/Product	Dose	No. of Doses	Schedule (Days)	Route
Not previously immunized	RIG plus	20 IU/kg body weight	1	0	Infiltrated at bite site (if possible possible); remainder intramuscular
	HDCV or PCEC	1.0 mL	5	0, 3, 7, 14, 28	Intramuscular
Previously immunized2,3	HDCV or PCEC	1.0 mL	2	0, 3	Intramuscular

RIG, rabies immune globulin; HDCV, human diploid cell (rabies) vaccine; PCEC, purified chick embryo cell.

¹All postexposure prophylaxis should begin with immediate, thorough cleansing of all wounds with soap and water.

²Pre-exposure immunization with HDCV or PCEC, prior postexposure prophylaxis with HDCV or PCEC, or persons previously immunized with any other type of rabies vaccine and a documented history of positive antibody response to the prior vaccination.

³RIG should not be administered.

Table 2-21.

Summary guide to tetanus prophylaxis in routine wound management¹

History of Tetanus Immunization (Doses)	Clean, Minor Wounds		All Other Wounds
	Td2	TIG	Td2	TIG
Uncertain or <3 doses	Yes	No	Yes	Yes
3 or more doses	No3	No	No4	No

¹Important details in the text.

²For children <7 years old, DTaP or DTP (DT, if pertussis vaccine contraindicated) preferred to tetanus toxoid alone. For children ≥7 years of age, Td preferred to tetanus toxoid alone. For adolescents and adults to age 64, tetanus toxoid as Tdap is preferred, if the patient has not previously been vaccinated with Tdap.

³Yes, if more than 10 years since last dose.

⁴Yes, if more than 5 years since last dose. More frequent boosters are not needed and can accentuate side effects.

Spacing of Immunobiologics

Simultaneous Administration

All commonly used vaccines can safely and effectively be given simultaneously (i.e., on the same day) at separate sites without impairing antibody responses or increasing rates of adverse reactions. This knowledge is particularly helpful for international travelers, for whom exposure to several infectious diseases might be imminent. Simultaneous administration of all indicated vaccines is encouraged for persons who are the recommended age to receive these vaccines and for whom no contraindications exist. If not administered on the same day, an inactivated vaccine may be given at any time before or after a different inactivated vaccine or a live-virus vaccine.

The immune response to an injected or intranasal live-virus vaccine (e.g., measles, mumps and rubella (MMR); varicella; yellow fever; or live attenuated influenza vaccine) might be impaired if administered within 28 days of another live-virus vaccine. Whenever possible, injected live-virus vaccines administered on different days should be given at least 28 days apart. If two injected or intranasal live-virus vaccines are not administered on the same day but less than 28 days apart, the second vaccine should be readministered at least 4 weeks after the first vaccine was administered.

Live-virus vaccines can interfere with the response to tuberculin testing. Tuberculin testing, if otherwise indicated, can be done either on the day that live-virus vaccines are administered or 4–6 weeks later. Tuberculin skin testing is not a prerequisite for administration of any vaccine.

Missed Doses and Boosters

Travelers may forget to return for a follow-up dose of vaccine or booster at the specified time. Occasionally the demand for a vaccine may exceed its supply, and providers may have difficulty obtaining vaccines. (Information on vaccine shortages and recommendations can be found on the CDC Vaccines and Immunization website at www.cdc.gov/vaccines/vac-gen/shortages/default.htm.) It is unnecessary in these cases to restart the interrupted series or to add any extra doses except for oral typhoid. The next scheduled dose should be given when the patient presents. (There are no data for interrupted dosing with oral typhoid vaccine; thus, a travel medicine specialist should be consulted.) Some vaccines require periodic booster doses to maintain protection (Table 2-1).

Antibody-Containing Blood Products

When MMR and varicella vaccines are given shortly before, simultaneously with, or after an antibody-containing blood product, such as immune globulin (IG) or a blood transfusion, response to the vaccine can be diminished. Antibody-containing blood products from the United States do not interfere with the immune response to yellow fever vaccine and are not believed to interfere with the response to live attenuated influenza vaccine or rotavirus vaccine. The duration of inhibition of MMR and varicella vaccines is related to the dose of IG in the product. MMR or its components and varicella vaccines either should be administered at least 2 weeks before receipt of a blood product or should be delayed 3–11 months after receipt of the blood product, depending on the vaccine (Table 2-2).

Immunoglobulin (IG) administration may become necessary for another indication after MMR or its individual components or varicella vaccines have been given. In such a situation, the IG may interfere with the immune response to the MMR or varicella vaccines. Vaccine virus replication and stimulation of immunity usually occur 2–3 weeks after vaccination. If the interval between administration of one of these vaccines and the subsequent administration of an IG preparation is 14 days or more, the vaccine need not be readministered. If the interval is less than 14 days, the vaccine should be readministered after the interval shown in Table 2-2, unless serologic testing indicates that antibodies have been produced. If administration of IG becomes necessary, MMR or its components or varicella vaccines can be administered simultaneously with IG, with the recognition that vaccine-induced immunity can be compromised. The vaccine should be administered at a body site different from that chosen for the IG injection. Vaccination should be repeated after the interval noted in Table 2-2, unless serologic testing indicates antibodies have been produced.

When IG is given with the first dose of hepatitis A vaccine, the proportion of recipients who develop a protective level of antibody is not affected, but antibody concentrations are lower. Because the final concentrations of antibody are many times higher than those considered protective, this reduced immunogenicity is not expected to be clinically important. IG preparations interact minimally with other inactivated vaccines and toxoids. Other inactivated vaccines may be given simultaneously or at any time interval after or before an antibody-containing blood product is used. However, such vaccines should be administered at different sites from the IG.

Vaccination of Persons with Acute Illnesses

Every opportunity should be taken to provide appropriate vaccinations. The decision to delay vaccination because of a current or recent acute illness depends on the severity of the symptoms and their cause. Although a moderate or severe acute illness is sufficient reason to postpone vaccination, minor illnesses (e.g., diarrhea, mild upper respiratory infection with or without low-grade fever, other low-grade febrile illness) are not contraindications to vaccination.

Persons with moderate or severe acute illness, with or without fever, should be vaccinated as soon as the condition has improved. This precaution is to avoid superimposing adverse effects from the vaccine on underlying illness or mistakenly attributing a manifestation of underlying illness to the vaccine. Antimicrobial therapy is not a contraindication to vaccination, with three exceptions. Antibacterial agents may interfere with the response to oral typhoid vaccine. Antiviral agents active against herpesviruses (e.g., acyclovir) may interfere with the response to varicella-containing vaccines (varicella, MMRV, zoster). Antiviral agents active against influenza virus (e.g., zanamivir, oseltamivir) may interfere with the response to live attenuated influenza vaccine.

A physical examination or temperature measurement is not a prerequisite for vaccinating a person who appears to be in good health. Asking if a person is ill, postponing a vaccination for someone with moderate or severe acute illness, and vaccinating someone without contraindications are appropriate procedures for clinic immunizations.

Altered Immunocompetence

Altered immunocompetence is a general term that is often used interchangeably with the terms immunosuppression and immunodeficiency. It can be caused either by a disease (e.g., leukemia, HIV infection) or by drugs or other therapies (e.g., cancer chemotherapy, prolonged high dose corticosteroids). It can also include conditions such as asplenia and chronic renal disease.

Determination of altered immunocompetence is important because the incidence or severity of some vaccine-preventable diseases is higher in persons with altered immunocompetence. Therefore, certain vaccines (e.g., inactivated influenza vaccine, pneumococcal vaccines) are recommended specifically for persons with these diseases. Inactivated vaccine may be safely administered to a person with altered immunocompetence, although response to the vaccine may be suboptimal. The vaccine may need to be repeated after immune function has improved.

Persons with altered immunocompetence may be at increased risk for an adverse reaction following administration of live attenuated vaccines because of reduced ability to mount an effective immune response. Live vaccines should generally be deferred until immune function has improved. This is particularly important when planning to give yellow fever vaccine (see the Yellow Fever section later in this chapter). MMR and varicella vaccines are recommended for persons with mild or moderate immunosuppression.

For an in-depth discussion, see The Immunocompromised Traveler section in Chapter 8.

Vaccination Scheduling for Last-Minute Travelers

As noted in the Simultaneous Administration section, most vaccine products can be given during one visit for persons anticipating imminent travel. Unless the vaccines given are booster doses of those typically given during childhood, vaccines may require a month or more to induce a sufficient immune response, depending on the vaccine and the number of doses in the series.

Some vaccines require more than one dose for best protection. Recommended spacing should be maintained between doses (Table 2-3). Doses given at less than minimum intervals can lessen the antibody response. Administration of a vaccine earlier than the recommended minimum age or at an interval shorter than the recommended minimum is discouraged. Table 2-3 lists the minimum age and minimum interval between doses for vaccines routinely recommended in the United States. Because some travelers visit their health-care providers without ample time for administration of the vaccine doses recommended for optimal protection against certain diseases, studies have been performed and others are ongoing to determine whether accelerated scheduling is adequate. This concern is primarily the case for hepatitis B vaccine or the combined hepatitis A and B vaccine. An accelerated schedule for combined hepatitis A and hepatitis B vaccine has been approved by the U.S. Food and Drug Administration (FDA). It is unclear what level of protection any given traveler will have if a full series of multidose vaccination is not completed.

Allergy to Vaccine Components

Vaccine components can cause allergic reactions in some recipients. These reactions can be local or systemic and can include anaphylaxis or anaphylactic-like responses. The vaccine components responsible can include the vaccine antigen, animal proteins, antibiotics, preservatives (e.g., thimerosal), or stabilizers (e.g., gelatin). The most common animal protein allergen is egg protein in vaccines prepared by using embryonated chicken eggs (influenza and yellow fever vaccines). Generally, persons who can eat eggs or egg products safely may receive these vaccines, while those with histories of anaphylactic allergy (e.g., hives, swelling of the mouth and throat, difficulty breathing, hypotension, shock) to eggs or egg proteins ordinarily should not. Screening persons by asking whether they can eat eggs without adverse effects is a reasonable way to identify those who might be at risk from receiving yellow fever and influenza vaccines. Recent studies have indicated that other components in vaccines in addition to egg proteins (e.g., gelatin) may cause allergic reactions, including anaphylaxis in rare instances. Protocols have been developed for testing and vaccinating persons with anaphylactic reactions to egg ingestion.

Some vaccines contain a preservative or trace amounts of antibiotics to which people might be allergic. Those administering the vaccine(s) should carefully review the information provided in the package insert before deciding if the rare person with such an allergy should receive the vaccine. No currently recommended vaccine contains penicillin or penicillin derivatives. Some vaccines (e.g., MMR and its individual component vaccines, inactivated polio vaccine [IPV], varicella, rabies) contain trace amounts of neomycin or other antibiotics; the amount is less than would normally be used for the skin test to determine hypersensitivity. However, persons who have experienced anaphylactic reactions to this antibiotic generally should not receive these vaccines. Most often, neomycin allergy is a contact dermatitis—a manifestation of a delayed-type (cell-mediated) immune response rather than anaphylaxis. A history of delayed-type reactions to neomycin is not a contraindication to receiving these vaccines.

Thimerosal, an organic mercurial compound in use since the 1930s, has been added to certain immunobiologic products as a preservative. Thimerosal is present at preservative concentrations (trace quantities) in multidose vials of some brands of inactivated influenza vaccine, pediatric DT, single-antigen tetanus toxoid, meningococcal polysaccharide vaccine, and Japanese encephalitis vaccine. Receiving thimerosal-containing vaccines has been postulated to lead to induction of allergy. However, there is limited scientific evidence for this assertion. Allergy to thimerosal usually consists of local delayed-type hypersensitivity reactions. Thimerosal elicits positive delayed-type hypersensitivity patch tests in 1%–18% of persons tested, but these tests have limited or no clinical relevance. The majority of persons do not experience reactions to thimerosal administered as a component of vaccines, even when patch or intradermal tests for thimerosal indicate hypersensitivity. A localized or delayed-type hypersensitivity reaction to thimerosal is not a contraindication to receipt of a vaccine that contains thimerosal.

Since mid-2001, vaccines routinely recommended for infants have been manufactured without thimerosal as a preservative. Additional information about thimerosal and the thimerosal content of vaccines is available on the FDA website at www.fda.gov/cber/vaccine/thimerosal.htm.

Reporting Adverse Events Following Immunization

Modern vaccines are extremely safe and effective. Benefits and risks are associated with the use of all immunobiologics—no vaccine is completely effective or completely free of side effects. Adverse events following immunization have been reported with all vaccines, ranging from frequent, minor, local reactions to extremely rare, severe, systemic illness, such as that associated with yellow fever vaccine (see Yellow Fever section later in this chapter). Side effects and adverse events following specific vaccines and toxoids are discussed in detail in each ACIP statement. Health-care providers are required by law to report selected adverse events occurring after vaccination with tetanus vaccine in any combination; pertussis in any combination; measles, mumps or rubella alone or in any combination, oral polio vaccine (OPV), IPV, hepatitis B; varicella; Haemophilus influenzae type b (conjugate); pneumococcal conjugate; and rotavirus vaccines. In addition, CDC strongly recommends that all vaccine adverse events be reported to the Vaccine Adverse Event Reporting System (VAERS), even if a causal relation to vaccination is not certain. VAERS reporting forms and information are available electronically at www.vaers.hhs.gov or may be requested by telephone: 800-822-7967. Health-care providers are encouraged to report electronically at https://secure.vaers.org/VaersDataEntryintro.htm.

Injection Route and Injection Site

Injectable vaccines are administered by intramuscular and subcutaneous routes. The method of administration of injectable vaccines depends in part on the presence of an adjuvant in some vaccines. The term adjuvant refers to a vaccine component distinct from the antigen, which enhances the immune response to the antigen. Vaccines containing an adjuvant (i.e., DTaP, DT, human papillomavirus, Td, Tdap, pneumococcal conjugate, Hib, hepatitis A, hepatitis B) should be injected into a muscle mass because administration subcutaneously or intradermally can cause local irritation, induration, skin discoloration, inflammation, and granuloma formation. Routes of administration are recommended by the manufacturer for each immunobiologic. Deviation from the recommended route of administration may reduce vaccine efficacy or increase local adverse reactions. Detailed recommendations on the appropriate route and site for all vaccines have been published in ACIP recommendations; a compiled list of these publications is available on the CDC website at www.cdc.gov/vaccines/pubs/ACIP-list.htm (also see Appendix C: Travel Vaccine Summary Table).

 

Travel-Related Vaccine-Preventable Diseases

HEPATITIS A

Steven T. Wiersma

Infectious Agent

Hepatitis A virus (HAV), a 27-nm RNA virus classified as a picornavirus.

Mode of Transmission

• •Transmission can occur through direct person-to-person contact; through exposure to contaminated water, ice, or shellfish harvested from sewage-contaminated water; or from fruits, vegetables, or other foods that are eaten uncooked and that were contaminated during harvesting or subsequent handling.
• •HAV is shed in the feces of persons with HAV infection. The virus reaches peak levels the week or two before onset of symptoms and diminishes rapidly after liver dysfunction or symptoms appear, which is concurrent with the appearance of circulating antibodies to HAV. Infants and children, however, may shed virus for up to 6 months following infection.

Occurrence

• •Worldwide, geographic areas can be characterized by high, intermediate, or low levels of endemicity (Map 2-1 ). Levels of endemicity are related to hygienic and sanitary conditions in the geographic areas.
• •HAV infection is common (high or intermediate endemicity) throughout the developing world, where infections most frequently are acquired during early childhood and usually are asymptomatic or mild.
• •In areas of high endemicity, adults are usually immune and epidemics of hepatitis A are uncommon.
• •In developed countries, HAV infection is less common (low endemicity), but community-wide outbreaks may occur.
• • Map 2-1 indicates the seroprevalence of antibody to HAV (total anti-HAV) as measured in selected cross-sectional studies among each country's residents. The seroprevalence of anti-HAV provides an estimate of the endemicity of HAV infections, including asymptomatic infections, within a population.

Map 2-1.

Prevalence of antibody to hepatitis A virus, 2006.1

(Seenote 1on opposite page.)

Box 2-1. Hepatitis A pre-travel case study.

Case study: You are a travel medicine professional preparing a group for travel to an eastern European country that is shown in Maps 2-1 to have an intermediate prevalence of antibody to hepatitis A virus (anti-HAV). You have recommended that all members of the group take precautions to prevent hepatitis A. The leader of the group questions your advice on the basis of an editorial from a major newspaper written by the ambassador to the U.S. from this country. The editorial claims that her country is stigmatized in the U.S. and cites the example of the Yellow Book, which indicates that travelers from the U.S. to this country are at risk for hepatitis A. The editorial states that cases of hepatitis A are at very low levels in this country and seem to be declining over time. How would you respond to the members of the group?

Points to consider in your response:

• •In most intermediate and high anti-HAV-endemic countries, many long-term residents are infected as children, at a time when they may not get symptoms. Cases of hepatitis A in the resident population will be very low; however, travelers from low endemic settings such as the United States are at risk for HAV infection and should be protected.
• •The determination of risk is based on CDC estimates of prevalence of anti-HAV, a marker of previous HAV infection. This country-level estimate is based on limited data and might not reflect the current prevalence.
• •Prevention of hepatitis A in travelers with vaccination should be used liberally because the vaccine is safe and effective and will give long-term benefits that go beyond the risk posed by any specific trip.

Risk for Travelers

• • Hepatitis A is one of the most common vaccine-preventable infections acquired during travel.
• •In 2006 in the United States, among cases for which information regarding exposures during the incubation period was collected, the most frequently identified risk factor for hepatitis A was international travel (reported by 15% of case-patients overall).
• •As in previous years, most travel-related cases (72%) were associated with travel to Mexico and Central/South America. As HAV transmission in the United States has decreased, cases among travelers to countries in which hepatitis is endemic have accounted for an increased proportion of all cases.
• •The risk of acquiring HAV infection for U.S. residents traveling abroad varies with living conditions, length of stay, and the incidence of HAV infection in the area visited. For travelers to other countries, risk for infection increases with duration of travel and is highest for those who live in or visit rural areas, trek in back-country areas, or frequently eat or drink in settings of poor sanitation.
• •Nevertheless, many cases of travel-related hepatitis A occur in travelers to developing countries with “standard” tourist itineraries, accommodations, and food consumption behaviors.

Clinical Presentation

• •HAV infection may be asymptomatic, or its clinical manifestations may range in severity from a mild illness lasting 1–2 weeks to a severely disabling disease lasting several months.
• •Clinical manifestations of hepatitis A often include the abrupt onset of fever, malaise, anorexia, nausea, and abdominal discomfort, followed within a few days by jaundice.
• • The incubation period for hepatitis A averages 28 days (range: 15–50 days).
• •The likelihood of having symptoms with HAV infection is related to the infected person's age. In children <6 years of age, most (70%) infections are asymptomatic; if illness does occur, its duration is usually less than 2 months.
• •No chronic or long-term infection is associated with hepatitis A, but 10% of infected persons will have prolonged or relapsing symptoms over a 6- to 9-month period.
• •The overall case–fatality rate among cases reported to CDC is 0.3%; however, the rate is 1.8% among adults >50 years of age.

Diagnosis

• •Demonstration of IgM antibodies against hepatitis A virus (IgM anti-HAV) in the serum of acutely or recently ill patients establishes the diagnosis.
• •IgM anti-HAV becomes detectable 5–10 days after exposure. A fourfold or greater rise in specific antibodies in paired sera, detected by commercially available EIA, also establishes the diagnosis.
• •If laboratory tests are not available, epidemiologic evidence may provide support for the diagnosis in a clinically compatible case.
• •HAV RNA can be detected in blood and stools of most persons during the acute phase of infection through nucleic acid amplification methods, but these are not generally used for diagnostic purposes.

Treatment

No specific treatment is available for persons with hepatitis A. Treatment is supportive.

Preventive Measures for Travelers

Health-care providers should administer hepatitis A vaccination for persons traveling for any purpose, frequency, or duration to countries that have high or intermediate endemicity of HAV infection. Providers may also consider its administration to persons for travel to any destination.

Vaccine and Immune Globulin

Monovalent Vaccines

• •
  Two monovalent hepatitis A vaccines are currently licensed in the United States for persons at least 12 months of age:

  • ○
    HAVRIX, manufactured by GlaxoSmithKline (Table 2-4), and
  • ○
    VAQTA manufactured by Merck & Co., Inc. (Table 2-5).
• •Both vaccines are made of inactivated HAV adsorbed to aluminum hydroxide as an adjuvant. HAVRIX is prepared with 2-phenoxyethanol as a preservative, while VAQTA is formulated without a preservative.
• •All hepatitis A vaccines should be administered intramuscularly in the deltoid muscle.

Combination Vaccine

• •TWINRIX, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B vaccine licensed for persons Δ18 years of age, containing 720 EL.U. of hepatitis A antigen (50% of the HAVRIX adult dose) and 20 mg of recombinant hepatitis B surface antigen protein (the same as the ENGERIX-B adult dose) (Table 2-6).
• •Primary immunization consists of three doses, given on a 0-, 1-, and 6-month schedule, the same schedule as that commonly used for monovalent hepatitis B vaccine.
• • TWINRIX contains aluminum phosphate and aluminum hydroxide as adjuvants and 2-phenoxyethanol as a preservative.
• •An accelerated schedule of TWINRIX (i.e., doses at days 0, 7, and 21) for travelers has been approved by the FDA. A booster dose should be given at 1 year.
• •The immunogenicity of TWINRIX is equivalent to that of the monovalent hepatitis vaccines when tested after completion of the licensed schedule.

Vaccination of Travelers

• •All susceptible persons traveling to or working in countries that have high or intermediate hepatitis A endemicity should be vaccinated or receive IG before departure. Hepatitis A vaccine at the age-appropriate dose is preferred to IG. The first dose of hepatitis A vaccine should be administered as soon as travel to countries with high or intermediate endemicity is considered.
• •One dose of monovalent hepatitis A vaccine administered at any time before departure can provide adequate protection for most healthy persons <40 years of age.
• •Completion of the vaccine series according to the licensed schedule is necessary for long-term protection.
• •Many persons will have detectable anti-HAV in response to the monovalent vaccine by 2 weeks after the first vaccine dose. The proportion of persons who develop a detectable antibody response at 2 weeks may be lower when smaller vaccine dosages are used, such as with the use of TWINRIX.
• •For optimal protection, older adults, immunocompromised persons, and persons with chronic liver disease or other chronic medical conditions planning to depart to an area in <2 weeks should receive the initial dose of vaccine along with IG (0.02 mL/kg) at a separate anatomic injection site.
• •Travelers who receive hepatitis A vaccine less than 2 weeks before traveling to an endemic area and who do not receive IG (either by choice or because of lack of availability) will be at lower risk for infection than those who do not receive hepatitis A vaccine or IG.
• • Although vaccination of an immune traveler is not contraindicated and does not increase the risk for adverse effects, screening for total anti-HAV before travel can be useful in some circumstances to determine susceptibility and eliminate unnecessary vaccination or IG prophylaxis of immune travelers. Such serologic screening for susceptibility might be indicated for adult travelers who are >40 years of age and those born in areas of the world with intermediate or high endemicity who are likely to have had prior HAV infection, if the cost of screening (laboratory and office visit) is less than the cost of vaccination or IG prophylaxis and if testing will not delay vaccination and interfere with timely receipt of vaccine or IG before travel. Postvaccination testing for serologic response is not indicated.
• •Travelers who are <12 months of age, are allergic to a vaccine component, or who otherwise elect not to receive vaccine should receive a single dose of IG (0.02 mL/kg), which provides effective protection against HAV infection for up to 3 months (Table 2-7).
• •Those who do not receive vaccination and plan to travel for >3 months should receive an IG dose of 0.06 mL/kg, which must be repeated if the duration of travel is >5 months.
• •In addition, health-care providers should be alert to opportunities to provide vaccination for all travelers whose plans might include travel at some time in the future to an area of high or intermediate endemicity, including those whose current medical evaluation is for travel to an area where hepatitis A vaccination is not currently recommended.
• •Those who refuse vaccine and IG should be advised to closely adhere to prevention tips listed below.

Other Vaccine Considerations

• •Using the vaccines according to the licensed schedules is preferable. However, an interrupted series does not need to be restarted.
• •Given their similar immunogenicity, a series that has been started with one brand of monovalent vaccine (i.e., HAVRIX or VAQTA) may be completed with the other brand.
• •Hepatitis A vaccine may be administered at the same time as IG or other commonly used vaccines for travelers, at different injection sites.
• •In adults and children who have completed the vaccine series, anti-HAV has been shown to persist for at least 5–12 years after vaccination. Results of mathematical models indicate that, after completion of the vaccination series, anti-HAV will likely persist for 20 years or more. For children and adults who complete the primary series, booster doses of vaccine are not recommended.

Vaccine Safety and Adverse Reactions

• •Among adults, the most frequently reported side effects occurring 3–5 days after a vaccine dose are tenderness or pain at the injection site (53%–56%) or headache (14%–16%).
• •Among children, the most common side effects reported are pain or tenderness at the injection site (15%–19%), feeding problems (8% in one study), or headache (4% in one study).
• • No serious adverse events in children or adults that could be definitively attributed to the vaccine or to increases in serious adverse events among vaccinated persons compared with baseline rates have been identified.
• •IG for intramuscular administration prepared in the United States has few side effects (primarily soreness at the injection site) and has never been shown to transmit infectious agents (hepatitis B virus, hepatitis C virus [HCV], or HIV).
• •Since December 1994, all IG products commercially available in the United States have had to undergo a viral inactivation procedure or be negative for HCV RNA before release.

Precautions and Contraindications

• •These vaccines should not be administered to travelers with a history of hypersensitivity to any vaccine component.
• •HAVRIX or TWINRIX should not be administered to travelers with a history of hypersensitivity reactions to the preservative 2-phenoxyethanol.
• •TWINRIX should not be administered to persons with a history of hypersensitivity to yeast.
• •Because hepatitis A vaccine consists of inactivated virus and hepatitis B vaccine consists of a recombinant protein, no special precautions need to be taken for vaccination of immunocompromised travelers.

Pregnancy

• •The safety of hepatitis A vaccine for pregnant women has not been determined.
• •However, because hepatitis A vaccine is produced from inactivated HAV, the theoretical risk to either the pregnant woman or the developing fetus is thought to be very low.
• •The risk of vaccination should be weighed against the risk of hepatitis A in female travelers who might be at high risk for exposure to HAV.
• •Pregnancy is not a contraindication to using IG.

Other Prevention Tips

• •Boiling or cooking food and beverage items for at least 1 minute to 185° F (85° C) inactivates HAV. Foods and beverages heated to this temperature and for this length of time cannot serve as vehicles for HAV infection unless they become contaminated after heating.
• •Adequate chlorination of water as recommended in the United States will inactivate HAV.
• •Travelers should be advised that, to minimize their risk of hepatitis A and other enteric diseases in developing countries, they should avoid potentially contaminated water or food.
• •Travelers should also be advised to avoid drinking beverages (with or without ice) of unknown purity, eating uncooked shellfish, and eating uncooked fruits or vegetables that are not peeled or prepared by the traveler personally.

HEPATITIS B

Sandra S. Chaves

Infectious Agent

Hepatitis B is caused by the hepatitis B virus (HBV), a small, circular, partially double-stranded DNA molecule in the Hepadnaviridae family.

Mode of Transmission

HBV is transmitted through activities that involve contact with blood or blood-derived fluids. Such activities include the following:

• •Unprotected sex with an HBV-infected partner
• •Shared needles used for injection of illegal drugs
• •Shared glucose-monitoring equipment
• •Work in health-care fields (e.g., medical, dental, laboratory) that entails direct exposure to potentially infected human blood
• •Transfusions with blood or blood products that have not been screened for HBV
• •Dental, medical, or cosmetic (e.g., tattooing, body piercing) procedures with needles or other equipment that are contaminated with HBV

In addition, open skin lesions, such as those due to impetigo, scabies, or scratched insect bites, can play a role in HBV transmission if direct exposure to wound exudates from HBV-infected persons occurs.

Occurrence

• •The prevalence of chronic HBV infection is low (<2%) in the general population in Northern and Western Europe, North America, Australia, New Zealand, Mexico, and southern South America (Map 2-2 ).
• •The prevalence of chronic HBV infection is intermediate (2%–7%) in South, Central, and Southwest Asia, Israel, Japan, Eastern and Southern Europe, Russia, most areas surrounding the Amazon River basin, Honduras, and Guatemala (see Maps 2-2).
• •The prevalence of chronic HBV infection is high (Δ8%) in all socioeconomic groups in: all of Africa; Southeast Asia, including China, Korea, Indonesia, and the Philippines; the Middle East, except Israel; South and Western Pacific islands; the interior Amazon River basin; and certain parts of the Caribbean (Haiti and the Dominican Republic) (see Maps 2-2).

Map 2-2.

Prevalence of chronic infection with hepatitis B virus, 2006.

Risk for Travelers

There are no data with which to assess the risk for HBV infection among U.S. travelers. The risk for HBV infection for international travelers is considered generally low, except for travelers to countries where the prevalence of chronic HBV infection is intermediate or high. Some travelers, such as adventure travelers, Peace Corps volunteers, missionaries, and military personnel, may be at increased risk for infection.

Situations or activities that may carry increased risk for HBV infection for travelers while overseas include the following:

• •An injury or illness that requires invasive medical attention (e.g., injection, IV drip, transfusion, stitching)
• •Dental treatment
• •Unprotected sexual contact
• •Sharing illegal drug injection equipment
• •Skin-perforation practices (e.g., tattooing, ear piercing, acupuncture)
• •Cosmetic practices with risk for skin perforation (e.g., manicure/pedicure)
• •Sharing personal grooming items (e.g., earrings, toothbrush, razor)

Clinical Presentation

• •Incubation period of hepatitis B is typically 90 days (range: 60–150 days) from exposure to onset of jaundice.
• •Constitutional symptoms such as malaise and anorexia may precede jaundice by 1–2 weeks.
• •Clinical symptoms and signs include nausea, vomiting, abdominal pain, and jaundice.
• •Skin rashes, joint pain, and arthritis may occur.
• •Infants, children <5 years of age, and immunosuppressed adults with newly acquired HBV infection typically are asymptomatic.
• •Infected persons Δ5 years of age, including immunocompetant adults, 30%–50% have initial clinical signs or symptoms.
• •The case–fatality rate of acute hepatitis B is approximately 1%.
• •Acute HBV infection causes chronic (long-term) infection in 30%–90% of persons infected as infants or young children and in <5% of adolescents and adults.
• •Chronic infection can lead to chronic liver disease, liver scarring (cirrhosis), and liver cancer.

Diagnosis

At least one serologic marker is present during each of the different phases of HBV infection. The serologic markers are typically used to differentiate between acute, resolving, and chronic infection (Table 2-8 ).

Table 2-8.

Typical interpretation of serologic test results for hepatitis B virus infection

Serologic Marker				Interpretation
HBsAg1	Total anti-HBc2	IgM3 anti-HBc	Anti-HBs4
–5	–	–	–	Never infected
+6,7	–	–	–	Early acute infection; transient (up to 18 days) after vaccination
+	+	+	–	Acute infection
–	+	+	+ or −	Acute resolving infection
–	+	–	+	Recovered from past infection and immune
+	+	–	–	Chronic infection
–	+	–	–	False-positive (i.e., susceptible); past infection; “low-level” chronic infection;8 or passive transfer of anti-HBc to infant born to HBsAg-positive mother
–	–	–	+	Immune if concentration is ≥10 mIU/mL after vaccine series completion;9 passive transfer after hepatitis B immune globulin administration

¹Hepatitis B surface antigen.

²IgG antibody to hepatitis B core antigen.

³Immunoglobulin M.

⁴Antibody to HBsAg.

⁵Negative test result.

⁶Positive test result.

⁷To ensure that an HBsAg-positive test result is not a false-positive, samples with reactive HBsAg results should be tested with a licensed neutralizing confirmatory test if recommended in the manufacturer's package insert.

⁸Persons positive only for anti-HBc are unlikely to be infectious except under unusual circumstances in which they are the source for direct percutaneous exposure of susceptible recipients to large quantities of virus (e.g., blood transfusion or organ transplant).

⁹Milli-international units per milliliter.

From CDC. MMWR Recomm Rep. 2006; 55(RR-16):1–25.

Treatment

No specific treatment is available for acute illness caused by hepatitis B. Antiviral drugs are approved for the treatment of chronic hepatitis B.

Preventive Measures for Travelers

Vaccine

• •Hepatitis B vaccination should be administered to all unvaccinated persons traveling to areas with intermediate to high levels of endemic HBV transmission (i.e., with hepatitis B surface antigen [HBsAg] prevalence Δ2%).
• •Hepatitis B vaccination is currently recommended for all U.S. residents who work in health-care fields (e.g., medical, dental, laboratory) that involve potential exposure to human blood.
• •All unvaccinated U.S. children and adolescents (<19 years of age) should receive hepatitis B vaccine.
• •Unvaccinated persons who have indications for hepatitis B vaccination independent of travel should be vaccinated (e.g., men who have sex with men, injection drug users, anyone who has recently had a sexually transmitted disease or has had more than one sex partner in the previous 6 months).

Vaccine Dose and Administration

• •The vaccine is usually administered as a three-dose series on a 0-, 1-, and 6-month schedule (see Table 2-9). The second dose should be given 1 month after the first dose; the third dose should be given at least 2 months after the second dose and at least 4 months after the first dose.
• •Alternatively, the vaccine ENGERIX-B, manufactured by GlaxoSmithKline, is also approved for administration on a four-dose schedule at 0, 1, 2, and 12 months.
• •There is also a two-dose schedule for RECOMBIVAX HB, a vaccine produced by Merck & Co., Inc., which has been licensed for children and adolescents 11–15 years of age. Using the two-dose schedule, the adult dose of RECOMBIVAX HB is administered, with the second dose given 4–6 months after the first dose.
• •A three-dose series that has been started with one brand of vaccine may be completed with the other brand.
• •TWINRIX, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B vaccine licensed for persons 18 years of age or older. Primary immunization consists of three doses, given on a 0-, 1-, and 6-month schedule.

Special Situations

• •Ideally, vaccination should begin at least 6 months before travel so the full vaccine series can be completed before departure. Because some protection is provided by one or two doses, the vaccine series should be initiated, if indicated, even if it cannot be completed before departure. Optimal protection, however, is not conferred until after the final vaccine dose. Travelers should be advised to return for completion of the vaccine series.
• • An accelerated vaccine schedule could be used for those traveling to endemic areas at short notice and facing imminent exposure because of behavioral risks or to emergency responders to disaster areas. The monovalent hepatitis B vaccines can be used at 0, 7, and 14 days. If an accelerated schedule is used, the patient should receive a booster dose at least 6 months after the start of the series to promote long-term immunity.
• •An accelerated vaccine schedule with TWINRIX (hepatitis A and hepatitis B vaccine) can also be used (doses at 0, 7, and 21–30 days). In this situation, a booster dose should be given at 12 months to promote long-term immunity.
• •For children and adults whose immune status is normal, booster doses of vaccine are not recommended. Serologic testing to assess antibody levels is not necessary for most vaccinees (see the Vaccine Recommendations for Infants and Children section in Chapter 7).

Vaccine Safety and Adverse Reactions

• •Hepatitis B vaccines have been shown to be safe for persons of all ages. Pain at the injection site (3%–29%) and elevated temperature higher than 37.7° C (99.9° F) (1%–6%) are the most frequently reported side effects among vaccine recipients.
• •These vaccines should not be administered to persons with a history of hypersensitivity to any vaccine component, including yeast. The vaccine contains a recombinant protein (HBsAg) that is noninfectious. Limited data indicate that there is no apparent risk of adverse events to the developing fetus when hepatitis B vaccine is administered to pregnant women. HBV infection affecting a pregnant woman can result in serious disease for the mother and chronic infection for the newborn. Neither pregnancy nor lactation should be considered a contraindication for vaccination.

Other Preventive Measures

• •As part of the pre-travel education process, all travelers should be given information about the risks for hepatitis B and other bloodborne pathogens from contaminated medical equipment, injection drug use, or sexual activity and informed of prevention measures (see below), including hepatitis B vaccination, that can be used to prevent transmission of HBV.
• •Regardless of destination, all persons who may engage in practices that put them at risk for HBV infection during travel should receive hepatitis B vaccination if previously unvaccinated.
• •Any adult seeking protection from HBV infection should be vaccinated. Acknowledgment of a specific risk factor is not a requirement for vaccination.
• •Behavioral preventive measures for HBV infection are similar to those for HIV infection and AIDS.
• •When seeking medical or dental care, travelers should be advised to be alert to the use of medical, surgical, and dental equipment that has not been adequately sterilized or disinfected, reuse of contaminated equipment, and unsafe injecting practices (e.g., reuse of disposable needles and syringes).
• •HBV and other bloodborne pathogens (e.g., HIV and hepatitis C) can be transmitted if tools are not sterile or if the tattoo artist or piercer does not follow other proper infection-control procedures (e.g., washing hands, using latex gloves, and cleaning and disinfecting surfaces and instruments).
• •Travelers should be advised to consider the health risks in deciding to get a tattoo or body piercing in areas where adequate sterilization or disinfection procedures might not be available or practiced.

TYPHOID AND PARATYPHOID FEVER

Eric Mintz

Infectious Agent

Typhoid fever is an acute, life-threatening febrile illness caused by the bacterium Salmonella enterica serotype Typhi. Paratyphoid fever is a similar illness caused by S. Paratyphi A, B, or C.

Mode of Transmission

• •Humans are the only source. No animal or environmental reservoirs have been identified.
• •Typhoid and paratyphoid fever are most often acquired through consumption of water or food that have been contaminated by feces of an acutely infected or convalescent individual or a chronic asymptomatic carrier.
• •Transmission through sexual contact, especially among men who have sex with men, has rarely been documented.

Occurrence

• •An estimated 22 million cases of typhoid fever and 200,000 related deaths occur worldwide each year; an additional 6 million cases of paratyphoid fever are estimated to occur annually.
• •Approximately 400 cases of typhoid fever and 150 cases of paratyphoid fever are reported to CDC each year among persons with onset of illness in the United States, most of whom are recent travelers.

Risk for Travelers

• •Risk is greatest for travelers to South Asia (6 to 30 times higher than all other destinations). Other areas of risk include East and Southeast Asia, Africa, the Caribbean, and Central and South America.
• •Travelers to South Asia are at highest risk for infections that are nalidixic acid-resistant or multidrug-resistant (i.e., resistant to ampicillin, chloramphenicol, and trimethoprim–sulfamethoxazole).
• •Travelers who are visiting friends or relatives are at increased risk (see the VFR section in Chapter 8).
• •Although the risk of acquiring typhoid or paratyphoid fever increases with the duration of stay, travelers have acquired typhoid fever even during visits of less than 1 week to countries where the disease is endemic.

Clinical Presentation

• •The incubation period of typhoid and paratyphoid infections is 6–30 days. The onset of illness is insidious, with gradually increasing fatigue and a fever that increases daily from low-grade to as high as 102° F–104° F (38.5° C–40° C) by the third to fourth day of illness. Headache, malaise, and anorexia are nearly universal. Hepatosplenomegaly can often be detected. A transient, macular rash of rose-colored spots can occasionally be seen on the trunk.
• •Fever is commonly lowest in the morning, reaching a peak in late afternoon or evening. Untreated, the disease can last for a month. The serious complications of typhoid fever generally occur only after 2–3 weeks of illness, mainly intestinal hemorrhage or perforation, which can be life threatening.

Diagnosis

• •Infection with typhoid or paratyphoid fever results in a very low-grade septicemia. Blood culture is usually positive in only half the cases. Stool culture is not usually positive during the acute phase of the disease. Bone-marrow culture increases the diagnostic yield to about 80% of cases.
• •The Widal test is an old serologic assay for detecting IgM and IgG antibodies to the O and H antigens of Salmonella. The test is unreliable, but is widely used in developing countries because of its low cost. Newer serologic assays are somewhat more sensitive and specific than the Widal test, but are infrequently available.
• •Because there is no definitive test for typhoid or paratyphoid fever, the diagnosis often has to be made clinically. The combination of a history of being at risk for infection and a gradual onset of fever that increases in severity over several days should raise suspicion of typhoid or paratyphoid fever.

Treatment

• •Specific antimicrobial therapy shortens the clinical course of typhoid fever and reduces the risk for death.
• •Empiric treatment of typhoid or paratyphoid fever in most parts of the world would utilize a fluoroquinolone, most often ciprofloxacin. However, resistance to fluoroquinolones is highest in the Indian subcontinent and increasing in other areas. Injectable third-generation cephalosporins are often the empiric drug of choice when the possibility of fluoroquinolone resistance is high.
• •Patients treated with an appropriate antibiotic still require 3–5 days to defervesce completely, although the height of the fever decreases each day. Patients may actually feel worse during the time that the fever is starting to go away. If fever does not subside within 5 days, alternative antimicrobial agents or other foci of infection should be considered.

Preventive Measures for Travelers

Vaccine

• •CDC recommends typhoid vaccine for travelers to areas where there is a recognized increased risk of exposure to S. Typhi.
• •The typhoid vaccines currently available do not offer protection against S. Paratyphi infection.
• •Travelers should be reminded that typhoid immunization is not 100% effective, and typhoid fever could still occur.
• •
  Two typhoid vaccines are currently available in the United States.

  • ○
    Oral live, attenuated vaccine (Vivotif Berna vaccine, manufactured from the Ty21a strain of S. Typhi by the Swiss Serum and Vaccine Institute)
  • ○
    Vi capsular polysaccharide vaccine (ViCPS) (Typhim Vi, manufactured by Sanofi Pasteur) for intramuscular use
• •Both vaccines protect 50%–80% of recipients.
• • Table 2-10 provides information on vaccine dosage, administration, and revaccination. The time required for primary vaccination differs for the two vaccines, as do the lower age limits.
• •Primary vaccination with oral Ty21a vaccine consists of four capsules, one taken every other day. The capsules should be kept refrigerated (not frozen), and all four doses must be taken to achieve maximum efficacy. Each capsule should be taken with cool liquid no warmer than 37° C (98.6° F), approximately 1 hour before a meal. This regimen should be completed 1 week before potential exposure. The vaccine manufacturer recommends that Ty21a not be administered to infants or children <6 years of age.
• •Primary vaccination with ViCPS consists of one 0.5-mL (25-mg) dose administered intramuscularly. One dose of this vaccine should be given at least 2 weeks before expected exposure. The manufacturer does not recommend the vaccine for infants and children <2 years of age.

Vaccine Safety and Adverse Reactions

Information on adverse reactions is presented in Table 2-11 . Information is not available on the safety of these vaccines in pregnancy; it is prudent on theoretical grounds to avoid vaccinating pregnant women. Live, attenuated Ty21a vaccine should not be given to immunocompromised travelers, including those infected with HIV. The intramuscular vaccine presents a theoretically safer alternative for this group. The only contraindication to vaccination with ViCPS vaccine is a history of severe local or systemic reactions after a previous dose. Neither of the available vaccines should be given to persons with an acute febrile illness.

Table 2-11.

Common adverse reactions to typhoid fever vaccines

Vaccine	Reactions
	Fever	Headache	Local Reactions
Ty21a1	0%–5%	0%–5%	Not applicable
Vi Capsular polysaccharide	0%–1%	16%–20%	7% erythema or induration 1 cm

¹The side effects of Ty21a are rare and mainly consist of abdominal discomfort, nausea, vomiting, and rash or urticaria.

Precautions and Contraindications

Theoretical concerns have been raised about the immunogenicity of live, attenuated Ty21a vaccine in persons concurrently receiving antimicrobials (including antimalarial chemoprophylaxis), IG, or viral vaccines. The growth of the live Ty21a strain is inhibited in vitro by various antibacterial agents. Vaccination with Ty21a should be delayed for >72 hours after the administration of any antibacterial agent. Available data do not suggest that simultaneous administration of oral polio or yellow fever vaccine decreases the immunogenicity of Ty21a. If typhoid vaccination is warranted, it should not be delayed because of administration of viral vaccines. Simultaneous administration of Ty21a and IG does not appear to pose a problem.

YELLOW FEVER

Mark Gershman, Betsy Schroeder, J. Erin Staples

Infectious Agent

Yellow fever virus (YFV) is a single-stranded RNA virus that belongs to the genus Flavivirus.

Mode of Transmission

• •Vector-borne transmission occurs via the bite of an infected mosquito, primarily Aedes or Haemagogus spp.
• •Nonhuman and human primates are the main reservoirs of the virus, with anthroponotic (human-to-vector-to-human) transmission occurring.
• •
  There are three transmission cycles for yellow fever: sylvatic (jungle), intermediate (savannah), and urban.

  • ○
    The sylvatic (jungle) transmission cycle involves transmission of the virus between nonhuman primates and mosquito species found in the forest canopy. The virus is transmitted via mosquitoes from monkeys to humans when the humans encroach into the jungle during occupational or recreational activities.
  • ○
    In Africa, an intermediate (savannah) cycle involves transmission of YFV from tree hole-breeding Aedes spp. to humans living or working in jungle border areas. In this cycle, the virus may be transmitted from monkeys to humans or from human to human via these mosquitoes.
  • ○
    The urban transmission cycle involves transmission of the virus between humans and urban mosquitoes, primarily Ae. aegypti.
• •Humans infected with YFV experience the highest levels of viremia and can transmit the virus to mosquitoes shortly before onset of fever and for the first 3–5 days of illness.
• •Given the high level of viremia attained in humans, bloodborne transmission can also occur (via transfusion, needlestick, and intravenous drug abuse).

Occurrence

• • Yellow fever occurs in sub-Saharan Africa and tropical South America (Maps 2-3 and 2-4 ), where it is endemic and intermittently epidemic (see Table 2-12 for a list of countries with risk of yellow fever transmission).
• •In Africa, natural immunity accumulates with age, and thus infants and children are at greatest risk for disease.
• •In South America, yellow fever occurs most frequently in unimmunized young men who are exposed to mosquito vectors through their work in forested or transitional areas.
• •Most yellow fever disease in humans is due to sylvatic or intermediate transmission cycles. However, urban yellow fever does occur periodically in Africa and sporadically in the Americas.

Map 2-3.

Yellow fever-endemic zones in Africa, 2009.

Map 2-4.

Yellow fever-endemic zones in the Americas, 2009.

Table 2-12.

Countries with risk of yellow fever transmission¹

Africa			Central and South America
Angola	Ethiopia	Nigeria	Argentina2
Benin	Gabon	Rwanda	Bolivia2
Burkina Faso	The Gambia	Sierra Leone	Brazil2
Burundi	Ghana	São Tomé and Príncipe	Colombia
Cameroon	Guinea	Senegal	Ecuador2
Central African Republic	Guinea-Bissau	Somalia	French Guiana
Chad2	Kenya	Sudan2	Guyana
Congo, Republic of the	Liberia	Tanzania	Panama2
Côte d'Ivoire	Mali2	Togo	Paraguay
Democratic Republic of the Congo	Mauritania2	Uganda	Peru2
Equatorial Guinea	Niger2		Suriname
			Trinidad and Tobago2
			Venezuela2

¹Countries/areas where “a risk of yellow fever transmission is present,” as defined by the World Health Organization, are countries or areas where “yellow fever has been reported currently or in the past, plus vectors and animal reservoirs currently exist” (see www.who.int/ith/countries/2008_country_list.pdf).

²These countries are not holoendemic (i.e., only a portion of the country has risk of yellow fever transmission). Please see Maps 2-3 and 2-4 and yellow fever vaccine recommendations (Table 2-14) for details.

Risk for Travelers

General

A traveler's risk for acquiring yellow fever is determined by various factors, including immunization status, location of travel, season, duration of exposure, occupational and recreational activities while traveling, and local rate of virus transmission at the time of travel. Although reported cases of human disease are the principal indicator of disease risk, case reports may be absent because of a low level of transmission, a high level of immunity in the population (e.g., due to vaccination), or failure of local surveillance systems to detect cases. This “epidemiologic silence” does not equate to absence of risk and should not lead to travel without the protection provided by vaccination.

Africa

YFV transmission in rural West Africa is seasonal, with an elevated risk during the end of the rainy season and the beginning of the dry season (usually July–October). However, YFV may be episodically transmitted by Ae. aegypti even during the dry season in both rural and densely settled urban areas.

South America

• •The risk for infection for South America is highest during the rainy season (January–May, with a peak incidence in February and March).
• • Given the high level of viremia in humans and the widespread distribution of Ae. aegypti in many towns and cities, South America is at risk for a large-scale urban epidemic.

Yellow Fever Cases in Travelers

• •During 1970–2002, a total of nine cases of yellow fever were reported in unvaccinated travelers from the United States and Europe who traveled to West Africa (five cases) or South America (four cases). Eight of these nine travelers died.
• •Only one documented case of yellow fever has occurred, which was in a vaccinated traveler from Spain, who visited several West African countries during 1988.

Risk Estimates for Travelers

• •
  The risk of acquiring yellow fever is difficult to predict because of variations in ecologic determinants of virus transmission. For a 2-week stay, the risks for illness and death due to yellow fever for an unvaccinated traveler traveling to an endemic area of

  • ○
    West Africa are 50 per 100,000 and 10 per 100,000, respectively
  • ○
    South America are 5 per 100,000 and 1 per 100,000, respectively
• •These estimates are a rough guideline based on the risk to indigenous populations, often during peak transmission season. Thus, these risk estimates may not accurately reflect the true risk to travelers, who may have a different immunity profile, take precautions against getting bitten by mosquitoes, and have less outdoor exposure.
• •The risk of acquiring yellow fever in South America is lower than that in Africa because the mosquitoes that transmit the virus between monkeys in the forest canopy do not often come in contact with humans, and there is a relatively high level of immunity in local residents secondary to vaccine use.

Clinical Presentation

• •Asymptomatic or clinically inapparent infection is believed to occur in the majority of persons infected with YFV.
• •The incubation period is typically 3–6 days.
• •The initial illness presents as a nonspecific influenza-like syndrome with sudden onset of fever, chills, headache, backache, myalgias, prostration, nausea, and vomiting. Most patients improve after the initial presentation.
• •After a brief remission of hours to a day, approximately 15% of cases progress to develop a more serious or toxic form of the disease characterized by jaundice, hemorrhagic symptoms, and eventually shock and multisystem organ failure.
• •The overall case–fatality ratio for cases with jaundice is 20%–50%.

Diagnosis

• •The preliminary diagnosis is based on the patient's clinical features, places and dates of travel, and activities.
• •Laboratory diagnosis is generally accomplished by testing serum to detect virus-specific IgM and IgG antibodies by serologic assays. Due to cross-reactivity between antibodies raised against other flaviviruses, more specific antibody testing, such as a neutralization test, should be done to confirm the infection.
• •Early in the illness, YFV or yellow fever viral RNA can often be detected in serum samples by virus isolation or nucleic acid amplification tests (NAAT). However, by the time more overt symptoms are recognized, the virus or viral RNA is usually undetectable. Therefore, virus isolation and NAAT should not be used for ruling out a diagnosis of yellow fever.
• • Health-care providers should contact their state or local health department or call 800-CDC-INFO (800-232-4636) for assistance with diagnostic testing for yellow fever infections and for questions about antibody response to vaccination.

Treatment

• •No specific treatments have been found to benefit patients with yellow fever.
• •Treatment is symptomatic. Rest, fluids, and use of analgesics and antipyretics may relieve symptoms of fever and aching. Care should be taken to avoid certain medications, such as aspirin or other nonsteroidal anti-inflammatory drugs, which may increase the risk for bleeding.
• •Infected persons should be protected from further mosquito exposure (staying indoors and/or under a mosquito net) during the first few days of illness, so they do not contribute to the transmission cycle.

Preventive Measures for Travelers

Personal Protection Measures

• •No drugs for preventing infection are available.
• •
  The best way to prevent mosquito-borne diseases, including yellow fever, is to avoid mosquito bites (see the Protection Against Mosquitoes, Ticks, and Other Insects and Arthropods section later in this chapter):

  • ○
    Use insect repellent containing DEET, Picaridin, oil of lemon eucalyptus, or IR3535 on exposed skin. Always follow the directions on the package.
  • ○
    Wear long sleeves, pants, and socks. If possible, treat clothes with permethrin.
  • ○
    Stay in screened or air-conditioned accommodations to keep mosquitoes out.
  • ○
    Get rid of mosquito sources by emptying standing water from flowerpots, buckets, car tires and barrels.

Yellow Fever Vaccine

• •Yellow fever is preventable by a relatively safe, effective vaccine.
• •All yellow fever vaccines currently manufactured are live attenuated viral vaccines.
• •YF-VAX, the only yellow fever vaccine approved for use in the United States, is manufactured by sanofi pasteur.
• •Studies comparing the reactogenicity and immunogenicity of various yellow fever vaccines, including those manufactured outside of the United States, suggest that there is no significant difference in the reactogenicity or immune response generated by the various vaccines. Thus, individuals who receive yellow fever vaccines in other countries should be considered protected against yellow fever.

Recommendations for the Use of Yellow Fever Vaccine for Travelers

• •Persons aged Δ9 months of age who are traveling to or living in areas with risk of yellow fever transmission in South America and Africa should be vaccinated. In addition, some countries require proof of yellow fever vaccination for entry. See the following section in this chapter (Yellow Fever Vaccine Requirements and Recommendations, by Country) for more detailed information on the requirements and recommendations for yellow fever vaccination for specific countries.
• •However, because severe adverse events (see below) can follow yellow fever vaccination, physicians should be careful to administer the vaccine only to persons truly at risk of exposure to YFV.
• •Refer to Yellow Fever Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP) for additional information at www.cdc.gov/vaccines/pubs/ACIP-list.htm.

Vaccine Dose and Administration

• • For all eligible persons, a single injection of 0.5 mL of reconstituted vaccine should be administered subcutaneously.
• •The International Health Regulations (IHR) published by WHO require revaccination at 10-year intervals.

Vaccine Safety and Adverse Reactions

Common Adverse Events

• •Reactions to yellow fever vaccine are generally mild, with 10%–30% of vaccinees reporting mild systemic adverse events.
• •Reported events typically include low-grade fever, headache, and myalgias that begin within days after vaccination and last 5–10 days.
• •Approximately 1% of vaccinees temporarily curtail their regular activities because of these reactions.

Severe Adverse Events

Hypersensitivity

Immediate hypersensitivity reactions, characterized by rash, urticaria, or asthma or a combination of these, are uncommon. Anaphylaxis following yellow fever vaccine is reported to occur at a rate of 1.8 cases per 100,000 doses administered.

Yellow Fever Vaccine-Associated Neurologic Disease (YEL-AND)

• •YEL-AND represents a conglomerate of different clinical syndromes, including meningoencephalitis, Guillain–Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM), bulbar palsy, and Bell's palsy.
• •Historically, YEL-AND was seen primarily among infants as encephalitis, but more recent reports have been among persons of all ages.
• •The onset of illness for documented cases ranges 3–28 days after vaccination, and almost all cases were in first-time vaccine recipients.
• •YEL-AND is rarely fatal.
• •The incidence of YEL-AND in the United States is 0.8 per 100,000 doses administered. The rate is higher in persons Δ60 years of age, with a rate of 1.6 per 100,000 doses in persons 60–69 years of age and 2.3 per 100,000 doses in persons Δ70 years of age.

Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD)

• •YEL-AVD is a severe illness similar to wild-type disease, with vaccine virus proliferating in multiple organs and often leading to multisystem organ failure and death.
• •Since the initial cases of YEL-AVD were published in 2001, more than 40 confirmed and suspected cases have been reported throughout the world.
• •The onset of illness for YEL-AVD cases averaged 3.5 days (range: 1–8 days) after vaccination. YEL-AVD appears to occur after the first dose of yellow fever vaccine rather than with booster doses.
• •The case–fatality ratio for reported YEL-AVD cases is 53%.
• •The incidence of YEL-AVD in the United States is 0.4 cases per 100,000 doses of vaccine administered. The rate is higher for persons Δ60 years of age, with a rate of 1 per 100,000 doses in persons 60–69 years of age and 2.3 per 100,000 doses in persons aged Δ70 years of age.

Contraindications

Infants <9 Months of Age

• •The vaccine is contraindicated for routine use in infants <9 months of age by the manufacturer and the FDA because of the increased risk of postvaccine encephalitis. However, ACIP and WHO recognize that situations occur in which vaccination of an infant 6–8 months of age might be considered, such as residence in or unavoidable travel to a yellow fever endemic or epidemic zone. The decision to immunize infants who are 6–8 months of age must balance the infant's risk for exposure with the risk for vaccine-associated encephalitis. YF vaccine should never be administered to infants <6 months of age.
• •Physicians considering vaccinating infants aged <9 months of age should contact their state health department or call 800-CDC-INFO (800-232-4636) for further advice.

Hypersensitivity

• •Yellow fever vaccine is contraindicated in anyone with a history of acute hypersensitivity reaction to any of the vaccine components, including gelatin. Because the yellow fever vaccine is produced in chicken embryos, vaccine should not be administered to anyone with a history of acute hypersensitivity to egg or chicken proteins.
• •If vaccination of a person with a questionable history of hypersensitivity to one of the vaccine components is considered essential because of a high risk for acquiring yellow fever, desensitizing and vaccinating procedures are described in the vaccine package insert and should be performed under close medical supervision.

Immunosuppression

• •The vaccine is contraindicated in persons with immunocompromising conditions, including symptomatic HIV infection or AIDS, malignancy, or diseases of the thymus (e.g., thymectomy) or those receiving immunosuppressant therapy (e.g., corticosteroids, alkylating agents, antimetabolites) or radiation therapy.
• •Immunosuppressed persons should not be immunized, and travel to yellow fever-endemic areas should be postponed or avoided.
• •If travel to yellow fever endemic areas is unavoidable, persons who cannot be immunized because of their immunosuppressive condition should be advised of the risk for acquiring yellow fever disease, instructed in methods for avoiding vector mosquitoes, and, if warranted, issued a medical waiver to fulfill international health regulations (see information in Exemption from Vaccination and Waiver Letters in this section).
• •Physicians considering vaccinating an immunosuppressed individual can contact their state health department or call for more information.
• •Family members of immunosuppressed or HIV-infected persons who themselves have no contraindications can receive yellow fever vaccine.

AIDS or Symptomatic HIV

No large-scale trials have been done to evaluate the safety of the yellow fever vaccine in individuals with HIV or AIDS. However, because yellow fever vaccine is a live, viral vaccine, it is contraindicated in persons with symptomatic HIV infection or AIDS. (For persons with asymptomatic HIV infection, see Precautions below.)

History of Thymus Disease

• •A history of thymus disease is a contraindication to yellow fever vaccine.
• •Four persons with a history of thymectomy for a thymoma were noted among the first 23 cases of YEL-AVD, suggesting that compromised thymus function is an independent risk factor for YEL-AVD.
• •Health-care providers should be careful to ask about a history of thymus disorder, including myasthenia gravis, thymoma, or prior thymectomy, when screening a patient before administering yellow fever vaccine.

Immunosuppressive Medication

• •Although no studies have been done to evaluate the safety of yellow fever vaccine in persons receiving immunosuppressive or immunomodulating medicines, the vaccine is contraindicated in those receiving medications that alter the ability to resist viral infections. The vaccine should not be given to individuals who are taking medications with a warning in the package insert against the use of live viral vaccines.
• •Low-dose (i.e., 20 mg or less of prednisone or equivalent/day); short-term (i.e., <2 weeks) systemic corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids; and intranasal corticosteroids are not thought to be sufficiently immunosuppressive to constitute an increased hazard to recipients of yellow fever vaccine (see The Immunocompromised Traveler section in Chapter 8).

Precautions

Adults 60 Years of Age or Older

• •Analysis of adverse events passively reported to the Vaccine Adverse Event Reporting System (VAERS) indicate that persons 60 years of age or older may be at increased risk for systemic adverse events following vaccination compared with younger persons.
• •The rate of any serious adverse event following vaccination is 1.5 times higher than the average rate for persons 60–69 years of age and 3 times higher for persons 70 years or older.
• •To determine if vaccination should be administered to travelers 60 years of age or older, the risks and benefits of vaccination should be weighed against their destination-specific risk for exposure to YFV.

Asymptomatic HIV

• •Persons who are HIV-infected but who do not have AIDS or other symptomatic manifestations of HIV infection, who have established laboratory verification of adequate immune system function (e.g., CD4+ T cell counts >200/mm³), and who cannot avoid potential exposure to YFV should be offered the choice of vaccination.
• •If international travel requirements are the only reason to vaccinate an asymptomatic HIV-infected person, rather than an increased risk for acquiring yellow fever, the person should be excused from immunization and issued a medical waiver to fulfill health regulations (see information in Exemption from Vaccination and Waiver Letters in this section).
• •Data are limited regarding seroconversion rates after yellow fever vaccination among asymptomatic HIV-infected persons, but indicate that the seroconversion rate among such persons may be reduced. Because vaccination of asymptomatic HIV-infected persons might be less effective than that of persons not infected with HIV, measurement of the neutralizing antibody response to vaccination should be considered before travel.

Pregnancy

• •The safety of yellow fever vaccination during pregnancy has not been studied in a large prospective trial. However, a recent study of women who were vaccinated with yellow fever vaccine early in their pregnancies found no major malformations in their infants. There was slight increased risk noted for minor, mostly skin, malformations.
• •In a similar study, a higher rate of spontaneous abortions in pregnant women receiving the vaccine was reported but not substantiated.
• •The proportion of women vaccinated during pregnancy who develop YF IgG-specific antibodies is variable depending on the study (38.6% or 98.2%) and may be correlated with the trimester in which they received the vaccine. Because pregnancy may affect immunologic function, serologic testing can be considered to document a protective immune response to the vaccine.
• •For pregnant women, if travel is unavoidable and the vaccination risks are felt to outweigh the risks of YF exposure, these women should be excused from immunization and, if applicable, issued a medical waiver to fulfill international health regulations (see information in Exemption from Vaccination and Waiver Letters in this section). Pregnant women who must travel to areas where the risk of yellow fever infection is high should be vaccinated, and their infants should be monitored after birth for evidence of congenital infection and other possible adverse effects resulting from yellow fever vaccination.
• •Although there are no specific data, it is recommended that a woman wait 4 weeks after receiving the live virus yellow fever vaccine before conceiving.

Breastfeeding

• • Whether the yellow fever vaccine is excreted in breast milk is not known.
• •One suspect case of YEL-AND has been reported in a 1-month old infant whose mother was vaccinated with yellow fever vaccine and the infant was exclusively breastfed. Testing was unable to determine if the breast milk was the mode of transmission.
• •It is recommended that vaccination of nursing mothers should be avoided. However, when travel of nursing mothers to high-risk yellow fever-endemic areas cannot be avoided or postponed, these women should be vaccinated.

Simultaneous Administration of Other Vaccines and Drugs

• •One study suggested that the immune response to yellow fever vaccine is not inhibited by administration of measles vaccine (also a live, attenuated vaccine) given concurrently or at various intervals of a few days to 1 month prior. However, to minimize the potential risk for interference, injectable or nasally administered live vaccines not administered on the same day should be given at least 4 weeks apart.
• •A prospective study of persons given yellow fever vaccine along with 5 mL of commercially available IG showed no alteration of the immunologic response to yellow fever vaccine when compared with controls.

International Certificate of Vaccination or Prophylaxis (ICVP)

Background

• •The International Health Regulations (IHR) allow countries to require proof of yellow fever vaccination for entry and from travelers arriving from certain countries, even if only in transit, to prevent importation and indigenous transmission of YFV.
• •Some countries require evidence of vaccination from all entering travelers, which includes direct travel from the United States (Table 2-13 ).
• •Travelers who arrive in a country with a yellow fever vaccination entry requirement without proof of yellow fever vaccination may be quarantined up to 6 days.
• •Travelers with a specific contraindication to yellow fever vaccine should request a waiver from a physician before traveling to countries requiring vaccination (see below).

Table 2-13.

Countries that require proof of yellow fever vaccination for all arriving travelers¹

Angola	French Guiana
Benin	Gabon
Bolivia (or signed affidavit at point of entry)	Ghana
Burkina Faso	Liberia
Burundi	Mali
Cameroon	Niger
Central African Republic	Rwanda
Congo, Republic of the	São Tomé and Príncipe
Côte d'Ivoire	Sierra Leone
Democratic Republic of the Congo	Togo

¹Country requirements for yellow fever vaccination are subject to change at any time; therefore, CDC encourages travelers to check with the destination country's embassy or consulate before departure.

Authorization to Provide Vaccinations and to Validate the ICVP

• •
  Under the revised IHR (2005), effective December 15, 2007, all state parties (countries) are required to issue a new ICVP. This is intended to replace the former International Certificate of Vaccination against Yellow Fever (ICV).

  • ○
    Persons who received a yellow fever vaccination after December 15, 2007, must provide proof of vaccination on an ICVP.
  • ○
    If the person received the vaccine before December 15, 2007, the original ICV is still valid, provided that the vaccination was given less than 10 years previously.
• •
  Vaccinees should receive a completed ICVP (Figure 2-1 ), validated (stamped and signed) with the center's stamp where the vaccine was given (see below).

  • ○
    An ICVP must be complete in every detail; if incomplete or inaccurate, it is not valid.
  • ○
    Failure to secure validations can cause a traveler to be quarantined, denied entry, or possibly revaccinated at the point of entry to a country. This is not a recommended option for the traveler.
• •A copy of the ICVP, CDC 731 (formerly PHS 731) may be purchased from the U.S. Government Printing Office, Washington, D.C., http://bookstore.gpo.gov/, telephone 866-512-1800. The stock number is 017-001-00567-3 for 25 copies and 017-001-00566-5 for 100 copies.
• •This certificate of vaccination is valid for a period of 10 years, beginning 10 days after vaccination. With booster doses of the vaccine, the certificate is considered valid from the day of vaccination.

Figure 2-1.

Example International Certificate of Vaccination or Prophylaxis (ICVP).

Persons Authorized to Sign the Certificate and Designated Yellow Fever Vaccination Centers

• •The ICVP must be signed by a licensed physician or by a health-care worker designated by the physician supervising the administration of the vaccine (Figure 2-1). A signature stamp is not acceptable.
• •Yellow fever vaccination must be given at a certified center in possession of an official “Uniform Stamp,” which can be used to validate the ICVP.
• •State health departments are responsible for designating nonfederal yellow fever vaccination centers and issuing Uniform Stamps to physicians.
• •Information about the location and hours of yellow fever vaccination centers may be obtained by visiting CDC's Travelers' Health website at wwwn.cdc.gov/travel/yellowfever.aspx.

Exemption from Vaccination and Waiver Letters

• •Some countries do not require an ICVP for infants younger than a certain age (e.g., <6 months, <9 months, or <1 year of age, depending on the country). Age requirements for vaccination for individual countries can be found in the Yellow Fever Vaccine Requirements and Recommendations section in this chapter.
• •
  For medical contraindications, a physician who has decided to issue a waiver should fill out and sign the Medical Contraindications to Vaccination section of the ICVP (Figure 2-2 ). The physician should also—

  • ○
    Give the traveler a signed and dated exemption letter on the physician's letterhead stationery, clearly stating the contraindications to vaccination and bearing the stamp used by the yellow fever vaccination centers to validate the ICVP.
  • ○
    Inform the traveler of any increased risk of yellow fever infection associated with nonvaccination and how to minimize this risk by using mosquito protection measures.
• •Reasons other than medical contraindications are not acceptable for exemption from vaccination.
• •The traveler should be advised that issuance of a waiver does not guarantee its acceptance by the destination country. On arrival at the destination, the traveler may be faced with quarantine, refusal of entry, or vaccination on site.
• •
  To potentially improve the likelihood of acceptance of a waiver upon arrival at the destination country, the provider can suggest that the traveler take the following additional measures before initiating travel:

  • ○
    Obtain specific and authoritative advice from the embassy or consulate of the country or countries he or she plans to visit.
  • ○
    Request documentation of requirements for waivers from embassies or consulates and retain these along with the completed Medical Contraindication to Vaccination section of the ICVP.

Figure 2-2.

Example International Certificate of Vaccination or Prophylaxis (ICVP) medical contraindication to vaccination.

Requirements Versus Recommendations

• •Country entry requirements for proof of yellow fever vaccination under the IHRs are different from CDC's recommendations.
• •Yellow fever vaccine entry requirements are established by countries in order to prevent the importation and transmission of YFV, and are allowed under the IHRs. Travelers must comply with these to enter the country, unless they have been issued a medical waiver. Certain countries require vaccination from travelers arriving from all countries, while some countries require vaccination only for travelers coming from “a country with risk of yellow fever transmission” (Table 2-14 ). WHO defines those areas “at risk of yellow fever transmission” as countries or areas where yellow fever has been reported currently or in the past, plus where vectors and animal reservoirs currently exist. Country requirements are subject to change at any time; therefore, CDC encourages travelers to check with the appropriate embassy or consulate before departure.
• •The information in the section on yellow fever vaccine recommendations is advice given by CDC to prevent yellow fever infections among travelers. Recommendations are subject to change at any time if disease conditions change; therefore, CDC encourages travelers to check for relevant travel notices on the CDC website www.cdc.gov/travel before departure.

Table 2-14.

Yellow fever vaccine requirements and recommendations, by country

Country	Yellow Fever Vaccine Requirements1,2	CDC Yellow Fever Vaccine Recommendations2,3,4
Afghanistan	If traveling from a country with risk of yellow fever transmission	None
Albania	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Algeria	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Andorra	Not required	None
Angola	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Anguilla (U.K.)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Antarctica	Not required	None
Antigua and Barbuda	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Argentina	Not required	Yellow fever vaccination is recommended for all travelers ≥9 months of age who are going to the northern and northeastern forested areas of Argentina, including Iguassu Falls and all areas bordering Paraguay and Brazil. These areas include all departments of Misiones and Formosa Provinces; and the Department of Bermejo in Chaco Province; Departments of Berón de Astrada, Capital, General Alvear, General Paz, Ituzaingó, Itatí, Paso de los Libres, San Cosme, San Miguel, San Martín, and Santo Tomé in Corrientes Province; Departments of Valle Grande, Ledesma, Santa Bárbara, and San Pedro in Jujuy Province; and Departments of General José de San Martín, Oran, Rivadavia, and Anta in Salta Province.
Armenia	Not required	None
Aruba	If traveling from a country with risk of yellow fever transmission and ≥6 months of age5	None
Australia	All persons ≥1 year of age who, within 6 days of arrival in Australia, have been in or have passed through a country with risk of yellow fever transmission	None
Austria	Not required	None
Azerbaijan	Not required	None
Azores (Portugal)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Bahamas, The	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Bahrain	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Bangladesh	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Barbados	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Belarus	Not required	None
Belgium	Not required	None
Belize	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Benin	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Bermuda (U.K.)	Not required	None
Bhutan	If traveling from a country with risk of yellow fever transmission	None
Bolivia	Required for all travelers ≥1 year of age For U.S. citizens: Medical waivers must be translated into Spanish and accompany the International Certificate of Vaccination or Prophylaxis (ICVP). Travelers who do not have a valid ICVP will still be allowed to enter Bolivia if they agree to sign an affidavit exempting the Bolivian state from any liability in the event the traveler gets sick with yellow fever within the Bolivian territory. This last option may cause delays at the point of entry.	For all travelers ≥9 months of age traveling to areas east of the Andes Mountains (see Map 2-4). Vaccination is NOT recommended for travel only to the cities of La Paz or Sucre.
Bosnia and Herzegovina	Not required	None
Botswana	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Brazil	Not required	For all travelers ≥9 months of age going to the following areas at risk of yellow fever transmission, including the ENTIRE states of Acre, Amapá, Amazonas, Distrito Federal (including the capital city of Brasilia), Goiás, Maranhão, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Pará, Rondônia, Roraima, and Tocatins; and the designated areas of the following states: northwest and west Bahia, central and west Paraná, southwest Piauí, northwest and west central Rio Grande do Sul, far west Santa Catarina, and north and west São Paulo. Vaccination is recommended for travelers visiting Iguassu Falls. Vaccination is NOT recommended for travel to the following coastal cities: Rio de Janeiro, São Paulo, Salvador, Recife, and Fortaleza.
British Indian Ocean Territory includes Diego Garcia (U.K.)	Not required	None
Brunei	Required from travelers ≥1 year of age arriving within 6 days from countries with risk of yellow fever transmission or having passed through areas partly or wholly at risk of yellow fever transmission within the preceding 6 days.	None
Bulgaria	Not required	None
Burkina Faso	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Burma (Myanmar)	If traveling from a country with risk of yellow fever transmission. Required also for nationals and residents of Burma (Myanmar) departing for a country with risk of yellow fever transmission	None
Burundi	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Cambodia	If traveling from a country with risk of yellow fever transmission	None
Cameroon	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Canada	Not required	None
Canary Islands (Spain)	Not required	None
Cape Verde	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Cayman Islands (U.K.)	Not required	None
Central African Republic	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Chad	If traveling from a country with risk of yellow fever transmission	For all travelers ≥9 months of age traveling to areas south of the Sahara Desert
Chile	Not required	None
China	If traveling from a country with risk of yellow fever transmission	None
Christmas Island (Australia)	All travelers ≥1 year of age, who within the past 6 days have traveled or passed through an endemic area, as listed by WHO	None
Cocos (Keeling) Islands	All persons ≥1 year of age who, within 6 days of arrival, have been in or have passed through a country with risk of yellow fever transmission	None
Colombia	Not required	For all travelers ≥9 months of age. Travelers whose itinerary is limited to the cities of Bogotá, Cali, or Medellín are at lower risk and may consider foregoing vaccination.
Comoros	Not required	None
Congo, Republic of the (Congo-Brazzaville)	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Cook Islands (New Zealand)	Not required	None
Costa Rica	Required from travelers coming from countries with risk of yellow fever transmission. No certificate is required for travelers <9 months of age and ≥60 years of age, pregnant or lactating women, persons with allergy to eggs or gelatin, immunosuppression, thymus disease, a personal or family history of adverse reactions associated with the yellow fever vaccine, or asymptomatic HIV infection with laboratory evidence of satisfactory immune functions. The following countries are considered at risk of yellow fever transmission: South America: Boliva, Brazil, Colombia, Ecuador, French Guyana, Peru, Venezuela Africa: Angola, Benin, Burkina Faso, Cameroon, Gabon, The Gambia, Ghana, Guinea, Liberia, Nigeria, Democratic Republic of the Congo, Sierra Leone, Sudan	None
Côte d'Ivoire (Ivory Coast)	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Croatia	Not required	None
Cuba	Not required	None
Cyprus	Not required	None
Czech Republic	Not required	None
Democratic Republic of the Congo (Congo-Kinshasa)	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Denmark	Not required	None
Djibouti	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Dominica	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Dominican Republic	Not required	None
Easter Island (Chile)	Required for travelers coming from a country with risk of yellow fever transmission	None
Ecuador (including the Galápagos Islands)	Required from travelers ≥1 year of age coming from countries with risk of yellow fever transmission. Nationals and residents of Ecuador are required to possess certificates of vaccination on their departure to an area with risk of yellow fever transmission.	For all travelers ≥9 months of age who are traveling to the following provinces in the Amazon Basin: Morona-Santiago, Napo, Orellana, Pastaza, Sucumbíos, and Zamorarisk Chinchipe, and all other areas in the eastern part of the Andes Mountains, NOT including the cities of Quito and Guayaquil or the Galápagos Islands
Egypt	If traveling from countries with risk of yellow fever transmission and ≥1 year of age. Air passengers without a certificate in transit, but coming from these countries or areas, will be detained in the precincts of the airport until they resume their journey. All travelers arriving from Sudan are required to have a vaccination certificate or a location certificate issued by a Sudanese official center, stating that they have not been in Sudan south of 15° N within the previous 6 days. Required also for travelers arriving or transiting from: Africa: Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Ethiopia, Gabon, The Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Liberia, Mali, Niger, Nigeria, Rwanda, São Tomé and Príncipe, Senegal, Sierra Leone, Somalia, Sudan (south of 15° N), Tanzania, Togo, Uganda, and Zambia Americas: Belize, Bolivia, Brazil, Colombia, Costa Rica, Ecuador, French Guiana, Guyana, Panama, Peru, Suriname, Trinidad and Tobago, and Venezuela	None
El Salvador	If traveling from a country with risk of yellow fever transmission and ≥6 months of age5	None
Equatorial Guinea	If traveling from a country with risk of yellow fever transmission	For all travelers ≥9 months of age
Eritrea	If traveling from a country with risk of yellow fever transmission	None
Estonia	Not required	None
Ethiopia	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age
Falkland Islands (U.K.)	Not required	None
Faroe Islands (Denmark)	Not required	None
Fiji	If traveling from a country with risk of yellow fever transmission within 10 days of having stayed overnight or longer and ≥1 year of age	None
Finland	Not required	None
France	Not required	None
French Guiana	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
French Polynesia, includes the island groups of Society Islands (Tahiti, Moorea, and Bora-Bora), Marquesas Islands (Hiva Oa and Ua Huka), and Austral Islands (Tubuai and Rurutu)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Gabon	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Gambia, The	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age
Georgia	Not required	None
Germany	Not required	None
Ghana	Required upon arrival from all countries	For all travelers ≥9 months of age
Gibraltar (U.K.)	Not required	None
Greece	Not required	None
Greenland (Denmark)	Not required	None
Grenada	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Guadeloupe, including St. Barthelemy and Saint Martin (France)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Guam (U.S.)	Not required	None
Guatemala	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Guinea	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age
Guinea-Bissau	If traveling from a country with risk of yellow fever transmission and ≥1 year of age Required also for travelers arriving from: Africa: Angola, Benin, Burkina Faso, Burundi, Cape Verde, Central African Republic, Chad, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Djibouti, Equatorial Guinea, Ethiopia, Gabon, The Gambia, Ghana, Guinea, Kenya, Liberia, Madagascar, Mali, Mauritania, Mozambique, Niger, Nigeria, Rwanda, São Tomé and Príncipe, Senegal, Sierra Leone, Somalia, Tanzania, Togo, Uganda, and Zambia Americas: Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Panama, Peru, Suriname, and Venezuela	For all travelers ≥9 months of age
Guyana	If traveling from a country with risk of yellow fever transmission Required also for travelers arriving from: Africa: Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Ethiopia, Gabon, The Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Liberia, Mali, Mauritania, Niger, Nigeria, Rwanda, São Tomé and Príncipe, Senegal, Sierra Leone, Somalia, Sudan, Tanzania, Togo, and Uganda Americas: Belize, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Panama, Peru, Suriname, and Venezuela	For all travelers ≥9 months of age
Haiti	If traveling from a country with risk of yellow fever transmission	None
Holy See	Not required	None
Honduras	Required from travelers ≥1 year of age coming from countries with risk of yellow fever transmission. The Government of Honduras is also recommending vaccine for travelers coming from Panama.	None
Hong Kong SAR (China)	Not required	None
Hungary	Not required	None
Iceland	Not required	None
India	Required from travelers ≥6 months of age coming from a country with risk of yellow fever transmission Specifically, per the Government of India, anyone (except infants ≥6 months old) arriving by air or sea without a certificate is detained in isolation for up to 6 days if that person (i) arrives within 6 days of departure from an area with risk of yellow fever transmission, or (ii) has been in such an area in transit (except those passengers and members of crew who, while in transit through an aiport situated in an area with risk of yellow fever transmission, remained within the airport premises during the period of their entire stay and the Health Officer agrees to such an exemption), or (iii) has come on a ship that started from or touched at any port in a yellow fever area with risk of yellow fever transmission up to 30 days before its arrival into India, unless such a ship has been disinsected in accordance with the procedure laid down by WHO, or (iv) has come by an aircraft which has been in an area with risk of yellow fever transmission and has not been disinsected in accordance with the provisions laid down in the Indian Aircraft Public Health Rules, 1954, or those recommended by WHO. The following countries and areas are regarded as at risk of yellow fever transmission: Africa: Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Congo, Côlte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Ethiopia, Gabon, The Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Liberia, Mali, Niger, Nigeria, Rwanda, São Tomé and Principe, Senegal, Sierra Leone, Somalia, Sudan, Togo, Uganda, Tanzania, and Zambia Americas: Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Panama, Peru, Suriname, Trinidad and Tobago, and Venezuela Note: When a case of yellow fever is reported from any country, that country is regarded by the Government of India as a country with risk of yellow fever and is added to the above list.	None
Indonesia	If traveling from a country with risk of yellow fever transmission and ≥9 months of age	None
Iran	If traveling from a country with risk of yellow fever transmission	None
Iraq	If traveling from a country with risk of yellow fever transmission	None
Ireland	Not required	None
Israel	Not required	None
Italy	Not required	None
Jamaica	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Japan	Not required	None
Jordan	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Kazakhstan	If traveling from a country with risk of yellow fever transmission	None
Kenya	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age. The cities of Nairobi and Mombasa have lower risk of transmission than rural areas.
Kiribati (formerly Gilbert Islands), includes Tarawa, Tabuaeran (Fanning Island), and Banaba (Ocean Island)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Korea, North	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Korea, South	Not required	None
Kosovo	Not required	None
Kuwait	Not required	None
Kyrgyzstan	Not required	None
Laos	If traveling from a country with risk of yellow fever transmission	None
Latvia	Not required	None
Lebanon	If traveling from a country with risk of yellow fever transmission and ≥6 months of age5	None
Lesotho	If traveling from a country with risk of yellow fever transmission	None
Liberia	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Libya	If traveling from a country with risk of yellow fever transmission	None
Liechtenstein	Not required	None
Lithuania	Not required	None
Luxembourg	Not required	None
Macau SAR (China)	Not required	None
Macedonia	Not required	None
Madagascar	If traveling from a country with risk of yellow fever transmission	None
Madeira Islands (Portugal)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Malawi	If traveling from a country with risk of yellow fever transmission	None
Malaysia	Required from travelers ≥1 year of age arriving within 6 days from countries with risk of yellow fever transmission	None
Maldives	If traveling from a country with risk of yellow fever transmission	None
Mali	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age going to areas south of the Sahara Desert
Malta	If traveling from a country with risk of yellow fever transmission and ≥9 months of age If indicated on epidemiological grounds, infants <9 months of age are subject to isolation or surveillance if coming from an area with risk of yellow fever transmission.	None
Marshall Islands	Not required	None
Martinique (France)	Not required	None
Mauritania	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age traveling to areas south of the Sahara Desert
Mauritius	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Mayotte (French territorial collectivity)	Not required	None
Mexico	Not required	None
Micronesia Federated States of; includes Yap Islands, Pohnpei, Chuuk, and Kosrae,	Not required	None
Moldova	Not required	None
Monaco	Not required	None
Mongolia	Not required	None
Montenegro	Not required	None
Montserrat (U.K.)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Morocco	Not required	None
Mozambique	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Namibia	If traveling from a country with risk of yellow fever transmission The countries, or parts of countries, included in the endemic zones in Africa and South America are regarded as areas with risk of yellow fever transmission. Travelers on scheduled flights that originated outside the countries with risk of yellow fever transmission, but who have been in transit through these areas, are not required to possess a certificate provided that they remained at the scheduled airport or in the adjacent town during transit. All passengers whose flights originated in countries with risk of yellow fever transmission or who have been in transit through these countries on unscheduled flights are required to possess a certificate. The certificate is not insisted upon in the case of children <1 year of age, but such infants may be subject to surveillance.	None
Nauru	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Nepal	If traveling from a country with risk of yellow fever transmission	None
Netherlands	Not required	None
Netherlands Antilles (Bonaire, Curaçao, Saba, St. Eustasius, and St. Maarten)	If traveling from a country with risk of yellow fever transmission and ≥6 months of age5	None
New Caledonia (France)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age Note: In the event of an epidemic threat to the territory, a specific vaccination certificate may be required.	None
New Zealand	Not required	None
Nicaragua	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Niger	Required upon arrival from all countries if traveler is ≥1 year of age. The Government of Niger recommends vaccine for travelers leaving Niger.	For all travelers ≥9 months of age traveling to areas south of the Sahara Desert
Nigeria	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age
Niue (New Zealand)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Norfolk Island (Australia)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Northern Mariana Islands (U.S.), includes Saipan, Tinian, and Rota Island	Not required	None
Norway	Not required	None
Oman	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Pakistan	Required from travelers coming from any part of a country in which there is a risk of yellow fever transmission; infants <6 months of age are exempt if the mother's vaccination certificate shows that she was vaccinated before the birth of the child.5	None
Palau	Required from all travelers ≥1 year of age coming from countries with risk of yellow fever transmission or from countries in any part of which there is a risk of yellow fever transmission	None
Panama	If traveling from a country with risk of yellow fever transmission	For all travelers ≥9 months of age traveling to the provinces of Darien, Kuna Yala (old San Blas), Comarca Emberá, and Panama east of the Canal Zone, EXCLUDING the Canal Zone, Panama City, and San Blas Islands
Papua New Guinea	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Paraguay	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age
Peru	Not required	For all travelers ≥9 months of age traveling to the areas east of the Andes Mountains (see Map 2-4) and for those who intend to visit any jungle areas of the country <2,300 m (<7,546 ft). Travelers who are limiting travel to the cities of Cuzco and Machu Picchu do NOT need vaccination.
Philippines	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Pitcairn Islands (U.K.)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Poland	Not required	None
Portugal	Required only for travelers ≥1 year of age arriving from a country with risk of yellow fever transmission and destined for the Azores and Madeira. However, no certificate is required for travelers in transit at Funchal, Santa Maria, and Porto Santo.	None
Puerto Rico (U.S.)	Not required	None
Qatar	Not required	None
Réunion (France)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Romania	Not required	None
Russia	Not required	None
Rwanda	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Saint Helena (U.K.)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Saint Kitts (Saint Christopher) and Nevis (U.K.)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Saint Lucia	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Saint Pierre and Miquelon (France)	Not required	None
Saint Vincent and the Grenadines	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Samoa (formerly Western Somoa)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Samoa, American (U.S.)	Not required	None
San Marino	Not required	None
São Tomé and Príncipe	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Saudi Arabia	If traveling from a country with risk of yellow fever transmission	None
Senegal	If traveling from a country with risk of yellow fever transmission	For all travelers ≥9 months of age
Serbia	Not required	None
Seychelles	If traveling from a country with risk of yellow fever transmission within the preceding 6 days and ≥1 year of age	None
Sierra Leone	Required upon arrival from all countries	For all travelers ≥9 months of age
Singapore	If traveling from a country with risk of yellow fever transmission within the preceding 6 days and ≥1 year of age	None
Slovakia	Not required	None
Slovenia	Not required	None
Solomon Islands	If traveling from a country with risk of yellow fever transmission	None
Somalia	If traveling from a country with risk of yellow fever transmission	For all travelers ≥9 months of age
South Africa	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
South Georgia	Not required	None
South Sandwich Islands	Not required	None
Spain	Not required	None
Sri Lanka	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Sudan	If traveling from a country with risk of yellow fever transmission and ≥9 months of age. A certificate may be required for travelers leaving Sudan.	For all travelers ≥9 months of age traveling to areas south of the Sahara Desert, EXCLUDING the city of Khartoum
Suriname	If traveling from a country with risk of yellow fever transmission fever transmission and ≥1 year of age	For all travelers ≥9 months of age
Swaziland	If traveling from a country with risk of yellow fever transmission	None
Sweden	Not required	None
Switzerland	Not required	None
Syria	If traveling from a country with risk of yellow fever transmission	None
Taiwan	If traveling from a country with risk of yellow fever transmission	None
Tajikistan	Not required	None
Tanzania	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age. The city of Dar es Salaam has a lower risk of transmission than rural areas.
Thailand	If traveling from a country with risk of yellow fever transmission and ≥9 months of age	None
Timor-Leste (East Timor)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Togo	Required upon arrival from all countries if traveler is ≥1 year of age	For all travelers ≥9 months of age
Tokelau (New Zealand)	Not required	None
Tonga	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Trinidad and Tobago	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age whose itinerary includes Trinidad. Port of Spain has lower risk of transmission than rural or forested areas. Cruise ship passengers who do not disembark from the ship or travelers visiting only the urban area of Port of Spain (including passengers in-transit only) may consider foregoing vaccination. Vaccination is NOT recommended for those visiting only Tobago.
Tunisia	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Turkey	Not required	None
Turkmenistan	Not required	None
Turks and Caicos Islands (U.K.)	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Tuvalu	Not required	None
Uganda	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	For all travelers ≥9 months of age
Ukraine	Not required	None
United Arab Emirates	Not required	None
United Kingdom (with Channel Islands and Isle of Man)	Not required	None
United States	Not required	None
Uruguay	If traveling from a country with risk of yellow fever transmission	None
Uzbekistan	Not required	None
Vanuatu	Not required	None
Venezuela	Not required	For all travelers ≥9 months of age traveling to Venezuela, EXCEPT the northern coastal area (see Map 2-4). The cities of Caracas and Valencia are NOT in the endemic zone.
Vietnam	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Virgin Islands British,	Not required	None
Virgin Islands, U.S.	Not required	None
Wake Island, U.S.	Not required	None
Western Sahara	Not required	None
Yemen	If traveling from a country with risk of yellow fever transmission and ≥1 year of age	None
Zambia	Not required	None
Zimbabwe	If traveling from a country with risk of yellow fever transmission	None

¹Yellow fever vaccine entry requirements are established by countries to prevent the importation and transmission of yellow fever virus, and are allowed under the International Health Regulations (IHR). Travelers must comply with these to enter the country, unless they have been issued a medical waiver. Certain countries require vaccination from travelers arriving from all countries, while some countries require vaccination only for travelers coming from “a country with risk of yellow fever transmission” (see Table 2-12). Country requirements are subject to change at any time; therefore, CDC encourages travelers to check with the destination country's embassy or consulate prior to departure.

²As a part of an ongoing project, CDC, WHO, and other partners have made every effort to harmonize the listed yellow fever vaccine requirements and recommendations wherever possible. These efforts will continue, and will likely result in further changes to the printed version of this table. Please check the online version of the Yellow Book (www.cdc.gov/yellowbook) for the latest information on country requirements and vaccine recommendations.

³The information in the section on yellow fever vaccine recommendations is advice given by CDC to prevent yellow fever infections among travelers. Note: CDC recommendations and country requirements may not be the same.

⁴Recommendations are subject to change at any time if disease conditions change; therefore, CDC encourages travelers to check for relevant travel notices on the website (www.cdc.gov/travel) prior to departure.

⁵Please note, the U.S. Advisory Committee on Immunization Practices (ACIP) recommends avoiding vaccination of infants <9 months of age.

Please note: Country requirements for yellow fever vaccine are subject to change at any time, and CDC vaccine recommendations are subject to change at any time if disease conditions change; therefore, CDC encourages health-care providers and travelers to check for updates on the CDC website www.cdc.gov/travel, and with the destination country's embassy or consulate in sufficient time to receive yellow fever vaccination or to obtain a waiver if recommendations or requirements have changed.

Vaccination for Travel on Military Orders

Because military requirements may exceed those indicated in this publication, any person who plans to travel on military orders (civilians and military personnel) should be advised to contact the nearest military medical facility to determine the requirements for the trip.

YELLOW FEVER VACCINE REQUIREMENTS AND RECOMMENDATIONS, BY COUNTRY

Mark Gershman, Betsy Schroeder, Emily S. Jentes, Nina Marano

JAPANESE ENCEPHALITIS (JE)

Marc Fischer, Anne Griggs, J. Erin Staples

Infectious Agent

Japanese encephalitis virus (JEV) is a single-stranded RNA virus that belongs to the genus Flavivirus and is closely related to West Nile and St. Louis encephalitis viruses.

Mode of Transmission

• •JEV is transmitted to humans through the bite of an infected mosquito, primarily Culex species. Wading birds are the main animal reservoir for the virus, but the presence of pigs greatly amplifies the transmission of JEV.
• •Humans are a dead-end host in the JEV transmission cycle.

Occurrence

• •JEV is the most common cause of encephalitis in Asia, occurring throughout most of Asia and parts of the western Pacific (Map 2-5 ). JEV has not been locally transmitted in Africa, Europe, or the Americas.
• •JEV transmission principally occurs in rural agricultural areas, often associated with rice production and flooding irrigation. In some areas of Asia, these ecologic conditions may occur near or occasionally within urban centers.
• •In temperate areas of Asia, transmission is seasonal, and human disease usually peaks in summer and fall. In the subtropics and tropics, seasonal transmission varies with monsoon rains and irrigation practices and may be extended or even occur year-round.
• •In endemic countries, JE is primarily a disease of children. However, travel-associated JE can occur among persons of any age.

Map 2-5.

Geographic distribution of Japanese encephalitis.

Risk for Travelers

• •The risk for JE for most travelers to Asia is extremely low but varies according to season, destination, duration, and activities. Fewer than 40 cases of confirmed JE have been reported in travelers in the last 40 years.
• •The overall incidence of JE reported among people from nonendemic countries traveling to Asia is <1 case per 1 million travelers. However, expatriates and travelers staying for prolonged periods in rural areas with active JEV transmission are likely at similar risk as the susceptible resident population (0.1–2 cases per 100,000 persons per week).
• • Travelers on even brief trips are probably at increased risk if they have extensive outdoor or nighttime exposure in rural areas, including persons staying in resort areas or with family.
• •Short-term travelers whose visits are restricted to major urban areas are at very minimal risk for JE.
• •In endemic areas where there are few human cases among residents because of vaccination or natural immunity, JEV is often maintained in an enzootic cycle between animals and mosquitoes. Therefore, susceptible visitors still may be at risk for infection.

Clinical Presentation

• •Most human infections with JEV are asymptomatic; <1% of people infected with JEV develop clinical disease.
• •Acute encephalitis is the most commonly recognized clinical manifestation of JEV infection. Milder forms of disease such as aseptic meningitis or undifferentiated febrile illness can also occur.
• •
  The incubation period is 5–15 days. Illness usually begins with sudden onset of fever, headache, and vomiting. Mental status changes, focal neurologic deficits, generalized weakness, and movement disorders may develop over the next few days.

  • ○
    A parkinsonian syndrome resulting from extrapyramidal involvement is a very distinctive clinical presentation of JE.
  • ○
    Acute flaccid paralysis, with clinical and pathological features similar to poliomyelitis, has also been associated with JEV infection.
  • ○
    Seizures are very common, especially among children.
• •Clinical laboratory findings include moderate leukocytosis, mild anemia, hyponatremia, and cerebrospinal fluid (CSF) pleocytosis with a lymphocytic predominance.
• •Case–fatality ratio is approximately 20%–30%. Among survivors, 30%–50% may still have significant neurologic or psychiatric sequelae, even years after their acute illness.

Diagnosis

• •JE should be suspected in a patient with evidence of a neurologic infection (e.g., encephalitis, meningitis, or acute flaccid paralysis) who has recently traveled or resided in an endemic country in Asia or the western Pacific.
• •Laboratory diagnosis of JEV infection should be performed by using JE-specific IgM-capture enzyme-linked immunosorbent assay (ELISA) on CSF or serum. JE-specific IgM antibodies will be present in the CSF or blood of almost all patients by 7 days following onset of symptoms. A fourfold or greater rise in JEV-specific neutralizing antibodies between acute- and convalescent-phase serum specimens may be used to confirm the diagnosis.
• •Vaccination history, date of onset of symptoms, and information regarding other flaviviruses known to circulate in the geographic area that may cross-react in serologic assays need to be considered when interpreting results.
• •Humans have low levels of transient viremia and usually have neutralizing antibodies by the time distinctive clinical symptoms are recognized. Virus isolation and nucleic-acid amplification tests (NAATs) are insensitive for the detection of JEV or JE viral RNA in blood or CSF and should not be used for ruling out a diagnosis of JE.
• •Health-care providers should contact their state or local health department or CDC's Division of Vector Borne Infectious Diseases at 970-221-6400 for assistance with diagnostic testing.

Treatment

There is no specific antiviral treatment for JE; therapy consists of supportive care and management of complications.

Preventive Measures for Travelers

Personal Protection Measures

• • No drugs for preventing JEV infection are available.
• •The best way to prevent mosquito-borne diseases, including JE, is to avoid mosquito bites (see the Protection Against Mosquitoes, Ticks, and Other Insects and Arthropods section later in this chapter).

JE Vaccines

• •An inactivated mouse brain-derived JE vaccine (JE-VAX, manufactured by sanofi pasteur) has been licensed for use in adult and pediatric travelers (Δ1 year of age) in the United States since 1992. Although production of JE-VAX was discontinued in 2006, stockpiles of the vaccine will be used for U.S. travelers until they are depleted.
• •An inactivated cell culture-derived JE vaccine (IXIARO, manufactured by Intercell) was approved for adult travelers (Δ18 years of age) in the United States on March 30, 2009. Recommendations for its use will be available at www.cdc.gov/travel. Other inactivated and live attenuated JE vaccines are manufactured and used in Asia but not licensed for use in the United States.

Inactivated Mouse Brain-Derived JE Vaccine (JE-VAX)

• •A randomized controlled trial among 65,000 children in Thailand showed an efficacy of 91% (95% CI 70%–97%) after two doses.
• •From 88% to 100% of adults from nonendemic settings developed neutralizing antibodies after receiving three doses of vaccine.
• •The duration of protection after primary immunization is unknown, but circulating neutralizing antibodies appear to last for at least 2–3 years.
• •Booster doses produce an anamnestic response in neutralizing antibody titers.

Recommendations for the Use of JE Vaccine for Travelers

• •Decisions regarding the use of JE vaccine for travelers must balance the low risk for disease and the small chance of an adverse event following immunization.
• •The U.S. Advisory Committee on Immunization Practices (ACIP) currently recommends JE vaccine for travelers who plan to spend a month or longer in endemic areas or areas with ongoing transmission. Vaccine should also be considered for shorter-term travelers whose itineraries may put them at increased risk for JEV exposure, such as rural stays during the rainy season.
• •Evaluation of an individual traveler's risk should take into account itinerary, activities, and best-available information on the current level of JE activity in the travel area (Table 2-15 ). Complicating the concept of risk assessment, however, is the fact that sporadic cases of JE have very rarely occurred in travelers whose itineraries would not ordinarily have indicated a risk for JE (e.g., a resort hotel in Bali, a standard tour of China).

Table 2-15.

Risk for Japanese encephalitis, by country¹

Country	Affected Areas	Transmission Season	Comments
Australia	Outer islands of Torres Strait	December to May; all human cases reported from February to April	One human case reported from north Queensland mainland
Bangladesh	Limited data; probably widespread	Unknown; most human cases reported from May to October	One outbreak of human disease reported from Tangail District in 1977. Sentinel surveillance has identified human cases in Chittagong, Khulna, and Rajshahi divisions, and Mymensingh district.
Bhutan	No data	No data
Brunei	No data; presumed to be endemic countrywide	Unknown; presumed year-round transmission
Burma (Myanmar)	Limited data; presumed be endemic countrywide	Unknown; most human cases reported from May to October	Outbreaks of human disease documented in Shan State. JEV antibodies documented in animals and humans in other areas
Cambodia	Presumed to be endemic countrywide	Probably year round with peaks reported from May to October	Sentinel surveillance has identified human cases in at least 14 provinces including Phnom Penh, Takeo, Kampong, Cham, Battambang, Svay Rieng, and Siem Reap.
China	Human cases reported from all provinces except Xizang (Tibet), Xinjiang, and Qinghai Hong Kong and Macau: Not considered endemic. Rare cases reported from the New Territories	Most human cases reported from April to October	Highest rates reported from the southwest and south central provinces Vaccine not routinely recommended for travel limited to Beijing or other major cities
India	Human cases reported from all states except Dadra, Daman, Diu, Gujarat, Himachal, Jammu, Kashmir, Lakshadweep, Meghalaya, Nagar Haveli, Punjab, Rajasthan, and Sikkim	Most human cases reported from May to October especially in northern India. The season may be extended or year round in some areas especially in southern India.	Highest rates of human disease reported from the states of Andhra Pradesh, Assam, Bihar, Goa, Haryana, Karnataka, Kerala, Tamil Nadu, Uttar Pradesh, and West Bengal
Indonesia	Presumed to be endemic countrywide	Human cases reported year round; peak season varies by island	Sentinel surveillance has identified human cases in Bali, Kalimantan, Java, Nusa Tenggara, Papua, and Sumatra.
Japan2	Rare sporadic human cases on all islands except Hokkaido. Enzootic activity ongoing	Most human cases reported from May to October	Large number of human cases reported until routine JE vaccination introduced in 1968. Most recent small outbreak reported from Chugoku district in 2002. Sporadic cases reported among U.S. military personnel on Okinawa. Enzootic transmission without human cases observed on Hokkaido Vaccine not routinely recommended for travel limited to Tokyo or other major cities
Korea, North	No data	No data
Korea, South2	Rare sporadic human cases countrywide. Enzootic activity ongoing	Most human cases reported from May to October	Large number of human casesreported until routine JE vaccinationintroduced in 1968. Highest rates ofdisease were reported from thesouthern provinces. Last majoroutbreak reported in 1982 Vaccine not routinely recommendedfor travel limited to Seoul or othermajor cities
Laos	No data; presumed to be endemic countrywide	Presumed to be May to October
Malaysia	Endemic in Sarawak; sporadic cases or outbreaks reported from all states of Peninsula, and probably Sabah	Year-round transmission	Most human cases reported from Penang and Sarawak Vaccine not routinely recommended for travel limited to Kuala Lumpur or other major cities
Mongolia	Not considered endemic
Nepal	Endemic in southern lowlands (Terai). Sporadic cases or outbreaks reported from the Kathmandu valley	Most human cases reported from May to November	Highest rates of human disease reported from western Terai districts, including Bankey, Bardia, Dang, and Kailali Vaccine not routinely recommended for travel limited to high-altitude areas
Pakistan	Limited data; human cases reported from around Karachi	Most human cases reported from May to October
Papua New Guinea	Limited data; sporadic human cases reported from Western, Gulf, and South Highland Provinces	Unknown	A case of JE was reported from near Port Moresby in 2004. Human cases documented in Papua Indonesia
Philippines	Limited data; presumed to be endemic on all islands	Unknown; probably year-round	Outbreaks reported in Nueva Ecija, Luzon, and Manila
Russia	Rare human cases reported from the Far Eastern maritime areas south of Khabarousk	Most human cases reported from July to September
Singapore	Rare sporadic human cases reported	Year-round transmission	Vaccine not routinely recommended
Sri Lanka	Endemic countrywide except in mountainous areas	Year-round with variable peaks based on monsoon rains	Highest rates of human disease reported from Anuradhapura, Gampaha, Kurunegala, Polonnaruwa, and Puttalam districts
Taiwan2	Rare sporadic human cases island-wide	Most human cases reported from May to October	Large number of human cases reported until routine JE vaccination introduced in 1968 Vaccine not routinely recommended for travel limited to Taipei or other major cities
Thailand	Endemic countrywide; seasonal epidemics in the northern provinces	Year-round with seasonal peaks from May to October, especially in the north	Highest rates of human disease reported from the Chiang Mai Valley. Sporadic human cases reported from Bangkok suburbs
Timor-Leste	Limited data; anecdotal reports of sporadic human cases	No data
Vietnam	Endemic countrywide; seasonal epidemics in the northern provinces	Year-round with seasonal peaks from May to October, especially in the north	Highest rates of disease in the northern provinces around Hanoi and northwestern provinces bordering China
Western Pacific Islands	Outbreaks of human disease reported in Guam in 1947–1948 and Saipan in 1990	Unknown; most human cases reported from October to March	Enzootic cycle might not be sustainable; outbreaks may follow introductions of JE virus.

¹Data are based on published reports and personal correspondence. Risk assessments should be performed cautiously because risk can vary within areas and from year to year, and surveillance data regarding human cases and JE virus transmission are incomplete.

²In some endemic areas, human cases among residents are limited because of vaccination or natural immunity. However, because JE virus is maintained in an enzootic cycle between animals and mosquitoes, susceptible visitors to these areas still may be at risk for infection.

Vaccine Safety and Adverse Events

• •Inactivated mouse brain-derived JE vaccine has been associated with localized erythema, tenderness, and swelling at the injection site in about 20% of recipients.
• •Mild systemic side effects (e.g., fever, chills, headache, rash, myalgia, gastrointestinal symptoms) have been reported in approximately 10% of vaccinees.
• •Serious allergic hypersensitivity reactions, including generalized urticaria and angioedema of the extremities, face, and oropharynx, have been reported. Accompanying bronchospasm, respiratory distress, and hypotension have been observed in some of these patients, although there have been no fatalities among vaccine recipients with these symptoms.
• • Estimates of the frequency of these reactions range from 20 to 600 cases per 100,000 vaccinees and vary by country, year, case definition, surveillance method, and vaccine lot.
• •Most hypersensitivity reactions occur within 24–48 hours after the first dose, when they occur following a subsequent dose, the onset of symptoms is often delayed (median: 3 days; range: up to 2 weeks).
• •Most reactions can be treated with antihistamines or corticosteroids on an outpatient basis; however, up to 10% of vaccinees with rare severe reactions are hospitalized.
• •At least four deaths due to anaphylactic shock temporally associated with receipt of this vaccine have been reported in the world literature, which includes endemic country national vaccine programs. None of these patients had evidence of urticaria or angioedema, and two had received other vaccines simultaneously.
• •Moderate to severe neurologic symptoms, including encephalitis, seizures, gait disturbances, and parkinsonian syndrome have been reported, with an incidence of 0.1 to 2 cases per 100,000 vaccinees.
• •In addition, there have been case reports of children in Japan and Korea with severe or fatal acute disseminated encephalomyelitis (ADEM) temporally associated with JE vaccination.

Vaccine Dose and Administration

• •For travelers Δ3 years of age, the recommended primary immunization series for JE-VAX is three doses of 1.0 mL each, administered subcutaneously on days 0, 7, and 30.
• •An abbreviated schedule (days 0, 7, and 14) provides similar rates of seroconversion but significantly lower neutralizing antibody titers.
• •Immunization routes and schedules for children 1 and 2 years of age are identical except that 0.5-mL doses should be administered.
• •Vaccine recipients should be observed for a minimum of 30 minutes after immunization and warned about the possibility of delayed allergic reactions.
• •The last dose should be administered at least 10 days before beginning travel to ensure an adequate immune response and access to medical care in the event of any delayed adverse reactions.
• •Booster doses may be administered 2–3 years after the primary series. The timing and immune response of subsequent boosters have not been studied in travelers.

Precautions and Contraindications

• • A history of allergy or hypersensitivity reaction to a previous dose of mouse brain-derived JE vaccine is a contraindication to receiving additional doses.
• •Proven or suspected hypersensitivity to thimerosal or proteins of rodent or neural origin is a contraindication to vaccination.
• •Persons with a previous history of urticaria are more likely to develop a hypersensitivity reaction following receipt of JE vaccine. This history should be considered when weighing the risks and benefits of the vaccine for an individual patient.
• •No specific information is available on the safety of JE vaccine in pregnancy. Therefore, the vaccine should not be routinely administered during pregnancy. Pregnant women who must travel to an area where risk for JE is high should be vaccinated when the theoretical risk for immunization is outweighed by the risk for infection.
• •No data are available on vaccine safety and efficacy in infants <1 year of age.
• •Two small studies of inactivated JE vaccine in children with underlying medical conditions did not show a change in the adverse reactions or immune response after vaccination.

MENINGOCOCCAL DISEASE

Amanda Cohn, Michael L. Jackson

Infectious Agent

• • The infectious agent is a gram-negative diplococci, Neisseria meningitidis. Meningococci are classified into serogroups on the basis of the composition of the capsular polysaccharide.
• •The five major meningococcal serogroups associated with disease are A, B, C, Y, and W-135.

Mode of Transmission

Person-to-person transmission occurs by close contact with respiratory secretions or saliva.

Occurrence

• • Neisseria meningitidis is found worldwide. At any time, 5%–10% of the population may be carriers of N. meningitidis.
• •Invasive disease is much rarer, occurring at a rate of 0.5–10 cases per 100,000 population in nonepidemic areas and up to 1,000 cases per 100,000 population in epidemic regions.
• •The incidence of meningococcal disease is highest in the “meningitis belt” of sub-Saharan Africa (Map 2-6 ). The incidence of meningococcal disease is several times higher in the meningitis belt than in the United States, with periodic epidemics during the dry season (December–June). During nonepidemic periods the rate of meningococcal disease is roughly 5–10 cases per 100,000 population per year. During epidemics the rate can be as high as 1,000 cases per 100,000 population.
• •Serogroup A predominates in the meningitis belt, although serogroups C, X, and W-135 are also found.
• •Young children have the highest risk for meningococcal disease.

Map 2-6.

Areas with frequent epidemics of meningococcal meningitis.

Risk for Travelers

• •Travelers to the meningitis belt may be at risk for meningococcal disease, particularly during the dry season.
• •Risk is likely highest in travelers who will have prolonged contact with local populations in the meningitis belt during an epidemic.
• •The incidence of meningococcal disease in international travelers who acquire sporadic disease is very low, estimated at 0.4 per 100,000 in one retrospective study.
• •The Hajj pilgrimage to Saudi Arabia has been associated with outbreaks of meningococcal disease in returning pilgrims and their contacts.

Clinical Presentation

• •Meningococcal disease generally occurs 1–14 days after exposure.
• •Meningococcal disease presents as meningitis in 50% or more of cases. Meningococcal meningitis is characterized by sudden onset of headache, fever, and stiffness of the neck, sometimes accompanied by nausea, vomiting, photophobia, and/or altered mental status.
• •Up to 20% of persons with meningococcal disease present with meningococcal sepsis. Meningococcal sepsis is characterized by an abrupt onset of fever and a petechial or purpuric rash. The rash may progress to purpura fulminans. Meningococcal sepsis may often involve hypotension, acute adrenal hemorrhage, and multiorgan failure.
• •Among infants and children <2 years of age, meningococcal disease may have nonspecific symptoms. Neck stiffness may be absent.

Diagnosis

• •Early diagnosis and treatment are critical.
• •If possible, a lumbar puncture should be done before starting antibiotic therapy to ensure that bacteria, if any, can be cultured from cerebrospinal fluid (CSF).
• •Diagnosis is generally made isolating N. meningitidis from blood or CSF, by detecting meningococcal antigen in CSF by latex agglutination, or by evidence of N. meningitidis DNA by polymerase chain reaction.
• •The signs and symptoms of meningococcal meningitis are similar to those of other causes of bacterial meningitis, such as Haemophilus influenzae and Streptococcus pneumoniae. Identification of the causative organism is important for selecting the correct antibiotics for treatment and prophylaxis.

Treatment

• •Invasive meningococcal disease is potentially fatal and should always be viewed as a medical emergency.
• •Antibiotic treatment must be started early in the course of the disease. Several antibiotic choices are available, including ceftriaxone, chloramphenicol, cefotaxime, and benzylpenicillin.

Preventive Measures for Travelers

Vaccine

• •ACIP recommends vaccination against meningococcal disease to persons who travel to or reside in countries where N. meningitidis is hyperendemic or epidemic, particularly if contact with the local population will be prolonged.
• •Vaccination is advised for persons traveling to the meningitis belt of Africa during the dry season (December through June).
• •Advisories for travelers to other countries will be issued when epidemics of meningococcal disease caused by vaccine-preventable serogroups are recognized (see the CDC Travelers' Health website at www.cdc.gov/travel).
• •Quadrivalent meningococcal polysaccharide–protein conjugate vaccine (MCV4) is licensed for use among persons 2–55 years of age.
• •Quadrivalent meningococcal polysaccharide vaccine (MPVS4) is licensed for use among persons 2 years of age or older.
• •Both vaccines protect against meningococcal disease caused by serogroups A, C, Y, and W-135. Approximately 7–10 days are required following vaccination for development of protective antibody levels.
• •MCV4 is the preferred vaccine for persons 2–55 years of age; MPSV4 should be used for persons >55 years of age. There is no licensed vaccine for persons <2 years old, but MPSV4 is safe to give to children <2 years of age who require vaccination before traveling to Mecca for the Hajj pilgrimage.

Requirement for Travel

Proof of quadrivalent vaccination against meningococcal disease is required for persons traveling to Mecca during the annual Hajj and Umrah pilgrimage.

Antibiotic Chemoprophylaxis

• • Antibiotic chemoprophylaxis among close contacts of a patient with invasive meningococcal disease is recommended for prevention of secondary cases in the United States and most industrialized countries.
• •Antibiotic regimens for prophylaxis include rifampin, ciprofloxacin, and ceftriaxone. Ceftriaxone is recommended for pregnant women.

RABIES

Charles E. Rupprecht, David R. Shlim

Infectious Agent

Rabies is an acute, progressive, fatal encephalomyelitis caused by neurotropic viruses in the family Rhabdoviridae, genus Lyssavirus. Regardless of the viral variant found throughout the world, all lyssaviruses cause rabies.

Mode of Transmission

• •The disease is almost always transmitted by an animal bite that inoculates virus into wounds.
• •Very rarely, rabies virus has been transmitted by exposures other than bites that introduce the virus into open wounds or mucous membranes.
• •All mammals are believed to be susceptible, but reservoirs are carnivores and bats.
• •Although dogs are the main reservoir in developing countries, the epidemiology of the disease differs sufficiently enough from one region or country to another to warrant the medical evaluation of all mammal bites.
• •Bat bites anywhere in the world are a cause of concern and an indication for prophylaxis.

Pathophysiology of Rabies

• •Rabies virus is present in the saliva of the biting mammal.
• •The virus that is inoculated into the wound does not enter the bloodstream. The virus must be taken up at a nerve synapse to travel to the brain, where it causes a fatal encephalitis. The virus may enter a nerve rapidly, or it may remain at the bite site for an extended period before gaining access to the nervous system. The density of nerve endings in the region of the bite increases the risk of developing rabies encephalitis more rapidly. The hands and face, because of the density of nerve endings, are considered higher-risk exposures.
• •Prevention of rabies encephalitis is dependent upon preventing the virus from entering a peripheral nerve. This can be accomplished by wound cleansing and disinfection, instillation of rabies virus neutralizing antibodies into the wound, and stimulating an active immune response with a series of rabies vaccine injections.

Occurrence

• •Rabies is found on all continents except Antarctica.
• •In certain areas of the world, canine rabies remains highly endemic, including but not limited to parts of Africa, Asia, and Central and South America. Table 2-16 lists countries that have reported no cases of rabies during the most recent period for which information is available (formerly referred to as “rabies-free” countries).
• •
  Additional information about the global occurrence of rabies can be obtained from:

  • ○
    The World Health Organization (www.who.int/rabies/rabnet/en/)
  • ○
    The Pan American Health Organization (www.paho.org/english/ad/dpc/vp/rabia.htm)
  • ○
    The Rabies Bulletin—Europe (www.rbe.fli.bund.de)
  • ○
    The World Organization for Animal Health (www.oie.int/eng/en_index.htm)
  • ○
    Other sources are local health authorities of the country, the embassy, or the local consulate's office in the United States.

Table 2-16.

Countries and political units reporting no indigenous cases of rabies during 2005¹

Region	Countries
Africa	Cape Verde, Libya, Mauritius, Réunion, São Tomé and Príncipe, and Seychelles
Americas	North: Bermuda, St. Pierre and Miquelon Caribbean: Antigua and Barbuda, Aruba, Bahamas, Barbados, Cayman Islands, Dominica, Guadeloupe, Jamaica, Martinique, Montserrat, Netherlands Antilles, Saint Kitts (Saint Christopher) and Nevis, Saint Lucia, Saint Martin, Saint Vincent and Grenadines, Turks and Caicos, and Virgin Islands (UK and US) South: Uruguay
Asia	Hong Kong, Japan, Kuwait, Lebanon, Malaysia (Sabah), Qatar, Singapore, United Arab Emirates
Europe	Austria, Belgium, Cyprus, Czech Republic,2 Denmark,2 Finland, France,2 Gibraltar, Greece, Iceland, Ireland, Isle of Man, Italy, Luxemburg, Netherlands,2 Norway, Portugal, Spain2 (except Ceuta/Melilla), Sweden, Switzerland, and United Kingdom2
Oceania3	Australia,2 Northern Mariana Islands, Cook Islands, Fiji, French Polynesia, Guam, Hawaii, Kiribati, Micronesia, New Caledonia, New Zealand, Palau, Papua New Guinea, Samoa, and Vanuatu

¹Bat rabies may exist in some areas that are reportedly free of rabies in other animals.

²Bat lyssaviruses are known to exist in these areas that are reportedly free of rabies in other animals.

³Most of Pacific Oceania is reportedly rabies-free.

Lists are provided only as a guide, because up-to-date information may not be available, surveillance standards vary, and reporting status can change suddenly as a result of disease re-introduction or emergence.

Risk for Travelers

• •The actual rate of possible rabies exposure in tourists has not been calculated with accuracy. However, studies have found a range of roughly 16 to 200 per 100,000 based on differing criteria.
• • Travelers to rabies-endemic countries should be warned about the risk of acquiring rabies and educated in animal bite prevention strategies.
• •Street dogs represent the most frequent risk for bite exposure to travelers, followed by monkeys, especially those that live near temples in parts of Asia. Travelers should be instructed not to approach these animals and to be aware of their surroundings so that they do not surprise a dog in a confined space. If a dog is charging at a person, stooping to pick up a rock (or pretending to pick up a rock) can often make the dog turn and run away.
• •Monkeys are attracted to food and may jump on travelers' backs if there is food in their backpacks.
• •Children are considered to be at high risk from rabies virus exposures because their small stature makes extensive bites more likely, they are attracted to animals, and there is the remote possibility that they may not report a possible exposure.
• •Casual exposure to cave air is not a concern, but cavers should be warned not to handle bats. Noncavers can occasionally encounter a bat. Many bats have tiny teeth, and not all wounds may be appreciated compared with the lesions caused by carnivores. Any suspected or documented bite or scratch from a bat should be grounds for seeking postexposure rabies immunoprophylaxis.

Clinical Presentation

• •After infection, the incubation period is highly variable, but lasts approximately 1–3 months.
• •The disease progresses from a nonspecific prodromal phase to paresis or paralysis; spasms of swallowing muscles can be stimulated by the sight, sound, or perception of water (hydrophobia); and delirium and convulsions can develop, followed rapidly by coma and death.

Diagnosis

• •Definitive diagnosis can be made by demonstrating the presence of the rabies virus in corneal impressions or nuchal biopsy, either through staining or polymerase chain reaction.
• •A serologic response to rabies virus can also prove the diagnosis.

Treatment

No treatment is effective after the development of clinical signs, but the extremely rare case of recovery after extensive medical intervention offers hope that future experimental therapeutics may be developed.

Preventive Measures for Travelers

• •Prevention of possible exposures to rabies virus is best accomplished by avoiding bites from mammals (mainly dogs, monkeys, bats, and cats in some countries).
• •Although licks from animals to fresh wounds or mucus membranes of humans are a theoretical risk of acquiring rabies and postexposure prophylaxis should be considered, there are no examples of rabies in travelers who were exposed in this way.
• •Travelers should be counseled to avoid approaching stray animals, to be aware of their surroundings so that they do not accidentally surprise a stray dog, to avoid contact with bats, and not to carry or eat food while walking among monkeys.
• •In addition to avoiding bite exposures, two strategies are available to travelers for the prevention of rabies: vaccination and management of a possible rabies exposure (see sections below for more specific details).
• •
  For certain international travelers, pre-exposure rabies vaccine may be recommended, based on the local incidence of rabies in the country to be visited, the availability of appropriate anti-rabies biologicals, and the intended activity and duration of stay of the traveler.

  • ○
    A decision to receive pre-exposure rabies immunization may also be based on the likelihood of repeat travel to at-risk destinations over time or taking up residence in a high-risk destination.
  • ○
    Pre-exposure vaccination may be recommended for veterinarians, animal handlers, field biologists, cavers, missionaries, and certain laboratory workers. Table 2-17 provides criteria for pre-exposure vaccination.
• •Immediate and adequate medical care after an animal bite is critical to preventing rabies (see Management of a Possible Rabies Exposure below). Regardless of whether or not pre-exposure vaccine is administered, travelers going to areas with a high risk for rabies should be especially encouraged to purchase medical evacuation insurance (see the Travel Insurance and Evacuation Insurance section later in this chapter).

Table 2-17.

Criteria for pre-exposure immunization for rabies

Risk Category	Nature of Risk	Typical Populations	Pre-exposure Regimen
Continuous	Virus present continuously, often in high concentrations Specific exposures likely to go unrecognized Bite, nonbite, or aerosol exposure	Rabies research laboratory workers,1 rabies biologics production workers	Primary course: serologic testing every 6 months; booster vaccination if antibody titer is below acceptable level2
Frequent	Exposure usually episodic with source recognized, but exposure might also be unrecognized Bite, nonbite, or aerosol exposure possible	Rabies diagnostic laboratory workers1, cavers, veterinarians and staff, and animal control and wildlife workers in rabies-epizootic areas	Primary course: serologic testing every 2 years; booster vaccination if antibody titer is below acceptable level2
Infrequent (greater than general population)	Exposure nearly always episodic with source recognized Bite or nonbite exposure	Veterinarians, animal control and wildlife workers in areas with low rabies rates; veterinary students; and travelers visiting areas where rabies is enzootic and immediate access to appropriate medical care, including biologics, is limited	Primary course: no serologic testing or booster vaccination
Rare (general population)	Exposure always episodic, with source recognized	U.S. population at large, including individuals in rabies-epizootic areas	No pre-exposure immunization necessary

¹Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor (see U.S. Department of Health and Human Services' Biosafety in Microbiological and Biomedical Laboratories, 1999)

²Pre-exposure booster immunization consists of one dose of human diploid cell (rabies) vaccine (HDCV) or purified chick embryo cell (PCEC) vaccine, 1.0-mL dose, intramuscular (IM) (deltoid area). Minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test. A booster dose should be administered if titer falls below this level.

Vaccine

Pre-Exposure Vaccination

• •In the United States, pre-exposure vaccination consists of a series of three injections with human diploid cell rabies vaccine (HDCV) or purified chick embryo cell (PCEC) vaccine.
• •The schedule for this series in given in Table 2-18.
• •In the event of a possible rabies exposure in someone who has received pre-exposure rabies immunization, rabies immune globulin (RIG) is not given, and two boosters of an acceptable rabies vaccine are given on days 0 and 3. The booster doses need to be modern cell culture vaccines, but they do not need to be the same brand as the vaccine given in the pre-exposure immunization series.
• •Pre-exposure immunization does not eliminate the need for additional medical attention after a rabies exposure, but it greatly simplifies postexposure prophylaxis.
• •Pre-exposure vaccination may also provide some degree of protection when there is an unapparent or unrecognized exposure to rabies virus and when postexposure prophylaxis might be delayed.
• •Travelers should receive all three pre-exposure immunizations before travel. If three doses of rabies vaccine cannot be completed prior to travel, the traveler should not start the series, as it would be problematic to plan postexposure prophylaxis after a partial immunization series.

Beginning in 2007 and anticipated to continue through 2009, the United States has experienced a limitation in supply of rabies vaccine. As a result, during this time, pre-exposure rabies vaccination has not been available to international travelers, except under special circumstances. The existing supplies of rabies vaccine are being reserved for postexposure prophylaxis.

Postexposure Vaccination

• •If pre-exposure rabies immunization is not given, the traveler will need to obtain full postexposure rabies prophylaxis in the event of a possible rabies virus exposure. This consists of injections of RIG (20 IU/kg) and a series of five injections of rabies vaccine over a 1-month period.
• •Because RIG or rabies vaccine may not be available in the destination country, travelers should have a strategy in place before travel as to how to respond to a possible exposure. This strategy may require the traveler to fly to a different country to obtain the appropriate prophylaxis.
• •Different postexposure vaccine schedules, alternative routes of administration and other rabies vaccines besides HDCV and PCEC may be found abroad. Although not approved for sale in the United States, purified vero cell rabies vaccine and purified chick embryo cell vaccine (manufactured abroad) are acceptable alternatives if available in a destination country.
• • Historically, rabies vaccine was once manufactured from viruses grown in animal brains, and some of these vaccines are still in use in developing countries. The brain-derived vaccines can be identified if the traveler is offered a large injection (5 mL) daily for 14–21 days. The traveler should not accept these vaccines, but rather travel to where acceptable vaccines and immune globulin are available.

Management of a Possible Rabies Exposure

• •Travelers should be advised that any animal bite or scratch should receive prompt local first aid by thorough cleansing of the wound with copious amounts of soap and water and povidone iodine, if available. This local care will substantially reduce the risk for rabies.
• • Wounds that might require suturing should have the suturing delayed for a few days. If suturing is necessary for control of bleeding or for functional or cosmetic reasons, RIG should be administered into the wound before closing the wound. The use of local anesthetic is not contraindicated in wound management.
• •Human rabies immune globulin (HRIG) is manufactured by plasmaphoresis of hyperimmunized volunteers. The manufactured quantity of HRIG falls short of world-wide requirements, and the substance is not available in many developing countries. Equine rabies immune globulin (ERIG) or purified fractions of ERIG have been used effectively in some developing countries where HRIG might not be available. If necessary, such heterologous products are preferable to no RIG administration in human rabies postexposure prophylaxis.
• •The incidence of adverse reactions after the use of these products has been low (0.8%–6.0%), and most of those reactions were minor. However, such products are neither evaluated by U.S. standards nor regulated by the FDA, and their use cannot be unequivocally recommended at this time. In addition, unpurified antirabies serum of equine origin might still be used in some countries where neither HRIG nor ERIG is available. The use of this antirabies serum is associated with higher rates of serious adverse reactions, including anaphylaxis.
• •After wound cleansing, as much of the calculated amount of RIG (see Table 2-19) as is anatomically feasible is infiltrated around the wound. The dose injected around the wound may be as small as 0.5 mL if the wound is small or on a finger. If the wounds are extensive, the calculated dose of RIG must not be exceeded. If the calculated dose is inadequate to inject all the wounds, the RIG should be diluted with normal saline to extend the number of wounds that can be injected. This is a particular issue in children, whose body weight may be small in relation to the size and number of wounds.
• •The remainder of the RIG dose, if any, should be injected intramuscularly. Care should be taken to guarantee that this remaining amount of RIG is deposited in a muscle and not injected subcutaneously, which may decrease its effectiveness. The remaining RIG can be given in the deltoid muscle, on the opposite side of the initial vaccine dose. The anterior thigh is also an alternative site.
• •RIG should not be given more than 7 days after the start of the postexposure vaccine series. This 7-day period does not relate to the time of the bite exposure itself.
• •Postexposure prophylaxis, including RIG, should be initiated after a possible bite exposure even if there has been a considerable delay between the exposure and the traveler presenting for evaluation.
• •Travelers who have completed a three-dose pre-exposure rabies immunization series or have received the full postexposure prophylaxis are considered pre-immunized and do not require routine boosters, except after a possible rabies exposure.
• •Periodic serum testing for rabies antibody is not necessary in routine international travelers.

Vaccine Safety and Adverse Reactions

• • Travelers should be advised that they may experience local reactions after vaccination, such as pain, erythema, swelling, or itching at the injection site, or mild systemic reactions, such as headache, nausea, abdominal pain, muscle aches, and dizziness.
• •Approximately 6% of persons receiving booster vaccinations with HDCV may experience an immune complex-like reaction characterized by urticaria, pruritus, and malaise. The likelihood of these reactions is less with PCECV.
• •Once initiated, rabies postexposure prophylaxis should not be interrupted or discontinued because of local or mild systemic reactions to rabies vaccine.

Precautions and Contraindications

• •Pregnancy is not a contraindication to postexposure prophylaxis.
• •In infants and children, the dose of HDCV or PCEC for pre-exposure or postexposure prophylaxis is the same as that recommended for adults. The dose of RIG for postexposure prophylaxis is based on body weight (Table 2-19).

 

Routine Vaccine-Preventable Diseases

DIPHTHERIA

Tejpratap S.P. Tiwari

Infectious Agent

• •Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae biotype mitis, gravis, intermedius, or belfanti.
• •The bacteria produce an exotoxin which, if absorbed in the bloodstream, may damage organs such as the heart, kidneys, and nerves.

Mode of Transmission

• •Humans are the only known reservoir of C. diphtheriae.
• • Person-to-person transmission occurs through oral or respiratory droplets, close physical contact, and rarely by fomites.
• •Cutaneous diphtheria is common in tropical countries, and contact with discharge from skin lesions may play an important role in transmission of infection in these environments.

Occurrence

• •Diphtheria is found worldwide. Countries with endemic diphtheria are shown in Table 2-20 .
• •Diphtheria causes significant morbidity and mortality in developing countries where vaccination coverage is low.
• •During the 1990s, large epidemics occurred in the newly independent states of the former Soviet Union. More recently in the Americas, diphtheria outbreaks occurred in Paraguay, the Dominican Republic, and Haiti.
• •Diphtheria is uncommon in industrialized countries because of long-standing routine use of DTP (diphtheria and tetanus toxoids and pertussis vaccine). Diphtheria is uncommon in the United States; and the last case occurred in an elderly traveler returning from Haiti in 2003.

Table 2-20.

Countries with endemic diphtheria

Regions	Countries
Africa	Algeria, Angola, Egypt, Niger, Nigeria, Sudan, and sub-Saharan countries
Americas	Bolivia, Brazil, Colombia, Dominican Republic, Ecuador, Haiti, and Paraguay
Asia/South Pacific	Afghanistan, Bangladesh, Bhutan, Burma (Myanmar), Cambodia, China, India, Indonesia, Laos, Malaysia, Mongolia, Nepal, Pakistan, Papua New Guinea, Philippines, Thailand, and Vietnam
Middle East	Iran, Iraq, Saudi Arabia, Syria, Turkey, and Yemen
Europe	Albania, Russia, and countries of the former Soviet Union

Risk for Travelers

• •Symptomatic infection is extremely rare in adequately immunized persons, although active immunization with diphtheria toxoid does not prevent colonization or transient carriage of C. diphtheriae.
• •Exposure and higher risk of acquiring disease and potentially life-threatening complications are possible in inadequately immunized or unimmunized travelers to countries with endemic diphtheria.

Clinical Presentation

• •The incubation period is 2–5 days (range 1–10 days).
• •Nasal diphtheria can be asymptomatic or mild, with a blood-tinged discharge.
• •Affected anatomic sites include the mucous membrane of the upper respiratory tract (nose, pharynx, tonsils, larynx, and trachea [respiratory diphtheria]), skin (cutaneous diphtheria), or rarely, mucous membranes at other sites (eye, ear, vulva).
• •Respiratory diphtheria has a gradual onset and is characterized by a mild fever (rarely >101° F or >38.3° C), sore throat, difficulty in swallowing, malaise, loss of appetite, and if the larynx is involved, hoarseness may occur.
• •The hallmark of respiratory diphtheria is the presence of a membrane that appears within 2–3 days of illness over the mucous membrane of the tonsils, pharynx, larynx, or nares, and which can extend into the trachea. The membrane is firm, fleshy, grey, and adherent, and bleeds following attempts to remove or dislodge it.
• • Local complications such as life-threatening or fatal airway obstruction can result from extension of the membrane or dislodgement of a piece of the membrane into the larynx or trachea.
• •In severe respiratory diphtheria, cervical lymphadenopathy and soft-tissue swelling in the neck give rise to a “bull-neck” appearance.
• •The case–fatality rate of respiratory diphtheria is 5%–10%.
• •Systemic complications, including myocarditis, and polyneuropathies, can result from absorption of diphtheria toxin from the infection site. However, cutaneous and nasal diphtheria are localized and rarely associated with systemic toxicity.

Diagnosis

• •A presumptive diagnosis is usually based on clinical features.
• •A confirmed diagnosis is made by isolation of C. diphtheriae from culture of nasal or throat swabs, or membrane tissue.
• •Toxin production is confirmed by performing a modified Elek test.
• •Polymerase chain reaction assays can also be performed on isolates, swabs, or membrane specimens to rapidly confirm the presence of tox gene responsible for production of diphtheria toxin, but the test is available only in research or reference laboratories.

Treatment

• •Patients with respiratory diphtheria require hospitalization to monitor response to treatment and manage complications.
• •Equine diphtheria antitoxin (DAT) is the mainstay of treatment and is administered after sensitivity testing, without waiting for laboratory confirmation. In the United States, DAT is available to physicians under an FDA-approved Investigational New Drug protocol by contacting CDC at 770-488-7100.
• •An appropriate antibiotic (erythromycin or penicillin) to eliminate the causative organisms, stop exotoxin production, and reduce communicability.
• •Supportive care (airway, cardiac monitoring) is required.
• •Antimicrobial prophylaxis (erythromycin or penicillin) is recommended for close contacts of patients.

Preventive Measures for Travelers

Vaccine

• •For protection against diphtheria, all travelers should be up-to-date with diphtheria toxoid vaccine before departure. Diphtheria toxoid is not manufactured as a monovalent vaccine but is available in pediatric (D) and adult formulations (d) that are combined with other vaccines such as tetanus toxoid (DT, Td), or tetanus toxoid and acellular or whole-cell pertussis antigens (DTaP, DTwP, Tdap), or as a DTwP/DTaP combination with other antigens (e.g., hepatitis B, inactivated poliovirus vaccines, or Hib vaccine).
• •In the United States, infants and children <7 years of age are vaccinated with diphtheria toxoid in combination with tetanus toxoid and acellular pertussis vaccine (DTaP) according to a routine childhood immunization schedule as recommended by the ACIP (see the Vaccine Recommendations for Infants and Children section in Chapter 7).
• •Immunization for infants and children <7 years of age consists of five doses of DTaP vaccine. The first three doses are usually given at ages 2, 4, and 6 months, followed by booster doses at ages 12–18 months and 4–6 years (see Table 7-2).
• • Adolescents 11–18 years of age should receive a dose of Tdap instead of Td for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood DTwP/DTaP vaccination series (see Table 7-3).
• •Adults 19–64 years of age should receive a single dose of age-appropriate Tdap to replace a single dose of Td for active booster immunization against tetanus, diphtheria and pertussis. Thereafter, routine booster doses with Td should be given every 10 years to maintain seroprotection against diphtheria as well as tetanus. This booster is particularly important for travelers who will live or work with local populations in countries where diphtheria is endemic.
• •Adults >65 years of age should receive Td; Tdap is not licensed for this age group.
• •Persons >7 years of age and with uncertain vaccination history or who have never been vaccinated against tetanus, diphtheria, or pertussis should receive three doses of an age-appropriate tetanus and diphtheria toxoid-containing vaccine. If a person is 10–65 years old, a single dose of Tdap may be substituted for one Td dose for added protection against pertussis.

HUMAN PAPILLOMAVIRUS (HPV)

Eileen F. Dunne

Infectious Agent

• •Human papillomavirus (HPV) is in the family Papillomaviridae, a family of DNA viruses that has a double-stranded, closed, circular genome of ∼8 kb and a nonenveloped icosahedral capsid.
• •Infection with human papillomavirus is specific to humans.

Mode of Transmission

• • There are more than 100 HPV types. Some types cause infection on the skin and others cause infection on the mucosa. More than 40 mucosal HPV types are commonly found on the genitals and are transmitted primarily by sexual contact, most commonly sexual intercourse.
• •Sometimes transmission of genital HPV types occurs by other routes (e.g., mother-to-child transmission).

Occurrence

• •HPV is common worldwide.
• •Studies in multiple countries demonstrate prevalence of HPV from 3% to 70%.

Risk for Travelers

There are no inherent risks for travelers. HPV is ubiquitous and common worldwide. Risk depends on the behavior of the traveler.

Clinical Presentation

• •HPV infection is usually subclinical and asymptomatic.
• •HPV infection with cutaneous types can cause the common skin wart.
• •HPV infection with mucosal types is presumed when anogenital warts or cervical cell changes are detected in screening.
• •HPV rarely causes recurrent respiratory papillomatosis (RRP); anogenital cancers such as vaginal, vulvar, anal, penile cancers; and some oral cancers.

Diagnosis

• •Infection is most commonly asymptomatic and transient.
• •When clinical disease occurs, diagnosis is usually made by detection of the lesion by visual inspection, and in women by a Papanicolaou test (Pap test), HPV test (done in similar fashion to a Pap test), or by colposcopy. Definitive diagnosis is made by biopsy.
• •Laboratory diagnosis of HPV in the clinical setting can be made by using the Digene hybrid capture 2 test (hc2); this test is recommended only in the setting of cervical cancer screening. Other DNA and serologic tests are available in research settings.

Treatment

There is no treatment for HPV, but there are treatments for HPV-associated conditions such as genital warts and cervical cell changes.

Preventive Measures for Travelers

• •There are no recommendations for preventive measures for travelers beyond abstinence or engaging in safe sexual behaviors.
• •The quadrivalent HPV vaccine prevents four HPV types (types 6, 11, 16, 18) commonly associated with genital warts and cervical cancers. Cervical cancer screening with the Pap test should be continued because the vaccine does not prevent all types associated with cancers.
• • ACIP recommendations for HPV vaccine are that 11- and 12-year-old girls should be routinely vaccinated, and the vaccine series can be started as young as 9 years of age. Girls and young women 13–26 years of age should be vaccinated if they have not received the vaccine or have not completed the series.
• •Vaccination consists of three intramuscular doses, on day 0, at 2 months, and 6 months; see product insert for some variability in administration timing. The vaccine is generally well tolerated, although pain at the injection site is common.

INFLUENZA (SEASONAL, AVIAN, AND PANDEMIC)

Margaret McCarron, David K. Shay

Infectious Agent

• •Influenza is caused by infection with influenza viruses.
• •Human influenza viruses can be divided into three types: A, B, and C. Only types A and B cause widespread illness in humans.
• •Influenza A viruses are further classified into subtypes on the basis of two surface proteins: hemagglutinin (H) and neuraminidase (N). There are 16 different hemagglutinin subtypes and 9 different neuraminidase subtypes.

Mode of Transmission

• •
  Person-to-person transmission results from respiratory droplets of coughs and sneezes.

  • ○
    Most healthy adults can infect others beginning 1 day before symptoms develop and up to 5 days after becoming sick.
  • ○
    Children can pass the virus for longer than 7 days.
  • ○
    Fomite transmission is also possible.

Occurrence

Seasonal Influenza

• •Infection with seasonal influenza viruses is common.
• •In temperate climates in the Northern Hemisphere, annual seasonal epidemics of influenza generally occur during the winter months, while in the temperate regions of the Southern Hemisphere most activity occurs from April through September.
• •In tropical and subtropical areas, influenza can occur throughout the year.
• •CDC has estimated that U.S. epidemics during the 1990s were associated with an annual average of 36,000 influenza-related deaths.
• •Influenza virus infections cause disease in all age groups. Rates of infection are highest among infants and children, but rates of serious morbidity and mortality are highest among persons Δ65 years of age and persons of any age who have medical conditions (e.g., chronic cardiopulmonary disease) that place them at increased risk for complications from influenza. Children <2 years of age have rates of influenza-related hospitalization that are as high as those in the elderly.

Avian Influenza

• •
  Avian influenza refers to influenza A viruses usually found in birds. Influenza A viruses infect a broad range of avian species and several mammalian species, including humans, swine, and horses.

  • ○
    Most cases of avian influenza infection in humans have resulted from contact with infected poultry (e.g., domesticated chickens, ducks, and turkeys) or surfaces contaminated with secretions or excretions from infected birds.
  • ○
    The spread of avian influenza viruses from one ill person to another has been reported very rarely and has thus far been limited, inefficient, and unsustained.
• •H5N1 is an influenza A virus, which is a type characterized by the ability to constantly undergo change. H5N1 virus has caused serious disease among wild birds and poultry on multiple continents. Human cases of H5N1 are very rare but have occurred in countries in Asia, Africa, Eastern Europe, and the Middle East since 2003. As of June 2008, only 385 human cases of H5N1 infection have been reported worldwide. These cases, however, are a concern because the mortality rate is high. There is a concern that H5N1 may gain the ability to spread easily between people. Vigilant monitoring for human infection and person-to-person transmission has become an important component of pandemic preparedness. For a current list of countries reporting outbreaks of H5N1 among birds, see the World Organization for Animal Health (OIE) website at www.oie.int/.
• •The global influenza research community conducts surveillance for novel influenza viruses in travelers. In a 2007 review of returned U.S. travelers suspected of having H5N1 infection, no evidence of infection with novel viruses was reported. Surveillance continues for human infection with H5N1 in travelers.
• •For current, continuously updated information, see CDC's Avian Influenza website (www.cdc.gov/flu/avian/index.htm).

Pandemic Influenza

• •The emergence of a novel human influenza A virus could lead to a global pandemic, during which rates of morbidity and mortality from influenza-related complications could increase dramatically. The public health threat of a pandemic arising from novel influenza A viruses, including influenza A (H5N1), becomes imminent only if the virus gains the ability to spread efficiently from one human to another.
• •Such transmission has not yet been observed with the currently circulating A (H5N1) viruses. Although a few cases of limited person-to-person spread of H5N1 viruses have been reported as of June 2008, no instances of transmission continuing beyond one person are thought to have occurred.
• •Because the situation has and may continue to evolve, for current information see the official U.S. government website for pandemic influenza (www.pandemicflu.gov/).

Risk for Travelers

Seasonal Influenza

• •The risk for exposure to seasonal influenza during international travel depends on the time of year and destination. In the tropics, influenza can occur throughout the year, while in the temperate regions of the Southern Hemisphere most activity occurs from April through September.
• •In temperate climates, travelers can also be exposed to influenza during the summer, especially when traveling as part of large tourist groups with travelers from areas of the world where influenza viruses are circulating.

Avian Influenza

• •
  In those countries where H5N1 has occurred most people become infected through direct contact with birds (e.g., domesticated chickens, ducks, and turkeys) that were carrying the H5N1 virus or from surfaces contaminated with secretions or excretions from these birds. Direct contact could happen during activities such as—

  • ○
    Visiting poultry farms
  • ○
    Visiting live bird or poultry markets
  • ○
    Preparing or consuming uncooked or undercooked bird products (such as meat, eggs, or blood).
• •
  Because the situation has and may continue to evolve, travelers can stay abreast of new developments by checking the following websites that are updated regularly:

  • ○
    U.S. government website for pandemic influenza (www.pandemicflu.gov/)
  • ○
    CDC's Travelers' Health website (wwwn.cdc.gov/travel/contentAvianFluInformation.aspx)
  • ○
    CDC's Avian Influenza website (www.cdc.gov/flu/avian/)
  • ○
    WHO website (www.who.int/csr/disease/avian_influenza/en/index.html).

Clinical Presentation

• •Onset of symptoms typically occurs 1–4 days after infection.
• •Uncomplicated influenza illness is characterized by the abrupt onset of constitutional and respiratory signs and symptoms (e.g., fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis). Among children, otitis media, nausea, and vomiting are also commonly reported with influenza illness.
• •Influenza illness typically resolves within 1 week for most persons, although cough and malaise can persist for >2 weeks. However, influenza virus infections can cause primary influenza viral pneumonia; exacerbate underlying medical conditions (e.g., pulmonary or cardiac disease); lead to secondary bacterial pneumonia, sinusitis, or otitis; or contribute to co-infections with other viral or bacterial pathogens. Influenza-related deaths can result from primary illnesses, secondary bacterial pneumonia, or exacerbations of chronic cardiac or pulmonary conditions.
• •Young children with influenza virus infection may have initial symptoms mimicking bacterial sepsis with high fevers, and febrile seizures have been reported in 6%–20% of children hospitalized with influenza virus infection. Population-based studies among hospitalized children with laboratory-confirmed influenza have demonstrated that, although the majority of hospitalizations are brief (2 days or less), 4%–11% of children hospitalized with laboratory-confirmed influenza required treatment in the intensive-care unit and 3% required mechanical ventilation. Among 1,308 hospitalized children in one study, 80% were <5 years of age and 27% were <6 months of age. Influenza virus infection also has been uncommonly associated with encephalopathy, transverse myelitis, myositis, myocarditis, pericarditis, and Reye syndrome.

Diagnosis

• •Respiratory illnesses caused by influenza virus infection are difficult to distinguish from illnesses caused by other respiratory pathogens on the basis of signs and symptoms alone. Sensitivity and predictive value of clinical definitions can vary, depending on the degree of circulation of other respiratory pathogens and the level of influenza activity. Among studies conducted with children and adults, the positive predictive value of clinical signs and symptoms for laboratory-confirmed influenza virus infection has ranged from 30% to 88%.
• • Laboratory testing can aid in diagnosis. Diagnostic tests available for influenza include viral culture, serology, rapid antigen testing, polymerase chain reaction, and immunofluorescence assays.
• •Respiratory specimens obtained via nasopharyngeal swabs typically yield better detection of influenza than specimens obtained via oropharyngeal swabs.
• •Commercial rapid diagnostic tests are available that can detect influenza viruses within 30 minutes. Some tests are approved for use in any outpatient setting, whereas others must be used in a moderately complex clinical laboratory. These rapid tests differ in the types of influenza viruses they can detect and whether they can distinguish between influenza types. Some tests can detect only influenza A viruses, some detect both influenza A and B viruses, but cannot distinguish between the two types, and some detect both influenza A and B and can distinguish between the two.
• •None of the commercially available rapid tests provides any information about influenza A subtypes. The types of specimens acceptable for use (i.e., throat, nasopharyngeal, or nasal aspirates, swabs, or washes) also vary by test. The specificity and, in particular, the sensitivity of rapid tests are lower than for viral culture and vary by test. Because of the lower sensitivity of the rapid tests, physicians should consider confirming negative tests with viral culture or other means because of the possibility of false-negative rapid test results.

Treatment

• •Influenza-specific antiviral drugs for chemoprophylaxis of influenza are important adjuncts to the influenza vaccine.
• •The four currently licensed U.S. antiviral agents are amantadine, rimantadine, zanamivir, and oseltamivir. Amantadine and rimantadine have a mechanism of action effective only against influenza A viruses, while the neuraminidase inhibitors oseltamivir and zanamivir are effective against both influenza A and B viruses.
• •Antiviral drug testing results conducted at CDC during the 2005–2006 influenza season, indicated 79% resistance among influenza A H3N2 viruses and 10% among H1N1. CDC recommends that neither amantadine nor rimantadine be used for the treatment or chemoprophylaxis of influenza A in the United States until susceptibility to these antiviral medications has been re-established among circulating influenza A viruses.
• •Oseltamivir or zanamivir can be prescribed if antiviral treatment of influenza is indicated. Oseltamivir is approved for treatment of persons aged Δ1 year, and zanamivir is approved for treatment of persons Δ7 years of age. Oseltamivir and zanamivir can be used for chemoprophylaxis of influenza; oseltamivir is licensed for use in persons Δ1 year of age, and zanamivir is licensed for use in persons Δ5 years of age. These two drugs differ in dosing, approved age groups for use, side effects, and cost. The package inserts should be consulted for more information.

Antiviral Resistance

• •In the winter of 2007–2008, oseltamivir-resistant influenza A (H1N1) viruses were found to be circulating in several countries, including the United States, but the highest rates of resistance were found in Northern Europe. Oseltamivir resistance appears to be geographically variable, both within Europe and globally. In the United States, approximately 12% of H1N1 viruses from the 2007–2008 season were resistant to oseltamivir, resistance was highest in Europe at 26%, and overall global resistance was approximately 16%. The oseltamivir-resistant H1N1 viruses remained sensitive to amantadine and rimantadine. This strain of oseltamivir-resistant influenza A (H1N1) may continue to circulate in future seasons or may spread geographically. Oseltamivir and zanamivir remain the preferred antiviral drugs to be used in the treatment of influenza virus infection, given their relatively low levels of resistance compared with the high resistance found to amantadine and rimantadine among currently circulating influenza A viruses.
• •Some H5N1 viruses currently infecting birds and humans are resistant to amantadine and rimantadine. Most of the H5N1 viruses tested have been susceptible to the antiviral medications oseltamivir and zanamivir, but resistance has been reported. The effectiveness of antivirals for treating H5N1 virus infections is unknown. For more information about influenza antiviral drugs, see www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm#antiviral.
• •For more detailed information on influenza vaccines, treatment, and general prevention and control, please refer to “Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP)” (the most recent version is available at: www.cdc.gov/vaccines/pubs/ACIP-list.htm).

Preventive Measures for Travelers

• •Handwashing and cough hygiene can play important roles in limiting person-to-person transmission of influenza. Where handwashing is not available, use of hand sanitizing gels containing greater than 60% alcohol can be used.
• •Annual vaccination of persons at high risk for complications and vaccination of health-care workers and close contacts of high risk persons before the influenza season are the most effective measure for preventing seasonal influenza and associated complications.
• •Vaccination of travelers is recommended when the vaccine is available and if there are no contraindications.

Vaccine

• •Two types of influenza vaccines are currently available for use in the United States: trivalent inactivated vaccine (TIV), administered by intramuscular injection; and live, attenuated influenza vaccine (LAIV), administered by nasal spray. LAIV is approved currently for use only in healthy persons 2–49 years of age who are not pregnant.
• •In the United States, annual influenza vaccination is recommended by CDC and ACIP for certain groups of people, primarily those who are at high risk of having serious flu complications or those who live with or care for those at high risk for serious complications. Annual recommendations are published by CDC and ACIP, including information about the season's vaccine composition, dosage and administration, and recommendations for specific populations. The current version of these routine recommendations is available at www.cdc.gov/vaccines/pubs/ACIP-list.htm.
• •The influenza vaccine must be administered annually to optimize protection because vaccine-derived immunity declines over time and because the vaccine strains must be updated regularly to reflect ongoing antigenic changes among circulating influenza viruses.
• •Dosages differ according to age group and type of vaccine used. For inactivated vaccines, two doses administered at least 1 month apart are required for previously unvaccinated infants and children through 8 years of age. In adults, studies have indicated little or no improvement in antibody response when a second dose of inactivated vaccine is administered during the same season; therefore, a booster is not recommended. Inactivated vaccine should be administered in infants and young children in the anterolateral aspect of the thigh; all other recipients should be vaccinated in the deltoid muscle.
• •The age groups for which influenza and pneumococcal vaccination are recommended overlap considerably. For travelers at high risk who have not previously been vaccinated with pneumococcal vaccine, health-care providers should strongly consider administering pneumococcal and influenza vaccines concurrently. Both vaccines can be administered at the same time at different sites without increasing side effects. Infants and children can receive influenza vaccine at the same time they receive other routine vaccinations.
• •Both influenza vaccines contain three strains of influenza viruses. Viruses in inactivated vaccines are killed, while those in LAIV are live. These live viruses are attenuated and do not cause influenza illnesses. The viruses used in both vaccines are representative of viruses likely to circulate in the upcoming season, and usually one or more vaccine strains are updated annually. Because the vaccine is grown in hen eggs, the vaccine may contain small amounts of egg protein. The package insert should be consulted regarding the use of other compounds to inactivate the viruses or to limit bacterial contamination.

Avian Influenza

• •H5N1 infections in humans, though rare, can cause serious disease and death.
• •
  CDC advises travelers to countries with known outbreaks of H5N1 to avoid—

  • ○
    Poultry farms
  • ○
    All poultry, whether or not symptomatic, and especially contact with sick or dead poultry
  • ○
    Contact with surfaces that may have been contaminated by poultry feces or secretions
  • ○
    Contact with animals in live food markets
• •Since transmission of H5N1 viruses to two persons through consumption of uncooked duck blood may have occurred in Vietnam in 2005, uncooked poultry or poultry products, including blood, should not be consumed. Care should be taken when preparing these foods.
• •For more information, see Human Infection with Avian Influenza A (H5N1) Virus Advice for Travelers (wwwn.cdc.gov/travel/contentAvianFluAsia.aspx) and the WHO Avian Influenza Fact Sheet (www.who.int/mediacentre/factsheets/avian_influenza/en/index.html#humans).
• •A vaccine to protect humans against influenza A (H5N1) is not yet available commercially, but candidate vaccines are undergoing human clinical trials in the United States, with one vaccine currently licensed in the United States. This vaccine is approved by the U.S. FDA for stockpiling purposes only.

MEASLES (RUBEOLA)

Amy A. Parker, Amra Uzicanin

Infectious Agent

• •Measles virus is a member of the genus Morbillivirus of the family Paramyxoviridae.
• •Humans are the only known natural host for the measles virus.
• •Measles, also known as rubeola, is one of the most highly communicable infectious diseases.

Mode of Transmission

• •Measles spreads by airborne droplets.
• •Direct contact with nasal or throat secretions of infected persons.
• •Less commonly it is spread by articles freshly soiled with nose and throat secretions.
• •Infected persons are usually contagious from 4 days before onset of signs or symptoms, and until 4 days after the onset of signs or symptoms.

Occurrence

• •An estimated 20 million measles cases still occur globally every year, and travelers could be exposed in almost any country they visit. However, the risks are greater in countries where measles remains endemic or where large outbreaks are occurring.
• •In the Americas, indigenous measles circulation was interrupted in 2002, but risk of measles due to virus importations from other parts of the world still remains.
• •The number of reported measles cases in the United States has declined from 894,134 in 1941 to fewer than 150 cases each year since 1997. However, from January 1 through April 25, 2008, a total of 64 confirmed measles cases were reported to CDC, which is the largest number of cases reported in the United States for the corresponding period for any year since 2001. Ten of these cases were acquired abroad by unvaccinated travelers (five in visitors to the United States and five in U.S. residents) and the remaining cases were considered to be associated with these importations of measles.

Risk for Travelers

• • All persons who do not have evidence of measles immunity are at risk for contracting measles during international travel.
• •
  Acceptable presumptive evidence of immunity to measles for international travelers includes—

  • ○
    For infants 6–11 months of age, documented administration of one dose of live measles-containing vaccine1 and, for persons Δ12 months of age, two doses of MMR2 vaccine at least 28 days apart, on or after the first birthday
  • ○
    Laboratory evidence of immunity
  • ○
    Birth before 1957
  • ○
    Documented physician-diagnosed measles

Clinical Presentation

• •Incubation period is ∼10 days (range 7–18 days) from exposure to onset of fever, usually 14 days before appearance of rash.
• •Symptoms include prodromal fever, conjunctivitis, coryza, cough, and small spots with white or bluish white centers on an erythematous base on the buccal mucosa (Koplik spots).
• •Characteristic red, blotchy (maculopapular) rash appears on third to seventh day that begins on the face, becomes generalized, and lasts 4–7 days.
• •Complications include diarrhea (8%), middle ear infection (7%–9%), and pneumonia (1%–6%). Encephalitis, frequently resulting in permanent brain damage, occurs in approximately 1 per 1,000–2,000 cases of measles. Subacute sclerosing panencephalitis (SSPE), a rare but serious degenerative central nervous system disease, is thought to occur in 1 per 100,000 cases, although a risk of 22 cases of SSPE per 100,000 measles cases was found during the 1989–1991 measles resurgence in the United States. SSPE, which is caused by a persistent infection with a defective measles virus, is manifested by mental and motor deterioration that starts an average of 7 years after measles virus infection (most frequently in children <2 years of age), progressing to coma and death.
• •The risk of serious complications and death is highest for children £5 years of age and adults Δ20 years of age. It is also higher in populations with poor nutritional status.

Diagnosis

• •
  A clinical case of measles illness is characterized by all of the following:

  • ○
    Generalized maculopapular rash lasting Δ3 days
  • ○
    Temperature Δ101° F (Δ38.3° C)
  • ○
    Cough, coryza, or conjunctivitis
• •Laboratory criteria for diagnosis is a positive serologic test for measles immunoglobulin M (IgM) antibody, seroconversion or significant rise in measles IgG antibody level by any standard serologic assay, or isolation of measles virus or identification by PCR of measles virus RNA from a clinical specimen.
• •A confirmed case is either laboratory confirmed or meets the clinical case definition and is epidemiologically linked to a confirmed case. A laboratory-confirmed case does not need to meet the clinical case definition.

Treatment

• •There is no specific antiviral therapy or treatment for measles.
• •Supportive therapy includes hydration, antipyretics, and treating complications such as pneumonia.
• •
  The WHO currently recommends vitamin A for all children with acute measles, regardless of their country of residence, to reduce morbidity and mortality. Vitamin A is administered once a day for 2 days, at the following doses:

  • ○
    50,000 IU for infants <6 months of age
  • ○
    100,000 IU for infants 6–11months of age
  • ○
    200,000 IU for children ages 12 months or older
• •A third age-specific dose of vitamin A is to be given 2–4 weeks later to case-patients with clinical signs and symptoms of vitamin A deficiency. Parenteral and oral formulations of vitamin A are available in the United States.

Preventive Measures for Travelers

Vaccine

• •Measles vaccine contains live, attenuated measles virus. It is available as a monovalent formulation and in combination formulations, such as measles–rubella (MR), measles–mumps–rubella (MMR), and measles–mumps–rubella–varicella (MMRV).
• •
  Ensure that all travelers who do not have evidence of measles immunity (see Risk for Travelers earlier in this section) are up to date on measles vaccination prior to departure.

  • ○
    Infants 6–11 months of age should have at least one dose of measles-containing vaccine.1
  • ○
    Preschool children Δ12 months of age should have two doses of MMR2 vaccine separated by at least 28 days.
  • ○
    School-age children should have two doses of MMR.2
  • ○
    Adults born in or after 1957 should have two doses of measles-containing vaccine.
  • ○
    If administered at Δ12 months of age, one dose of measles-containing vaccine or MMR is 95% effective in preventing measles disease and two doses are 99% effective. One dose of measles-containing vaccine or MMR is approximately 85% effective if administered at 9 months of age.
• •For persons Δ12 months of age, combined MMR vaccine is recommended whenever one or more of the individual components is indicated to provide optimal protection against mumps and rubella. For infants <12 months of age, measles vaccine alone is recommended if it is available; otherwise MMR should be used.
• •MMR vaccine, if administered within 72 hours of initial measles exposure, may provide some protection. If the exposure does not result in infection, the vaccine should induce protection against subsequent measles virus infection.
• •Immune globulin (IG) can be used to prevent or mitigate measles in a susceptible person when administered within 6 days of exposure. However, any immunity conferred is temporary unless modified or typical measles occurs, and the person should receive measles-containing vaccine 5–6 months after IG administration.

Adverse Reactions, Precautions, and Contraindications to Measles Vaccine

Allergy

Persons with severe allergy (i.e., hives, swelling of the mouth or throat, difficulty breathing, hypotension, and shock) to gelatin or neomycin or who have had a severe allergic reaction to a prior dose of MMR or MMRV should not be revaccinated except with extreme caution. MMR or MMRV vaccines may be administered to egg-allergic persons without prior routine skin testing or the use of special protocols.

Immunosuppression

Replication of vaccine viruses can be potentiated in persons who have immune deficiency disorders. Death related to vaccine-associated measles infection has been reported among severely immunocompromised persons. Therefore, severely immunosuppressed individuals should not be vaccinated with MMR or MMRV vaccines

• •MMR or MMRV should be avoided for at least 1 month after cessation of high-dose corticosteroid therapy. Some experts, however, recommend waiting only 2 weeks after completion of therapy among individuals receiving high doses of systemic corticosteroids daily or on alternate days even if they were receiving therapy for less than 14 days.
• •Other immunosuppressive therapy: MMR or MMRV vaccines in general should be withheld for at least 3 months. This interval is based on the assumption that the immunologic responsiveness will have been restored in 3 months and the underlying disease for which the therapy was given is in remission.

Thrombocytopenia

The benefits of primary immunization are usually greater than the potential risks. However, avoiding a subsequent dose of MMR or MMRV vaccine may be prudent if an episode of thrombocytopenia occurred within approximately 6 weeks after a previous dose of vaccine.

MUMPS

Preeta K. Kutty, Albert E. Barskey, IV, Kathleen M. Gallagher

Infectious Agent

• • Mumps virus is an enveloped, negative-strand RNA virus, a member of the genus Rubulavirus.
• •Humans are the only known natural host for mumps virus.

Mode of Transmission

• •Transmission is by respiratory droplets, saliva, or contact with contaminated fomites.
• •Patients are usually contagious 1–2 days (occasionally as long as 7 days) before symptom onset until 5 days afterward.

Occurrence

• •With the exception of the multistate outbreak in 2006, mumps is an uncommon disease in the United States because of a successful vaccination program.
• •Mumps virus remains endemic in many countries throughout the world because mumps vaccine is used in only 57% of the World Health Organization member countries.

Risk for Travelers

• •The risk of exposure to mumps among travelers can be high in most countries of the world, especially for travelers >12 months of age who do not have evidence of mumps immunity (see Preventive Measures for Travelers later in this section). Although some countries have had variable successes with a national vaccination program—including Finland, which has declared elimination—the risk of contacting imported mumps in these countries is still a concern.
• •
  Acceptable presumptive evidence of immunity to mumps for international travelers includes—

  • ○
    Documented administration of two doses of live mumps virus vaccine at least 28 days apart, on or after the first birthday
  • ○
    Laboratory evidence of immunity
  • ○
    Birth before 1957
  • ○
    Documentation of physician-diagnosed mumps

Clinical Presentation

• •Incubation period from exposure to onset of symptoms is generally 16–18 days (range 12–25 days).
• •Onset of illness is usually nonspecific, with symptoms of fever, headache, malaise, myalgia, and anorexia.
• •Mumps is characterized by parotitis, either unilateral or bilateral.
• •Although mumps is generally a mild and self-limited disease, complications of mumps infection can include deafness; orchitis, oophoritis, or mastitis (inflammation of the testicles, ovaries or breasts, respectively); pancreatitis; and meningitis or encephalitis. With the exception of deafness, these complications are more frequent in adults than in children.

Diagnosis

• • Mumps may occur in epidemics; mumps virus is the only cause of epidemic parotitis.
• •Diagnosis is usually clinical, based on the presence of parotitis and associated signs, symptoms, or complications.
• •Clinical case definition: An illness with acute onset of unilateral or bilateral tender, self-limited swelling of the parotid glands, other salivary gland(s), or both, lasting at least 2 days, and without other apparent cause.
• •
  Laboratory criteria include—

  • ○
    Isolation of mumps virus from clinical specimen
  • ○
    Detection of mumps nucleic acid (e.g., standard or real-time RT-PCR assays)
  • ○
    Detection of mumps IgM antibody
  • ○
    Demonstration of specific mumps antibody response in the absence of recent vaccination, either a fourfold increase in IgG titer as measured by quantitative assays, or seroconversion from negative to positive by using a standard serologic assay of paired acute- and convalescent-phase serum specimens
• •Laboratory specimens that can be collected are serum for serology (IgM, IgG) and a buccal swab (or a throat swab) for viral specimens. For more information see www.cdc.gov/vaccines/vpd-vac/mumps/outbreak/faqs-lab-spec-collect.htm.
• •Laboratory confirmation is more challenging in highly vaccinated populations. Serologic tests should be interpreted with caution. A negative laboratory test should not rule out a clinically compatible case, especially in a two-dose vaccine recipient.

Treatment

There is no specific antiviral therapy for mumps, and the basic treatment consists of supportive care.

Preventive Measures for Travelers

Vaccine

• •Although vaccination against mumps is not a requirement for entry into any country (including the United States), travelers leaving the United States or living abroad should ensure they are immune to mumps.
• •Mumps vaccine contains live, attenuated mumps virus. It is available as a monovalent formulation and in combination formulations, such as MMR. Combined MMR vaccine is recommended whenever one or more of the individual components is indicated to provide optimal protection against measles and rubella. Mumps vaccine is highly, but not 100%, effective in preventing mumps. One dose of mumps vaccine is approximately 80%–85% effective in preventing clinical mumps with parotitis, and two doses are approximately 90% effective.
• •Mumps vaccine has not been demonstrated to be effective in preventing infection after exposure; however, it can be administered postexposure to provide protection against subsequent exposures. Immune globulin is not effective in preventing mumps infection following an exposure and is not recommended.

Adverse Reactions, Precautions, and Contraindications to Mumps Vaccine

• •Refer to the Measles (Rubeola) section earlier in this chapter for information on reactions following MMR vaccine and additional precautions and contraindications.

General Vaccine Recommendations, Pediatric and Catch-Up Schedules, and Recommendations for Special Populations

• •Refer to Chapters 7 and 8.

PERTUSSIS

Tami H. Skoff, Cynthia G. Thomas

Infectious Agent

Pertussis is caused by fastidious gram-negative coccobacillus, Bordetella pertussis.

Mode of Transmission

It is spread by person-to-person transmission via aerosolized respiratory droplets or by direct contact with respiratory secretions.

Occurrence

• • B. pertussis circulates worldwide, but disease rates are highest among young children in countries where vaccination coverage is low, which is primarily in the developing world.
• •In developed countries, the incidence of pertussis is highest among unvaccinated infants and increases again among adolescents.
• •Immunity from childhood vaccination and natural disease wanes with time; therefore, adolescents and adults who have not received a Tdap booster vaccination can become infected or re-infected.

Risk for Travelers

• •Pertussis remains endemic worldwide, even in areas with high vaccination rates.
• • Travelers who come in close contact with infected persons are at risk for disease. Infants too young to be protected by a complete vaccination series are at greatest risk for severe pertussis requiring hospitalization.

Clinical Presentation

• •In classic disease, mild upper respiratory tract symptoms begin 7–10 days (range 6–21 days) after exposure, followed by a cough that becomes paroxysmal. Coughing paroxysms may be frequent or relatively infrequent and are often followed by vomiting. Fever is absent or minimal. The CDC/Council of State and Territorial Epidemiologists' clinical case definition for pertussis includes cough for Δ2 weeks with paroxysms, whoop, and/or post-tussive vomiting.
• •Disease in infants <6 months of age can be atypical with a short catarrhal stage, gagging, gasping, or apnea as early manifestations; among infants <2 months of age, the case–fatality rate is approximately 1%.
• •Recently immunized children may have mild cough illness; older children and adults may have prolonged cough with or without paroxysms. The cough gradually wanes over several weeks to months.

Diagnosis

• •Factors such as prior vaccination status, stage of disease, antibiotic use, specimen collection and transport conditions, and nonstandardized tests may affect the sensitivity, specificity, and interpretation of available diagnostic tests for B. pertussis.
• •Current CDC guidelines for the laboratory confirmation of pertussis cases include culture and PCR (when the above clinical case definition is met); serology and direct fluorescent antibody (DFA) tests are not confirmatory tests included in the case definition.

Treatment

• •Macrolide antibiotics (azithromycin, clarithromycin, and erythromycin) are recommended for the treatment of pertussis in persons Δ1 month of age; for infants <1 month of age, azithromycin is the preferred antibiotic.
• •Antimicrobial therapy with a macrolide antibiotic administered <3 weeks after cough onset can limit transmission to others.
• •Postexposure prophylaxis is recommended for close contacts of cases and for individuals at high risk of developing severe disease. The recommended agents and dosing regimens for prophylaxis are the same as those indicated for the treatment of pertussis.

Preventive Measures for Travelers

Vaccine

• •Travelers should be up to date with pertussis vaccinations prior to departure.
• •Complete vaccination of children <7 years of age with five doses of acellular pertussis vaccine in combination with diphtheria and tetanus toxoids (DTaP) is recommended; an accelerated schedule of doses may be used to complete the DTaP series.
• •There is no pertussis-containing vaccine licensed for children 7–9 years of age. If a child turns 10 years old during the vaccination series with Td (tetanus and diphtheria toxoids vaccine), a single dose of Tdap may be substituted for one of the Td doses.
• • Adolescents aged 11–18 years should receive a single dose of Tdap instead of Td for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood DTwP/DTaP vaccination series. Adolescents who received their last Td (tetanus and diphtheria toxoids vaccine) 5 years or more previously should also receive a single dose of Tdap.
• •Adults 19–64 years of age should receive a single dose of Tdap to replace a single dose of Td for booster immunization against tetanus, diphtheria, and pertussis if their last tetanus toxoid-containing vaccine (e.g., Td) was administered 10 years or more prior. Tdap is not licensed for adults 65 years of age or older.
• •Tdap can be given in intervals <10 years from the last Td to provide pertussis protection prior to travel, except in those individuals with a contraindication to vaccination.
• •Adolescents and adults who have never been immunized against pertussis, tetanus, or diphtheria, have incomplete immunization, or whose immunity is uncertain should follow the catch-up schedule established for Td/Tdap. Tdap can be substituted for any one of the Td doses in the series.

PNEUMOCOCCAL DISEASE (STREPTOCOCCUS PNEUMONIAE)

J. Pekka Nuorti

Infectious Agent

• • Streptococcus pneumoniae (pneumococcus) is a bacterium that frequently colonizes the nasopharynx of healthy persons, particularly young children, without causing illness.
• •There are 91 known pneumococcal serotypes.
• •The major clinical syndromes include life-threatening infections such as meningitis, bacteremia, and pneumonia.
• •Pneumococcus is the most commonly identified cause of community-acquired pneumonia. It is also a major cause of milder but more common illnesses, such as sinusitis and otitis media.

Mode of Transmission

• •Direct person-to-person transmission is through close contact via respiratory droplets.
• •Transmission is thought to be common, but clinical illness occurs infrequently among casual contacts.

Occurrence

• • Pneumococcal disease occurs worldwide, and the reported incidence varies by geographic region.
• •Rates are higher in developing countries than in industrialized countries.
• •Pneumococcal disease is more common during winter and early spring, when respiratory viruses such as influenza are circulating. Most illnesses are sporadic.
• •Outbreaks of pneumococcal disease are uncommon but may occur in closed populations such as nursing homes, childcare centers or other institutions.
• •In the United States, most deaths from pneumococcal disease occur in older adults, although in developing countries, many children die of pneumococcal pneumonia.
• •Routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) in the United States since 2000 has dramatically reduced the incidence of pneumococcal disease in both children and adults. Because the vaccine interrupts transmission of vaccine-type pneumococci, rates of pneumococcal disease in unvaccinated older children and adults have also decreased.
• •As of 2008, 18 industrialized countries are routinely using pneumococcal conjugate vaccines, including Canada, Australia, the United Kingdom, and other Western European and Middle Eastern countries.

Risk for Travelers

• •The risk for pneumococcal disease is generally highest among young children, the elderly, and persons of any age who have chronic medical conditions, such as heart disease, lung disease, diabetes or asplenia, or conditions that suppress the immune system, such as HIV.
• •Cigarette smokers are also at increased risk.
• •Most travelers, however, are not in these categories. It is important to recognize that healthy travelers in their twenties or thirties have developed pneumococcal pneumonia while traveling in developing countries.

Clinical Presentation

• •Sudden onset with fever and malaise are typical symptoms for all forms of pneumococcal infections and may be the only symptoms in young children with bacteremia.
• •In pneumococcal pneumonia, fever may precede the usual symptoms of cough, pleuritic chest pain, and the production of purulent or blood-tinged sputum.
• •In elderly persons, the onset of pneumococcal pneumonia may be less abrupt, with fever, shortness of breath, or altered mental status as the initial symptoms; sputum production may be absent.
• •Pneumococcal meningitis may present with a stiff neck, headache, lethargy, or seizures; otitis media or sinusitis typically cause pain in the ears or sinuses.

Diagnosis

• •A definitive diagnosis of pneumococcal infection can be made by isolation of the bacterium from blood or other normally sterile body sites, such as cerebrospinal fluid. Most patients with pneumococcal pneumonia, however, do not have detectable bacteremia.
• •The diagnosis of pneumococcal pneumonia can be suspected if on microscopy a sputum specimen contains many gram-stain positive diplococci and polymorphonuclear leukocytes and very few epithelial cells.
• •Typical chest radiography may show lobar, segmental, or multilobar consolidation.
• • Pneumococcal pneumonia is usually, but not always, associated with a high white blood cell count. High white blood cell counts should raise suspicion for this diagnosis, since other serious travel-related diseases causing fever, such as hepatitis, typhoid fever, malaria, dengue fever, or typhus, all have normal or low white blood cell counts.

Treatment

• •All types of pneumococcal infections are usually treated with antibiotics.
• •Worldwide, many strains are increasingly resistant to penicillin, cephalosporin, and macrolides, and some are resistant to multiple classes of drugs, complicating treatment choices. Antimicrobial susceptibility of strains isolated from blood and cerebrospinal fluid should be determined, and treatment should be targeted based on the susceptibility results.
• •In 2008, the Clinical and Laboratory Standards Institute adopted new susceptibility breakpoints for penicillin treatment of nonmeningitis cases of pneumococcal disease. However, empiric antibiotic therapy should not be delayed and should begin before microbiological confirmation of etiology.
• •In the United States and other countries where beta-lactam resistance among pneumococcal isolates is common, the initial regimen for suspected pneumococcal meningitis should include vancomycin until the antimicrobial susceptibility pattern of the organism is available.

Preventive Measures for Travelers

Vaccine

• •No specific recommendations for the use of pneumococcal vaccines in travelers have been formulated.
• •
  Currently, two vaccines are available for prevention of pneumococcal disease in the United States.

  • ○
    Pneumococcal conjugate vaccine—The 7-valent pneumococcal conjugate vaccine (PCV7) (Prevnar, Wyeth Vaccines) is mainly used in children. It is part of the routine infant immunization schedule in the United States and is now recommended for all children <5 years of age (see the Vaccine Recommendations for Infants and Children section in Chapter 7). The infant schedule consists of a three-dose primary series at ages 2, 4, and 6 months and a booster dose at 12–15 months of age. Fewer doses are required for children who begin the series after 7 months of age.
  • ○
    Pneumococcal polysaccharaide vaccine—A 23-valent pneumococcal polysaccharide vaccine (PPV23) (Pneumovax, Merck) is mainly used in older adults and persons with underlying medical conditions. PPV23 is recommended for all adults Δ65 years of age and for persons 2–64 years of age with underlying medical conditions at the time the condition is recognized. In 2006, only about 57% of adults aged Δ65 years of age had received the vaccine. Children 2–4 years of age who have underlying medical conditions that are indications for PPV23 should also receive polysaccharide vaccine after receiving the conjugate vaccine series.
• •Both vaccines induce antibodies to the specific types of pneumococcal capsule and have been shown to be effective against invasive disease.
• •Additional pneumococcal conjugate vaccine formulations are expected to be licensed soon. The WHO recommends that inclusion of pneumococcal conjugate vaccines in all national immunization programs should be a priority.
• •
  Routine revaccination is not recommended for most people. A second dose of PPV23 is recommended 5 years after the first dose for the following groups:

  • ○
    Persons with sickle cell disease, asplenia, renal disease, hematologic or generalized malignancy, or other immunocompromising condition
  • ○
    Persons Δ65 years of age who received PPV23 before age 65 years for an underlying medical condition, if at least 5 years have passed since their previous dose
• •Because of limited data regarding the duration of protection provided by PPV23 and the safety of multiple doses, only a single revaccination is recommended. Persons should receive one dose if they have an indication for polysaccharide vaccine and their vaccination history is unknown.

Safety and Side Effects

• •After receipt of PCV7, mild local reactions, such as redness, swelling, or tenderness, occur in 10%–23% of infants. Larger areas of redness or swelling or limitations in arm movement may occur in 1%–9% of infants. Low-grade fever can occur in up to 24% and fever higher than 102.2° F may occur in up to 2.5% of vaccinees.
• •After receipt of PPV23, self-limiting local side effects occur in approximately half of vaccine recipients and are more common after revaccination than with first dose. These reactions usually resolve within 48 hours. More severe local reactions and systemic symptoms, including myalgias and fever, are rare.

Precautions and Contraindications

• •PCV7 is contraindicated for children known to have hypersensitivity to any component of the vaccine.
• •Health-care providers may delay vaccination of children with moderate or severe illness until the child has recovered, although minor illnesses, such as mild upper-respiratory tract infection with or without low-grade fever, are not contraindications.
• •Revaccination with PPV23 is contraindicated for persons who had a severe reaction (e.g., anaphylactic reaction or localized arthus-type reaction) to the initial dose.

Additional Preventive Measures

• •
  The following may reduce the risk of pneumococcal disease:

  • ○
    improving control of chronic conditions that predispose to pneumococcal disease, such as diabetes and HIV,
  • ○
    stopping smoking, and
  • ○
    avoiding crowded living conditions.
• •Chemoprophylaxis is not routinely recommended for close contacts of pneumococcal meningitis or other cases of invasive disease or for travelers unless otherwise recommended by the health-care practitioner supervising their care.

POLIOMYELITIS

James P. Alexander, Steven Wassilak

Infectious Agent

• •The infectious agent is poliovirus (genus Enterovirus) types 1, 2, and 3.
• •Polioviruses are small (27–30 nm), nonenveloped viruses with capsids enclosing a single-stranded, positive-sense RNA genome about 7,500 nucleotides long.
• •Most of the properties of polioviruses are shared with the other enteroviruses.

Mode of Transmission

Fecal–oral or oral transmission. Acute infection involves the gastrointestinal tract and occasionally the central nervous system.

Occurrence

• •In the prevaccine era, infection with poliovirus was common worldwide, with seasonal peaks and epidemics in the summer and fall in temperate areas.
• •The incidence of poliomyelitis in the United States declined rapidly after the licensure of inactivated polio vaccine (IPV) in 1955 and live oral polio vaccine (OPV) in the 1960s. The last cases of indigenously acquired polio in the United States occurred in 1979.
• •The Global Polio Eradication Initiative (GPEI) subsequently led to elimination of polio in the Americas, where the last wild poliovirus (WPV)-associated polio case was detected in 1991.
• •In 1999, a change in vaccination policy in the United States from use of OPV to exclusive use of IPV resulted in the elimination of the 8–10 vaccine-associated paralytic poliomyelitis (VAPP) cases that had occurred annually since the introduction of OPV in the 1960s.
• •
  In the United States, two events that occurred in 2005 highlighted the continuing but low risk for poliovirus infection for unvaccinated persons, whether residing in the United States or traveling.

  • ○
    A case of imported VAPP occurred in an unvaccinated U.S. adult who had traveled abroad, likely from contact with an infant recently vaccinated with OPV.
  • ○
    An unvaccinated immunocompromised infant and four children in two other families in the same small rural community were found to be asymptomatically infected with a vaccine-derived poliovirus, presumably originating outside the United States in a country that uses OPV.
• •The GPEI has built upon the success in the Americas and made great progress in eradicating wild polioviruses. There are only four countries where wild poliovirus circulation has never been interrupted: Afghanistan, India, Nigeria, and Pakistan. WPV type 2 has not been detected since October 1999.
• •During 2002–2006, 22 previously polio-free countries were affected by importations of WPV type 1 from the remaining polio-endemic countries, primarily Nigeria. In 2007–2008, polio cases occurred in 12 countries following importations of WPV originating from Nigeria or India.
• •In spite of recent WPV outbreaks and continued circulation in the four countries where WPV circulation has never been interrupted, the GPEI has reduced the number of reported polio cases worldwide by more than 99% since the mid-1980s. With intensified efforts, worldwide eradication of polio appears feasible in the future.

Risk for Travelers

• •Because of polio eradication efforts, the number of countries where travelers are at risk for polio has decreased dramatically.
• •At the time of publication, most of the world's population resides in areas considered free of WPV circulation, including the Western Hemisphere, the Western Pacific region (which encompasses China), and the European region.
• •Vaccination is recommended for all travelers to polio-endemic or epidemic areas, including countries with recent proven WPV circulation and neighboring countries. As of September 2008, these areas include some but not all countries in Africa, South Asia, Southeast Asia, and the Middle East. For current information on the status of polio eradication efforts and vaccine recommendations, consult the Travel Notices on the CDC Travelers' Health website (www.cdc.gov/travel/) or the GPEI website (www.polioeradication.org/).

Clinical Presentation

Clinical manifestations of poliovirus infection range from asymptomatic (most infections) to symptomatic, including acute flaccid paralysis of a single limb to quadriplegia, respiratory failure, and, rarely, death.

Diagnosis

The diagnosis is made by the identification of poliovirus in clinical specimens (usually stool) obtained from an acutely ill patient. Poliovirus may be detected from stool specimens for up to 4 weeks after onset of illness.

Treatment

Only symptomatic treatment is available, ranging from pain and fever relief to intubation and mechanical ventilation for those with respiratory insufficiency.

Preventive Measures for Travelers

• •A person is considered to be fully immunized if he or she has received a primary series of at least three doses of IPV, three doses of OPV, or four doses of any combination of IPV and OPV.
• •To eliminate the risk for VAPP, OPV has not been recommended for routine immunization in the United States since January 1, 2000, and is no longer available in this country.
• •OPV continues to be used in the majority of countries and for global polio eradication activities.

Vaccine

Infants and Children

• • Because OPV is no longer recommended for routine immunization in the United States, all infants and children should receive four doses of IPV at 2, 4, and 6–18 months and 4–6 years of age. The fourth (booster) dose is not needed if the third dose of the primary series is administered on or after the fourth birthday.
• •If accelerated protection is needed, the minimum interval between doses is 4 weeks, although the preferred interval between the second and third doses is 2 months.
• •The minimum age for IPV administration is 6 weeks. Infants and children who have initiated the poliovirus vaccination series with one or more doses of OPV should receive IPV to complete the series.

Adults

• •Adults who are traveling to areas where poliomyelitis cases are still occurring and who are unvaccinated, incompletely vaccinated, or whose vaccination status is unknown should receive two doses of IPV administered at an interval of 4–8 weeks; a third dose should be administered 6–12 months after the second.
• •
  If three doses of IPV cannot be administered within the recommended intervals before protection is needed, the following alternatives are recommended:

  • ○
    If >8 weeks is available before protection is needed, three doses of IPV should be administered at least 4 weeks apart.
  • ○
    If <8 weeks but >4 weeks is available before protection is needed, two doses of IPV should be administered at least 4 weeks apart.
  • ○
    If <4 weeks is available before protection is needed, a single dose of IPV is recommended.
• •If fewer than three doses are administered, the remaining IPV doses to complete a three-dose series should be administered when feasible, at the intervals recommended above, if the person remains at increased risk for poliovirus exposure.
• •Adults (Δ18 years of age) who are traveling to areas where poliomyelitis cases are occurring and who have received a primary series with either IPV or OPV in childhood should receive another dose of IPV before departure.
• •For adults, available data do not indicate the need for more than a single lifetime booster dose with IPV.

Allergy to Vaccine

• •Minor local reactions (pain and redness) can occur following IPV. No serious adverse reactions to IPV have been documented.
• •IPV should not be administered to persons who have experienced a severe allergic (anaphylactic) reaction after a previous dose of IPV or after receiving streptomycin, polymyxin B, or neomycin which IPV contains in trace amounts; hypersensitivity reactions can occur following IPV among persons sensitive to these three antibiotics.

Pregnancy and Breastfeeding

• •If a pregnant woman is unvaccinated or incompletely vaccinated and requires immediate protection against polio because of planned travel to a country or area where polio cases are occurring, IPV can be administered as recommended for adults.
• •Breastfeeding is not a contraindication to immunization of an infant or mother against polio.

Precautions and Contraindications

• •IPV may be administered to persons with diarrhea.
• •Minor upper respiratory illnesses with or without fever, mild to moderate local reactions to a previous dose of IPV, current antimicrobial therapy, and the convalescent phase of acute illness are not contraindications for vaccination.

Immunosuppression

• • IPV may be administered safely to immunodeficient travelers and their household contacts. Although a protective immune response cannot be ensured, IPV might confer some protection to the immunodeficient person.
• •Persons with certain primary immunodeficiency diseases should avoid contact with excreted OPV virus (e.g., exposure to a child vaccinated with OPV within the previous 6 weeks); however, this situation no longer occurs in the United States unless a child receives OPV overseas.

RUBELLA

Susan E. Reef

Infectious Agent

Rubella virus is a member of Togaviridae family and the only member of the genus Rubivirus.

Mode of Transmission

• •Rubella virus is transmitted through person-to-person contact or droplets shed from the respiratory secretions of infected persons.
• •If a woman with rubella is infected during pregnancy, the virus can cross the placenta and infect the fetus.

Occurrence

• •Rubella occurs worldwide.
• • In the United States, endemic rubella has been eliminated. However, since 2005, an average of 10 cases is reported each year. Of these cases, approximately 33% are imported or linked to importations.

Risk for Travelers

• •All susceptible persons are at risk for infection from exposure to rubella during travel outside the United States.
• •Because asymptomatic rubella infections are common, travelers may be unaware that they have been in contact with an infected person.

Clinical Presentation

• •The average incubation period is 14 days, with a range of 12–23 days.
• •Rubella usually presents as a nonspecific, maculopapular, generalized rash lasting 3 days or fewer (hence the term “3-day measles”) with generalized lymphadenopathy, particularly of the posterior auricular, suboccipital and posterior cervical lymph nodes.
• •Asymptomatic rubella virus infections are common, and up to 50% of infections occur without rash.
• •In adults and adolescents, the rash may be preceded by a 1- to 5-day prodrome of low-grade fever, malaise, anorexia, mild conjunctivitis, coryza, sore throat, and lymphadenopathy.
• •The most important and serious consequence of rubella is infection during early pregnancy. These consequences may include miscarriages, fetal deaths/stillbirths, and an infant born with constellation of severe birth defects known as congenital rubella syndrome (CRS). The most common congenital defects are cataracts, heart defects, and hearing impairment.

Diagnosis

• •Many illnesses can mimic rubella, and up to 50% of rubella infections are asymptomatic. Therefore, the only reliable evidence of acute rubella virus infection is laboratory diagnosis.
• •Serologic testing for rubella-specific IgM antibody is the most commonly used for diagnosis of rubella.
• •Diagnosis can also be made by demonstration of seroconversion of rubella-specific IgG antibody titers and by detection of virus either through virus culture or PCR.

Treatment

There is no specific antiviral therapy for rubella; basic treatment consists of supportive care.

Preventive Measures for Travelers

Vaccine

• •Before international travel, persons should be immune to rubella.
• •
  Acceptable presumptive evidence of immunity to rubella for international travelers includes—

  • ○
    Documentation of receipt of one or more doses of rubella-containing vaccine on or after the first birthday
  • ○
    Laboratory evidence of rubella immunity (a positive serologic test for rubella-specific IgG antibody)

Adverse Reactions, Precautions, and Contraindications to Rubella Vaccine

• • Refer to the Measles (Rubeola) section earlier in this chapter for information on reactions following MMR vaccine and additional precautions and contraindications.

TETANUS

M. Patricia Joyce

Infectious Agent

• • Clostridium tetani, the tetanus bacillus, is a spore-forming, anaerobic gram-positive bacterium.
• •Clinical disease is caused by a neurotoxin produced by anaerobic tetanus bacilli growing in contaminated wounds.

Mode of Transmission

• •Tetanus is a global health problem because C. tetani spores are ubiquitous in the environment.
• •Lesions that are considered “tetanus prone” are wounds contaminated with dirt, feces, or saliva, deep wounds, burns, crush injuries, or those with necrotic tissue.
• •Tetanus has also been associated with apparently clean superficial wounds, surgical procedures, insect bites, dental infections, chronic sores and infections, and intravenous drug use.
• •A reservoir of tetanus bacteria exists in the intestines of horses and other animals, including humans, in which the organism is a harmless normal inhabitant. Soil or fomites contaminated with animal and human feces propagate transmission.
• •Tetanus has no direct person-to-person transmission.

Occurrence

• • In 2006, an estimated 290,000 people worldwide died of tetanus, most of them in Asia, Africa, and South America.
• •The disease occurs almost exclusively in persons who are inadequately immunized.
• •Worldwide, the disease is more common in agricultural regions and in areas where contact with animal excreta is more likely and immunization is inadequate.
• •In developing countries, tetanus in neonates born to unvaccinated mothers (neonatal tetanus) is the most common form of the disease.
• •In 10% of reported cases in the United States, no antecedent wound was identified.

Risk for Travelers

Tetanus can occur anywhere in the world in inadequately vaccinated persons.

Clinical Presentation

• •Acute manifestations of tetanus are characterized by muscle rigidity and painful spasms, often starting in the muscles of the jaw and neck. Severe tetanus can lead to respiratory failure and death.
• •The incubation period is usually 3–21 days (average 10 days), although it may range from 1 day to several months, depending on the character, extent, and location of the wound. Most cases occur within 14 days. In general, shorter incubation periods are associated with more heavily contaminated wounds, more severe disease, and a worse prognosis.

Clinical Syndromes

Generalized Tetanus

• •Generalized tetanus is the most common form, accounting for more than 80% of cases.
• •Neonatal tetanus is generalized tetanus in neonates, usually due to umbilical stump infections.
• •The average incubation period from injury to symptom onset is 7–8 days (range 3 days–3 weeks).
• •The most common initial sign is trismus (spasm of the muscles of mastication or “lockjaw”). Trismus may be followed by painful spasms in other muscle groups in the neck, trunk, and extremities and by generalized, tonic, seizure-like activity or frank convulsions in severe cases.
• •Generalized tetanus can be accompanied by autonomic nervous system abnormalities, as well as a variety of complications related to severe spasm and prolonged hospitalization.
• •The clinical course of generalized tetanus is variable and depends on the degree of prior immunity, the amount of toxin present, and the age and general health of the patient.
• •Even with modern intensive care, generalized tetanus is associated with mortality rates of 10%–20%.

Localized Tetanus

• •Localized tetanus is an unusual form of the disease consisting of spasm of muscles in a confined area close to the site of the injury.
• •Although localized tetanus often occurs in persons with partial immunity and is usually mild, progression to generalized tetanus can occur.

Cephalic Tetanus

• •The rarest form, cephalic tetanus, is associated with lesions of the head or face and has been described in association with ear infections (i.e., otitis media).
• • The incubation period is short, usually 1–2 days.
• •Unlike generalized and localized tetanus, cephalic tetanus results in flaccid cranial nerve palsies rather than spasm. Trismus may also be present. Like localized tetanus, cephalic tetanus can progress to the generalized form.

Diagnosis

• •The diagnosis is almost always made clinically.
• •The disease is characterized by painful muscular contractions, primarily of the masseter and neck muscles, secondarily of trunk muscles.
• •A common first sign suggestive of tetanus in older children and adults is abdominal rigidity, though rigidity is sometimes confined to the region of injury.
• •Generalized spasms occur, frequently induced by sensory stimuli; typical features of the tetanic spasm are the position of opisthotonos and the facial expression known as “risus sardonicus.”
• •History of an injury or apparent portal of entry may be lacking.
• •The organism is rarely recovered from the site of infection, and usually there is no detectable antibody response.

Treatment

• •
  Tetanus is a medical emergency requiring hospitalization, immediate treatment with human tetanus immune globulin (TIG) (or equine antitoxin if human immune globulin is not available), a tetanus toxoid booster, agents to control muscle spasm, and, if indicated, aggressive wound care and antibiotics.

  • ○
    Specific treatment: TIG administered intramuscularly in doses of 3000–6000 IU. If immunoglobulin is not available, tetanus antitoxin (equine origin) in a single large dose should be given intravenously, following testing for hypersensitivity.
• •Metronidazole is the most appropriate antibiotic. It is associated with the shortest recovery time and lowest case–fatality rate. It should be given for 7–14 days in large doses; this also allows for a reduction in the amount of muscle relaxants and sedatives required.
• •The wound should be debrided widely and excised if possible. Wide debridement of the umbilical stump in neonates is not indicated.
• •Depending on the severity of disease, mechanical ventilation and agents to control autonomic nervous system instability may be required.
• •An adequate airway should be maintained, and sedation should be used as indicated; muscle relaxant drugs, together with tracheostomy or nasotracheal intubation and mechanically assisted respiration, may be lifesaving.
• •Active immunization should be initiated concurrently with treatment.

Preventive Measures for Travelers

• •
  Travelers should ensure they have adequate immunity to tetanus.

  • ○
    Active immunity is induced by tetanus toxoid and persists for at least 10 years after full immunization; transient passive immunity follows injection of TIG or tetanus antitoxin (equine origin).
  • ○
    Infants of actively immunized mothers acquire passive immunity that protects them from neonatal tetanus.
  • ○
    Recovery from tetanus may not result in immunity; second attacks can occur, and primary immunization is indicated after recovery.
• •Wounded travelers who received their most recent tetanus toxoid-containing vaccine more than 5 years previously or who have not received at least three doses of tetanus toxoid-containing vaccines may require a dose of tetanus toxoid-containing vaccine (Tdap, Td, or DTaP), depending on the nature of the wound.
• •Human tetanus immune globulin (TIG) is indicated in travelers with tetanus-prone wounds who have an unknown or incomplete history of primary tetanus vaccination.

General Preventive Measures

• •Universal active immunization with adsorbed tetanus toxoid, gives durable protection for at least 10 years; after the initial basic series has been completed, single booster doses elicit high levels of immunity.
• •In children <7 years of age, the toxoid is generally administered together with diphtheria toxoid and pertussis vaccine as a triple (DTP or DTaP) antigen, or as a double (DT) antigen when contraindications to pertussis vaccine exist.
• •Td is used for children >7 years of age.
• •For adolescents 11–12 years of age, a single dose of Tdap is recommended for routine booster, and for adolescents and adults 13–64 years of age, a single dose of Tdap is recommended to replace the next decennial Td booster or when indicated as part of wound prophylaxis.
• •In countries with incomplete immunization programs for children, all pregnant women should receive two doses of tetanus toxoid in the first pregnancy, with an interval of at least 1 month, and with the second dose at least 2 weeks prior to childbirth.
• •Vaccine-induced maternal immunity is important in preventing maternal and neonatal tetanus. Active protection should be maintained by administering booster doses of Td every 10 years, preferably before or between pregnancies.
• •For children and adults who are severely immunocompromised or infected with HIV, tetanus toxoid is indicated in the same schedule and dose as for immunocompetent persons even though the immune response may be suboptimal.
• •Minor local reactions following tetanus toxoid injections are relatively frequent; severe local and systemic reactions are infrequent but do occur, particularly after excessive numbers of prior doses have been given.

Prophylaxis in Wound Management (see Table 2-21)

• •Tetanus prophylaxis in patients with wounds is based on careful assessment of whether the wound is clean or contaminated, the immunization status of the patient, proper use of tetanus toxoid and/or TIG, wound cleaning and, where required, surgical debridement and the proper use of antibiotics.
• •Those who have been completely immunized and who sustain minor and uncontaminated wounds require a booster dose of toxoid only if more than 10 years have elapsed since the last dose was given. For major or contaminated wounds, a single booster injection of tetanus toxoid (preferably as Td or Tdap) should be administered promptly on the day of injury if the patient has not received tetanus toxoid within the preceding 5 years.
• •Persons who have not completed a full primary series of tetanus toxoid require a dose of toxoid as soon as possible following the wound and may require passive immunization with human TIG if the wound is major or if it is contaminated with soil containing animal excreta. DTP/DTaP, DT, or Td, as determined by the age of the patient and previous immunization history, should be used at the time of the wound and ultimately to complete the primary series.
• •Passive immunization with at least 250 IU of TIG intramuscularly (or 1,500 to 5,000 IU of antitoxin of animal origin, if globulin is not available), regardless of the patient's age, is indicated for patients with other than clean, minor wounds and a history of no, unknown, or fewer than three previous tetanus toxoid doses. When tetanus toxoid and TIG or antitoxin are given concurrently, separate syringes and separate sites must be used.

VARICELLA (CHICKENPOX)

Kathleen H. Harriman, Gilberto F. Chavez

Infectious Agent

• •Varicella-zoster virus (VZV) is a member of the herpesvirus family.
• •Humans are the only reservoir of the virus, and disease occurs only in humans.

Mode of Transmission

• •VZV is transmitted from person to person by direct contact, inhalation of aerosols from vesicular fluid of skin lesions of acute varicella or zoster, or infected respiratory tract secretions that might also be aerosolized.
• •The virus enters the host through the upper respiratory tract or the conjunctiva.
• • In utero infection can also occur as a result of transplacental passage of virus during maternal varicella infection.
• •The period of contagiousness is estimated to begin 1–2 days before the onset of rash and to end when all lesions are crusted, typically 4–7 days after onset of rash in immunocompetent persons, but this period may be longer in immunocompromised persons.

Occurrence

• •Varicella occurs worldwide. In temperate climates, varicella tends to be a childhood disease, with peak incidence during late winter and early spring. In tropical climates, infection tends to occur at older ages, resulting in higher susceptibility among adults than in temperate climates.
• •Before introduction of varicella vaccine in the United States in 1995, varicella was endemic, and virtually all persons were infected by adulthood. Since implementation of the varicella vaccination program, the epidemiology and clinical characteristics of varicella have changed, with substantial declines in morbidity and mortality. The incidence of varicella has steadily declined in all age groups, with the greatest decline among children 1–4 years of age.

Risk for Travelers

• •Varicella vaccine is routinely used for vaccination of healthy children in only some countries, including the United States, Uruguay, Qatar, Australia, Canada, Costa Rica, Germany, and South Korea.
• •The risk for varicella infection is higher for people traveling to most other parts of the world than it is in the United States. However, VZV is still widely circulating in the United States. Additionally, exposure to herpes zoster (shingles), while less common than varicella, poses a risk for varicella infection in susceptible travelers.
• •Travelers at highest risk for severe varicella disease are immunocompromised persons or pregnant women without a history of varicella disease or vaccination.

Clinical Presentation

• •Varicella is generally a mild disease in children. It usually lasts 4–7 days and is characterized by a short (1- to 2-day) or absent prodromal period (low-grade fever, malaise) and by a pruritic rash consisting of crops of macules, papules, and vesicles (on average 250–500 lesions), which appear in three or more successive waves and resolve by crusting.
• •Serious complications are the exception but can occur, mainly in infants, adolescents, adults, and immunocompromised persons. They include secondary bacterial infections of skin lesions, pneumonia, cerebellar ataxia, and encephalitis.
• •The average incubation period for varicella is 14–16 days (range 10–21 days).
• •A modified varicella, known as breakthrough disease, can occur in some vaccinated persons, because the vaccine is 70%–90% effective in preventing disease. Breakthrough varicella is most commonly (∼70%–80% of cases) mild, with <50 skin lesions, less fever, and shorter duration of rash. The rash may be atypical in appearance with fewer vesicles and predominance of maculopapular lesions. Nevertheless, breakthrough varicella is infectious (although less than varicella in unvaccinated persons). Persons with breakthrough varicella should be isolated for as long as lesions persist.

Diagnosis

• •
  Skin lesions are the preferred specimen for laboratory confirmation of varicella disease.

  • ○
    Vesicular fluid or a scab can be used to identify VZV by using polymerase chain reaction (PCR). Rapid diagnostic tests (PCR, direct fluorescent antibody) are the methods of choice.
  • ○
    VZV can also be isolated from scrapings of a vesicle base during the first 3–4 days of the eruption.
  • ○
    Collecting skin lesion specimens from breakthrough cases can be challenging because the rash is often maculopapular with few or no vesicles. If lesions are not present, scraping of the lesion is recommended.
• •
  Serologic tests for confirmation of disease:

  • ○
    A significant rise in serum varicella IgG antibody from acute- and convalescent-phase samples by any standard serologic assay can confirm a diagnosis retrospectively, but may not be reliable in immunocompromised people.
  • ○
    Commercially available tests are not sufficiently sensitive to reliably demonstrate vaccine-induced immunity.

Postexposure Prophylaxis

Vaccine

• •Varicella vaccine is recommended for postexposure administration for healthy unvaccinated persons without other evidence of immunity.
• •Administration of varicella vaccine to exposed susceptible persons Δ12 months of age, as soon as possible within 72 hours and possibly up to 120 hours after exposure, may prevent or modify disease and is recommended if there are no contraindications to use. In several studies, protective efficacy was reported as Δ90% when children were vaccinated within 3 days of exposure.

Use of Varicella Zoster Immune Globulin (VZIG)

• •In certain circumstances, postexposure prophylaxis with VZIG is recommended.
• •The decision to administer VZIG to a person exposed to varicella should be based on 1) whether the person is susceptible, 2) whether the exposure is likely to result in infection, and 3) whether the person is at greater risk for complications than the general population.
• •
  Persons at greater risk for severe complications who are not candidates for varicella vaccination who may benefit from postexposure prophylaxis with VZIG include:

  • ○
    susceptible immunocompromised persons (including people being treated with chronic corticosteroids Δ2 mg/kg of body weight or a total of 20 mg/day of prednisone or equivalent)
  • ○
    susceptible pregnant women
  • ○
    newborns whose mothers had onset of varicella within 5 days before and 2 days after delivery
  • ○
    preterm infants at Δ28 weeks gestation whose mothers are susceptible to varicella
  • ○
    preterm infants at <28 weeks gestation or £1,000 g birth weight, regardless of maternal history or serostatus.
• •VZIG provides maximum benefit when administered as soon as possible after exposure, but may be effective if administered as late as 96 hours after exposure.
• •The product currently in use in the United States, VariZIG, is available under an Investigational New Drug protocol and can be obtained from the sole authorized U.S. distributor, FFF enterprises (Temecula, California) (24-hour telephone, 800-843-7477 or www.fffenterprises.com).
• •If administration of VariZIG does not appear possible within 96 hours of exposure, administration of immune globulin intravenous (IGIV) should be considered as an alternative (IGIV should also be administered within 96 hours of exposure).

Treatment

• • Oral acyclovir is not recommended for routine use in healthy children with varicella but should be considered for otherwise healthy people at increased risk for moderate to severe disease, e.g.: persons aged >12 years; people with chronic cutaneous or pulmonary disorders; receiving long-term salicylate therapy; and receiving short, intermittent or aerosolized courses of corticosteroids.
• •Intravenous antiviral therapy, when administered within 24 hours of onset of rash is recommended for immunocompromised persons, including patients being treated with chronic corticosteroids.

Preventive Measures for Travelers

Although vaccination against varicella is not a requirement for entry into any country (including the United States), persons traveling or living abroad should ensure that they are immune.

Vaccine

• •Varicella vaccine contains live, attenuated VZV. It is available as a monovalent formulation and in combination formulation, as measles–mumps–rubella–varicella (MMRV) vaccine, which is licensed in the United States for children 1–12 years only.
• •Two doses of varicella-containing vaccine are now recommended for all susceptible persons older than one year without contraindications. The first dose should be administered at 12–15 months of age and the second dose at 4–6 years of age. A second catch-up dose of varicella vaccination is recommended for children, adolescents and adults who previously have received one dose. The minimum interval for children younger than 13 years is 3 months. The ACIP now recommends that all others at least 13 years of age without evidence of immunity be vaccinated with two doses of varicella vaccine at an interval of 4–8 weeks. In case of uncertainty, prior varicella disease is not a contraindication to varicella vaccination.
• •
  Evidence of immunity to varicella includes any of the following:

  • ○
    Documentation of age-appropriate vaccination:

    • □
      Preschool-age children aged Δ12 months: 1 dose
    • □
      School-age children, adolescents, and adults: 2 doses
  • ○
    Laboratory evidence of immunity or laboratory confirmation of disease
  • ○
    Birth in the United States before 1980 (not a criterion for health-care personnel, pregnant women, and immunocompromised persons)
  • ○
    A health-care provider diagnosis of varicella or a health-care provider verification of a history of varicella disease
  • ○
    A health-care provider diagnosis of herpes zoster or a health-care provider verification of a history of herpes zoster disease

Adverse Reactions

• •The most common adverse reactions following varicella vaccine are injection site complaints (pain, soreness, redness, and swelling) that are self-limited. Fever was reported in uncontrolled trials in 15% of children and 10% of adolescents and adults. A macular or vaccine rash usually consisting of a few lesions at the injection site was reported in 3% and 1% of persons receiving the first and second dose, respectively. A generalized rash with a small number of lesions may rarely occur, within 3 weeks of vaccination.
• •Varicella vaccine is a live-virus vaccine that induces latent infection similar to that caused by wild VZV. Consequently, zoster caused by vaccine virus has been reported. This appears to occur at a lower rate than following natural infection but longer term follow-up is needed.

Contraindications

Allergy

• • Persons with severe allergy (hives, swelling of the mouth or throat, difficulty breathing, hypotension, and shock) to gelatin or neomycin or who have had a severe allergic reaction to a prior dose of vaccine should not be vaccinated.
• •Single-antigen varicella vaccine does not contain egg protein or preservative. For the combination MMRV vaccine, live measles and live mumps vaccine are produced in chick embryo culture. However, the risk for serious allergic reactions after administration of measles- or mumps-containing vaccines in persons who are allergic to eggs is low.

Altered Immunity

Persons with immunosuppression of cellular immune function resulting from leukemia, lymphomas of any type, generalized malignancy, immunodeficiency disease, or immunosuppressive therapy should not be vaccinated. Treatment with low-dose prednisone (e.g., <2 mg/kg of body weight/day or <20 mg/day) or aerosolized steroid preparations is not a contraindication to varicella vaccination. Persons whose immunosuppressive therapy with steroids has been stopped for 1 month (3 months for chemotherapy) may be vaccinated. In addition, persons with impaired humoral immunity may now be vaccinated. Because children infected with HIV are at greater risk for morbidity from varicella and herpes zoster than are healthy children, the ACIP recommends that varicella vaccine should be considered for HIV-infected children at least 12 months of age with CD4+ T-lymphocyte percentages Δ15% and without evidence of varicella immunity. Eligible children should receive two doses of single-antigen varicella vaccine, with a minimum 3-month interval between doses. Vaccination (two doses, administered 3 months apart) may be considered for HIV-infected older children, adolescents and adults with CD4+ T-lymphocyte count Δ200 cells/mL, after weighing the risks and benefits.

Pregnancy

Women known to be pregnant or attempting to become pregnant should not receive varicella vaccine. Pregnancy should be avoided for 1 month following varicella vaccination. Breastfeeding is not a contraindication to the varicella vaccination.

Precautions

Illness

Vaccination of persons who have acute severe illness, including untreated, active tuberculosis, should be postponed until recovery.

Recent Administration of Blood, Plasma, or Immune Globulin

The effect of the administration of immune globulin (IG) on the response to varicella virus vaccine is unknown. Because of the potential inhibition of the antibody response by passively transferred antibodies, varicella vaccines should not be administered for 3–11 months, depending on the dosage, after administration of blood (except washed red cells), plasma, or IG.

Use of Salicylates

No adverse events following varicella vaccination related to the use of salicylates (e.g., aspirin) have been reported to date. However, the manufacturer recommends that vaccine recipients avoid the use of salicylates for 6 weeks after receiving varicella vaccine because of the association between aspirin use and Reye syndrome following varicella.

 

Malaria

MALARIA

Paul M. Arguin, Stefanie F. Steele

Infectious Agent

Malaria in humans is caused by one of four protozoan species of the genus Plasmodium: P. falciparum, P. vivax, P. ovale, or P. malariae. Recently, P. knowlesi, a parasite of Old World monkeys, has been documented as a cause of human infections and some fatalities in Southeast Asia. Investigations are ongoing to determine the extent of its transmission to humans.

Mode of Transmission

All species are transmitted by the bite of an infected female Anopheles mosquito. Occasionally, transmission occurs by blood transfusion, organ transplantation, needle sharing, or congenitally from mother to fetus.

Occurrence

• •Each year malaria causes 350–500 million infections worldwide and approximately 1 million deaths.
• •Transmission occurs in large areas of Central and South America, parts of the Caribbean, Africa, Asia (including South Asia, Southeast Asia, and the Middle East), Eastern Europe, and the South Pacific (Maps 2-7 and 2-8 ).
• •Information about malaria transmission in specific countries (see the Malaria Risk Information and Prophylaxis, by Country, section later in this chapter) is derived from various sources, including WHO.
• •Tools such as the interactive malaria map can assist in locating more unusual destinations and determining if malaria transmission occurs there (see www.cdc.gov/malaria/risk_map/).

Map 2-7.

Malaria-endemic countries in the Western Hemisphere.

Map 2-8.

Malaria-endemic countries in the Eastern Hemisphere.

Risk for Travelers

• •The risk for a traveler acquiring malaria differs substantially from region to region and from traveler to traveler, even within a single country.
• • From 1997 through 2006, 10,745 cases of malaria among U.S. residents were reported to CDC. Of these, 6,376 (59.3%) were acquired in sub-Saharan Africa; 1,498 (13.9%) in Asia; 1,427 (13.3%) in the Caribbean and Central and South America; and 278 (0.03%) in Oceania. During this period, 54 fatal malaria infections occurred among U.S. residents; 46 (85.2%) were caused by P. falciparum, of which 33 (71.1%) were acquired in sub-Saharan Africa.
• •These absolute numbers of cases should be considered within the context of the volume of travel to these locations. Regions with the highest estimated relative risk for infection for travelers are West Africa and Oceania. Regions with moderate estimated relative risk for infection are the other parts of Africa, South Asia, and South America. Regions with lower estimated relative risk are Central America and other parts of Asia. There is considerable country-by-country variation, as well as variable transmission within countries and sometimes seasonal variation.
• •Prevention of malaria involves striking a balance between ensuring that all people who will be at risk for infection use the appropriate prevention measures, while preventing adverse effects of those interventions among people using them unnecessarily. An individual risk assessment should be conducted for every traveler, taking into account not only the destination country, but also the detailed itinerary, including specific cities, types of accommodation, season, and style of travel. In addition, conditions such as pregnancy or the presence of antimalarial drug resistance at the destination may modify the risk assessment.
• •Depending on level of risk, it may be appropriate to recommend no specific interventions, mosquito avoidance measures only, or mosquito avoidance measures plus chemoprophylaxis.
• •For areas of intense transmission, such as West Africa, exposure for even short periods of time can result in transmission, so this area should be considered high risk.
• •Malaria risk is not distributed homogeneously throughout all countries. Some destinations have malaria transmission occurring throughout the whole country, while in others it occurs in defined pockets. If travelers are going to the high-risk pockets during peak transmission times, even though the country as a whole may be low risk, this destination for this individual may be high risk.
• •Geography is just one part of determining a traveler's risk for infection. Risk can differ substantially for different travelers if their behaviors and circumstances differ. For example, travelers staying in air-conditioned hotels may be at lower risk than backpackers or adventure travelers. Similarly, long-term residents living in screened and air-conditioned housing are less likely to be exposed than are persons living without such amenities.
• •The highest risk is associated with first- and second-generation immigrants living in nonendemic countries who return to their countries of origin to visit friends and relatives (VFRs). VFR travelers often consider themselves to be at no risk because they grew up in a malarious country and consider themselves immune. However, acquired immunity is lost very quickly, and VFRs should be considered as having the same risk as otherwise nonimmune travelers.
• •Travelers should also be reminded that even if one has had malaria before, one can get it again and preventive measures are still necessary. All travelers going to malaria-endemic countries, even for short periods of time, such as cruise ship passengers, may be at risk for becoming infected with malaria.
• •Persons who have been in an area where malaria transmission occurs, either during daytime or nighttime hours, are not permitted to donate blood in the United States for a period of time after returning from the malarious area. Persons who are residents of nonmalarious countries are not permitted to donate blood for 1 year after they have returned from a malarious area. Persons who are residents of malarious countries are not permitted to donate blood for 3 years after leaving a malarious area. Persons who have had malaria are not allowed to donate blood for 3 years after treatment for malaria.
• • Risk assessments may differ between travel medicine providers and blood banks. A travel medicine provider advising a traveler going to a relatively low-risk country for a short period of time and engaging in behaviors that place them at lower risk for exposure may choose insect avoidance only and no chemoprophylaxis for the traveler. However, upon the traveler's return, a blood bank may still choose to defer that traveler for 1 year because of the travel to an area where transmission occurs.

Clinical Presentation

• •Malaria is characterized by fever and influenza-like symptoms, including chills, headache, myalgias, and malaise; these symptoms can occur at intervals.
• •Uncomplicated disease may be associated with anemia and jaundice. In severe disease, most commonly caused by P. falciparum, seizures, mental confusion, kidney failure, acute respiratory disease syndrome (ARDS), coma, and death may occur.
• •Malaria symptoms can develop as early as 7 days (usually at least 14 days) after initial exposure in a malaria-endemic area and as late as several months or more after departure.

Diagnosis

• •Travelers who have symptoms of malaria should be advised to seek medical evaluation as soon as possible.
• •Smear microscopy remains the gold standard for malaria diagnosis. Microscopy can also be used to determine the species of malaria parasite and quantify the parasitemia—both of which are necessary pieces of information for providing the most appropriate treatment.
• •Various test kits are available to detect antigens derived from malaria parasites. Such immunologic (immunochromatographic) tests most often use a dipstick or cassette format and provide results in 2–15 minutes. These rapid diagnostic tests (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. The U.S. Food and Drug Administration (FDA) has approved one RDT for use in the United States by hospital and commercial laboratories, not by individual clinicians or by patients themselves. This RDT, called BinaxNOW Malaria test, is produced by Inverness Medical Professional Diagnostics, located in Scarborough, Maine.
• •Polymerase chain reaction (PCR) tests are also available for detecting malaria parasites; however, none are FDA-approved. Although these tests are slightly more sensitive than routine microscopy, results are not usually available as quickly as microscopy results should be, thus limiting the clinical utility of this test. PCR testing can be used to determine the species of the parasite if the microscopic results are ambiguous.
• •In sub-Saharan Africa, the rate of false-positive blood films for malaria may be very high. Travelers to this region should be warned they may be diagnosed with malaria incorrectly, even though they are taking a reliable antimalarial regimen. In such cases, acutely ill travelers should be advised to seek the best available medical services and follow the treatment offered locally (except the use of halofantrine which is not recommended; see below), but not to stop their chemoprophylaxis regimen.

Treatment

• •Malaria can be treated effectively early in the course of the disease, but delay of appropriate therapy can have serious or even fatal consequences.
• •Travelers who have symptoms of malaria should be advised to seek medical evaluation as soon as possible.
• • Specific treatment options depend on the species of malaria, the likelihood of drug resistance (based on the location of acquisition of infection), the age of the patient, pregnancy status, and the severity of infection. If possible, it is advisable to consult with a provider who has specialized travel/tropical medicine expertise or with an infectious disease physician.
• •CDC recommendations for malaria treatment can be found at www.cdc.gov/malaria/diagnosis_treatment/treatment.htm.
• •Medications that are not used in the United States for the treatment of malaria, such as halofantrine (Halfan), are widely available overseas. CDC does not recommend halofantrine for treatment because of cardiac adverse events, including deaths, which have been documented following treatment doses. These adverse events have occurred in persons with and without pre-existing cardiac problems and both in the presence and absence of other antimalarial drugs (e.g., mefloquine).

Self-Treatment (Table 2-22)

Table 2-22.

Presumptive self-treatment of malaria

Drug	Adult Dose	Pediatric Dose	Comments
Atovaquone/proguanil (Malarone). Self-treatment drug to be used if professional medical care is not available within 24 hours. Medical care should be sought immediately after treatment.	4 tablets (each dose contains 1,000 mg atovaquone and 400 mg proguanil) orally as a single daily dose for 3 consecutive days	Daily dose to be taken for 3 consecutive days: 5–8 kg: 2 pediatric tablets; 9–10 kg: 3 pediatric tablets; 11–20 kg: 1 adult tablet; 21–30 kg: 2 adult tablets; 31–40 kg: 3 adult tablets; >41 kg: 4 adult tablets	Contraindicated in persons with severe renal impairment (creatinine clearance <30 mL/min). Not recommended for self-treatment in persons on atovaquone/proguanil prophylaxis. Not currently recommended for children <5 kg, pregnant women, and women breastfeeding infants weighing <5 kg

• •Travelers who reject the advice to take prophylaxis, who choose a suboptimal drug regimen (e.g., chloroquine in an area with chloroquine-resistant P. falciparum), or who require a less-than-optimal drug regimen for medical reasons are at greater risk for acquiring malaria and needing prompt treatment.
• •Travelers who are taking effective prophylaxis but who will be in very remote areas may decide, in consultation with their health-care provider, to take along a full course of an approved malaria treatment regimen for self-treatment. This should occur very rarely.
• •Travelers should be advised to take their presumptive self-treatment promptly if they have fever, chills, or other influenza-like illness and if professional medical care is not available within 24 hours. Travelers should be advised that this self-treatment of a possible malarial infection is only a temporary measure and that prompt medical evaluation is imperative.
• •Atovaquone/proguanil may be used for presumptive self-treatment for travelers NOT taking atovaquone/proguanil for prophylaxis. If taking atovaquone/proguanil for prophylaxis, the use of the same drug at therapeutic doses is not recommended to empirically treat fever (suspected malaria). The CDC Malaria Branch (Malaria Hotline 770-488-7788) can provide consultation to health-care providers on other potential options for self-treatment if atovaquone/proguanil cannot be used.

Malaria Hotline

• • Health-care professionals who require assistance with the diagnosis or treatment of malaria should call the CDC Malaria Hotline (770-488-7788) from 8:00 am to 4:30 pm Eastern time. After hours or on weekends and holidays, health-care providers requiring assistance should call the CDC Emergency Operations Center at 770-488-7100 and ask the operator to page the person on call for the Malaria Branch.
• •Information on diagnosis and treatment is available at www.cdc.gov/malaria.

Preventive Measures for Travelers

Malaria prevention consists of a combination of mosquito avoidance measures and chemoprophylaxis. Although very efficacious, none of the recommended interventions are 100% effective.

Mosquito Avoidance Measures

• •Because of the nocturnal feeding habits of Anopheles mosquitoes, malaria transmission occurs primarily between dusk and dawn.
• •Contact with mosquitoes can be reduced by remaining in well-screened areas, using mosquito bed nets (preferably insecticide-treated nets), using a pyrethroid-containing flying-insect spray in living and sleeping areas during evening and nighttime hours, and wearing clothes that cover most of the body.
• •All travelers should use an effective mosquito repellent.
• •The most effective repellent against a wide range of vectors is DEET (N,N-diethylmetatoluamide), an ingredient in many commercially available insect repellents. The actual concentration of DEET varies widely among repellents. DEET formulations as high as 50% are recommended for both adults and children older than 2 months of age (see the Protection Against Mosquitoes, Ticks, and Other Insects and Arthropods section later in this chapter). DEET should be applied to the exposed parts of the skin when mosquitoes are likely to be present.
• •In addition to using a topical insect repellent, a permethrin-containing product may be applied to bed nets and clothing for additional protection against mosquitoes.

Chemoprophylaxis

• •All currently recommended primary chemoprophylaxis regimens involve taking a medicine before travel, during travel, and for a period of time after leaving the malaria endemic area. Beginning the drug before travel allows the antimalarial agent to be in the blood before the traveler is exposed to malaria parasites.
• •Presumptive antirelapse therapy (also known as terminal prophylaxis) uses a medication towards the end of the exposure period (or immediately thereafter) to prevent relapses or delayed-onset clinical presentations of malaria caused by hypnozoites (dormant liver stages) of P. vivax or P. ovale. Because most malarious areas of the world (except the Caribbean) have at least one species of relapsing malaria, travelers to these areas have some risk for acquiring either P. vivax or P. ovale, although the actual risk for an individual traveler is difficult to define. Presumptive anti-relapse therapy is generally indicated only for persons who have had prolonged exposure in malaria-endemic areas (e.g., missionaries, volunteers).
• •In choosing an appropriate chemoprophylactic regimen before travel, the traveler and the health-care provider should consider several factors. The travel itinerary should be reviewed in detail and compared with the information on where malaria transmission occurs within a given country (see the Malaria Risk Information and Prophylaxis, by Country, section later in this chapter) to determine whether the traveler will actually be traveling in a part of the country where malaria occurs and if significant antimalarial drug resistance has been reported in that location.
• •The resistance of P. falciparum to chloroquine has been confirmed in all areas with P. falciparum malaria except the Caribbean, Central America west of the Panama Canal, and some countries in the Middle East. In addition, resistance to sulfadoxine–pyrimethamine (e.g., Fansidar) is widespread in the Amazon River Basin area of South America, much of Southeast Asia, other parts of Asia, and in large parts of Africa. Resistance to mefloquine has been confirmed on the borders of Thailand with Burma (Myanmar) and Cambodia, in the western provinces of Cambodia, in the eastern states of Burma (Myanmar), on the border between Burma and China, along the borders of Laos and Burma, and the adjacent parts of the Thailand–Cambodia border, as well as in southern Vietnam (Map 2-9 ).
• •Additional factors to consider are the patient's other medical conditions, medications being taken (to assess potential drug–drug interactions), the cost of the medicines, and the potential side effects.
• •The medications recommended for chemoprophylaxis of malaria may also be available at overseas destinations. However, combinations of these medications and additional drugs that are not recommended may be commonly prescribed and used in other countries. Travelers should be strongly discouraged from obtaining chemoprophylactic medications while abroad. The quality of these products is not known, and they may not be protective and may be dangerous. These medications may have been produced by substandard manufacturing practices, may be counterfeit, or may contain contaminants. Additional information on this topic can be found in Perspectives: Counterfeit Drugs later in this chapter and in an FDA document Purchasing Medications Outside the United States (www.fda.gov/ora/import/purchasing_medications.htm).

Map 2-9.

Geographic distribution of mefloquine-resistant malaria.

Medications Used for Chemoprophylaxis

Atovaquone/Proguanil (Malarone)

• •Atovaquone/proguanil is a fixed combination of the two drugs, atovaquone and proguanil.
• •Prophylaxis should begin 1–2 days before travel to malarious areas and should be taken daily, at the same time each day, while in the malarious areas, and daily for 7 days after leaving the area (see Table 2-23 for recommended dosages).
• •Malarone is very well tolerated, and side effects are rare. The most common adverse effects reported in persons using atovaquone/proguanil for prophylaxis or treatment are abdominal pain, nausea, vomiting, and headache. Malarone should not be used for prophylaxis in children weighing <5 kg, pregnant women, or patients with severe renal impairment (creatinine clearance <30 mL/min). It should be used with caution by patients taking coumadin (warfarin) for anticoagulation.

Table 2-23.

Drugs used in the prophylaxis of malaria

Drug	Usage	Adult Dose	Pediatric Dose	Comments
Atovaquone/proguanil (Malarone)	Prophylaxis in all areas	Adult tablets contain 250 mg atovaquone and 100 mg proguanil hydrochloride. 1 adult tablet orally, daily	Pediatric tablets contain 62.5 mg atovaquone and 25 mg proguanil hydrochloride. 5-8 kg: frac12; pediatric tablet daily; >8–10 kg: frac34; pediatric tablet daily; >10-20 kg: 1 pediatric tablet daily; >20-30 kg: 2 pediatric tablets daily; >30-40 kg: 3 pediatric tablets daily; >40 kg: 1 adult tablet daily	Begin 1-2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in persons with severe renal impairment (creatinine clearance <30 mL/min). Atovaquone/proguanil should be taken with food or a milky drink. Not recommended for prophylaxis for children <5 kg, pregnant women, and women breastfeeding infants weighing <5 kg. Partial tablet dosages may need to be prepared by a pharmacist and dispensed in individual capsules, as described in the text.
Chloroquine phosphate (Aralen and generic)	Prophylaxis only in areas with chloroquine-sensitive malaria	300 mg base (500 mg salt) orally, once/week	5 mg/kg base (8.3 mg/kg salt) orally, once/week, up to maximum adult dose of 300 mg base	Begin 1-2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas. May exacerbate psoriasis
Doxycycline (many brand names and generic)	Prophylaxis in all areas	100 mg orally, daily	>8 years of age: 2 mg/kg up to adult dose of 100 mg/day	Begin 1-2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in children <8 years of age and pregnant women
Hydroxychloroquine sulfate (Plaquenil)	An alternative to chloroquine for prophylaxis only in areas with chloroquine-sensitive malaria	310 mg base (400 mg salt) orally, once/week	5 mg/kg base (6.5 mg/kg salt) orally, once/week, up to maximum adult dose of 310 mg base	Begin 1-2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas.
Mefloquine (Lariam and generic)	Prophylaxis in areas with mefloquine-sensitive malaria	228 mg base (250 mg salt) orally, once/week	<9 kg: 4.6 mg/kg base (5 mg/kg salt) orally, once/week; >9–19 kg: frac14; tablet once/week; >19-30 kg: frac12; tablet once/week;	Begin 1-2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in persons allergic to mefloquine or related compounds (e.g., quinine, quinidine) and in persons with active depression, a recent history of depression, generalized anxiety disorder,
Mefloquine (Lariam and generic)			>31–45 kg: frac34; tablet once/week; >45 kg: 1 tablet once/week	psychosis, schizophrenia, other major psychiatric disorders, or seizures. Use with caution in persons with psychiatric disturbances or a previous history of depression. Not recommended for persons with cardiac conduction abnormalities
Primaquine	Prophylaxis for short-duration travel to areas with principally P. vivax	30 mg base (52.6 mg salt) orally, daily	0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, daily	Begin 1-2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in persons with G6PD deficiency. Also contraindicated during pregnancy and lactation unless the infant being breastfed has a documented normal G6PD level
Primaquine	Used for presumptive antirelapse therapy (terminal prophylaxis) to decrease the risk for relapses of P. vivax and P. ovale	30 mg base (52.6 mg salt) orally, once/day for 14 days after departure from the malarious area	0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, once/day for 14 days after departure from the malarious area	Indicated for persons who have had prolonged exposure to P. vivax and P. ovale or both. Contraindicated in persons with G6PD deficiency. Also contraindicated during pregnancy and lactation unless the infant being breastfed has a documented normal G6PD level

1 Glucose-6-phosphate dehydrogenase. All persons who take primaquine should have a documented normal G6PD level before starting the medication.

Chloroquine (Aralen) and Hydroxychloroquine (Plaquenil)

• •Chloroquine phosphate or hydroxychloroquine sulfate can be used for prevention of malaria only in destinations where chloroquine resistance is not present (see Maps 2-7 and 2-8 or the next section in this chapter, Malaria Risk Information and Prophylaxis, by Country).
• •Prophylaxis should begin 1–2 weeks before travel to malarious areas. It should be continued by taking the drug once a week, on the same day of the week, during travel in malarious areas and for 4 weeks after a traveler leaves these areas (see Table 2-23 for recommended dosages).
• •Reported side effects include gastrointestinal disturbance, headache, dizziness, blurred vision, insomnia, and pruritus, but generally these effects do not require that the drug be discontinued. High doses of chloroquine, such as those used to treat rheumatoid arthritis, have been associated with retinopathy; this serious side effect appears to be extremely unlikely when chloroquine is used for routine weekly malaria prophylaxis. Chloroquine and related compounds have been reported to exacerbate psoriasis. Persons who experience uncomfortable side effects after taking chloroquine may tolerate the drug better by taking it with meals. As an alternative, the related compound hydroxychloroquine sulfate may be better tolerated.

Box 2-2. Clinical pearls.

• •Overdose of antimalarial drugs, particularly chloroquine, can be fatal. Medication should be stored in childproof containers out of the reach of infants and children.
• •Chemoprophylaxis can be started earlier if there are particular concerns about tolerating one of the medications. For example, mefloquine can be started 3–4 weeks in advance to allow potential adverse events to occur before travel. If unacceptable side effects develop, there would be time to change the medication before the traveler's departure.
• •The drugs used for antimalarial chemoprophylaxis are generally well tolerated. However, side effects can occur. Minor side effects usually do not require stopping the drug. Travelers who have serious side effects should see a health-care provider who can determine if their symptoms are related to the medicine and make an appropriate medication change.
• •In comparison with drugs with short half-lives, which are taken daily, drugs with longer half-lives, which are taken weekly, offer the advantage of a wider margin of error if the traveler is late with a dose. For example, if a traveler is 1–2 days late with a weekly drug, prophylactic blood levels can remain adequate; if the traveler is 1–2 days late with a daily drug, protective blood levels are less likely to be maintained.
• •In those who are G6PD deficient, primaquine can cause hemolysis, which can be fatal. Be sure to document a normal G6PD level before prescribing primaquine.
• •Travelers should be informed that malaria can be fatal if treatment is delayed. Medical help should be sought promptly if malaria is suspected, and a blood sample should be taken and examined for malaria parasites on one or more occasions.
• •Malaria smear results or an RDT test must be available immediately. Sending specimens to offsite laboratories where results are not available for extended periods of time (days) is not acceptable. If a patient has an illness suggestive of severe malaria and a compatible travel history in an area where malaria transmission occurs, it is advisable to start treatment as soon as possible, even before the diagnosis is established. CDC recommendations for malaria treatment can be found at www.cdc.gov/malaria/diagnosis_treatment/treatment.htm.

Doxycycline (Many Brand Names and Generic)

• •Doxycycline prophylaxis should begin 1–2 days before travel to malarious areas. It should be continued once a day, at the same time each day, during travel in malarious areas and daily for 4 weeks after the traveler leaves such areas.
• •Insufficient data exist on the antimalarial prophylactic efficacy of related compounds such as minocycline (commonly prescribed for the treatment of acne). Persons on a long-term regimen of minocycline who are in need of malaria prophylaxis should stop taking minocycline 1–2 days before travel and start doxycycline instead. The minocycline can be restarted after the full course of doxycycline is completed (see Table 2-23 for recommended dosages).
• • Doxycycline can cause photosensitivity, usually manifested as an exaggerated sunburn reaction. The risk for such a reaction can be minimized by avoiding prolonged, direct exposure to the sun and by using sunscreens. In addition, doxycycline use is associated with an increased frequency of vaginal yeast infections. Gastrointestinal side effects (nausea or vomiting) may be minimized by taking the drug with a meal. To reduce the risk for esophagitis, travelers should be advised not to take doxycycline before going to bed. Doxycycline is contraindicated in persons with an allergy to tetracyclines, during pregnancy, and in infants and children <8 years of age.
• •Vaccination with the oral typhoid vaccine Ty21a should be delayed for at least 24 hours after taking a dose of doxycycline.

Mefloquine (Lariam)

• •Mefloquine prophylaxis should begin 1–2 weeks before travel to malarious areas. It should be continued once a week, on the same day of the week, during travel in malarious areas and for 4 weeks after a traveler leaves such areas (see Table 2-23 for recommended dosages).
• •Mefloquine has been associated with rare serious adverse reactions (e.g., psychoses, seizures) at prophylactic doses; these reactions are more frequent with the higher doses used for treatment. Other side effects that have occurred in chemoprophylaxis studies include gastrointestinal disturbance, headache, insomnia, abnormal dreams, visual disturbances, depression, anxiety disorder, and dizziness. Other more severe neuropsychiatric disorders occasionally reported during postmarketing surveillance include sensory and motor neuropathies (including paresthesia, tremor, and ataxia), agitation or restlessness, mood changes, panic attacks, forgetfulness, confusion, hallucinations, aggression, paranoia, and encephalopathy. On occasion, psychiatric symptoms have been reported to continue long after mefloquine has been stopped. Mefloquine is contraindicated for use by travelers with a known hypersensitivity to mefloquine or related compounds (e.g., quinine, quinidine) and in persons with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures. It should be used with caution in persons with psychiatric disturbances or a previous history of depression. A review of available data suggests that mefloquine may be used in persons concurrently on beta blockers, if they have no underlying arrhythmia. However, mefloquine is not recommended for persons with cardiac conduction abnormalities.
• • Any traveler receiving a prescription for mefloquine must also receive a copy of the FDA Medication Guide, which can be found at the following website: www.fda.gov/cder/foi/label/2003/19591s19lbl_Lariam.pdf.

Primaquine

• •Primaquine phosphate has two distinct uses for malaria prevention: primary prophylaxis and presumptive antirelapse therapy (also called terminal prophylaxis).
• •When taken for primary prophylaxis, primaquine should be taken 1–2 days before travel to malarious areas, daily, at the same time each day, while in the malarious areas, and daily for 7 days after leaving the areas (see Table 2-23 for recommended dosages). Primary prophylaxis with primaquine obviates the need for presumptive antirelapse therapy.
• •When used for presumptive antirelapse therapy, primaquine is administered for 14 days after the traveler has left a malarious area. When chloroquine, doxycycline, or mefloquine is used for primary prophylaxis, primaquine is usually taken during the last 2 weeks of postexposure prophylaxis. When atovaquone/proguanil is used for prophylaxis, primaquine may be taken during the final 7 days of atovaquone/proguanil, and then for an additional 7 days. It is preferable that primaquine be given concurrently with the primary prophylaxis medication. However, if that is not feasible, the primaquine course should still be administered after the primary prophylaxis medication has been completed.
• •The most common adverse event in glucose-6-phosphate dehydrogenase (G6PD) in normal persons is gastrointestinal upset if primaquine is taken on an empty stomach. This problem is minimized or eliminated if primaquine is taken with food.
• •In G6PD-deficient persons, primaquine can cause hemolysis that can be fatal. Before primaquine is used, G6PD deficiency MUST be ruled out by appropriate laboratory testing.

Travel to Areas with Limited Malaria Transmission

For destinations (see the next section in this chapter, Malaria Risk Information and Prophylaxis, by Country) where malaria cases occur sporadically and risk for infection to travelers is assessed as being very low, it is recommended that travelers use mosquito avoidance measures only, and no chemoprophylaxis should be prescribed.

Travel to Areas with Mainly P. vivax Malaria

• •For destinations where the main species of malaria present is P. vivax, in addition to mosquito avoidance measures, primaquine is a good choice for primary prophylaxis for travelers who are not G6PD-deficient. Its use for this indication is considered off-label use in the United States.
• •The predominant species of malaria and the recommended chemoprohylaxis medicines are listed in the following section in this chapter, Malaria Risk Information and Prophylaxis, by Country.
• •For persons unable to take primaquine, other drugs can be used as described below, depending on the presence of antimalarial drug resistance.

Travel to Areas with Chloroquine-Sensitive Malaria

• •For destinations where chloroquine-sensitive malaria is present, in addition to mosquito avoidance measures, the many effective chemoprophylaxis alternatives include chloroquine, atovaquone/proguanil, doxycycline, mefloquine, and in some instances primaquine for travelers who are not G6PD-deficient.
• •Longer-term travelers may prefer the convenience of weekly chloroquine, while shorter-term travelers may prefer the shorter course of atovaquone/proguanil or primaquine.

Travel to Areas with Chloroquine-Resistant Malaria

For destinations where chloroquine-resistant malaria is present, in addition to mosquito avoidance measures, chemoprophylaxis options are limited to atovaquone/proguanil, doxycycline, and mefloquine.

Travel to Areas with Mefloquine-Resistant Malaria

For destinations where mefloquine-resistant malaria is present, in addition to mosquito avoidance measures, chemoprophylaxis options are reduced to either atovaquone/proguanil or doxycycline.

Chemoprophylaxis for Infants, Children, and Adolescents

• •Infants of any age or weight or children and adolescents of any age can contract malaria. Therefore, all children traveling to malaria-risk areas should take an antimalarial drug.
• •In the United States, antimalarial drugs are available only in tablet form and may taste quite bitter. Pediatric dosages should be carefully calculated according to body weight but should never exceed adult dosage. Pharmacists can pulverize tablets and prepare gelatin capsules for each measured dose. If the child is unable to swallow the capsules or tablets, parents should prepare the child's dose of medication by breaking open the gelatin capsule and mixing the drug with a small amount of something sweet, such as applesauce, chocolate syrup, or jelly, to ensure the entire dose is delivered to the child. Giving the dose on a full stomach may minimize stomach upset and vomiting.
• •Chloroquine and mefloquine are options for use in infants and children of all ages and weights, depending on the presence of drug resistance at their destination.
• •Primaquine can be used for children who are not G6PD-deficient traveling to areas with principally P. vivax.
• •Doxycycline may be used for children who are at least 8 years of age.
• •Atovaquone/proguanil may be used for prophylaxis for infants and children weighing at least 5 kg (11 lbs). Providers should note that this prophylactic dosing for children weighing <11 kg constitutes off-label use in the United States.
• •Pediatric dosing regimens are contained in Table 2-23.

Chemoprophylaxis during Pregnancy and Breastfeeding

• •Malaria infection in pregnant women can be more severe than in nonpregnant women. Malaria can increase the risk for adverse pregnancy outcomes, including prematurity, abortion, and stillbirth. For these reasons, and because no chemoprophylactic regimen is completely effective, women who are pregnant or likely to become pregnant should be advised to avoid travel to areas with malaria transmission if possible (see the Traveling while Pregnant section in Chapter 8). If travel to a malarious area cannot be deferred, use of an effective chemoprophylaxis regimen is essential.
• •Pregnant women traveling to areas where chloroquine-resistant P. falciparum has not been reported may take chloroquine prophylaxis. Chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for malaria prophylaxis; therefore, pregnancy is not a contraindication for malaria prophylaxis with chloroquine phosphate or hydroxychloroquine sulfate.
• •For travel to areas where chloroquine resistance is present, mefloquine is currently the only medication recommended for malaria chemoprophylaxis during pregnancy. A review of mefloquine use in pregnancy from clinical trials and reports of inadvertent use of mefloquine during pregnancy suggests that its use at prophylactic doses during the second and third trimesters of pregnancy is not associated with adverse fetal or pregnancy outcomes. More limited data suggest it is also safe to use during the first trimester.
• •Because of insufficient data regarding the use during pregnancy, atovaquone/proguanil is not currently recommended for the prevention of malaria in pregnant women.
• • Doxycycline is contraindicated for malaria prophylaxis during pregnancy because of the risk for adverse effects seen with tetracycline, a related drug, on the fetus, which include discoloration and dysplasia of the teeth and inhibition of bone growth.
• •Primaquine should not be used during pregnancy because the drug may be passed transplacentally to a G6PD-deficient fetus and cause hemolytic anemia in utero.
• •Health-care professionals who require additional assistance with the management of pregnant travelers who are unable to take mefloquine chemoprophylaxis should call the CDC Malaria Hotline (770-488-7788).
• •Very small amounts of antimalarial drugs are excreted in the breast milk of lactating women. Because the quantity of antimalarial drugs transferred in breast milk is insufficient to provide adequate protection against malaria, infants who require chemoprophylaxis must receive the recommended dosages of antimalarial drugs listed in Table 2-23.
• •Because chloroquine and mefloquine may be safely prescribed to infants, it is also safe for infants to be exposed to the small amounts excreted in breast milk.
• •Although data are very limited about the use of doxycycline in lactating women, most experts consider the theoretical possibility of adverse events to the infant to be remote.
• •Although no information is available on the amount of primaquine that enters human breast milk, the mother and infant should be tested for G6PD deficiency before primaquine is given to a woman who is breastfeeding.
• •Because data are not yet available on the safety of atovaquone/proguanil prophylaxis in infants weighing <5 kg (<11 lbs), CDC does not currently recommend it for the prevention of malaria in women breastfeeding infants weighing <5 kg. However, it can be used for treatment of women who are breastfeeding infants of any weight when the potential benefit outweighs the potential risk to the infant (e.g., treating a breastfeeding woman who has acquired P. falciparum malaria in an area of multidrug-resistant strains and who cannot tolerate other treatment options).

Changing Medications during Chemoprophylaxis as a Result of Side Effects

• •Medications recommended for prophylaxis against malaria have different modes of action that affect the parasites at different stages of the life cycle. Thus, if the medication needs to be changed because of side effects before a full course has been completed, there are some special considerations.
• •If a traveler starts prophylaxis with a medication such as mefloquine or doxycycline and then changes to atovaquone/proguanil during or after travel, the standard duration of prophylaxis for atovaquone/proguanil would be insufficient.
• •If the switch occurs 3 weeks or more before departure from the risk area, atovaquone/proguanil should be taken for the remainder of the stay in the risk area and for 1 week thereafter.
• •If the switch occurs <3 weeks before departure from the risk area, atovaquone/proguanil should be taken for 4 weeks after the switch.
• •If the switch occurs following departure from the risk area, atovaquone/proguanil should be continued until 4 weeks after the date of departure from the risk area.
• •Due to their pharmacokinetics, switching from a daily medicine such as doxycycline to a weekly medicine such as mefloquine should be avoided.
• •Health-care professionals who require additional assistance with the management of travelers who need to change medications during prophylaxis should call the CDC Malaria Hotline (770-488-7788).

MALARIA RISK INFORMATION AND PROPHYLAXIS, BY COUNTRY

Kathrine R. Tan, Sonja Mali, Paul M. Arguin

Table 2-24.

Malaria risk information and prophylaxis, by country¹

Country	Areas with Malaria	Drug Resistance2	Malaria Species3	Recommended Chemoprophylaxis4
Afghanistan	April–December in all areas at altitudes <2,000 m (<6,561 ft)	Chloroquine	P. vivax 80%–90% P. falciparum 10%–20%	Atovaquone/proguanil, doxycycline, or mefloquine
Albania	None	Not applicable	Not applicable	Not applicable
Algeria	None	Not applicable	Not applicable	Not applicable
Andorra	None	Not applicable	Not applicable	Not applicable
Angola	All	Chloroquine	P. falciparum 90% P. ovale 5% P. vivax 5%	Atovaquone/proguanil, doxycycline, or mefloquine
Anguilla (U.K.)	None	Not applicable	Not applicable	Not applicable
Antarctica	None	Not applicable	Not applicable	Not applicable
Antigua and Barbuda	None	Not applicable	Not applicable	Not applicable
Argentina	Rural areas of Salta and Jujuy provinces (along Bolivian border) and Misiones and Corrientes provinces (along border of Paraguay). Malaria present in Iguassu Falls	None	P. vivax 100%	Atovaquone/proguanil, chloroquine, doxycycline, mefloquine, or primaquine5
Armenia	Previously limited to the Ararat Valley in the Ararat and Artashat regions and Masis district. No cases reported since 2006	None	Historically P. vivax 100%	Mosquito avoidance only
Aruba	None	Not applicable	Not applicable	Not applicable
Australia, including Cocos (Keeling) Islands	None	Not applicable	Not applicable	Not applicable
Austria	None	Not applicable	Not applicable	Not applicable
Azerbaijan	Rural areas <1,500 m (4,921 ft). None in Baku	None	P. vivax 100%	Atovaquone/proguanil, chloroquine, doxycycline, mefloquine, or primaquine5
Azores (Portugal)	None	Not applicable	Not applicable	Not applicable
Bahamas, The	Present only in Great Exuma Island	None	P. falciparum 100%	Atovaquone/proguanil, chloroquine, doxycycline, or mefloquine
Bahrain	None	Not applicable	Not applicable	Not applicable
Bangladesh	All areas, except in city of Dhaka	Chloroquine	P. falciparum 77% P. vivax 23%	Atovaquone/proguanil, doxycycline, or mefloquine
Barbados	None	Not applicable	Not applicable	Not applicable
Belarus	None	Not applicable	Not applicable	Not applicable
Belgium	None	Not applicable	Not applicable	Not applicable
Belize	All areas, except in Belize City	None	P. vivax 95% P. falciparum 5%	Atovaquone/proguanil, chloroquine, doxycycline, mefloquine, or primaquine5
Benin	All	Chloroquine	P. falciparum 85% P. ovale 5%–10% P. vivax rare	Atovaquone/proguanil, doxycycline, or mefloquine
Bermuda (U.K.)	None	Not applicable	Not applicable	Not applicable
Bhutan	Rural areas <1,700 m (<5,577 ft) of the southern belt districts along the border with India: Chirang, Geylegphug, Samchi, Samdrup Jongkhar, Sarpang and Shemgang	Chloroquine	P. falciparum 50% P. vivax 50%	Atovaquone/proguanil, doxycycline, or mefloquine
Bolivia	All areas <2,500 m (<8,202 ft) in the following departments: Beni, Chuquisaca, Cochabamba, La Paz, Pando, Santa Cruz, and Tarija. None in city of La Paz	Chloroquine	P. vivax 70%-95% P. falciparum 5%-30%	Atovaquone/proguanil, doxycycline, or mefloquine
Bosnia and Herzegovina	None	Not applicable	Not applicable	Not applicable
Botswana	North of 22° S in the northern provinces of Central, Chobe, Ghanzi, and Ngamiland, including safaris to the Okavango Delta area. None in the city of Gaborone	Chloroquine	P. falciparum 90% P. vivax 5% P. ovale 5%	Atovaquone/proguanil, doxycycline, or mefloquine
Brazil	States of Acre, Rondônia, Amapá, Amazonas, Roraima, and Tocantins. Parts of states of Maranhaõ (western part), Mato Grosso (northern part), and Pará (except Belem City). Also present in urban areas, including large cities such as Porto Velho, Boa Vista, Macapa, Manaus, Santarem, and Maraba, where the transmission occurs on the periphery of these cities Malaria in Iguassu Falls	Chloroquine	P. vivax 75% P. falciparum 25%	Atovaquone/proguanil, doxycycline, or mefloquine
British Indian Ocean Territory, includes Diego Garcia (U.K.)	None	Not applicable	Not applicable	Not applicable
Brunei	None	Not applicable	Not applicable	Not applicable
Bulgaria	None	Not applicable	Not applicable	Not applicable
Burkina Faso	All	Chloroquine	P. falciparum 80% P. ovale 5%-10% P. vivax rare	Atovaquone/proguanil, doxycycline, or mefloquine
Burma (Myanmar)	Rural areas throughout the country at altitudes <1,000 m (<3,281 ft). None in cities of Rangoon (Yangon) and Mandalay	Chloroquine Mefloquine (see Map 2-9)	P. falciparum 80% P. vivax 20%	In the provinces of Bago, Kayah, Kachin, Kayin, Shan, and Tanintharyi: Atovaquone/proguanil or doxycycline All other areas: Atovaquone/proguanil, doxycycline, or mefloquine
Burundi	All	Chloroquine	P. falciparum >85% P. malariae, P. ovale, and P. vivax <15%	Atovaquone/proguanil, doxycycline, or mefloquine
Cambodia	Present throughout country, including the temple complex at Angkor Wat, except none in Phnom Penh and around Lake Tonle Sap	Chloroquine Mefloquine (see Map 2-9)	P. falciparum 86% P. vivax 12% P. malariae 2%	In the provinces of Preah Vihear, Siemreap, Oddar Meanchey, Banteay Meanchey, Battambang, Pailin, Kampot, Koh Kong, and Pursat bordering Thailand: Atovaquone/proguanil or doxycycline All other areas: Atovaquone/proguanil, doxycycline, or mefloquine
Cameroon	All	Chloroquine	P. falciparum 80% P. ovale 5%–10% P. vivax rare	Atovaquone/proguanil, doxycycline, or mefloquine
Canada	None	Not applicable	Not applicable	Not applicable
Canary Islands (Spain)	None	Not applicable	Not applicable	Not applicable
Cape Verde	Limited to Sao Tiago Island	Chloroquine	P. falciparum primarily	Atovaquone/proguanil, doxycycline, or mefloquine
Cayman Islands (U.K.)	None	Not applicable	Not applicable	Not applicable
Central African Republic	All	Chloroquine	P. falciparum 85% P. malariae, P. ovale, and P. vivax 15%	Atovaquone/proguanil, doxycycline, or mefloquine
Chad	All	Chloroquine	P. falciparum 85% P. malariae, P. ovale, and P. vivax 15%	Atovaquone/proguanil, doxycycline, or mefloquine
Chile	None	Not applicable	Not applicable	Not applicable
China	Rural parts of Anhui, Yunnan, Hainan provinces. Rare cases occur in other rural parts of the country <1,500m(<4,921 ft) during May-December. None in major river cruises and urban areas	Chloroguine (Vlefloguine (see Map 2-9)	P. falciparum primarily in Hainan and Yunnan. P. vivax primarily elsewhere	Along China-Burma border in the western part of Yunnan province: Atovaguone/proguanil or doxycycline Hainan and the other parts of Yunnan province: Atovaguone/proguanil, doxycycline or mefloguine Anhui province: Atovaguone/proguanil, chloroguine, doxycycline, or mefloguine All other areas with malaria transmission: Mosguito avoidance
Christmas Island (Australia)	None	Not applicable	Not applicable	Not applicable
Colombia	All rural areas at altitudes < 1,800 m (<5,906 ft). None in Bogota and Cartagena	Chloroguine	P. falciparum 50% P. vivax 50%	Atovaguone/proguanil, doxycycline, or mefloguine
Comoros	All	Chloroguine	P. falciparum primarily	Atovaguone/proguanil, doxycycline, or mefloguine
Congo, Republic of the (Congo-Brazzavi1le)	All	Chloroguine	P. falciparum primarily	Atovaguone/proguanil, doxycycline, or mefloguine
Cook Islands (New Zealand)	None	Not applicable	Not applicable	Not applicable
Costa Rica	Limon province, but not in Limon city (Puerto Limon). Rare cases in Puntarenas, Alajuela, Guanacaste, and Heredia provinces	None	P. vivax 90% P. falciparum 10%	Limon province: Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5 All other areas with malaria transmission: Mosguito avoidance
Côte d'Ivoire (Ivory Coast)	All	Chloroguine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloguine
Croatia	None	Not applicable	Not applicable	Not applicable
Cuba	None	Not applicable	Not applicable	Not applicable
Cyprus	None	Not applicable	Not applicable	Not applicable
Czech Republic	None	Not applicable	Not applicable	Not applicable
Democratic Republic of the Congo (Congo-Kinshasa)	All	Chloroguine	P. falciparum 90% P. ovale 5% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloguine
Denmark	None	Not applicable	Not applicable	Not applicable
Djibouti	All	Chloroguine	P. falciparum 90% P. vivax 5%-10%	Atovaguone/proguanil, doxycycline, or mefloguine
Dominica	None	Not applicable	Not applicable	Not applicable
Dominican Republic	All areas (including resort areas), except not present in the cities of Santo Domingo and Santiago	None	P. falciparum 100%	Atovaguone/proguanil, chloroguine, doxycycline, or mefloguine
Easter Island (Chile)	None	Not applicable	Not applicable	Not applicable
Ecuador, including the Galapagos Islands	All areas at altitudes <1,500m(<4,921 ft). Not present in the cities of Guayaguil, Quito, and the Galapagos Islands	Chloroguine	P. vivax 75% P. falciparum 25%	Atovaguone/proguanil, doxycycline, or mefloguine
Egypt	None	Not applicable	Not applicable	Not applicable
El Salvador	Rural areas of Santa Ana, Ahuachapãn, La Paz, and La Union departments	None	P. vivax 99% P. falciparum < 1 %	Atovaguone/proguanil, chloroguine, doxycycline, mefloguine or primaquine5
Equatorial Guinea	All	Chloroguine	P. falciparum 85% P. malariae, P. ovale, and P. vivax 15%	Atovaguone/proguanil, doxycycline, or mefloguine
Eritrea	All areas at altitudes <2,200m(<7,218ft). None in Asmara	Chloroguine	P. falciparum 85% P. vivax 10%-15% P. ovale rare	Atovaguone/proguanil, doxycycline, or mefloguine
Estonia	None	Not applicable	Not applicable	Not applicable
Ethiopia	All areas at altitudes <2,500m (<8,202 ft), except none in Addis Ababa	Chloroguine	P. falciparum 85% P vivax 10%-15% P. malariae and P. ovale <5%	Atovaguone/proguanil, doxycycline, or mefloguine
Falkland, South Georgia & South Sandwich Islands (U.K.)	None	Not applicable	Not applicable	Not applicable
Faroe Islands (Denmark)	None	Not applicable	Not applicable	Not applicable
Fiji	None	Not applicable	Not applicable	Not applicable
Finland	None	Not applicable	Not applicable	Not applicable
France	None	Not applicable	Not applicable	Not applicable
French Guiana	All areas, except none in city of Cayenne or Devil's Island (Ile du Diable)	Chloroguine	P. falciparum >50% P. vivax, <50%	Atovaguone/proguanil, doxycycline, or mefloguine
French Polynesia, includes the island groups of Society Islands (Tahiti, Moorea, and Bora-Bora), Marquesas Islands (Hiva Oa and Ua Huka), and Austral Islands (Tubuai and Rurutu)	None	Not applicable	Not applicable	Not applicable
Gabon	All	Chloroguine	P. falciparum 95% P. malariae, P. ovale, P. vivax 5%	Atovaguone/proguanil, doxycycline, or mefloguine
Gambia, The	All	Chloroguine	P. falciparum 85% P. malariae, P. ovale, P. vivax 15%	Atovaguone/proguanil, doxycycline, or mefloguine
Georgia	Present in the southeastern part of the country near the Azerbaijan border, mainly in the Kakheti and Kveno Kartli regions. None in Tblisi	None	P. vivax 100%	Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5
Germany	None	Not applicable	Not applicable	Not applicable
Ghana	All	Chloroguine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloguine
Gibraltar (U.K.)	None	Not applicable	Not applicable	Not applicable
Greece	None	Not applicable	Not applicable	Not applicable
Greenland (Denmark)	None	Not applicable	Not applicable	Not applicable
Grenada	None	Not applicable	Not applicable	Not applicable
Guadeloupe (France)	None	Not applicable	Not applicable	Not applicable
Guam (U.S.)	None	Not applicable	Not applicable	Not applicable
Guatemala	Rural areas only at altitudes < 1,500 m (<4,921ft). None in Guatemala City, Antigua or Lake Atitlán	None	P. vivax 97% P. falciparum 3%	Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5
Guinea	All	Chloroguine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Guinea-Bissau	All	Chloroguine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Guyana	All rural areas <900 m (<2,953 ft)	Chloroguine	P. falciparum 60% P. vivax 40% P. malariae < 1 %	Atovaguone/proguanil, doxycycline, or mefloquine
Haiti	All (including Port Labadee)	None	P. falciparum 100%	Atovaguone/proguanil, chloroguine, doxycycline, or mefloguine
Holy See	None	Not applicable	Not applicable	Not applicable
Honduras	Present throughout the country at altitudes <1000m(<3,281 ft) and in Roatãn and other Bay Island. None in Tegucigalpa and San Pedro Sula	None	P. vivax 50%-95% P. falciparum 5%-50%	Atovaguone/proguanil, chloroguine, doxycycline, or mefloquine
Hong Kong SAR (China)	None	Not applicable	Not applicable	Not applicable
Hungary	None	Not applicable	Not applicable	Not applicable
Iceland	None	Not applicable	Not applicable	Not applicable
India	All areas throughout country except no malaria in areas >2,000 m (>6,561 ft) in Himachal Pradesh, Jammu, Kashmir, and Sikkim. Present in cities of Delhi and Bombay (Mumbai)	Chloroguine	P. vivax 40% P. falciparum 20%-40% P. malariae and P. ovale 20%-40%	Atovaguone/proguanil, doxycycline, or mefloquine
Indonesia	Present in rural areas of Sumatra, Sulawesi, Kalimantan (Borneo) and Nusa Tenggara Barat (includes the island of Lombok) All areas of eastern Indonesia (provinces of Papua Indonesia, Irian Jaya Barat, Nusa Tenggara Timur, Maluku, and Maluku Utara) None in Jakarta, resort areas of Bali and the island of Java, except for the Menoreh Hills in central Java. None in urban areas in Sumatra, Kalimantan, Nusa Tenggara Barat and Sulawesi	Chloroguine	P. falciparum 66% P. vivax 34%	Atovaguone/proguanil, doxycycline, or mefloquine
Iran	Rural areas of Sistan-1 Baluchestan, the southern tropical part of Kerman, and Hormozgan province Ardebil and East Azerbijan provinces north of the Zagros mountains during March through November	Chloroguine	P. vivax 88% P. falciparum 11 %	Atovaguone/proguanil, doxycycline, or mefloquine
Iraq	Present in areas at altitudes < 1,500 m (<4,921 ft) in provinces of Duhok, Erbil, Ninawa, Sulaimaninya, and Ta'mim. None in Baghdad, Tikrit, and Ramadi	None	P. vivax 100%	Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5
Ireland	None	Not applicable	Not applicable	Not applicable
Israel	None	Not applicable	Not applicable	Not applicable
Italy	None	Not applicable	Not applicable	Not applicable
Jamaica	Rare local cases in Kingston	None	P. falciparum 100%	(Mosquito avoidance only)
Japan	None	Not applicable	Not applicable	Not applicable
Jordan	None	Not applicable	Not applicable	Not applicable
Kazakhstan	None	Not applicable	Not applicable	Not applicable
Kenya	Present in all areas (including game parks) at altitudes <2,500 m (<8,202 ft). None in Nairobi	Chloroguine	P. falciparum 85% P. vivax5%-10% P. ovale up to 5%	Atovaguone/proguanil, doxycycline, or mefloquine
Kiribati (formerly Gilbert Islands), includes Tarawa, Tabuaeran (Fanning Island), and Banaba (Ocean Island)	None	Not applicable	Not applicable	Not applicable
Korea, North	Present in southern provinces	None	Presumed to be P. vivax 100%	Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5
Korea, South	Limited to rural areas in the northern parts of Kyonggi and Kangwon provinces including the demilitarized zone (DMZ)	None	P. vivax 100%	Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5
Kosovo	None	Not applicable	Not applicable	Not applicable
Kuwait	None	Not applicable	Not applicable	Not applicable
Kyrgyzstan	Frequent border crossings between neighboring countries with malaria poses a small risk of malaria transmission in the southern and western parts of the country along the borders of Tajikistan and Uzbekistan No malaria transmission reported in Bishkek	None	P. vivax 99% P. falciparum rare imported cases	Mosquito avoidance only
Laos	All, except none in the city of Vientiane	Chloroquine (Vlefloquine (see Map 2-9)	P. falciparum 95% P. vivax 4% P. malariae and P. ovale 1%	Along the Laos-Burma border in the provinces of Bokéoand Louang Namtha and along the Laos-Thailand border in the province of Saravane and Champassack: Atovaquone/proguanil or doxycycline All other areas: Atovaquone/proguanil, doxycycline, or mefloquine
Latvia	None	Not applicable	Not applicable	Not applicable
Lebanon	None	Not applicable	Not applicable	Not applicable
Lesotho	None	Not applicable	Not applicable	Not applicable
Liberia	All	Chloroquine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaquone/proguanil, doxycycline, or mefloquine
Libya	None	Not applicable	Not applicable	Not applicable
Liechtenstein	None	Not applicable	Not applicable	Not applicable
Lithuania	None	Not applicable	Not applicable	Not applicable
Luxembourg	None	Not applicable	Not applicable	Not applicable
Macau SAR (China)	None	Not applicable	Not applicable	Not applicable
Macedonia	None	Not applicable	Not applicable	Not applicable
Madagascar	All	Chloroquine	P. falciparum 85% P. vivax 5%-10% P. ovale 5%	Atovaquone/proguanil, doxycycline, or mefloquine
Madeira Islands (Portugal)	None	Not applicable	Not applicable	Not applicable
Malawi	All	Chloroquine	P. falciparum 90% P. malariae, P. ovale, a nd P. vivax 10%	Atovaquone/proguanil, doxycycline, or mefloquine
Malaysia	Present in rural areas of Malaysian Borneo, and to a lesser extent in rural areas of peninsular Malaysia	Chloroquine	P. falciparum 40% P. vivax 50% IP ovale <1% P. knowlesi reported to cause some human infections here	Atovaquone/proguanil, doxycycline, or mefloquine
Maldives	None	Not applicable	Not applicable	Not applicable
Mali	All	Chloroquine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaquone/proguanil, doxycycline, or mefloquine
Malta	None	Not applicable	Not applicable	Not applicable
Marshall Islands	None	Not applicable	Not applicable	Not applicable
Martinique (France)	None	Not applicable	Not applicable	Not applicable
Mauritania	Present in southern provinces. None in Dakhlet-Nouadhibou, Inchiri, Adrar and Tiris-Zemmour regions	Chloroquine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaquone/proguanil, doxycycline, or mefloquine
Mauritius	None	Not applicable	Not applicable	Not applicable
Mayotte (French territorial collectivity)	All	Chloroquine	P. falciparum 40%-50% P. vivax 35%-40% P ovale <1%	Atovaquone/proguanil, doxycycline, or mefloquine
Mexico	Limited to areas infrequently visited by travelers, including small foci along the Guatemala and Belize borders in the states of Chiapas, Quintana Roo, and Tabasco; rural areas in the states of Nayarit, Oaxaca, and Sinaloa; and in an area between 24° N and 28° N latitude, and 106°W and 110°W longitude, which lies in parts of Sonora, Chihuahua, and Durango. No malaria along the United States-Mexico border and in the major resorts along the Pacific and Gulf coasts	None	P. vivax 99% P. falciparum 1 %	Atovaquone/proguanil, chloroquine, doxycycline, mefloquine, or primaquine5
Micronesia, Federated States of; includes Yap Islands, Pohnpei, Chuuk, and Kosrae	None	Not applicable	Not applicable	Not applicable
Moldova	None	Not applicable	Not applicable	Not applicable
Monaco	None	Not applicable	Not applicable	Not applicable
Mongolia	None	Not applicable	Not applicable	Not applicable
Montenegro	None	Not applicable	Not applicable	Not applicable
Montserrat (U.K.)	None	Not applicable	Not applicable	Not applicable
Morocco	None	Not applicable	Not applicable	Not applicable
Mozambique	All	Chloroguine	P. falciparum 95% P. malariae and P. ovale 5% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Namibia	Present in the provinces of Kunene, Ohangwena, Okavango, Omaheke, Omusati, Oshana. Oshikoto, Otjozondjupa, and the Caprivi Strip	Chloroguine	P. falciparum 90% P. malariae, P. ovale, and P. vivax 10%	Atovaguone/proguanil, doxycycline, or mefloquine
Nauru	None	Not applicable	Not applicable	Not applicable
Nepal	Present throughout country at altitudes <1,200m(<3,937ft). None in Kathmandu and on typical Himalayan treks	Chloroguine	P. vivax 88% P. falciparum 12%	Atovaguone/proguanil, doxycycline, or mefloquine
Netherlands	None	Not applicable	Not applicable	Not applicable
Netherlands Antilles (Bonaire, Curaçao, Saba, St. Eustasius, and St. Maarten)	None	Not applicable	Not applicable	Not applicable
New Caledonia (France)	None	Not applicable	Not applicable	Not applicable
New Zealand	None	Not applicable	Not applicable	Not applicable
Nicaragua	Present in rural areas. None in Managua	None	P. vivax 95% P. falciparum 5%	Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5
Niger	All	Chloroguine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Nigeria	All	Chloroguine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Niue (New Zealand)	None	Not applicable	Not applicable	Not applicable
Norfolk Island (Australia)	None	Not applicable	Not applicable	Not applicable
Northern Mariana Islands (U.S.), includes Saipan, Tinian, and Rota Island	None	Not applicable	Not applicable	Not applicable
Norway	None	Not applicable	Not applicable	Not applicable
Oman	None	Not applicable	Not applicable	Not applicable
Pakistan	All areas (including all cities) at altitudes <2,500 m (<8202 ft)	Chloroguine	P. falciparum 70% P. vivax 30%	Atovaguone/proguanil, doxycycline, or mefloquine
Palau	None	Not applicable	Not applicable	Not applicable
Panama	Present in rural areas of the provinces of Bocas Del Toro, Darién, Veragaus, San Blas and San Blas Islands. None in Panama City or in the former Canal Zone	Chloroguine	P. vivax 90%-95% P. falciparum 5%-10%	Bocas Del Toro: Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5 Darién, San Bias, and Veragaus provinces: Atovaguone/proguanil, doxycycline, mefloguine, or primaquine5
Papua New Guinea	Present throughout at altitudes < 1,800 m (<5,906 ft)	Chloroguine (both P. falciparum and P. vivax)	P. falciparum 65%-80% P. vivax 10%-30% P. malariae and P. ovale rare	Atovaguone/proguanil, doxycycline, or mefloquine
Paraguay	Present in the departments of Alto Parana, Caaguazu, and Canendiyu	None	P. vivax 95% P. falciparum 5%	Atovaguone/proguanil, chloroguine, doxycycline, mefloguine, or primaquine5
Peru	All departments <2000 m (6,561 ft) except none in Areguipa, (Vloguegua), Puno, and Tacna. Present in Puerto (Vlaldonado)	Chloroguine	P. vivax 70% P. falciparum 30% P. malariae < 1 %	Lima, coastal areas south of Lima, or the highland tourist areas (Cuzco, (Vlachu Picchu, and LakeTiticaca): (Mosquito avoidance only) Other areas: Atovaguone/proguanil, doxycycline, or mefloquine
Philippines	Present in rural areas <600 m (1,969 ft), on islands of Luzon, Palawan, and Mindanao. None in urban areas	Chloroguine	P. falciparum 70%-80% P. vivax 20%-30%	Atovaguone/proguanil, doxycycline, or mefloquine
Pitcairn Islands (U.K.)	None	Not applicable	Not applicable	Not applicable
Poland	None	Not applicable	Not applicable	Not applicable
Portugal	None	Not applicable	Not applicable	Not applicable
Puerto Rico (U.S.)	None	Not applicable	Not applicable	Not applicable
Qatar	None	Not applicable	Not applicable	Not applicable
Réunion (France)	None	Not applicable	Not applicable	Not applicable
Romania	None	Not applicable	Not applicable	Not applicable
Russia	Rare local cases by border with Azerbaijan	None	P. vivax 100%	By border with Azerbaijan: Mosguito avoidance only
Rwanda	All	Chloroguine	P. falciparum >85% P. vivax 5% P. ovale 5%	Atovaguone/proguanil, doxycycline, or mefloquine
Saint Barthélémy (France)	None	Not applicable	Not applicable	Not applicable
Saint Helena (U.K.)	None	Not applicable	Not applicable	Not applicable
Saint Kitts (Saint Christopher) and Nevis (U.K.)	None	Not applicable	Not applicable	Not applicable
Saint Lucia	None	Not applicable	Not applicable	Not applicable
Saint Martin (France)	None	Not applicable	Not applicable	Not applicable
Saint Pierre and Miquelon (France)	None	Not applicable	Not applicable	Not applicable
Saint Vincent and the Grenadines	None	Not applicable	Not applicable	Not applicable
Samoa (formerly Western Samoa)	None	Not applicable	Not applicable	Not applicable
Samoa, American (U.S.)	None	Not applicable	Not applicable	Not applicable
San Marino	None	Not applicable	Not applicable	Not applicable
São Tomé and Principé	All	Chloroguine	P. falciparum 85% P. malariae, P. ovale 5% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Saudi Arabia	Provinces of AI (Vladinah, Asir (excluding high-altitude areas >2,000 m), Jazan, and Mecca. None in cities of Jeddah, Mecca, Medina, Riyadh, and Ta'if	Chloroguine	P. falciparum predominantly P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Senegal	All	Chloroguine	P. falciparum >85% P. ovale 5%-10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Serbia	None	Not applicable	Not applicable	Not applicable
Seychelles	None	Not applicable	Not applicable	Not applicable
Sierra Leone	All	Chloroguine	P. falciparum 85% P. malariae, P. ovale, and P. vivax 5%	Atovaguone/proguanil, doxycycline, or mefloquine
Singapore	None	Not applicable	Not applicable	Not applicable
Slovakia	None	Not applicable	Not applicable	Not applicable
Slovenia	None	Not applicable	Not applicable	Not applicable
Solomon Islands	All	Chloroguine	P. falciparum 60% P. vivax 35%-40% P. ovale <1%	Atovaguone/proguanil, doxycycline, or mefloquine
Somalia	All	Chloroguine	P. falciparum 95% P. vivax, P. malariae, and P. ovale 5%	Atovaguone/proguanil, doxycycline, or mefloquine
South Africa	Present in the (Vlpumalanga Province, Limpopo (Northern) Province, and northeastern KwaZulu-Natal as far south as the Tugela River. Present in Kruger National Park	Chloroguine	P. falciparum 90% P. vivax 5% P. ovale 5%	Atovaguone/proguanil, doxycycline, or mefloquine
Spain	None	Not applicable	Not applicable	Not applicable
Sri Lanka	All areas, except none in the districts of Colombo, Galle, Gampaha, Kalutara, (Vlatara, and Nuvvara Eliya)	Chloroguine	P. vivax 88% P. falciparum 12%	Atovaguone/proguanil, doxycycline, or mefloquine
Sudan	All	Chloroguine	P. falciparum 90% P. malariae, P. vivax, and P. ovale 10%	Atovaguone/proguanil, doxycycline, or mefloquine
Suriname	All areas, except none in Paramaribo	Chloroguine	P. falciparum 70% P. vivax 15%-20%	Atovaguone/proguanil, doxycycline, or mefloquine
Swaziland	Present in the northern and eastern areas bordering (Vlozambigue and Zimbabwe, including all of Lubombo district)	Chloroguine	P. falciparum 90% P. vivax 5% P. ovale 5%	Atovaguone/proguanil, doxycycline, or mefloquine
Sweden	None	Not applicable	Not applicable	Not applicable
Switzerland	None	Not applicable	Not applicable	Not applicable
Syria	Rare cases in the northern border in El Hassaka province	None	P. vivax predominantly	(Mosquito avoidance only)
Taiwan	None	Not applicable	Not applicable	Not applicable
Tajikistan	All areas <2,000 m (6562 ft)	Chloroguine	P. vivax 90% P. falciparum 10%	Atovaguone/proguanil, doxycycline, mefloguine, or primaguine5
Tanzania	All areas at altitudes <1,800m(<5,906ft)	Chloroguine	P. falciparum >85% P. malariae, and P. ovale > 10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Thailand	Rural, forested areas that border Cambodia, Laos, and Myanmar (Burma). Rare local cases in Phang Nga and Phuket. None in cities and in major tourist resorts. None in cities of Bangkok, Chiang Mai, Chiang Rai, Pattaya, Koh Samui, and Koh Phangan	Chloroguine Mefloguine (see Map 2-9)	P. falciparum 50% (up to 75% some areas) P. vivax 50% (up to 60% some areas) P. ovale, rare	Phang Nga and Phuket: Mosguito avoidance only All other areas: Atovaguone/proguanil or doxycycline
Timor-Leste (East Timor)	All	Chloroguine	P. falciparum 50% P. vivax 50% P. ovale <1% P. malariae < 1 %	Atovaguone/proguanil, doxycycline, or mefloquine
Togo	All	Chloroguine	P. falciparum 85% P. ovale 5%-10% P. vivax rare	Atovaguone/proguanil, doxycycline, or mefloquine
Tokelau (NewZealand)	None	Not applicable	Not applicable	Not applicable
Tonga	None	Not applicable	Not applicable	Not applicable
Trinidad and Tobago	None	Not applicable	Not applicable	Not applicable
Tunisia	None	Not applicable	Not applicable	Not applicable
Turkey	Present by border with Syria. None on the Incerlik U.S. Air Force base and on typical cruise itineraries	None	P. v/Vaxand P. falciparum present	Atovaguone/proguanil, chloroguine, doxycycline, or mefloquine
Turkmenistan	Rare local cases by Afghanistan border	None	P. vivax 100%	Mosguito avoidance only
Turks and Caicos Islands (U.K.)	None	Not applicable	Not applicable	Not applicable
Tuvalu	None	Not applicable	Not applicable	Not applicable
Uganda	All	Chloroguine	P. falciparum >85% P. malariae, P. ovale, and P. vivax <15%	Atovaguone/proguanil, doxycycline, or mefloquine
Ukraine	None	Not applicable	Not applicable	Not applicable
United Arab Emirates	None	Not applicable	Not applicable	Not applicable
United Kingdom (with Channel Islands and Isle of Man)	None	Not applicable	Not applicable	Not applicable
United States	None	Not applicable	Not applicable	Not applicable
Uruguay	None	Not applicable	Not applicable	Not applicable
Uzbekistan	Rare cases along the Afghanistan and Tajikistan border	None	P vivax 100%	Mosguito avoidance only
Vanuatu	All	Chloroguine	P. falciparum 60% P. vivax 35%-40% P. ovale <1%	Atovaguone/proguanil, doxycycline, or mefloquine
Venezuela	Rural areas of the following states: Apure, Amazonas, Barinas, Bolivar, Sucre, Tachira, and Delta Amacuro. Present in Angel Falls. None in Margarita Island	Chloroguine	P. vivax 80%-90% P. falciparum 10%-20%	Atovaguone/proguanil, doxycycline, or mefloquine
Vietnam	Rural, forested areas, except none in the Red River delta and the coast north of Nha Trang. None in Can Tho, Da Nang, Haiphong, Hanoi, Ho Chi Minh City (Saigon), Hue, Nha Trang, and Qui Nhon	Chloroguine (Vlefloguine (see Map 2-9)	P. falciparum 50%-80% P. vivax 20%-50%	Southern part of the country in the provinces of Dae Lac, Gia Lai, Khan h Hoa, Kon Turn, Lam Dong, Ninh Thuan, Song Be, Tay Ninh: Atovaguone/proguanil or doxycycline All other areas: Atovaguone/proguanil, doxycycline, or mefloquine
Virgin Islands, British	None	Not applicable	Not applicable	Not applicable
Virgin Islands, U.S.	None	Not applicable	Not applicable	Not applicable
Western Sahara	Rare cases	None	Unknown	Mosguito avoidance only
Yemen	All areas at altitudes <2,000 m (<6,561 ft). None in Sana'a	Chloroguine	P. falciparum 95% P. malariae, P. vivax, and P. ovale 5%	Atovaguone/proguanil, doxycycline, or mefloquine
Zambia	All	Chloroguine	P. falciparum >90% P. vivax up to 5% P. ovale up to 5 %	Atovaguone/proguanil, doxycycline, or mefloquine
Zimbabwe	All	Chloroguine	P. falciparum >90% P. vivax up to 5% P. ovale up to 5 %	Atovaguone/proguanil, doxycycline, or mefloquine

¹The information presented herein was accurate at the time of publication; however, factors that can change rapidly and from year to year, such as local weather conditions, mosquito vector density, and prevalence of infection, can markedly affect local malaria transmission patterns. Updated information may be found on the CDC Travelers' Health website at www.cdc.gov/travel.

²Refers to P. falciparum malaria.

³Estimates of malaria species are based on best available data from multiple sources.

⁴Several medications are available for chemoprophylaxis. When deciding which drug to use, consider specific itinerary, length of trip, cost of drug, previous adverse reactions to antimalarials, drug allergies, and current medical history. All travelers should seek medical attention in the event of fever during or after return from travel to areas with malaria.

⁵Primaquine can cause hemolytic anemia in persons with G6PD deficiency. Patients must be tested and documented to have a normal level of G6PD activity prior to starting primaquine.

 

Self-Treatable Diseases

SELF-TREATABLE DISEASES

Alan J. Magill

Despite our best efforts at helping to prevent illness, travelers will often become ill while traveling. Obtaining reliable and timely medical care can be problematic in many destinations. As a result, prescribing certain medications in advance can empower the traveler to self-diagnose and treat common health problems. During an activity in a remote setting, such as trekking, the only alternative to self-treatment would be no treatment. In some developing countries, appropriate pre-travel counseling may result in a more accurate diagnosis and treatment than relying on local medical care. In addition, the increasing awareness of counterfeit drugs in pharmacies in the developing world (as many as 20%–30% of the drugs on the shelves) makes it more important for travelers to carry reliable drugs from their own country.

Providing education and prescriptions is part of the pre-travel consultation. The key aspect to this strategy is to recognize which travelers may be at risk and to educate them as to the diagnosis and treatment of the particular illness. The keys to successful self-treatment strategies are providing a simple disease definition, providing one choice of treatment, and educating the traveler about the expected outcome of treatment. Using travelers' diarrhea as an example, one could provide the following advice:

• •Travelers' diarrhea is defined as “the sudden onset of relatively uncomfortable diarrhea.”
• •The treatment is ciprofloxacin 500 mg every 12 hours for 1 day (two doses).
• •The traveler should feel better within 6 to 24 hours.

To minimize the potential negative effects of a self-treatment strategy, the recommendations should follow a few key points:

• •Drugs used must be safe, well tolerated, and effective for use as self-treatment.
• •A drug's toxicity or potential for harm, if used incorrectly or in an overdose situation, should be minimal.
• •Good directions are critical. Consider providing simple but clear handouts describing how to use the drugs. Keeping the directions simple will greatly increase the effectiveness of the strategy.

Following are some of the most common situations in which people would find self-treatment useful. The extent of self-treatment recommendations offered to the traveler should reflect the remoteness and difficulty of travel and the availability of reliable medical care at the particular destination. The recommended self-treatment options for each disease are provided in the designated section of the Yellow Book.

Travelers' diarrhea (TD) is perhaps most frequent indication for self-treatment. The success of this strategy is based on the epidemiologic evidence that bacterial pathogens account for more than 90% of TD in short-term travelers. The recognition of antibiotic resistance for certain organisms in specific destinations has made the empiric choice of treatment somewhat more problematic in recent times (see the Travelers' Diarrhea section next in this chapter).

Altitude illness or acute mountain sickness (AMS) is a risk for travelers who ascend rapidly to altitudes >8,000 ft (2,440 m). Certain common travel destinations, such as Cuzco, Peru, or Lhasa, Tibet, involve flying to altitudes of 11,300 ft (3,445 m) or 12,700 ft (3,870 m). The symptoms of headache, anorexia, nausea, fatigue, lassitude, and poor sleep can largely be prevented or treated with acetazolamide (see the Altitude Illness section later in this chapter).

Jet lag affects almost everyone who crosses three or more time zones. There is no consensus on the optimal pharmacologic treatment or prevention of the symptoms of jet lag, but sleeping medication taken at the destination may help regularize sleep patterns (see the Jet Lag section later in this chapter).

Motion sickness can be a major deterent to enjoyment for any susceptible person on a boat or a winding road. Premedication may help alleviate or ameliorate this bothersome syndrome (see the Motion Sickness section later in this chapter).

The self-treatment of suspected respiratory infections with empiric antibiotics is controversial. Almost all upper respiratory tract infections are initially caused by viruses. However, these viral infections, under the stress of travel, can lead to bacterial sinusitis, bronchitis or pneumonia. Respiratory infections that last longer than a week without signs of improvement may require empiric antibiotics for recovery. Prolonged respiratory infections may have more of a negative impact on a trip than diarrheal disease (see the Respiratory Infections section later in this chapter).

Bacterial skin infections are not common among travelers, but when they occur, they can be particularly distressing. Bacterial abscesses or cellulitis can worsen rapidly and be very painful. If the traveler is in a remote area or even more than a day's travel from medical care, the use of empiric antibiotic treatment can be extremely beneficial (see the Skin and Soft Tissue Infections in Returned Travelers section in Chapter 4).

Urinary tract infections are common among many women, and carrying an antibiotic for empiric treatment of this condition may be valuable in many circumstances.

Vaginal yeast infections in women can be a very annoying and debilitating problem. For women who know they are prone to infections, all sexually active women, and those who may be receiving antibiotics for other reasons, including doxycycline for antimalarial prophylaxis, a self-treatment course of their preferred antifungal medication can be prescribed.

Occupational/HIV needlestick is a particular risk to those participating in medical-related activities. Every year thousands of such individuals are now working in areas of sub-Saharan Africa, where the HIV prevalence may be higher than 15%–20%. A significant needlestick in this setting should prompt immediate wound care and the possible use of antiretroviral medications (see the Occupational Exposure to HIV section later in this chapter).

Malaria self-treatment is often referred to as stand-by emergency treatment (SBET). This strategy asks the traveler to use a therapeutic dose of an appropriate antimalarial drug when the traveler has a significant fever accompanied by systemic illness, and then proceed to reliable medical care within 24 hours. The goal is to prevent death or severe malaria. Since most travelers at risk of malaria should be advised to use prophylactic medication, this strategy is usually discouraged and reserved for a specific type of traveler under certain defined circumstances (see the Malaria section earlier in this chapter).

TRAVELERS' DIARRHEA

Bradley A. Connor

Description

Travelers' diarrhea (TD) is the most predictable travel-related illness. Attack rates range from 30% to 70% of travelers, depending on the destination. Traditionally, it was thought that TD could be prevented by following eating rules, but studies have found that people who follow the rules still get ill. Poor hygiene practice in local restaurants is likely the largest contributor to the risk for TD.

TD itself is a clinical syndrome that can result from a variety of intestinal pathogens. Bacterial pathogens are the predominant risk, thought to account for 80%–90% of TD. Intestinal viruses have been isolated in studies of TD, but they usually account for 5%–8% of illnesses. Protozoal pathogens are slower to manifest symptoms, and collectively account for about 10% of diagnoses in longer-term travelers. What is commonly known as “food poisoning” involves the ingestion of preformed toxins in food. In this syndrome, vomiting and diarrhea may both be present, but symptoms usually resolve spontaneously within 12 hours.

Infectious Agent

• •Bacteria are the most common cause of TD. The most common pathogen is enterotoxigenic Escherichia coli, followed by Campylobacter jejuni, Shigella sp., and Salmonella sp. Enteroadherent and other E. coli species have been found to also be common pathogens in bacterial diarrhea.
• •Viral diarrhea can be caused by a number of viral pathogens, including norovirus, rotavirus, and astrovirus.
• • Giardia is the main protozoal pathogen found in travelers. Entamoeba histolytica is a relatively uncommon pathogen in travelers. Cryptosporidium is also relatively uncommon. The risk for Cyclospora is highly geographic and seasonal, with the most well-known risks in Nepal, Peru, Haiti, and Guatemala. Dientamoeba fragilis is a low-grade but persisent pathogen that is occasionally diagnosed in travelers.
• •The individual pathogens are each discussed in their own sections in Chapter 5, and persistent diarrhea is discussed in Chapter 4.

Occurrence

• •The most important determinant of risk is travel destination, and there are regional differences in both the risk for and etiology of diarrhea.
• •
  The world is generally divided into three grades of risk: low, intermediate, and high.

  • ○
    Low-risk countries include the United States, Canada, Australia, New Zealand, Japan, and countries in Northern and Western Europe.
  • ○
    Intermediate-risk countries include those in Eastern Europe, South Africa, and some of the Caribbean islands.
  • ○
    High-risk areas include most of Asia, the Middle East, Africa, Mexico, and Central and South America.

Risk for Travelers

Travelers' diarrhea occurs equally in male and female travelers and is more common in young adults than in older people. In short-term travelers, bouts of TD do not appear to protect against future attacks, and more than one episode of TD may occur during a single trip. A cohort of expatriates taking up residence in Kathmandu, Nepal, experienced an average of 3.2 episodes of TD per person in their first year. In more temperate regions, there may be seasonal variations in diarrhea risk. In South Asia, for example, during the hot months preceding the monsoon, much higher TD attack rates are commonly reported.

In environments where large numbers of people do not have access to plumbing or outhouses, the amount of stool contamination in the environment will be higher and more accessible to flies. Inadequate electrical capacity may lead to frequent blackouts or poorly functioning refrigeration, which can result in unsafe food storage and an increased risk for disease. Inadequate water supplies can lead to the absence of sinks for handwashing by restaurant staff. Poor training in handling and preparation of food may lead to cross-contamination from meat and inadequate sterilization of food preparation surfaces and utensils. In destinations in which effective food handling courses have been provided, the risk for TD has been demonstrated to decrease. It should be noted, however, that pathogens that cause TD are not unique to developing countries. The risk of TD is associated with the hygiene practices in specific destinations and the handling and preparation of food in restaurants in developed countries as well.

Clinical Presentation

• •Bacterial diarrhea presents with the sudden onset of bothersome symptoms that can range from mild cramps and urgent loose stools, to severe abdominal pain, fever, vomiting, and bloody diarrhea.
• •Viral enteropathogens present in a similar fashion to bacterial pathogens, although with norovirus vomiting may be more prominent.
• •Protozoal diarrhea, such as that caused by Giardia intestinalis, or Entamoeba histolytica, generally has a more gradual onset of low-grade symptoms, with 2–5 loose stools per day.
• •
  The incubation period of the pathogens can be a clue to the etiology of TD.

  • ○
    Bacterial and viral pathogens have an incubation period of 6–48 hours.
  • ○
    Protozoal pathogens generally have an incubation period of 1–2 weeks and rarely present in the first few weeks of travel. An exception can be Cyclospora cayetanensis, which can present quickly in areas of high risk.
• •Untreated bacterial diarrhea lasts 3–5 days. Viral diarrhea lasts 2–3 days. Protozoal diarrhea can persist for weeks to months without treatment.
• •An acute bout of gastroenteritis can lead to persistent gastrointestinal symptoms, even in the absence of continued infection (see the Persistent Travelers' Diarrhea section in Chapter 4). Other postinfectious sequelae include reactive arthritis and Guillain–Barré syndrome.

Preventive Measures for Travelers

• •
  For travelers to high-risk areas, several approaches may be recommended that can reduce but never completely eliminate the risk for TD. These include—

  • ○
    Instruction regarding food and beverage selection
  • ○
    Use of agents other than antimicrobial drugs for prophylaxis
  • ○
    Use of prophylactic antibiotics
• •Carrying small containers of hand-sanitizing solutions or gels (containing at least 60% alcohol) may make it easier for travelers to clean their hands before eating.

Food and Beverage Selection

Care in selecting food and beverages for consumption might minimize the risk for acquiring TD. Travelers should be advised that foods that are freshly cooked and served piping hot are safer than foods that may have been sitting for some time in the kitchen or in a buffet. Care should be taken to avoid beverages diluted with nonpotable water (reconstituted fruit juices, ice, and milk) and foods washed in nonpotable water, such as salads. Other risky foods include raw or undercooked meat and seafood, and unpeeled raw fruits and vegetables. Safe beverages include those that are bottled and sealed, or carbonated. Boiled beverages and those appropriately treated with iodine or chlorine may also be safely consumed. Although food and water precautions continue to be recommended, travelers may not always be able to always adhere to the advice. Furthermore, many of the factors that ensure food safety, such as restaurant hygiene, are out of the traveler's control.

Nonantimicrobial Drugs for Prophylaxis

The primary agent studied for prevention of TD, other than antimicrobial drugs, is bismuth subsalicylate (BSS), which is the active ingredient in Pepto-Bismol. Studies from Mexico have shown this agent (taken daily as either 2 oz of liquid or two chewable tablets four times per day) reduces the incidence of TD from 40% to 14%. BSS commonly causes blackening of the tongue and stool and may cause nausea, constipation, and rarely tinnitus. BSS should be avoided by travelers with aspirin allergy, renal insufficiency, and gout, and by those taking anticoagulants, probenecid, or methotrexate. In travelers taking aspirin or salicylates for other reasons, the use of BSS may result in salicylate toxicity. Caution should be used in administering BSS to children with viral infections, such as varicella or influenza, because of the risk for Reye syndrome. BSS is not recommended for children <3 years of age. Studies have not established the safety of BSS use for periods >3 weeks.

The use of probiotics, such as Lactobacillus GG and Saccharomyces boulardii, has been studied in the prevention of TD in limited numbers of subjects. Results are inconclusive, partially because standardized preparations of these bacteria are not reliably available.

Prophylactic Antibiotics

Prophylactic antibiotics have been demonstrated to be quite effective in the prevention of TD. Controlled studies have shown that diarrhea attack rates are reduced from 40% to 4% by the use of antibiotics. The prophylactic antibiotic of choice has changed over the past few decades as resistance patterns have evolved. Agents such as trimethoprim-sulfamethoxazole and doxycycline are no longer considered effective antimicrobial agents against enteric bacterial pathogens. The fluoroquinolones have been the most effective antibiotics for the prophylaxis and treatment of bacterial TD pathogens, but increasing resistance to these agents, mainly among Campylobacter species, may limit their benefit in the future. A nonabsorbable antibiotic, rifaximin, is being investigated for its potential use in TD prophylaxis. In the only study published to date, rifaximin reduced the risk for TD in travelers to Mexico by 77%. At this time, prophylactic antibiotics should not be recommended for most travelers. In addition to affording no protection against nonbacterial pathogens, the use of antibiotics may be associated with allergic or adverse reactions in a certain percentage of travelers. The use of prophylactic antibiotics should be weighed against the result of using prompt, early self-treatment with antibiotics when TD occurs, which can limit the duration of illness to 6–24 hours in most cases.

Prophylactic antibiotics may be considered for short-term travelers who are high-risk hosts (such as those who are immunosuppressed) or are taking critical trips during which even a short bout of diarrhea could impact the purpose of the trip.

Treatment

Antibiotics are the principal element in the treatment of TD. Adjunctive agents used for symptomatic control may also be recommended.

Antibiotics

As bacterial causes of TD far outnumber other microbial etiologies, empiric treatment with an antibiotic directed at enteric bacterial pathogens remains the best therapy for TD. The benefit of treatment of TD with antibiotics has been proven in numerous studies. The effectiveness of a particular antimicrobial depends on the etiologic agent and its antibiotic sensitivity. Both as empiric therapy or for treatment of a specific bacterial pathogen, first-line antibiotics include those of the fluoroquinolone class, such as ciprofloxacin or levofloxacin. Increasing microbial resistance to the fluoroquinolones, especially among Campylobacter isolates, may limit their usefulness in some destinations such as Thailand, where Campylobacter is prevalent. Isolated anecdotal case reports of resistant Campylobacter diarrhea occur periodically from other destinations. An alternative to the fluoroquinolones in this situation is azithromycin. Rifaximin has been approved for the treatment of TD caused by noninvasive strains of E. coli. However, since it is often difficult for travelers to distinguish between invasive and noninvasive diarrhea and since they would have to carry a back-up drug in the event of invasive diarrhea, the overall usefulness of rifaximin as empiric self-treatment remains to be determined.

Single-dose or 1-day therapy for TD with a fluoroquinolone is well established, both by clinical trials and clinical experience. The best regimen for azithromycin treatment is not yet established. One study used a single dose of 1,000 mg, but side effects (mainly nausea) may limit the acceptability of this large dose. Azithromycin, 500 mg per day for 1–2 days, appears to be effective in most cases of TD.

Antimotility Agents

Antimotility agents provide symptomatic relief and serve as useful adjuncts to antibiotic therapy in TD. Synthetic opiates, such as loperamide and diphenoxylate, can reduce bowel movement frequency and enable travelers to ride on an airplane or bus while awaiting the effects of antibiotics. Loperamide appears to have antisecretory properties as well. The safety of loperamide when used along with an appropriate antibiotic has been well established, even in cases of invasive pathogens. Loperamide can be used in children, and liquid formulations are available. In practice, however, these drugs are rarely given to small children.

Oral Rehydration Therapy

Fluids and electrolytes are lost in cases of TD, and replenishment is important, especially in young children or adults with chronic medical illness. In adult travelers who are otherwise healthy, severe dehydration resulting from TD is unusual unless prolonged vomiting is present. Nonetheless, replacement of fluid losses remains an important adjunct to other therapy and helps the traveler feel better more quickly. Travelers should remember to use only beverages that are sealed or carbonated, or otherwise known to be purified. For more severe fluid loss, replacement is best accomplished with oral rehydration solutions (ORS), such as the WHO ORS solutions, which are widely available at stores and pharmacies in most developing countries (see Table 2-25 for details). ORS is prepared by adding one packet to the appropriate volume of boiled or treated water. Travelers may find most ORS formulations to be relatively unpalatable, due to their saltiness. In most cases, rehydration can be maintained with any palatable liquid.

Table 2-25.

Composition of WHO oral rehydration solution (ORS) for diarrheal illness

Ingredient	Amount	Measurement
Sodium chloride	3.5 g/L	½ tsp
Potassium chloride	1.5 g/L	1¼ tsp
Glucose	20.0 g/L	2 tbsp
Trisodium citrate (or sodium bicarbonate)	2.9 g/L (or 2.5 g/L)	½ tsp
Water	1,000 g	1 liter

Treatment of TD Caused by Protozoa

The most common parasitic cause of TD is Giardia intestinalis, and treatment options include metronidazole, tinidazole, and nitazoxanide. Although cryptosporidiosis is usually a self-limited illness in immunocompetent persons, nitazoxanide can be considered as a treatment option. Cyclosporiasis is treated with trimethoprim–sulfamethoxazole. Treatment of amebiasis is with metronidazole or tinidazole, followed by treatment with a luminal agent such as paromomycin.

Treatment for Children

Children who accompany their parents on trips to high-risk destinations may be expected to have TD as well. There is no reason to withhold antibiotics from children who contract TD. In older children and teenagers, treatment recommendations for TD follow those for adults, with possible adjustments in the dose of medication. Macrolides such as azithromycin are considered first-line antibiotic therapy in children, although some experts now use short-course fluoroquinolone therapy for travelers <18 years of age. Rifaximin is approved for use starting at 12 years of age.

Infants and younger children are at higher risk for developing dehydration from TD, which is best prevented by the early use of ORS solutions. Breastfed infants should continue to nurse on demand, and bottle-fed infants can continue to drink their formula. Older infants and children may eat a regular diet, depending on the level of their appetite while they are ill. Infants in diapers are at risk for developing a painful, ecxematous rash on their buttocks in response to the liquid stool. Hydrocortisone cream will quickly improve this rash. More information about diarrhea and dehydration are discussed in the Traveling Safely with Infants and Children section in Chapter 7.

PERSPECTIVES: GLOBAL IMPACT OF DIARRHEAL DISEASE

Sean W. Pawlowski, Richard L. Guerrant

Travelers frequently acquire the enteric pathogens that are present in food and water at their destinations and develop travelers' diarrhea. Mercifully, this is usually a nonfatal nuisance for travelers from developed nations, who, due to their well-nourished state, lack of other co-morbidities, antibiotic availability, and lack of repetitive infections, recover from their illness (more often than not) with few lasting effects.

In the short term, for those living in developing countries, infections due to enteric organisms are potentially life threatening, particularly in children and when combined with other illnesses, such as measles. Oral rehydration is the mainstay of treatment, but children suffering repeated, malnourishing illnesses at weaning require critical nutrient and micronutrient therapy as well.

While those traveling to aid in humanitarian efforts, including missionaries and volunteers, may feel they are well prepared to meet the challenges they face, many may not fully understand the profound impact that the lack of availability of clean water and sanitation has on indigenous populations. Travel health advisors, as well, should understand the serious implications and consequences of the global burden of these diarrheal illnesses as their occurrence is centered in the destinations of many U.S. travelers. Recent figures estimate 1.6 million deaths per year worldwide in children <5 years of age in these areas. Fortunately, this rate is dramatically down from 4.6 million per year (estimates from 1955 to 1979), in large part due to the implementation of oral rehydration therapy. However, the morbidity rates either have not fallen or have slightly increased. In addition, as the AIDS pandemic continues to spread, complications associated with endemic enteric pathogens will likely increase both mortality and morbidity.

More difficult to quantify is the global burden of repeated or persistent diarrheal illnesses. Unfortunately, these contribute significantly to the impairment of physical and cognitive development of children and to long-term disability, which ultimately result in substantial national economic losses.

ALTITUDE ILLNESS

Peter H. Hackett, David R. Shlim

Occurrence

The stresses of the high-altitude environment include cold, low humidity, increased ultraviolet (UV) radiation, and decreased air pressure, all of which can cause problems for travelers. The greatest concern, however, is hypoxia. At 10,000 ft (3,000 m), for example, the inspired PO₂ is only 69% of sea-level value. The degree of hypoxic stress depends upon altitude, rate of ascent, and duration of exposure. Sleeping at high altitude produces the greatest hypoxia; day trips to high altitude with return to low altitude are much less stressful on the body.

Acclimatization

The human body adjusts very well to moderate hypoxia, but requires time to do so (Box 2-3 ). The process of acute acclimatization to high altitude takes 3–5 days; therefore, acclimatizing for a few days at 8,000–9,000 ft before proceeding to higher altitude is ideal. Acclimatization prevents altitude illness, improves sleep, and increases comfort and well-being, although exercise performance will always be reduced compared with low altitude. Increase in ventilation is the most important factor in acute acclimatization; therefore, respiratory depressants must be avoided. Increased red-cell production does not play a role in acute acclimatization.

Box 2-3. Tips for acclimatization.

The following are helpful tips for people traveling to high altitude destinations.

• •Ascend gradually, if possible. Try not to go directly from low altitude to >9,000 ft (2,750 m) sleeping altitude in one day.
• •Consider using acetazolamide (Diamox) to speed acclimatization if abrupt ascent is unavoidable.
• •Avoid alcohol for the first 48 hours.
• •Participate in only mild exercise for the first 48 hours.
• •Having a high-altitude exposure at >9,000 ft (2,750 m), for 2 nights or more within 30 days prior to the trip is useful.
• •Treat an altitude headache with simple analgesics.

Risk for Travelers

Inadequate acclimatization may lead to altitude illness in any traveler going to 8,000 ft (2,500 m) or higher. Susceptibility and resistance to altitude illness are genetic traits, and no screening tests are available to predict risk. Risk is not affected by training or physical fitness. Children are equally susceptible as adults; persons >50 years of age have slightly lower risk. How a traveler has responded to high altitude previously is the most reliable guide for future trips but is not infallible. However, given certain baseline susceptibility, risk is greatly influenced by rate of ascent and exertion.

Determining an itinerary that will avoid any occurrence of altitude illness is difficult because of variations in individual susceptibility, as well as in starting points and terrain. Itineraries with a high risk for altitude illness include flying directly to >9,000 ft or rapid hiking ascents, such as climbing Mt. Kilimanjaro. It is best to average no more than 1,000 ft (300 m) ft per day in altitude gain above 12,000 ft (3,660 m).

Examples of high-altitude cities with airports are Cuzco, Peru (11,000 ft; 3,326 m); La Paz, Bolivia (12,000 ft; 3,660 m); and Lhasa, Tibet (12,500 ft; 3,810 m). Travelers flying into these locations may require a period of acclimatization before proceeding higher, and drug prophylaxis may be indicated.

Clinical Presentation

Altitude illness is divided into three syndromes:

• •Acute mountain sickness (AMS)
• •High-altitude cerebral edema (HACE)
• •High-altitude pulmonary edema (HAPE)

Acute Mountain Sickness (AMS)

AMS is the most common form of altitude illness, striking, for example, 25% of all visitors sleeping above 8,000 ft (2,500 m) in Colorado. Symptoms are those of an alcohol hangover: headache is the cardinal symptom, sometimes accompanied by fatigue, loss of appetite, nausea, and, occasionally, vomiting. Headache onset is usually 2–12 hours after arrival at a higher altitude, and often during or after the first night. Preverbal children may develop loss of appetite, irritability, and pallor. AMS generally resolves with 24–72 hours of acclimatization.

High-Altitude Cerebral Edema (HACE)

HACE is a severe progression of AMS and is rare; it is most often associated with pulmonary edema. In addition to AMS symptoms, lethargy becomes profound, with drowsiness, confusion, and ataxia on tandem gait test. A person with HACE requires immediate descent; death from HACE can ensue within 24 hours of developing ataxia if the person fails to descend.

High-Altitude Pulmonary Edema (HAPE)

HAPE can occur by itself or in conjunction with AMS and HACE; incidence is 1/10,000 skiers in Colorado and up to 1 of 100 climbers at >14,000 ft (4,270 m). Initial symptoms are increased breathlessness with exertion, and eventually increased breathlessness at rest, associated with weakness and cough. Oxygen or descent of 1,000 m or more is life-saving. HAPE can be more rapidly fatal than HACE.

Pre-Existing Medical Problems

• •Travelers with medical conditions, such as heart failure, myocardial ischemia (angina), sickle cell disease, or any form of pulmonary insufficiency, should be advised to consult a physician familiar with high-altitude medical issues before undertaking high-altitude travel.
• •The risk for new ischemic heart disease in previously healthy travelers does not appear to be increased at high altitudes.
• •Diabetics can travel safely to high altitude, but they must be accustomed to exercise and carefully monitor their blood glucose. Diabetic ketoacidosis may be triggered by altitude illness and may be more difficult to treat in those on acetazolamide. Not all glucose meters may read accurately at high altitudes.
• •Most people do not have visual problems at high altitude. However, at very high altitudes some persons who have had radial keratotomy may develop acute farsightedness and be unable to climb by themselves. LASIK and other newer procedures may produce only minor visual disturbances at high altitudes.
• •There are no studies or case reports of harm to a fetus if the mother travels briefly to high altitude during pregnancy. However, it may be prudent to recommend that pregnant women stay at sleeping altitudes of 12,000 ft (3,658 m) if possible. The dangers of having a pregnancy complication in remote, mountainous terrain should also be discussed.

Treatment

Acetazolamide

Acetazolamide (Diamox) prevents AMS when taken before ascent and can speed recovery if taken after symptoms have developed. The drug works by acidifying the blood, which causes an increase in respiration and thus aids acclimatization. An effective dose that minimizes the common side effects of increased urination and paresthesias of the fingers and toes is 125 mg every 12 hours, beginning the day before ascent and continuing the first 2 days at altitude, or longer if ascent continues. Allergic reactions to acetazolamide are uncommon, but the drug is related to sulfonamides and should not be used by sulfa-allergic persons with history of anaphylaxis. A trial dose taken in a safe environment before travel may be useful for those with a more mild allergic history to sulfonamides. People with history of severe penicillin allergy have occasionally had allergic reactions to acetazolamide.

Dexamethasone

Dexamethasone is very effective for prevention and treatment of AMS and HACE, and perhaps HAPE as well. Unlike acetazolamide, rebound can occur if the drug is discontinued at altitude prior to acclimatization. Acetazolamide is preferable to prevent AMS while ascending, with dexamethasone reserved for treatment during descent. Adult dosage is 4 mg every 6 hours.

HAPE is always associated with increased pulmonary artery pressure, and pulmonary vasodilators are useful for preventing and treating HAPE.

Nifedipine

Nifedipine prevents and ameliorates HAPE in persons who are particularly susceptible to the condition. The adult dosage is 20 mg of extended release every 8–12 hours. PDE-5 inhibitors can also selectively lower pulmonary artery pressure, with less effect on systemic blood pressure.

Other Medications

Tadalafil (Cialis), 10 mg twice a day, during ascent can prevent HAPE and is being studied for treatment. When taken before ascent, gingko biloba, 100–120 mg twice daily, was shown to reduce AMS in adults in some trials, but it was not effective in others, probably due to variation in ingredients. Gingko biloba has not yet been compared directly with acetazolamide.

Preventive Measures for Travelers

The main point of instructing travelers about altitude illness is not to prevent any possibility of altitude illness, but to prevent death from altitude illness. The onset of symptoms and clinical course is sufficiently slow and predictable that there is no reason for someone to die from altitude illness unless trapped by weather or geography in a situation in which descent is impossible. The three rules that travelers should be made aware of to prevent death from altitude illness are—

• • Know the early symptoms of altitude illness and be willing to acknowledge when they are present.
• •Never ascend to sleep at a higher altitude when experiencing symptoms of altitude illness, no matter how minor they seem.
• •Descend if the symptoms become worse while resting at the same altitude.

For trekking groups and expeditions going into remote high-altitude areas, where descent to a lower altitude could be problematic, a pressurization bag (such as the Gamow bag) can prove extremely beneficial. A foot pump produces an increased pressure of 2 lbs. per in², mimicking a descent of 5,000–6,000 ft (1,500–1,800 m), depending on the starting altitude. The total packed weight of bag and pump is 6.5 kg.

For most travelers, the best way to avoid altitude illness is by gradual ascent, with extra rest days at intermediate altitudes every 3,000 ft (900 m) or less. If ascent must be rapid, acetazolamide may be used prophylactically, and dexamethasone and pulmonary artery pressure-lowering drugs, such as nifedipine or sildenafil, may be carried for emergencies.

JET LAG

Emad Yanni

Description

Jet lag is a temporary disorder among air travelers who rapidly travel across three or more time zones. Jet lag results from the slow adjustment of the body clock to the destination time, so that daily rhythms and the internal drive for sleep and wakefulness are out of synchrony with the new environment.

The intrinsic body clock resides in the suprachiasmatic nuclei at the base of the hypothalamus, which contains melatonin receptors. The body clock receives information about light from the eyes and is also thought to receive input via the intergeniculate leaflet that carries information about physical activities and general excitement. Melatonin is manufactured in the pineal gland from tryptophan, and its synthesis and release are stimulated by darkness and suppressed by light; consequently, the secretion of melatonin is responsible for setting our sleep–wake cycle. The body clock is adjusted to the solar day by rhythmic cues in the environment known as zeitgebers (time-givers). The main zeitgebers are the light–dark cycle and this rhythmic secretion of melatonin. Exercise might also exert a weaker effect on the body clock than other zeitgebers. Although incompletely understood, the body clock is partly responsible for the daily rhythms in core temperature and plasma hormone concentrations as well.

Occurrence

• • Eastward travel is associated with difficulty in falling asleep at the destination bedtime and difficulty arising in the morning.
• •Westward travel is associated with early evening sleepiness and predawn awakening.
• •Travelers flying within the same time zone typically experience the fewest problems.
• •Crossing more time zones or traveling eastward generally increases the time required for adaptation.
• •Jet lag lasts for several days, roughly equal to two-thirds the number of time zones crossed for eastward flights, and about half the number of time zones crossed after westward flights.

Risk for Travelers

• •
  Individual responses to crossing time zones and the ability to adapt to new time zones vary. The intensity and duration of jet lag are related to the following:

  • ○
    Number of time zones crossed
  • ○
    Direction of travel
  • ○
    Ability to sleep while traveling
  • ○
    Availability and intensity of local circadian time cues at the destination
  • ○
    Individual differences in phase tolerance
• •
  Although more data are needed, risk factors cited by the American Academy of Sleep Medicine include the following:

  • ○
    Older individuals tend to experience fewer jet lag symptoms than those who are younger.
  • ○
    Exposure to local (natural) light–dark cycle usually accelerates adaptation after jet travel over 2 to 10 time zones

Clinical Presentation

Signs of jet lag include the following:

• •Poor sleep, including delayed sleep onset (after eastward flight), early awakening (after westward flight), and fractionated sleep (after flights in either direction).
• •Poor performance in both physical and mental tasks during the new daytime.
• •Negative subjective changes, such as increased fatigue, frequency of headaches and irritability, and decreased ability to concentrate.
• •Gastrointestinal disturbances (indigestion, frequency of defecation, and the altered consistency of stools) and decreased interest in and enjoyment of meals.

Preventive Measures for Travelers

Prior to Travel

• •Stay healthy by continuing to exercise, eating a nutritious diet, and getting plenty of rest.
• •Consider timed bright light exposure prior to and during travel (although it requires high motivation and strict compliance with the prescribed light–dark schedules).
• •Break up the journey with a stop-over.

Note: The use of the nutritional supplement melatonin is controversial for the prevention of jet lag. Some clinicians advocate the use of 0.5 mg to 5 mg of melatonin during the first few days of travel, and there are data to suggest its efficacy. However, the quality control of its production is not regulated by the U.S. Food and Drug Administration, and contaminants have been found in commercially available products.

Current information does not support the use of special diets to ameliorate jet lag.

During Travel

Travelers should be advised to—

• •Avoid large meals, alcohol, and caffeine.
• •Drink plenty of water.
• •Move around on the plane to promote mental and physical acuity.
• •Wear comfortable shoes and clothing.
• •Sleep, if possible, during long flights.

On Arrival at the Destination

Travelers should be advised to—

• •Avoid situations requiring critical decision-making, such as important meetings, on the first day after arrival.
• •Adapt to the local schedule as soon as possible. However, if the travel period is 2 days or less, travelers should remain on home time.
• •Optimize exposure to sunlight following arrival in either direction.
• •Eat meals appropriate to the local time.

Treatment

• •The 2008 American Academy of Sleep Medicine (AASD) recommendations include promoting sleep with hypnotic medication, although the effects of hypnotics on daytime symptoms of jet lag have not been well studied.
• •The prescription of nonaddictive sedative hypnotics (nonbenzodiazepines), such as zolpidem, has been shown in some studies to promote longer periods of high-quality sleep. If a benzodiazepine is preferred, a short-acting one, such as temazepam, is recommended to minimize oversedation the following day.
• •Because alcohol intake is often high during international travel, the risk for interaction with hypnotics should be emphasized with patients.

MOTION SICKNESS

I. Dale Carroll

Occurrence

Motion sickness is the result of a conflict between the various senses in regard to motion. The semicircular canals and otoliths in the inner ear sense angular and vertical motion, while the eyes and the proprioceptors determine the body's position in space. When signals received by the eyes or the proprioceptors do not match those being transmitted by the inner ear, motion sickness occurs. It can occur in either the presence or absence of actual motion, such as when viewing a slide through a microscope. Symptoms include nausea, vomiting, pallor, sweating, and often a sense of impending doom. Motion sickness is likely to occur when there is movement simultaneously in multiple planes, such as on amusement rides, on board ships, or during air travel.

Risk for Travelers

• •All individuals, given sufficient stimulus, will develop motion sickness.
• •Children 2–12 years of age are especially susceptible, while infants and toddlers seem relatively immune.
• •Women, especially when pregnant, menstruating, or on hormones, are more likely to have motion sickness.
• •Persons with migraine are more prone to either migraine or motion sickness at the same time as the other malady.
• •Those who expect to be sick are more apt to experience symptoms.

Treatment

There are both nonpharmacologic and pharmacologic interventions for the prevention or management of motion sickness. None are ideal, and the medications typically cause drowsiness or similar adverse effects. Some feel that permitting continued exposure to motions that induce motion sickness will decondition the response and diminish the symptoms; however, most persons traveling for a limited time will understandably not be willing to endure the symptoms in the hope of deconditioning and will instead want to avail themselves of some of the suggestions that follow or the medications listed in Table 2-26 .

Table 2-26.

Pharmacologic interventions for motion sickness (adult dosing)

Medication	Dose	Caution/Safety Information	Adverse Effects	Drug Interactions
Vitamin supplements Vitamin B6	Various
Pyridoxine-doxylamine (Example of brand: Diclectin)	Fixed combination available by Rx. in Canada. Sold separately in U.S.	More than 200,000 participants in controlled studies of nausea in pregnancy
Anticholinergic Scopolamine (Examples of brands: Scopace, Transderm-scop)	Patch: 1.5 mg q 3 days, apply behind ear at least 4 hrs before travel Oral: 0.4-0.8 mg q 8 hrs beginning 1 hr before travel	Contraindicated in narrow-angle glaucoma, urinary retention, Gl obstruction, myasthenia gravis. Wash hands after patch application to prevent transfer to eyes. Caution in hot environment or with thyroid, cardiopulmonary, GE reflux, liver, or kidney disease, seizure or psychotic disorder	Common: dry mouth/nose/throat, blurred vision, drowsiness Less common: palpitations, urinary retention, bloating, constipation, headache, confusion, hyperexcitability, insomnia, toxic psychosis	Additive effects with alcohol and other CNS depressants. Antacids impair absorption of oral scopolamine. May impair Gl motility when used with antidiarrheal drugs. May impair absorption of oral medications
Antihistamines Dimenhydrinate (Examples of brands: Calm X, Dramamine, Triptone)	Tablets 50 mg, syrup 12.5 mg/5 ml_. Take 30 min before travel. Adults 50-100 mg q 4-6 hours	Caution in glaucoma, urinary retention, GI obstruction, liver or kidney disease, chronic obstructive pulmonary disease (COPD), seizure disorder. Should not be used in children <2 yrs. Take with food or milk to reduce nausea.	Common: drowsiness, anticholinergic symptoms (dry mouth/nose/throat, blurred vision, urinary retention), thick respiratory secretions Less common: dizziness, weakness, hypotension or hypertension, cardiac arrhythmia, wheezing, sweating, nausea, vomiting, bloating, diarrhea, constipation, jaundice, anorexia, headache, confusion, tinnitus, paradoxical hyperexcitability, seizures, psychosis, acute dystonic reaction, paresthesias, photosensitivity, anaphylaxis	Additive effects with alcohol and other CNS depressants. Antihistamine effects may be potentiated by monamine oxidase inhibitors. Antacids may impair absorption.
Diphenhydramine (Brands: multiple)	Available in oral capsules and tablets (25 mg, 50 mg),	As above	As above	As above
Diphenhydramine	elixir (12.5 mg/5 mL). Adults 10-50 mg q 4-6 hours 12.5 mg, 25 mg, 50 mg
Meclizine (Brands: Antivert [Rx], Bonine [OTC], Dramamine II [OTC], Meclicot [Rx], Medivert [Rx])	Adult dose 25-50 mg q 24 hours	As above	As above	As above
Cyclizine (Brand: Marezine [OTC])	50 mg tablets. Adult dose 50 mg q 4-6 hrs	As above	As above	As above
Antidopaminergic Promethazine (Brands: Phenergan, Promacot)	Available in oral tablets (12.5 mg, 25 mg, 50 mg), syrup (6.25 mg/5 mL, 25 mg/5 mL), rectal suppositories, and intramuscular injection. Adults: 25 mg every 8-12 hrs 5 mg and 10 mg tablets	Caution in sulfite allergy (some formulations contain sulfite), cardiovascular disease, peptic ulcer disease	Pronounced sedation, postural hypotension, skin rash, body temperature dysregulation, extrapyramidal symptoms, delirium, neuroleptic malignant syndrome	May interact with other neurologic drugs
Metoclopramide (Brands: Reglan)	Adults: 10-15 mg q 6 hrs	Unproven benefit as antinausea agent with motion sickness, but may help by hastening gastric emptying	Sedation, insomnia, extrapyramidal symptoms	May decrease absorption of medications from stomach while increasing absorption from intestine. May necessitate change in insulin dose or timing in diabetics
Sympathomimetics Pseudoephedrine	Adults: 60 mg q 6 hours	Sometimes used to counteract sedating effect of other medications	Difficult urination, dry mouth, restlessness, headache
Benzodiazepines Diazepam (Brand: Valium)	2 mg, 5 mg and 10 mg tablets. Adult dose 2-10 mg q 6 hrs	Very sedating; perhaps of value when added to other medications
Other antiemetics Prochlorperazine (Brand: Compazine)	5 mg and 10 mg tablets. Adult dose 5-10 mg q 6 hrs	Effective against nausea but not specific for motion sickness.	May cause photosensitization, extrapyramidal symptoms
Ondansetron (Brand: Zofran)	4 mg and 8 mg tablets; Adult dose 4-8 mg q 8-12 hrs	Orally disintegrating tablets contain phenylalanine	Contraindicated with apomorphine. Effect may be decreased with some anticonvulsants (carbamazepine, phenytoin) and rifamycin (rifampin, rifabutin)

Medications

• •Antihistamines are the most commonly used and available medications, although nonsedating ones appear to be the least effective.
• •Pyridoxine hydrochloride (vitamin B₆) plus doxylamine succinate (an antihistamine) is prescribed under the brand name of Diclectin in Canada and often recommended in their separate forms by clinicians in the United States.
• •
  Sedation is the primary side effect of all the efficacious drugs.

  • ○
    Sedation is problematic when treating patients who perform essential tasks such as flying a plane or acting as crew on a ship, or in travelers who wish to participate in activities such as scuba diving or hang gliding.
• •Some common prescription medications used by travelers may aggravate the nausea of motion sickness (see Table 2-27 ).

Table 2-27.

Medications that may increase nausea

Medication Class	Examples
Antibiotics	Azithromycin, metronidazole, erythromycin, trimethoprim-sulfamethoxazole
Antiparasitics	Albendazole, thiabendazole, iodoquinol, chloroquine, mefloquine
Estrogens	Oral contraceptives, estradiol
Cardiovascular	Digoxin, levodopa
Narcotic analgesics	Codeine, morphine, meperidine
Nonsteroidal analgesics	Ibuprophen, naproxen, indomethacin
Antidepressants	Fluoxetine, paroxitene, sertraline
Asthma medication	Aminophylline
Bisphosphonates	Alendronate sodium, ibandronate sodium, risedronate sodium

Medications in Children

• •For symptomatic treatment of children 2–12 years of age, dimenhydrinate, 1–1.5 mg/kg per dose, or diphenhydramine, 0.5–1 mg/kg per dose up to 25 mg, can be given 1 hour before travel and every 6 hours during the trip.
• •Because some children have paradoxical agitation with these medicines, a test dose should be given at home before departure.
• •Scopalamine causes potentially dangerous adverse effects in children and should not be used; prochlorperazine and metoclopramide should be used with caution in children.
• •Antihistamines are not FDA approved for use for the prevention or treatment of motion sickness in children. Caregivers should be reminded to always ask a physician, pharmacist, or other health-care professional if they have any questions about how to use or dose antihistamines in children before they administer the medication. Oversedation of young children with antihistamines can lead to life-threatening side effects.

Medications in Pregnancy

• •Drugs with the most safety data regarding the treatment of the nausea of pregnancy would seem to be the logical first choice.
• •Letter scoring of the safety of medications in pregnancy may not be helpful, and practitioners should review the actual safety data or call the patient's obstetrical provider for suggestions.
• •Web-based information may be found at www.Motherisk.org and www.Reprotox.org.

Preventive Measures for Travelers

Nonpharmacologic interventions include—

• •Being aware of those situations which tend to trigger symptoms.
• • Optimizing positioning—Driving a vehicle instead of riding in it, as well as sitting in the front seat of a car or bus, sitting over the wing of an aircraft or being in the central cabin on a ship can help reduce symptoms.
• • Eating or drinking—Eating before the onset of symptoms may hasten gastric emptying, but in some individuals, can aggravate motion sickness. Drinking caffeinated beverages along with taking one of the medications suggested can help manage motion sickness.
• • Reducing sensory input—The reduction of aggravating stimuli (e.g., lying prone, looking at the horizon, or shutting eyes) can help alleviate symptoms.
• • Adding distractions—Aromatherapy using mint, lavender, or ginger (oral) helps some; flavored lozenges may help as well. They may function as placebos or, in the case of oral ginger, may hasten gastric emptying.
• • Using acupressure or magnets—Advocated by some to prevent or treat nausea (not specifically for motion sickness), although scientific data are lacking.

RESPIRATORY INFECTIONS

Regina C. LaRocque, Edward T. Ryan

Respiratory infections are an underappreciated risk for travel. Respiratory infection is a leading cause of seeking medical care in returning travelers and has been reported to occur in up to 20% of all travelers. Thus, respiratory infections may be almost as common as travelers' diarrhea. Upper respiratory infection is more common than lower respiratory infection. In general, the types of respiratory infections that affect travelers are similar to those in nontravelers, and exotic causes are rare. Travelers may be exposed to respiratory tract pathogens while in transit, while in close contact with other individuals, and while at their final destination.

Infectious Agent

• •Viral pathogens are the most common cause of respiratory infection in travelers; causative agents include coronavirus, adenovirus, rhinovirus, influenza virus, parainfluenza virus, human metapneumovirus, and respiratory syncytial virus.
• •Bacterial pathogens are less common but include Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, and Legionella species. Viral pathogens may set the stage for subsequent bacterial sinusitis or bronchitis.

Occurrence

• •Outbreaks are usually associated with common exposure in hotels and cruise ships or among tour groups.
• •A few specific pathogens have been associated with outbreaks in travelers, including influenza, Legionella pneumophila, severe acute respiratory syndrome (SARS), and histoplasmosis.
• •The peak influenza season in the temperate northern hemisphere is December through February. In the temperate southern hemisphere, the peak influenza season is June through August. Travelers to tropical zones are at risk year round.
• •Exposure to an infected individual from another hemisphere, such as on a cruise ship or package tour, can lead to an outbreak of influenza at any time or place.

Risk for Travelers

Factors contributing to respiratory infection in travelers include—

• •Air-pressure changes during ascent and descent of aircraft. These baropressure changes can facilitate the development of sinusitis and otitis media.
• •Intermingling of large numbers of people in airports, travel hubs, transport vehicles, cruise ships, and hotels can facilitate transmission.
• •Direct air-borne transmission of respiratory tract pathogens aboard aircraft is unusual because of frequent air recirculation and filtration, although sporadic cases of SARS, influenza, tuberculosis, and other agents have occurred in modern aircraft. Transmission of infection may occur between passengers who are seated in proximity to one another, usually through direct contact or droplets.
• •Air quality at many travel destinations may not be optimal, and exposure to sulfur dioxide, nitrogen dioxide, carbon monoxide, ozone, and particulate matter in air is associated with a number of health risks, including increased risk for respiratory tract inflammation, exacerbations of asthma and chronic obstructive pulmonary disease, and increased risks of bronchitis and pneumonia.
• •Certain epidemiologic characteristics of travelers that have been associated with a higher risk for respiratory tract infection include children, the elderly, and individuals with co-morbid pulmonary conditions, such as asthma and chronic obstructive pulmonary disease.
• •The risk for tuberculosis among travelers is very low (see the Tuberculosis section in Chapter 5).

Clinical Presentation

• •Most respiratory tract infections, especially those of the upper respiratory tract, are mild and not incapacitating.
• •Lower respiratory tract infections, particularly pneumonia, can be more severe.
• •Individuals with influenza commonly have acute onset of fever, myalgia, headache, and cough.
• •Travelers with a viral upper respiratory infection may have persistent symptoms and should consider the possibility of subsequent bacterial sinusitis or bronchitis with symptoms that worsen after one week.

Diagnosis

• •Identifying a specific etiologic agent, especially in the absence of pneumonia, is often difficult and not clinically necessary.
• •
  If indicated, the following methods of diagnosis can be used:

  • ○
    Molecular methods are available for the diagnosis of a number of respiratory viruses, including influenza virus, parainfluenza virus, adenovirus, human metapneumovirus, and respiratory syncytial virus, and for certain nonviral pathogens such as Legionella pneumophila.
  • ○
    Rapid tests are also available for detecting group A streptococcal pharyngitis.
  • ○
    Microbiologic culturing of sputum and blood, although insensitive, can assist in identifying a causative respiratory pathogen in persons with pneumonia.

Treatment

• •Affected travelers are usually managed similarly to nontravelers, although travelers with progressive or severe illness should be evaluated for illnesses specific to their travel destinations and exposure history.
• •Most respiratory infections of travelers are due to viruses, are mild, and do not require specific treatment or antibiotics. No systematic study of self-treatment of travelers with respiratory infections has been reported.
• •Self-treatment usually involves supportive measures and may include the use of analgesics, decongestants, increased fluid intake, and inhaled moisture.
• •Self-treatment with antibiotics can be considered for upper respiratory infections that are worsening after 7 days of symptoms, particularly if specific symptoms of sinusitis or bronchitis are present. A respiratory-spectrum fluoroquinolone such as levofloxacin or a macrolide such as azithromycin may be prescribed to the traveler for this purpose prior to travel.
• •The rate of influenza infection among travelers is not known. The difficulty in self-diagnosing influenza makes it problematic to decide whether to provide travelers with a self-treatment dose of a neuraminidase inhibitor. This practice should probably be limited to travelers with a specific underlying condition that may predispose them to severe influenza.

Medical Interventions

Specific situations that may require medical intervention include—

• •Pharyngitis without rhinorrhea, cough, or other symptoms that may indicate infection with group A streptococcus.
• •Sudden onset of cough, chest pain, and fever that may indicate pneumonia, resulting in a situation where the traveler may be sick enough to seek medical care right away.
• •Travelers with underlying medical conditions, such as asthma, pulmonary disease, or heart disease, who may need to seek medical care earlier than otherwise healthy travelers.

Preventive Measures for Travelers

• •Vaccines are available for the prevention of a number of respiratory tract pathogens, including influenza, S. pneumoniae, H. influenzae type B (in young children), pertussis, diphtheria, varicella, and measles. Unless contraindicated, travelers should be vaccinated against influenza.
• •
  The prevention of respiratory illness while traveling may not be possible, but common-sense preventive measures include—

  • ○
    Trying to minimize close contact with persons who are coughing and sneezing
  • ○
    Frequent handwashing, either with soap and water or alcohol-based hand sanitizers (containing at least 60% alcohol)
  • ○
    Using a vasoconstricting nasal spray immediately prior to air travel, if the traveler has a pre-existing eustachean tube dysfunction.

OCCUPATIONAL EXPOSURE TO HIV

Eli W. Warnock, III, L. Casey Chosewood

Risk for Health-Care Workers in International Locations

The safety practices and facility standards in health-care settings of developing countries may be less stringent than those in developed settings. The health-care resources and training of health-care workers in these settings may also be limited. These conditions have the potential to increase the risk for occupational HIV exposure to visiting health-care workers in developing countries. Lack of access to personal protective equipment may also increase risk.

Additionally, the prevalence of HIV infection in some developing countries is higher than that in the United States. Due to limited access to adequate treatment, infected source material in some developing countries may have higher viral loads than source material in the United States. Occupational exposure to source material with higher viral loads increases the risk for acquiring HIV occupationally.

Infectious Agent

Human immunodeficiency virus (HIV) is one of the pathogens, along with hepatitis C virus (HCV) and hepatitis B virus (HBV), that may be transmitted occupationally to health-care workers.

Mode of Transmission

Occupational transmission of HIV and transmission of other blood-borne pathogens typically occur via percutaneous exposure to contaminated sharps, including needles, lancets, scalpels, and broken glass. It can also occur when mucous membranes or nonintact skin comes into contact with infected blood or other body fluids.

Occurrence

• •The estimated annual number of health-care workers worldwide exposed to sharps injuries contaminated with HIV was 327,000 in 2005.
• • The risk of HIV infection following percutaneous exposure with a contaminated sharp is estimated to be 0.3%, or approximately 3 infections per 1,000 exposures.
• •Worldwide, the total number of HIV infections attributable to sharps injuries has been estimated to be 1,000 (range 200–5,000).
• •A 2005 study estimated that these infections would result in the worldwide premature deaths of 736 (range 129–3,578) health-care workers during the years 2000 to 2030.

Preventive Measures for Travelers

Health-care providers working internationally who will be engaging in high-risk occupational activities, such as drawing blood or the other use of sharps during patient care, should—

• •Consistently follow standard precautions to reduce the risk of occupational exposure to HIV and other blood-borne pathogens. Standard precautions involve the use of protective barriers such as gloves, gowns, aprons, masks, or protective eyewear, which can reduce the risk of exposure of the health-care worker's skin or mucous membranes to potentially infective materials. Additional information about occupational health and safety standards for blood-borne pathogens can be found on the Occupational Safety and Health Administration (OSHA) website at www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10051.
• •Always be mindful of the hazards posed by sharps injuries.
• •Maintain strict safety standards while working in environments that may have less stringent standards.
• •Use devices with safety features and improved work practices as recommended by the National Institute for Occupational Safety and Health (NIOSH) to prevent injuries caused by needles, scalpels, and other sharp instruments or devices. Additional information about preventing needlestick injuries in health-care settings can be found on the NIOSH website: www.cdc.gov/niosh/2000-108.html#8.
• •Consider bringing their own protective equipment if they are unsure of its availability at their destination.
• •Consider bringing postexposure prophylaxis (PEP) for HIV with them for use in the event that they experience a sharps injury with a contaminated or potentially contaminated needle.

Postexposure Management

Health-care providers who have been occupationally exposed to HIV or have been exposed to potentially infectious material from a source person who is likely to be infected with HIV should immediately—

• •Wash the exposed area with soap and water thoroughly. If mucous membrane exposure has occurred, flush the area with copious amounts of water or saline.
• •Seek qualified medical evaluation as soon as possible to guide decisions on postexposure treatment and testing.
• •Contact the National Clinicians' Postexposure Prophylaxis Hotline (PEPline) at 1-888-448-4911 (24 hours/7 days a week) for assistance in assessing risk and advice on managing occupational exposures to HIV, hepatitis, and other blood-borne pathogens. Additional information about PEPline can be found on the National HIV/AIDS Clinicians' Consultation Center website at www.ucsf.edu/hivcntr/Hotlines/PEPline.html.
• •Consider beginning postexposure prophylaxis (PEP) for HIV.

Postexposure Prophylaxis

• •A number of medication combinations are available for PEP.
• • Refer to MMWR's Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HIV, Recommendations for Postexposure Prophylaxis, Updated Information Regarding Antiretroviral Agents Used as HIV Postexposure Prophylaxis for Occupational HIV Exposures (www.aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=10&ClassID=3) and the PEPline for more information about PEP recommendations.
• •Specific regimens should be individually determined for those travelers at risk by health-care providers familiar with the medications and the traveler's medical history.
• •If the exposed person chooses to initiate PEP, they must do so within hours, as delays lead to a significant decline in PEP effectiveness.
• •If indicated, arrange for procurement or shipment of additional postexposure prophylaxis from a credible source to complete the recommended 4-week course of treatment.
• •Consider other potential infectious disease exposures from the source material as well, to include HBV or HCV, and manage if appropriate.

Postexposure Testing

• •Persons with occupational exposure to HIV should receive baseline postexposure HIV-antibody testing by enzyme immunoassay, postexposure counseling, and medical evaluation, whether or not they receive PEP. In addition to baseline HIV-antibody testing, persons occupationally exposed should receive follow-up HIV-antibody testing by enzyme immunoassay for 6 months following exposure, at 6 weeks, 12 weeks, and 6 months (aidsinfo.nih.gov/contentfiles/HealthCareOccupExpoGL.pdf).
• •The U.S. Public Health Service also recommends that health-care workers occupationally exposed to a source co-infected with HIV and HCV and who acquire HCV infection receive extended HIV postexposure surveillance for up to 12 months following exposure.
• •Exposed health-care providers should be advised to use precautions (e.g., avoid blood or tissue donations, breastfeeding, or pregnancy) to prevent secondary transmission, especially during the first 6–12 weeks postexposure.
• •
  For exposures for which PEP is prescribed, health-care providers should be informed about—

  • ○
    possible drug toxicities and the need for monitoring
  • ○
    possible drug interactions
  • ○
    the need for adherence to PEP regimens
• •Consider re-evaluation of exposed health-care providers, if possible, 72 hours postexposure, especially after additional information about the exposure or source person becomes available and when adverse events of any medication can be assessed.

 

Counseling and Advice for Travelers

PROTECTION AGAINST MOSQUITOES, TICKS, AND OTHER INSECTS AND ARTHROPODS

Emily Zielinski-Gutierrez, Robert A. Wirtz, Roger S. Nasci

Although vaccines or chemoprophylactic drugs are available to protect against some important vector-borne diseases such as yellow fever and malaria, travelers still should be advised to use repellents and other general protective measures against biting arthropods. The effectiveness of malaria chemoprophylaxis is variable, depending on patterns of drug resistance, bio-availability, and compliance with medication, and no similar preventive measures exist for other mosquito-borne diseases such as dengue or chikungunya.

CDC recommends the use of products containing active ingredients that have been registered by the U.S. Environmental Protection Agency (EPA) for use as repellents applied to skin and clothing (see below). EPA registration of active ingredients indicates the materials have been reviewed and approved for efficacy and human safety when applied according to the instructions on the label.

General Protective Measures

• • Avoid outbreaks: To the extent possible, travelers should avoid known foci of epidemic disease transmission. The CDC Travelers' Health webpage provides alerts and information on regional disease transmission patterns and outbreak alerts (www.cdc.gov/travel).
• • Be aware of peak exposure times and places: Exposure to arthropod bites may be reduced if travelers modify their patterns of activity or behavior. Although mosquitoes may bite at any time of day, peak biting activity for vectors of some diseases (e.g., dengue, chikungunya) is during daylight hours. Vectors of other diseases (e.g., malaria) are most active in twilight periods (i.e., dawn and dusk) or in the evening after dark. Avoiding the outdoors or focusing preventive actions during peak hours may reduce risk. Place also matters; ticks are often found in grasses and other vegetated areas. Local health officials or guides may be able to point out areas with greater arthropod activity.
• • Wear appropriate clothing: Travelers can minimize areas of exposed skin by wearing long-sleeved shirts, long pants, boots, and hats. Tucking in shirts and wearing socks and closed shoes instead of sandals may reduce risk. Repellents or insecticides such as permethrin can be applied to clothing and gear for added protection; this measure is discussed in detail below.
• • Check for ticks: Travelers should be advised to inspect themselves and their clothing for ticks during outdoor activity and at the end of the day. Prompt removal of attached ticks can prevent some infections.
• • Bed nets: When accommodations are not adequately screened or air conditioned, bed nets are essential to provide protection and to reduce discomfort caused by biting insects. If bed nets do not reach the floor, they should be tucked under mattresses. Bed nets are most effective when they are treated with an insecticide or repellent such as permethrin. Pretreated, long-lasting bed nets can be purchased prior to traveling, or nets can be treated after purchase. The permethrin will be effective for several months if the bed net is not washed. (Long-lasting pretreated nets may be effective for much longer.)
• • Insecticides: Aerosol insecticides, vaporizing mats and mosquito coils can help to clear rooms or areas of mosquitoes; however, some products available internationally may contain pesticides that are not registered in the United States. Insecticides should always be used with caution, avoiding direct inhalation of spray or smoke.

Optimum protection can be provided by applying the repellents described in the following sections to clothing and to exposed skin.

Repellents for Use on Skin and Clothing

CDC has evaluated information published in peer-reviewed scientific literature and data available from EPA to identify several EPA-registered products that provide repellent activity sufficient to help people avoid the bites of disease-carrying mosquitoes. Products containing the following active ingredients typically provide reasonably long-lasting protection:

• • DEET (chemical name: N,N-diethyl-m-toluamide or N,N-diethly-3-methyl-benzamide). Products containing DEET include but are not limited to Off!, Cutter, Sawyer, and Ultrathon.
• • Picaridin (KBR 3023, aka Bayrepel, and icaridin outside the United States; chemical name 2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester). Products containing picaridin include but are not limited to Cutter Advanced, Skin So Soft Bug Guard Plus and Autan (outside the United States).
• • Oil of lemon eucalyptus * or PMD (chemical name: para-menthane-3,8-diol) the synthesized version of oil of lemon eucalyptus. Products containing OLE and PMD include but are not limited to Repel.
• • IR3535 (chemical name: 3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester) Products containing IR3535 include but are not limited to Skin so Soft Bug Guard Plus Expedition.

EPA characterizes the active ingredients DEET and picaridin as “conventional repellents” and oil of lemon eucalyptus, PMD, and IR3535 as “biopesticide repellents,” which are derived from natural materials.

Repellent Efficacy

• •Published data indicate that repellent efficacy and duration of protection vary considerably among products and among mosquito species.
• •Product efficacy and duration of protection are also markedly affected by ambient temperature, amount of perspiration, exposure to water, abrasive removal, and other factors.
• •In general, higher concentrations of active ingredient provide longer duration of protection, regardless of the active ingredient. Products with £10% active ingredient may offer only limited protection, often from 1–2 hours.
• •Products that offer sustained release or controlled release (i.e., micro-encapsulated) formulations, even with lower active ingredient concentrations, may provide longer protection times.
• •Studies suggest that concentrations of DEET above ∼50% do not offer a marked increase in protection time against mosquitoes (i.e., DEET efficacy tends to plateau at around 50%).
• •Regardless of what product is used, if travelers start to get mosquito bites they should reapply the repellent according to the label instructions or leave the area with biting insects if possible.

Repellents should be purchased before traveling and can be found in hardware stores, drug stores and supermarkets. A wider variety of repellents can be found in camping, sporting goods, and military surplus stores. When purchasing repellents overseas, look for the EPA-registered active ingredients on the product labels; some names of products available internationally have been specified above.

Repellents and Sunscreen

Repellents that are applied according to label instructions may be used with sunscreen with no reduction in repellent activity. Products that combine sunscreen and repellent are not recommended, because sunscreen may need to be reapplied with greater frequency and in greater amounts than are needed to provide protection from biting insects. In general, the recommendation is to apply sunscreen first, before applying the repellent.

Repellents/Insecticides for Use On Clothing

• • Clothing, shoes, bed nets, mesh jackets, and camping gear can be treated with permethrin for added protection.
• •Products such as Permanone and Sawyer permethrin are registered with EPA specifically for this use.
• •Permethrin is a highly effective insecticide and repellent. Permethrin-treated clothing repels and kills ticks, mosquitoes, and other arthropods. Clothing and other items must be treated several days in advance of travel to allow them to dry. As with all pesticides, follow the label instructions when using permethrin clothing treatments. Alternatively, clothing pretreated with permethrin is commercially available (e.g., products from Buzz Off/Insect Shield).
• •Permethrin-treated materials retain repellency/insecticidal activity after repeated laundering but should be retreated as described on the product label to provide continued protection. Clothing treated with the other repellent products described above (e.g., DEET) provides protection from biting arthropods but will not last through washing and will require more frequent reapplications.

Precautions when Using Insect Repellents

• • Apply repellents only to exposed skin and/or clothing, as directed on the product label. Do not use repellents under clothing.
• •Never use repellents over cuts, wounds or irritated skin.
• •Do not apply repellents to eyes or mouth, and apply sparingly around ears. When using sprays, do not spray directly on face-spray on hands first and then apply to face. Wash hands after application to avoid accidental exposure to eyes.
• •Do not allow children to handle repellents. When using on children, adults should apply repellents to their hands first, and then put it on the child. It may be advisable to avoid applying to children's hands.
• •Use just enough repellent to cover exposed skin and/or clothing. Heavy application and saturation are generally unnecessary for effectiveness. If biting insects do not respond to a thin film of repellent, apply a bit more.
• •After returning indoors, wash treated skin with soap and water or bathe. This is particularly important when repellents are used repeatedly in a day or on consecutive days. Also, wash treated clothing before wearing it again. (This precaution may vary with different repellents—check the product label.)
• •If anyone experiences a rash or other bad reaction from an insect repellent, the repellent use should be discontinued, the repellent should be washed off with mild soap and water, and a local poison control center should be called for further guidance. If seeking health care because of the repellent, take the repellent to the doctor's office and show the doctor.
• •Permethrin should never be applied to skin, but only to clothing, bed nets, or other fabrics as directed on the product label.

Children

• •Most repellents can be used on children >2 months of age.
• •Protect infants <2 months of age from biting mosquitoes by using an infant carrier draped with mosquito netting with an elastic edge for a tight fit.
• •Products containing oil of lemon eucalyptus specify that they should not be used on children <3 years of age.
• •Other than the safety tips listed above, EPA does not recommend any additional precautions for using registered repellents on children or on pregnant or lactating women.

Useful Links

• •U.S. Environmental Protection Agency. How to Use Insect Repellents Safely; [updated 2007 July 5; cited 2008 Nov 29]. Available from: www.epa.gov/pesticides/health/mosquitoes/insectrp.htm.
• •Centers for Disease Control and Prevention. Insect Repellent Use and Safety; [updated 2008 May 14; cited 2008 Nov 29]. Available from: www.cdc.gov/ncidod/dvbid/westnile/qa/insect_repellent.htm.
• •Health Canada's Pest Management Regulatory Agency. Safety Tips on Using Personal Insect Repellents; [updated 2004 September 17; cited 2008 Nov 29]. Available from: www.pmra-arla.gc.ca/english/consum/insectrepellents-e.html.

WATER DISINFECTION FOR TRAVELERS

Howard D. Backer

Risk for Travelers

Waterborne disease is a risk for international travelers who visit countries that have poor hygiene and inadequate sanitation, and for wilderness users relying on surface water in any country, including the United States. Worldwide, more than one billion people have no access to potable water and 2.4 billion do not have adequate sanitation. In developing countries, the influence of high-density population and rampant pollution, along with absent, overwhelmed, or insufficient sanitation and water treatment systems, means that surface water may be highly polluted with human waste and even urban tap water may become contaminated. Primarily humans, but also animals, are the source of microorganisms that contaminate water sources and cause intestinal infections.

The list of potential waterborne pathogens is extensive and includes bacteria, viruses, protozoa, and parasitic helminths. Most of the organisms that can cause travelers' diarrhea can be waterborne, although the majority of travelers' intestinal infections are probably transmitted by food. Microorganisms with small infectious doses can even cause illness through recreational water exposure, via inadvertent water ingestion.

Bottled water has become the convenient solution for most travelers, but in some places, it may not be superior to tap water. Moreover, the plastic bottles create a huge ecological problem, since most developing countries do not recycle plastic bottles. All international travelers, especially long-term travelers or expatriates, should become familiar with and utilize simple methods to ensure safe drinking water. Disinfection, the desired result of field water treatment, means the removal or destruction of harmful microorganisms. The goal of disinfection is to reduce the risk of gastrointestinal infection and diarrheal illness. Table 2-28 compares benefits and limitations of different methods.

Table 2-28.

Comparison of water disinfection techniques

Technique	Advantages	Disadvantages
Heat	• Does not impart additional taste or color • Single step that inactivates all enteric pathogens • Efficacy is not compromised by contaminants or particles in the water as for halogenation and filtratino	• Does not improve taste, smell or appearance of poor quality water • Fuel sources may be scarce, expensive or unavailable • Does not prevent recontamination during storage
Filtration	• Simple to operate • Requires no holding time for treatment • Large choice of commercial products • Adds no unpleasant taste and often improves taste and appearance of water • Rationally combined with halogens for removal or destruction of all pathogenic waterborne microbes	• Adds bulk and weight to baggage • Many are not reliable for removal of viruses • Channeling of water or high pressure can force microorganisms through the filter • Relatively expensive, compared to chemical treatment • Eventually clogs from suspended particulate matter and may require some maintenance or repair in the field
Halogens	• Inexpensive and widely available in liquid or tablet forms • Taste can be removed by several techniques • Flexible dosing • Equally easy to treat large and small volumes	• Corrosive and stains clothing • Imparts taste and odor to water • Flexibility requires understanding of principles • Iodine is physiologically active, with potential adverse effects • Not readily effective against Cryptosporidium oocysts • Efficacy decreases with low water temperature and decreasing water clarity
Chlorine Dioxide	• Low doses have no taste or color • Simple to use and available in liquid or tablet form • More potent than equivalent doses of chlorine • Effective against all waterborne pathogens	• Volatile and sensitive to sunlight: do not expose tablets to air and use generated solutions rapidly • No persistent residual, so does not prevent recontamination during storage
Ultraviolet	• Imparts no taste • Portable devices now available • Effective against all waterborne pathogens	• Requires clear water • Does not improve taste or appearance of water • Relatively expensive • Requires batteries or power source • Difficult to know if devices are delivering required UV doses

Field Techniques for Water Treatment

Heat

Common intestinal pathogens are readily inactivated by heat. Microorganisms are killed in a shorter time at higher temperatures, whereas temperatures as low as 140° F (60° C) are effective with a longer contact time. Pasteurization uses this principle to kill food-borne enteric pathogens and spoiling organisms at temperatures between 140° F (60° C) and 158° F (70° C), well below the boiling point of water (212° F; 100° C).

Although attaining boiling temperature is not necessary for inactivation of common intestinal pathogens, it is the only easily recognizable endpoint without using a thermometer. Microorganisms begin to die as water is heated on a stove or fire from 150° F (65° C) to boiling. All organisms except bacterial spores, which are not usually waterborne enteric pathogens, are killed within seconds at boiling temperature. Therefore, any water brought to a boil should be adequately disinfected. CDC and the Environmental Protection Agency recommend boiling for 1 minute to allow for a margin of safety and so users are clear that the water is truly boiling. Because the boiling point decreases with increasing altitude, CDC advises boiling water for 3 minutes at altitudes greater than 6,562 feet (>2000 m).

If no other means of water treatment is available, a potential alternative to boiling is to use tap water that is too hot to touch, which is probably at a temperature between 131° F (55° C) and 140° F (60° C). This temperature may be adequate to kill pathogens if the water has been kept hot in the tank for some time. However, because one cannot know for certain that this temperature has been maintained for long enough to kill all waterborne pathogens, boiling is still advisable if possible. Travelers with access to electricity can bring a small electric heating coil or a lightweight beverage warmer to boil water.

Filtration

Filter pore size is the primary determinant of a filter's effectiveness, but microorganisms also adhere to filter media by electrochemical reactions. Microfilters with “absolute” pore sizes of 0.1–0.4 mm are usually effective for removal of cysts and bacteria but may not adequately remove viruses, which are a major concern in water with high levels of fecal contamination (Table 2-29 ). Environmental Protection Agency (EPA) designation of water “purifier” indicates that company-sponsored testing has substantiated claims for removing 10⁴ (9,999 of 10,000) viruses although EPA does not independently test the validity of these claims.

Table 2-29.

Microorganism size and susceptibility to filtration

Organism	Average Size (μm)	Maximum recommended filter rating (μm Absolute)1
Viruses	0.03	Not specified
Enteric bacteria (E. coli)	0.5 × 3.0–8.0	0.2–0.4
Cryptosporidium oocyst	4–6	1
Giardia cyst	6.0–10.0 × 8.0–15.0	3.0–5.0

¹NSF 53 rating on a filter certifies for cyst/oocyst removal.

Reverse osmosis filtration can both remove microbiologic contamination and desalinate water. The high price and slow output of small hand-pump reverse-osmosis units currently prohibit use by land-based travelers; however, they are important survival aids for ocean voyagers.

If the water supply is suspected of being heavily contaminated with biologic wastes and additional assurance is needed, then a second step with chemical treatment of the water before filtration can kill viruses. Many filters contain a charcoal stage that will remove the taste of added chlorine or iodine.

Chemical Disinfection

The most common chemical water disinfectants are chlorine and iodine (halogens). Worldwide, chemical disinfection with chlorine is the most commonly used method for improving and maintaining microbiologic quality of drinking water. Sodium hypochlorite, common household bleach, is the primary disinfectant promoted by CDC and the WHO Safe Water System for individual household use in the developing world.

Primary factors that determine the rate and proportion of microorganisms killed are the concentration of halogen (measured in mg/L or parts per million) and the length of time microorganisms are exposed to the halogen (contact time, measured in minutes). Given adequate concentrations and contact times, both chlorine and iodine have similar activity and are effective against many bacteria. Due to many uncontrolled factors in the field, extending the contact time adds a margin of safety. Cloudy water contains material that will use added disinfectant so it will require higher concentrations or contact times. However, some common waterborne parasites such as Cryptosporidium, are poorly inactivated by halogen disinfection, even at practical extended contact times. Therefore, chemical disinfection should be supplemented with adequate filtration to remove these disease-causing microorganisms from drinking water.

Both chlorine and iodine are available in liquid and tablet form (Table 2-30 ). Iodine has physiologic activity (it is used by the thyroid), so WHO recommends limiting iodine water disinfection to a few weeks of emergency use. It is not recommended in persons with unstable thyroid disease, known iodine allergy, or pregnancy (because of the potential effect on the fetal thyroid).

Table 2-30.

Iodine and chlorine formulations and doses

Iodination Techniques added to 1 liter or quart of water	Yield 4 mg/L Contact (Wait) Time 45 min at 30° C 180 min at 5° C1	Yield 8 mg/L Contact (Wait) Time 15 min at 30° C 60 min at 5° C1
Iodine tablets (tetraglycine hydroperiodide) (e.g., Potable Aqua, Globaline)	½ tablet	1 tablet
2% iodine solution (tincture)	0.2 mL 5 gtts2	0.4 mL 10 gtts2
Saturated solution: iodine crystals in water (e.g., Polar Pure)	13.0 mL	26.0 mL
Chlorination techniques	Yield 5 mg/L	Yield 10 mg/L
Sodium hypochlorite	0.1 mL	0.2 mL
Household bleach 5%	2 drops	4 drops
Sodium dichloroisocyanurate (e.g., AquaClear)		1 tablet
Chlorine plus flocculating agent (e.g., Chlor-floc)		1 tablet

¹Very cold water requires prolonged contact time with iodine or chlorine to kill Giardia cysts. These contact times have been extended from the usual recommendations in cold water to account for this and for the uncertainty of residual concentration.

²Drops per minute.

The taste of halogens in water can be improved by several means:

• •Reduce concentration and increase contact time.
• •Use a filter that contains activated carbon after contact time.
• •Add a tiny pinch of ascorbic acid (vitamin C, available in powder or crystal form and an ingredient in most flavored drink mixes) after the required contact time to remove the taste of halogens. (This works by converting iodine to iodide or chlorine to chloride, which have no taste or color.)

Iodine Resins

Iodine resins transfer iodine to microorganisms that come into contact with the resin, but leave little iodine dissolved in the water. The resins have been incorporated into many different filter designs available for field use. Most contain a 1-mm cyst filter, which should effectively remove protozoan cysts (it should say 1-mm or 1 micron “absolute”). Few models are sold in the United States because of inconsistent test results, but some models are still available for international use.

Salt (Sodium Chloride) Electrolysis

Passing a current through a simple brine salt solution generates mixed oxidants, primarily chlorine, which can be used for disinfection of microbes. See the discussion on chlorine above. The process was recently designed in a pocket-sized instrument that uses salt, water and electrical current generated from camera batteries to produce a disinfectant solution that is added to water.

Chlorine Dioxide

Chlorine dioxide (ClO₂) is capable of inactivating most water-borne pathogens, including Cryptosporidium oocysts, at practical doses and contact times. There are several new chemical methods for generating chlorine dioxide in the field for small-quantity water treatment.

Ultraviolet (UV) Light

UV light can be used as a pathogen reduction method against microorganisms. The technology requires effective pre-filtering due to its dependence on low water turbidity (cloudiness), the correct power delivery, and correct contact times to achieve maximum pathogen reduction. UV might be an effective method in pathogen reduction in backcountry water. However, there is a lack of independent testing data available on specific systems.

Solar Irradiation and Heating

UV irradiation by sunlight in the UVA range can substantially improve the microbiologic quality of water. Recent work has confirmed the efficacy and optimal procedures of the solar disinfection (SODIS) technique. Transparent bottles (e.g., clear plastic beverage bottles), preferably lying on a dark surface, are exposed to sunlight for a minimum of 4 hours. UV and thermal inactivation are synergistic for solar disinfection of drinking water. Use of a simple reflector or solar cooker can achieve temperatures of 149° F (65° C), which will pasteurize the water after 4 hours. In emergency situations such as refugee camps and disaster areas, where strong sunshine is available, solar disinfection of drinking water can improve water quality.

Silver and Other Products

Silver ion has bactericidal effects in low doses and some attractive features, including absence of color, taste, and odor. The use of silver as a drinking water disinfectant is popular in Europe, but it is not approved for this purpose in the United States because silver concentration in water is strongly affected by adsorption onto the surface of the container and there has been limited testing on viruses and cysts.

Several other common products have known antibacterial effects in water and are marketed in commercial products for travelers, including hydrogen peroxide, citrus juice, and potassium permanganate. None have sufficient data to recommend them for water disinfection in the field.

Granular activated carbon (GAC) removes organic and inorganic chemicals (including chemical disinfectants) through adsorption onto carbon particles, thereby improving odor and taste. GAC may trap but does not kill microorganisms. GAC is a common component of field filters.

Coagulation–flocculation (CF) removes suspended particles that cause a cloudy appearance and bad taste and do not settle by gravity; this process removes many but not all microorganisms. Alum, or one of several other substances, is added to the water, stirred well, allowed to settle, then poured through a simple coffee filter or fine cloth to remove the sediment. CF is an ancient technique that is still used routinely in municipal water treatment in conjunction with other treatment methods, such as disinfection, filtration, UV radiation, and ozonation.

The Preferred Technique

The optimal technique for an individual or group depends on personal preference, size of the group, water source, and the style of travel. Boiling is most effective but may not be practical in all situations. Unfortunately, alternative treatment may require a two-step process of 1) coagulation–flocculation and/or filtration and 2) halogenation. It is best to filter first and then add the halogen. On long-distance, oceangoing boats where water must be desalinated during the voyage, only reverse-osmosis membrane filters are adequate.

When the water will be stored for a period of time, such as on a boat, motor home, or a home with rainwater collection, halogens should be used to prevent the water from becoming recontaminated. A tightly sealed container is best to decrease risk of contamination. A minimum residual of 3–4 mg/L of hypochlorite should be maintained in the stored water. For short-term home storage, narrow-mouth jars or containers with water spigots prevent contamination from repeated contact with hands or utensils.

SUNBURN

Vernon E. Ansdell

Description

• •Travelers to the tropics and subtropics are at increased risk of overexposure to the sun. Important consequences include sunburn, premature aging of the skin, wrinkling, and skin cancer, including melanoma.
• •
  Sunlight consists of ultraviolet (UV) rays (i.e., UVA, UVB, and UVC).

  • ○
    UVA rays are present throughout the day and are the most important cause of premature aging of the skin. In addition, UVA rays are responsible for photosensitivity reactions and also contribute to skin cancer.
  • ○
    UVB rays are intense from 10 am to 4 pm and are most responsible for sunburn and skin cancer development.
  • ○
    UVC rays are filtered by the ozone layer and do not reach the earth's surface.
• •The benefits of UV radiation include vitamin D protection, which is important for calcium absorption.

Occurrence and Risk For Travelers

Increased exposure to UV radiation occurs nearer the equator, during summer months, at higher elevation and between 10 am and 4 pm. Reflection from the snow, sand, and water increases exposure, a particularly important consideration for beach activities, skiing, swimming, and sailing.

Commonly Used Medications that May Cause Photosensitivity Reactions

Antimicrobials

Fluoroquinolones, sulfonamides, and tetracyclines (especially demeclocycline); less frequently, doxycycline, oxytetracycline, and tetracycline; rarely, minocycline.

Antimalarials

Doxycycline.

Others

Nonsteroidal anti-inflammatory drugs, thiazide diuretics, furosemide, amiodarone, sulfonylureas, acetazolamide (Diamox), phenothiazines.

Clinical Presentation

• • Symptoms from sunburn appear 3–5 hours after overexposure, worsen over the next 24–36 hours, and resolve in 3–5 days.
• •Serious burns are painful, and the skin may be tender, swollen and blistered. There may be fever, headache, itching, and malaise. Skin peeling occurs 3–8 days after excessive sun exposure.
• •Overexposure to the sun over several years leads to premature aging of the skin, wrinkling, age spots, and an increased risk for skin cancer, including melanoma.
• •Overexposure to the sun can cause red, dry painful eyes. Repeated exposure to sunlight results in pterygium formation and important causes of blindness such as cataracts and macular degeneration.

Preventive Measures for Travelers

Sun Protection Factor (SPF)

SPF defines the extra protection against UVB rays that an individual will get by using a sunscreen. For example, if a person using SPF 15 sunscreen normally acquires a sunburn within 20 minutes without protection, the benefit will be 20 × 15 minutes extra protection with sunscreen (i.e., 300 minutes = 5 hours). SPF does not refer to protection against UVA rays. Products containing Mexoryl, Parsol 1789, titanium dioxide, zinc oxide, or avobenzone block UVA rays.

UV Index

The UV index provides travelers with an indication of the risk of UV radiation. Information is often available on the Internet or in local newspapers. The UV index ranges from 1 (low) to 11 or higher (extremely high).

Sun Avoidance

Staying indoors or seeking shade between 10 am and 4 pm is very important in limiting exposure to UV rays, particularly UVB rays. Be aware that sunburn and sun damage can occur even on cloudy days.

Protective Clothing

• •Wide-brimmed hats and long sleeves and pants provide important protection against UV rays.
• •Tightly woven clothing and darker fabrics provide additional protection.
• •High SPF sun-protective clothing is recommended for those at increased risk of sunburn or with a history of skin cancer. This type of clothing contains colorless compounds, fluorescent brighteners, or specifically treated resins that absorb UV rays and often provides an SPF of 30 or higher.
• •Sunglasses that provide 100% protection against UV radiation are strongly recommended.

Sunscreens

Sunscreens protect the skin by absorbing or reflecting UV radiation.

Physical Sunscreens contain large particulate substances such as titanium dioxide and zinc oxide, which act to reflect and scatter both visible and UV light. They are effective sunscreens but are less popular because of aesthetically unappealing characteristics such as opaqueness and tendency to stain clothing. They are recommended for those who burn easily or who take medications that may cause photosensitivity reactions.

Chemical Sunscreens absorb rather than reflect UV radiation. A combination of agents is recommended to provide broad-spectrum protection against UVA and UVB rays.

Key Points Regarding Sunscreens

• • Choose a sunscreen with at least 15 SPF.
• •Select a water- and sweat-resistant product that provides protection against both UVA and UVB rays.
• •Look for a sunscreen with at least three different active ingredients to provide broad-spectrum UVA and UVB ray protection. These ingredients generally include PABA derivatives, salicylates (homosalate, octyl salicylate), or cinnamates (octyll methoxycinnamate and cinoxate) for UVB ray absorption; benzophenones (oxybenzone, dioxybenzone, sulisobenzone) for shorter-wavelength UVA ray protection; and avobenzone (Parsol1789), ecamsule (Mexoryl), titanium dioxide, or zinc oxide for the remaining UVA spectrum.
• •Apply 30 minutes before exposure to the sun.
• •At least 1 oz of sunscreen is needed for total body application (i.e., quarter of a 4-oz bottle).
• •Apply to all exposed areas, especially the ears, scalp, lips, back of the neck, tops of the feet, and backs of the hands.
• •Reapply after 1–2 hours and after sweating, swimming, or toweling (even on cloudy days).
• •Many sunscreens lose potency after 1–2 years.
• •Sunscreens should be applied to the skin before insect repellents.
• •Avoid products that contain sunscreens and insect repellents. (DEET-containing insect repellents may decrease the effectiveness of sunscreens and may increase absorption of DEET through the skin.)

Treatment

• •Hydration and staying in a cool, shaded, or indoor environment
• •Topical and oral nonsteroidal anti-inflammatory drugs decrease erythema if used before or soon after exposure to UVB rays and may relieve symptoms such as headache, fever, and local pain. Topical steroids are of limited benefit, and systemic steroids appear to be ineffective.
• •Moisturizing creams, aloe vera, and diphenhydramine may help to relieve symptoms.
• •In severe cases, narcotic analgesics may be indicated to relieve pain.

PROBLEMS WITH HEAT AND COLD

Howard D. Backer, David R. Shlim

Background

Foreign travel involves heading into new environments, and climate is one of the most important factors to consider. Travelers may encounter temperature and weather extremes that are either much hotter or colder than they are used to, and either extreme can have health consequences.

Travelers should try to determine the likely climate extremes that they will face during their journey and to prepare with proper clothing, knowledge, and equipment. This section gives a brief overview of the topic.

Problems Associated with a Hot Climate

Risk for Travelers

Many of the most popular travel destinations are tropical or desert areas. Travelers who sit on the beach or by the pool and do only short walking tours incur minimal risk of heat illness. Those who do strenuous hiking or biking in the heat may have significant risk, especially travelers coming from cool or temperate climates who are not in good physical condition and unacclimatized to the heat.

Clinical Presentations

Physiology of Heat Injuries

Tolerance to heat depends primarily on physiologic factors, unlike cold environments where adaptive behaviors are more important. The major means of heat dissipation are radiation at rest and evaporation of sweat during exercise, both of which become minimal with air temperatures above 95° F (35° C) and high humidity.

The major organs involved in temperature regulation are the skin, where sweating and heat exchange take place, and the cardiovascular system, which must greatly increase blood flow to shunt heat from the core to the surface while meeting the metabolic demands of exercise. Cardiovascular status and conditioning are the major physiologic variables affecting the response to heat stress at all ages. Dehydration is the most important predisposing factor in heat illness; temperature and heart rate increase in direct proportion to the level of dehydration. Sweat is a hypotonic fluid containing sodium and chloride. Sweat rates commonly reach 1–2 L/hr, which may result in significant fluid and sodium loss.

Minor Heat Disorders

Heat cramps are painful muscle contractions following exercise in heat. They begin an hour or more after stopping exercise, most often involving heavily used muscles in the calves, thighs, and abdomen. If rest and passive stretching of the muscle do not resolve cramps, an oral salt solution, as in rehydration solutions, will rapidly relieve symptoms.

Heat syncope is sudden fainting in heat that occurs in unacclimatized people while standing or after 15–20 minutes of exercise. Consciousness rapidly returns to normal when the patient is supine. Rest, relief from heat, and oral fluids are sufficient treatments.

Heat edema is mild swelling of the hands and feet, which is more frequent in women during the first few days of heat exposure. It resolves spontaneously and should not be treated with diuretics, which may delay acclimatization and cause dehydration.

Prickly heat (e.g., miliaria, heat rash) manifests as small, red, pruritic lesions on the skin caused by obstruction of the sweat ducts. It is best prevented by wearing light, loose clothing and avoiding heavy, continuous sweating.

Major Heat Disorders

Heat Exhaustion

• •Most people who experience acute collapse or other symptoms associated with exercise in the heat are suffering from heat exhaustion, simply defined as the inability to continue exertion in the heat.
• •The presumed cause of heat exhaustion is loss of fluid and electrolytes, but there are no objective markers to define the syndrome, which is a spectrum ranging from minor complaints to a vague boundary shared with heat stroke.
• • Transient mental changes, such as irritability, confusion, or irrational behavior, may be present, but neurologic signs, such as seizures or coma, would indicate heat stroke or hyponatremia.
• •Body temperature may be normal or elevated.
• •Most cases can be treated with supine rest in a cool place and oral water or fluids containing glucose and salt. Spontaneous cooling occurs, and patients recover within hours, preventing progression to more serious illness. An oral solution for treating minor heat disorders or for fluid and electrolyte replacement can be made by adding ¼ teaspoon or two l-gm salt tablets to l liter of water, plus 4–8 tsp of sugar if desired for taste.
• •Subacute heat exhaustion may develop over several days and is often misdiagnosed as “summer flu” because of findings of weakness, fatigue, headache, dizziness, anorexia, nausea, vomiting, and diarrhea. Treatment is as described for acute heat exhaustion.

Exercise-Induced Hyponatremia

• •Some travelers are so concerned about preventing heat illness and dehydration that they adopt the attitude that “you can't drink too much.” Sadly, this attitude can lead to tragic outcomes.
• •Hyponatremia due to excessive water intake occurs in both endurance athletes and recreational hikers, particularly if the person is replacing sodium loss through sweating with plain water.
• •In the field setting, altered mental status with normal body temperature and a history of large volumes of water intake are highly suggestive of hyponatremia. The vague and nonspecific symptoms are the same as those described for hyponatremia in other settings (e.g., anorexia, nausea, emesis, headache, muscle weakness, lethargy, confusion, and seizures).
• •Until clinically apparent alterations in mental status appear, heat exhaustion is difficult to distinguish from early hyponatremia.
• •A delay before onset of major symptoms or deterioration after cessation of exercise and heat exposure are unique aspects of hyponatremia.
• •Prevention includes sodium supplementation with prolonged exercise or heat exposure. For hikers and wilderness users, food is the most efficient vehicle for salt replacement. Trail snacks should include salty foods (e.g., trail mix, crackers, pretzels, jerky), and not just sweets.

Heat Stroke

• •Heat stroke is an extreme medical emergency requiring aggressive cooling measures and hospitalization for support.
• •Heat stroke is the only form of heat illness in which the mechanisms for thermal homeostasis have failed. As a result of uncontrolled fever and circulatory collapse, organ damage can occur in the brain, liver, kidneys, and heart.
• •The onset of heat stroke may be acute (exertional heat stroke) or gradual (nonexertional heat stroke, also referred to as classic or epidemic).
• •A presumptive diagnosis of heatstroke is made when patients have hyperpyrexia and marked alteration of mental status.
• •Body temperatures in excess of 106° F (41° C) can be observed; even without a thermometer, these patients will feel hot to touch. If a thermometer is available, a rectal temperature is the safest and most reliable way to check the temperature in someone who may have heatstroke.
• •In the field, institute evaporative cooling by maximizing skin exposure, spraying tepid water on the skin, and maintaining air movement over the body by fans. If ice is available, apply cold packs to the neck, axillas, and groin and massage the skin with ice. Immersion in a nearby pool or natural body of water can initiate cooling.
• •Unless the recovery is very rapid, the person should be evacuated to a hospital. If that is not possible, encourage rehydration, if the person is able to take oral fluids, and monitor closely for several hours.

Prevention of Heat Disorders

Heat Acclimatization

Heat acclimatization is a process of physiologic adaptation to a hot environment that occurs in both residents and visitors. The result of acclimatization is an increase in sweating, and decreased energy expenditure with lower rise in body temperature for a given workload. Only partial adaptation occurs by passive exposure to heat. Full acclimatization, especially cardiovascular response, requires 1–2 hours of exercise in the heat each day. Most acclimatization changes occur within 10 days, provided a suitable amount of exercise is taken each day in the heat. After this time, only increased physical fitness will result in further exercise tolerance. Decay of acclimatization occurs within days to weeks if there is no heat exposure.

Physical Conditioning and Acclimatization

Higher levels of physical fitness improve exercise tolerance and capacity in heat, but not as much as acclimatization. If possible, travelers should acclimatize before leaving by exercising at least 1 hour daily in the heat. If this is not possible before departing, exercise in heat during the first week of travel should be limited in intensity and duration (30- to 90-minute periods) with rest in between. It is a good idea to conform to the local practice in most hot regions and avoid strenuous activity during the hottest part of the day.

Clothing

Clothing should be lightweight, loose, and light-colored to allow maximum air circulation for evaporation yet give protection from the sun. A wide-brimmed hat markedly reduces radiant heat exposure.

Fluid and Electrolyte Replacement

During exertion, fluid intake improves performance and decreases the likelihood of illness. Reliance on thirst alone is not sufficient to prevent significant dehydration. During mild to moderate exertion, electrolyte replacement offers no advantage over plain water. However, for those exercising many hours in heat, a weak solution similar to commercial electrolyte drinks is recommended. Salty snacks or light salting of mealtime food or fluids is the most efficient way to replace salt losses. Salt tablets, when swallowed whole, may cause gastrointestinal irritation and vomiting, but two tablets can be dissolved in one liter of water. Urine volume and color are a readily available means to monitor fluid needs.

Problems Associated with a Cold Climate

Risk for Travelers

Travelers do not have to be in an arctic or high-altitude environment to encounter problems with the cold. Humidity, rain, and wind can produce hypothermia even with temperatures around 50° F (12° C–14° C). Reports of severe hypothermia in international travelers are rare. Many high-altitude destinations are not wilderness areas, and villages offer an escape from extreme weather. In Nepal, trekkers almost never experience hypothermia except in the rare instance in which they may get lost in a storm. Even in a temperate climate, the traveler in a small boat that overturns in very cold water can rapidly become hypothermic.

Clinical Presentations

Hypothermia

Hypothermia can be defined, in general terms, as having a core body temperature of <95° F (35° C). When persons are faced with an environment in which they cannot keep warm, they first feel chilled, then begin to shiver, and eventually stop shivering as their metabolic reserves are exhausted. At that point, body temperature continues to decrease, dependent upon the ambient temperatures. As the core temperature falls, neurologic functioning decreases until almost all hypothermic people with a core temperature of £86° F (30° C) are comatose. The record low core body temperature in an adult who survived is 56° F (13° C). Travelers headed to a cold climate should be encouraged to ask questions and research appropriate clothing and equipment.

Travelers who will be recreating or working around cold water face a different sort of risk. Immersion hypothermia can render a person unable to swim or keep floating within 30–60 minutes. In these cases, a personal flotation device is critical, as is knowledge about self-rescue and righting a capsized boat.

The other medical conditions associated with cold affect mainly the skin and the extremities. These can be divided into nonfreezing cold injuries and freezing injuries (frostbite).

Nonfreezing Cold Injury

The nonfreezing cold injuries are—

• • Trench foot (immersion foot): This condition is caused by prolonged immersion of the feet in cold water (32° F–59° F, 0° C–15° C). The damage is mainly to nerves and blood vessels, and the result is pain that is aggravated by heat and a dependent position of the limb. Severe cases can take months to resolve. Unlike the treatment for frostbite, immersion foot should not be rapidly rewarmed, which can make the damage much worse.
• • Pernio (chilblains): Pernio are localized, inflammatory lesions that occur mainly on the hands of susceptible individuals. They can occur with exposure to only moderately cold weather. The bluish-red lesions are thought to be caused by prolonged, cold-induced vasoconstriction. As with trench foot, rapid rewarming should be avoided, as it makes the pain worse. Nifedipine may be an effective treatment.
• • Cold urticaria: This condition involves the formation of localized or general wheals and itching after exposure to cold. It is not the absolute temperature that induces this form of urticara, but the rate of change of temperature in the skin.

Freezing Cold Injury

Categories of Frostbite

• •Frostbite is the term that is used to describe tissue damage from direct freezing of the skin.
• •Modern equipment and clothing have greatly decreased the risk of frostbite in most adventurous tourist destinations, and frostbite occurs mainly during an accident, severe unexpected weather, or as a result of poor planning.
• •Once frostbite injury has occurred, little can be done to reverse the changes. Therefore, taking great care to prevent frostbite is crucial.
• •
  Frostbite is usually graded like burns.

  • ○
    First-degree frostbite involves reddening of the skin without deeper damage. The prognosis for complete healing is virtually 100%.
  • ○
    Second-degree frostbite involves blister formation. Blisters filled with clear fluid have a better prognosis than blood-tinged blisters.
  • ○
    Third-degree frostbite represents full-thickness injury to the skin, and possibly the underlying tissues. No blister forms, the skin darkens over time and may turn black, and if the tissue is completely devascularized, amputation will be necessary.

Management of Frostbite

Frostbitten skin is numb and appears whitish or waxy. The generally accepted method for treating a frozen digit or limb is through rapid rewarming in water heated to 104° F–108° F (40° C–42° C). The frozen area should be completely immersed in the warm water. A thermometer is needed to maintain the water at the correct temperature. Rewarming can be associated with severe pain, and analgesics can be given if needed. Once the area is rewarmed, it must be safeguarded against freezing again. It is thought to be better to keep digits frozen a little longer and rapidly rewarm them, than to allow them to thaw out slowly or to thaw and refreeze. A cycle of freeze–thaw–refreeze is devastating to tissue and leads more directly to the need for amputation.

Once the area has rewarmed, it can be examined. If blisters are present, it is important to note whether they extend to the end of the digit. Proximal blisters usually mean that the tissue distal to the blister has suffered full-thickness damage. Treatment consists of avoiding further mechanical trauma to the area and preventing infection. Reasonable field treatment consists of washing the area thoroughly with a disinfectant such as povidone–iodine, putting dressings between the toes or fingers to prevent maceration, using fluffs (expanded gauze sponges) for padding, and covering with a roller gauze bandage. These dressings can safely be left on for up to 3 days at a time. By leaving the dressings on longer, the traveler can preserve what may be limited supplies of bandages. Prophylactic antibiotics are not needed in most situations.

Once the patient has reached a definitive medical setting, there should be no rush to do surgery. The usual time from injury to surgery is 4–5 weeks. By that time the dead tissue has begun to separate from viable tissue, and the surgeon can plan surgery that maximizes the remaining digits.

FOOD POISONING FROM MARINE TOXINS

Vernon E. Ansdell

Description

• •Seafood poisoning from marine toxins is an underrecognized hazard for travelers, particularly in the tropics and subtropics. Furthermore, the risk is increasing as a result of multiple factors such as global warming, coral reef damage, and spread of toxic algal blooms.
• • Ciguatera fish poisoning and shellfish poisoning are caused by potent toxins that originate in small marine organisms (dinoflagellates and diatoms).
• • Scombroid poisoning is caused by eating improperly chilled fish that contains large quantities of histamine.

Ciguatera Fish Poisoning

Ciguatera fish poisoning occurs after eating reef fish contaminated with toxins such as ciguatoxin or maitotoxin. These potent toxins originate from small marine organisms (dinoflagellates) that grow on and around coral reefs. Dinoflagellates are ingested by herbivorous fish, and the toxins are concentrated as they pass up the food chain to large (usually >6 pounds) carnivorous fish and finally to humans. Toxin in fish is concentrated in the liver, intestinal tract, roe, and head.

Gambierdiscus toxicus, which produces ciguatoxin, tends to proliferate on dead coral reefs. The risk of ciguatera is likely to increase as more coral reefs die as a result of factors such as global warming, construction, and nutrient runoff.

Risk for Travelers

• •Over 50,000 cases of ciguatera poisoning occur every year.
• •The incidence in travelers to endemic areas has been estimated as high as 3/100.
• •Ciguatera is widespread in tropical and subtropical waters, usually between the latitudes of 35 degrees north and 35 degrees south; it is particularly common in the Pacific and Indian Oceans and the Caribbean Sea.
• •Fish that are most likely to cause ciguatera poisoning are carnivorous reef fish, including barracuda, grouper, moray eel, amberjack, sea bass, or sturgeon. Omnivorous and herbivorous fish such as parrot fish, surgeon fish, and red snapper can also be a risk.

Clinical Presentation

• •Typical ciguatera poisoning results in a gastrointestinal illness, followed by neurologic symptoms and, very rarely, cardiovascular collapse.
• •The first symptoms usually appear 1–3 hours after eating contaminated fish and include nausea, vomiting, diarrhea, and abdominal pain.
• •Neurologic symptoms appear 3–72 hours after the meal and include paresthesias, pain in the teeth or the sensation that the teeth are loose, itching, metallic taste, blurred vision, or even transient blindness. Temperature reversal (hot objects feel cold and cold objects feel hot) is very characteristic. Neurologic symptoms usually last a few days to several weeks.
• •Chronic neuropsychiatric symptoms resembling chronic fatigue syndrome may be very disabling, last several months, and include malaise, depression, headaches, myalgias, and fatigue. Cardiac manifestations include bradycardia, other arrythmias, and hypotension.
• •Overall mortality from ciguatera poisoning is about 0.1% but varies due to the toxin dose absorbed and availability of adequate medical care to deal with serious complications such as cardiovascular collapse or respiratory failure.
• •The diagnosis of ciguatera poisoning is based on the clinical signs and symptoms and a history of eating fish that are known to carry ciguatera toxin. Commercial kits are available to test for ciguatera in fish, but there is no test for ciguatera in humans.

Preventive Measures for Travelers

• •Avoid or limit consumption of the reef fish listed above, particularly when the individual fish weighs 6 pounds or more.
• •Never eat high-risk fish such as barracuda or moray eel.
• •Avoid the parts of the fish that concentrate ciguatera toxin, such as liver, intestines, roe, and head.
• •Remember that ciguatera toxins do not affect the texture, taste or smell of fish, and they are not destroyed by gastric acid, cooking, smoking, freezing, canning, salting, or pickling.
• •Commercial kits (if available) can be used to check if the fish is safe to eat.

Treatment

• •There is no specific antidote for ciguatoxin or maitotoxin.
• • Treatment is generally symptomatic and supportive.
• •Intravenous mannitol has been reported to reduce the severity and duration of neurologic symptoms, particularly if given early.

Scombroid

Scombroid, one of the commonest fish poisonings, occurs worldwide in both temperate and tropical waters. The illness occurs after eating improperly refrigerated or preserved fish containing high levels of histamine and often resembles a moderate to severe IgE-mediated allergic reaction.

Fish that cause scombroid have naturally high levels of histidine in the flesh and include tuna, mackerel, mahimahi (dolphin fish), sardine, anchovy, herring, bluefish, amberjack, and marlin. Histidine is converted to histamine by bacterial overgrowth in fish that has been improperly stored (over 20° C) after capture. Histamine and other scombrotoxins are resistant to cooking, smoking, canning, or freezing.

Scombroid fish poisoning occurs worldwide in both temperate and tropical waters.

Clinical Presentation

• •Symptoms of scombroid poisoning resemble an acute allergic reaction and usually appear 10–60 minutes after eating contaminated fish. They include flushing of the face and upper body (resembling sunburn), severe headache, palpitations, itching, blurred vision, abdominal cramps, and diarrhea.
• •Untreated, symptoms usually resolve within 12 hours. Rarely, there may be respiratory compromise, malignant arrythmias, and hypotension requiring hospitalization.
• •Diagnosis is usually clinical. A clustering of cases helps to exclude the possibility of fish allergy.

Preventive Measures for Travelers

• •Fish contaminated with histamine may have a peppery, sharp, salty, or bubbly taste, but may also look, smell, and taste normal.
• •The key to prevention is to make sure that the fish is promptly chilled (below 15° C–20° C) after capture.
• •Cooking, smoking, canning, or freezing will not destroy histamine in contaminated fish.

Treatment

• •Scombroid poisoning usually responds well to H1 antihistamines.
• •H2 antihistamines may also be of benefit.

Shellfish Poisoning

There are several forms of shellfish poisoning. All occur after ingesting filter-feeding bivalve mollusks, such as mussels, oysters, clams, scallops, and cockles containing potent toxins. The toxins originate in small marine organisms (dinoflagellates or diatoms) that are ingested and concentrated by shellfish.

Risk for Travelers

Contaminated shellfish may be found in temperate and tropical waters, typically during or after dinoflagellate blooms or “red tides.”

Clinical Presentation

Poisoning results in gastrointestinal and neurologic illness of varying severity. Symptoms typically appear 30–60 minutes after ingesting toxic shellfish but can be delayed for several hours. Diagnosis is usually made clinically together with a history of recent shellfish ingestion.

Paralytic Shellfish Poisoning

This is the most common and most severe form of shellfish poisoning. Symptoms usually appear 30–60 minutes after eating toxic shellfish and include numbness and tingling of the face, lips, tongue, arms, and legs. There may be headache, nausea, vomiting, and diarrhea. Severe cases are associated with ingestion of large doses of toxin and clinical features such as ataxia, dysphagia, mental status changes, flaccid paralysis, and respiratory failure. The case–fatality rate averages 6% and may be particularly high in children.

Neurotoxic Shellfish Poisoning

Usually presents as gastroenteritis accompanied by minor neurologic symptoms, resembling mild ciguatera poisoning or mild paralytic shellfish poisoning. Inhalation of aerosolized toxin in the sea spray associated with a red tide may cause an acute respiratory illness, rhinorrhea, and bronchoconstriction.

Diarrheic Shellfish Poisoning

This produces chills, nausea, vomiting, abdominal cramps, and diarrhea. No fatalities have been reported.

Amnesic Shellfish Poisoning

This is a rare form of shellfish poisoning that produces a gastroenteritis that may be accompanied by headache, confusion, and permanent short-term memory loss. In severe cases, seizures, paralysis, and death may occur.

Preventive Measures for Travelers

• •Shellfish poisoning can be prevented by avoiding potentially contaminated bivalve molluscs. This is particularly important in areas during or shortly after “red tides.”
• •Travelers to developing countries should avoid eating all shellfish, because they carry a high risk of viral and bacterial infections.
• •Marine shellfish toxins cannot be destroyed by cooking or freezing.

Treatment

• •Treatment is symptomatic and supportive.
• •Severe cases of paralytic shellfish poisoning may require mechanical ventilation.

ANIMAL-ASSOCIATED HAZARDS

Nina Marano, G. Gale Galland

Human Interaction with Animals: A Risk Factor for Injury

Animals in general tend to avoid human beings, but they can attack if they perceive threat, are protecting their young or territory, or are injured or ill. Although attacks by wild animals are more dramatic, attacks by domestic animals are far more common. Animals cause injury through bites, kicks, or blunt trauma, or by the use of horns or claws. Further damage can occur if injuries become secondarily infected, as these infections may result in serious systemic disease. In addition, animals can transmit zoonotic infections such as rabies. A recent 10-year retrospective review of dog bites in Austria showed that 75% of the bites were preventable because the person intentionally interacted with the dog.

Bite Wounds

Prevention

• •Before departure, travelers should have a current tetanus vaccination or should have documentation of receiving a booster vaccination within the prior 5–10 years. An assessment of the traveler's need for pre-exposure rabies immunization should be made according to guidelines in Table 2-17.
• •During travel, travelers should never try to pet, handle, or feed unfamiliar animals, domestic or wild, particularly in areas of endemic rabies. Young children are more likely to be bitten by animals and sustain more severe injuries from animal bites.

Management

• •All wounds should receive prompt local treatment by thorough cleansing and debridement of the wound if necrotic tissue or dirt is present to prevent infection and illness, especially tetanus or rabies-prone wounds (see the Rabies and Tetanus sections earlier in this chapter).
• •
  Any animal bite should be evaluated by a health-care provider as soon as possible, after cleaning the wound. Travelers who might have been exposed to rabies should contact a reliable health practitioner for advice about rabies postexposure prophylaxis (see the Rabies section earlier in this chapter). Since rabies immune globulin or rabies vaccine may not be available in the destination country, travelers should have a strategy in place prior to travel as to how to respond to a possible rabies exposure. This strategy may require the traveler to fly to a different country to obtain the appropriate treatment.

  • ○
    Travelers who have purchased medical evacuation insurance should contact their insurance provider for guidance on seeking medical care.
  • ○
    U.S. citizens can contact the local U.S. Embassy or Consulate in the country they are visiting for assistance in locating a health-care professional at their destination. Consular personnel at U.S. Embassies and Consulates abroad and in the United States are available 24 hours a day, 7 days a week, to provide emergency assistance to U.S. citizens. To contact the U.S. Department of State's Overseas Citizens Services:

    • □
      Dial: 888-407-4747 if calling from the U.S. or Canada
    • □
      Dial: 202-501-4444 if calling from overseas
• •Travelers who received their most recent tetanus toxoid-containing vaccine >5 years previously or who have not received at least three doses of tetanus toxoid-containing vaccines may require a dose of tetanus toxoid-containing vaccine (Tdap, Td, or DTaP), according to the guidelines in Table 2-21.

A wide variety of animals and insects can cause illness and injury to travelers; a short synopsis of risks by species is provided below.

Monkeys

• •Macaques, a type of monkey, pose a threat for rabies and herpes B virus. Macaques are native to Asia and Northern Africa. They are also housed in research facilities, zoos, wildlife or amusement parks, and are kept as pets in private homes throughout the world. Monkey bites occasionally occur in certain urban sites, such as temples in Nepal or India.
• •Herpes B virus is related to the herpes simplex viruses, which cause oral and genital ulcers. Herpes B virus was discovered in 1933, and since that time approximately 50 cases have been reported in humans, with an 80% mortality rate. Herpes B infection is rare in humans, and most documented cases have resulted from occupational exposures. No cases of herpes B infection have been reported in travelers or others exposed to monkeys in the wild. However, travelers to areas where free-ranging macaques exist should be aware of the potential risk. An infected monkey may appear completely healthy.
• •Documented routes of human infection include animal bites and scratches, exposure to infected tissue or body fluids from splashes, and, in one instance, human-to-human spread. Even minor scratches or bites should be considered potential exposures as, experimentally, herpes B virus has been isolated from surfaces for up to 2 weeks after it was applied (unpublished data, National Institutes of Health B Virus Reference Laboratory).
• •The incubation period for herpes B may be less than 1 week to a month or longer.
• •Neurologic symptoms develop as the virus infects the central nervous system and may lead to ascending paralysis and respiratory failure.
• •Increased public and physician awareness about the risks associated with an injury from a macaque, improved first aid postexposure, the availability of better diagnostic tests, and improved anti-viral therapeutics have decreased the mortality rate to 20% in treated individuals. As a result, from 1987 to 2004 there have been only five fatal infections.

Prevention

Travelers should never attempt to feed, pet, or otherwise handle any monkeys.

Management

• •Travelers should seek first aid immediately after being bitten or scratched by a monkey. The wound should be thoroughly cleaned, and travelers should seek health care immediately.
• •If the history is strongly suggestive of exposure to herpes B through contact with monkeys, there are published guidelines for the prevention of herpes B infection after exposure and for the treatment of established infection. These guidelines have recommendations for serologic tests and postexposure prophylaxis. When potentially exposed travelers return home, they should follow up with their health-care providers for care. Additional information and photos of macaques can be found at the website for the National B Virus Resource Center at the Georgia State University Viral Immunology Center: www2.gsu.edu/∼wwwvir/.

Snakes

• •Poisonous snakes are hazards in many locations, although deaths from snakebites are rare. Snakebites usually occur in areas where dense human populations coexist with dense snake populations (e.g., Southeast Asia, sub-Saharan Africa, and tropical America).
• •Common sense is the best precaution. Most snakebites are the direct result of startling, handling, or harassing snakes. Therefore, all snakes should be left alone. Travelers should maintain awareness of their surroundings, especially at night and during warm weather when snakes tend to be more active. For extra precaution, when practical, travelers should wear heavy, ankle high or higher boots, and long pants when walking outdoors at night in areas possibly inhabited by venomous snakes.

Management

• •Travelers should be advised to seek immediate medical attention any time a bite wound breaks the skin, or when snake venom is ejected into their eyes or mucous membranes.
• •Immobilization of the affected limb and application of a pressure bandage that does not restrict blood flow are recommended first-aid measures while the victim is moved as quickly as possible to a medical facility.
• •Incision of the bite site and tourniquets that restrict blood flow to the affected limb are not recommended.
• •Specific therapy for snakebites is controversial and should be left to the judgment of local emergency medical personnel. Specific antivenins are available for some snakes in some areas, so trying to ascertain the species of snake that bit the victim may be critical.

Insects

Bites and stings from insects such as spiders and scorpions can be painful and can result in significant morbidity and mortality, particularly among infants and children. Many insects can transmit communicable diseases, even without the traveler's awareness of the bite. This is particularly true when camping or staying in rustic accommodations.

Prevention

Exposure to insect bites and scorpion envenomations can be avoided by wearing long sleeves and pants while hiking, sleeping under mosquito nets, and shaking clothing and shoes before putting them on.

Management

Travelers should be advised to seek medical attention if an insect bite or sting causes redness, swelling, bruising, or persistent pain. Those who have a history of severe allergic reactions to insect bites or stings should also ask their physician to evaluate them for the need to carry an epinephrine autoinjector (EpiPen) to use in case of recurrence (both in general and especially while traveling).

Bats

• •Bats can be found almost anywhere in the world except the polar regions and extreme deserts. Bats are reservoir hosts for viruses that can cross species barriers to infect humans and other domestic and wild mammals. Viruses such as rabies virus can be transmitted directly from bats to people.
• •It is not possible to tell if a bat has rabies; however, any bat that is active by day, is found in a place where bats are not usually seen (for example, indoors or outdoors in areas in close proximity to humans), or is unable to fly is far more likely than others to be rabid.
• • Human exposure to bats can occur during adventure activities such as caving. Exposure can include bites, scratches, and mucosal or cutaneous exposure to bat saliva. Like any other wild animal, any bat, whether it is sick or healthy, will bite in self-defense if handled.

Prevention

Bats should never be handled. Travelers should be discouraged from going into caves that have a large bat infestation. Depending on the country being visited, pre-exposure rabies vaccination may be recommended for persons engaged in outdoor activities such as caving and spelunking.

Management

• •If a bite occurs or if infectious material (such as saliva) from a bat gets into the eyes, nose, mouth, or a wound, the traveler should wash the affected area thoroughly and get medical advice immediately. Any suspected or documented bite or scratch from a bat should be grounds for seeking postexposure rabies immunoprophylaxis.
• •People usually know when they have been bitten by a bat. However, bats have tiny teeth and not all wounds may be apparent. There are situations in which travelers should seek medical advice even in the absence of an obvious bite wound, such as upon awakening and finding a bat in the room or seeing a bat in the room of a child.

Marine Animals

• •Venomous injuries from marine fish and invertebrates are increasing with the popularity of surfing, scuba diving, and snorkeling. The majority of species responsible for human injuries and envenomation reside in tropical coastal waters and include stingrays, jellyfish, stonefish, and scorpionfish.
• •Travelers should be advised to use protective footwear and maintain vigilance while engaging in recreational water activities. Traumatic injury, envenomation and wound infection are common sequelae. Identification of the species involved is helpful in determining the best course of treatment.

Birds

• •When traveling in an area that is experiencing an outbreak of avian influenza (www.cdc.gov/flu/avian/outbreaks/current.htm), travelers should avoid all contact with poultry (e.g., chickens, ducks, geese, pigeons, turkeys, and quail) or any wild birds, and avoid settings where H5N1-infected poultry may be present, such as commercial or backyard poultry farms and live poultry markets.
• •Travelers should not eat uncooked or undercooked poultry or poultry products, including dishes made with uncooked poultry blood.

DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

Deborah Nicolls Barbeau

Background

Venous thromboembolism (VTE) consists of two related conditions: 1) deep vein thrombosis (DVT) and 2) pulmonary embolism (PE). DVT occurs when there is a partial or complete blockage of a deep vein by a blood clot, most commonly in the legs. The clot may break off and travel to the vessels in the lung, causing a life-threatening PE.

VTE associated with air travel was first described in the early 1950s. Previous studies have shown a two- to four-fold increased risk of VTE following air travel. In 2001, the World Health Organization set up the WHO Research into Global Hazards of Travel (WRIGHT) Project, a large collaborative research study to confirm the association between VTE and air travel. The goals of this project are to determine the magnitude of the risk of VTE due to air travel, to determine the effect of other factors on the association, and to study the effect of preventive measures on risk. The results of Phase I of the project were published recently. Phase II will address the effect of preventive measures.

Risk for Travelers

Several factors have been associated with an increased risk for developing VTE (Box 2-4 ).

Box 2-4.

Risk factors for venous thromboembolism (VTE)

Rights were not granted to include this box in electronic media. Please refer to the printed publication.

© 2009 American Heart Association

Combined effects have been observed between these established risk factors and different forms of travel. A population-based case–control study of adults receiving treatment for their first VTE found that long-distance travel (Δ4 hours) doubled the risk of VTE. The effect was greatest in the first week after travel but remained elevated for 2 months. Travel by air increased the risk to the same extent as travel by bus, train, or car, suggesting that the increased risk of air travel is due primarily to prolonged immobility. Synergistic effects were noted with factor V Leiden mutations, women who used oral contraceptives, BMI >30 kg/m², and height >1.9 m (approximately 6 ft 3 in). Some of these effects were greatest following air travel. Furthermore, people shorter than 1.6 m (approximately 5 ft 3 in) had an increased risk of VTE only after prolonged air travel. These findings suggest that additional factors related to air travel may be involved in the increased risk for VTE.

Occurrence

Two recent retrospective cohort studies address the issue of air travel-associated VTE incidence. The first was a cohort of 2,499 healthy Dutch commercial pilots. The incidence of VTE in this group was 0.3 per 1,000 person-years. When the data were adjusted for age and sex, the rate was not different from that in the general Dutch population. There was no association between the number of hours flown.

The second study was among 8,755 employees of several international organizations. The overall incidence of VTE following flights >4 hours was 1.4 per 1,000 person-years. The absolute risk of VTE was 1 per 4,656 flights. The rates of VTE were higher in women, especially those using oral contraceptives. Incidence was also higher in employees with a BMI >25 kg/m² and those with height <1.65 m (5 ft 5 in) or >1.85 m (6 ft 1 in). The risk of VTE increased with flight duration and with the number of times the employee flew during an 8-week period; the risk of VTE tripled in employees who went on five or more long-haul (Δ4 hours) flights. Each extra flight increased the risk of VTE 1.4-fold. The risk of VTE was highest in the first 2 weeks after a long-haul flight and gradually decreased to baseline after 8 weeks.

Both these studies were performed among populations that are younger (mean age 35–40 years) and healthier than the general population and are not, therefore, generalizable to a higher-risk population.

Clinical Presentation

Symptoms of DVT include swelling, redness, pain, or tenderness, and increased warmth over the skin. It may be difficult to distinguish from muscle strain, injury, or skin infection.

Symptoms of PE range from mild and nonspecific to acute, resembling heart attack or stroke. Once a clot has traveled to the lungs, common symptoms of PE are chest pain and shortness of breath. Other symptoms include dizziness, fainting, anxiety, and malaise. PE can occur in the absence of overt signs of DVT.

Diagnosis

Specialized imaging tests (e.g., duplex venous ultrasound, venography, computed tomography (CT) scans, and magnetic resonance imaging) are needed to make a definitive diagnosis of DVT. Helical CT or ventilation–perfusion scans are commonly used to diagnose PE.

Preventive Measures for Travelers

Several randomized, controlled trials have been performed to assess the effect of prophylactic measures on VTE risk after air travel. All studies examined the risk of asymptomatic DVT in travelers making flights Δ7 hours. All travelers were encouraged to do regular exercises and to drink nonalcoholic beverages during the flight. DVT was diagnosed by venous ultrasound from 90 minutes to 48 hours after the flight. Interventions that were studied include compression stockings, aspirin, low-molecular weight heparin, and various natural extracts with anticoagulant properties. No significant effect was seen in any of the pharmacologic interventions. Compression stockings (10–20 mm Hg and 20–30 mm Hg) were shown to significantly reduce the risk of asymptomatic DVT; however, four travelers wearing compression stockings in one study developed superficial thrombophlebitis. Symptomatic DVT and PE were not observed in any of the travelers enrolled in the studies.

All travelers should keep hydrated, wear loose-fitting clothing, and make efforts to walk and stretch at regular intervals during long-distance travel. Compression stockings may be beneficial to travelers with other risk factors for VTE. Currently no convincing data suggest that pharmacologic interventions reduce the risk of significant VTE during travel.

The American College of Chest Physicians published the 8th edition of their Antithrombotic and Thrombolytic Therapy Evidence-Based Clinical Practice Guidelines in a June 2008 Supplement to Chest. Recommendations for long-distance travel associated VTE are the following:

• •For travelers who are taking flights >8 hours, the following general measures are recommended: avoidance of constrictive clothing around the lower extremities or waist, maintenance of adequate hydration, and frequent calf muscle contraction (Grade 1C).
• •For long-distance travelers with additional risk factors for VTE, we recommend the general measures listed above. If active thromboprophylaxis is considered because of a perceived high risk of VTE, we suggest the use of properly fitted, below-knee graduated compression stockings (GCS), providing 15–30 mm Hg of pressure at the ankle (Grade 2C), or a single prophylactic dose of low-molecular-weight heparin (LMWH), injected prior to departure (Grade 2C).
• •For long-distance travelers, we recommend against the use of aspirin for VTE prevention (Grade 1B).

INJURIES AND SAFETY

David A. Sleet, L.J. David Wallace, David R. Shlim

Overview

According to the World Health Organization, injuries are among the leading causes of death and disability in the world, and they are the leading cause of preventable death in travelers. Of the approximately five million people killed due to injuries in the world, approximately 1.2 million people died of road traffic incidents, 815,000 from suicide and 520,000 from homicides. In addition to the considerable number of deaths, millions more are wounded or suffer other nonfatal health consequences. Worldwide, among persons aged 5–44 years, injuries account for 6 of the 15 leading causes of death.

In 2007, just over 64 million Americans traveled outside the United States. The vast majority of these trips occurred without any serious health problems, but fatal and serious injuries occur to Americans every year while traveling internationally. Among travelers abroad, injuries are one of the leading causes of death. Compared with injuries, infectious diseases, for example, only account for a small proportion (2%) of deaths to overseas travelers.

The U.S. Department of State collects data on U.S. citizens who die in a foreign country from non-natural causes for the most recent 3-year period and makes these data available on the Department of State website. These deaths are categorized by location where the death occurred, date of death, and cause of death. These deaths should be considered a conservative estimate of the true number of U.S. citizens who die in foreign countries, as some deaths may not be reported to the Department of State. We analyzed these data and found that from 2003 to 2005 an estimated 2,276 U.S. citizens died from injuries and violence while in foreign countries (excluding deaths occurring in Iraq and Afghanistan). Road traffic crashes headed the list of causes (34%), followed by homicide (17%), and drowning (13%) (Figure 2-3 ). By comparison to U.S. injury fatalities in 2003, road traffic crashes accounted for 27%, homicide 11%, and drowning 2% of all injury deaths.

Figure 2-3.

Leading causes of injury death of U.S. citizens in foreign countries, 2003–2005.

(From U.S. Department of State. U.S. citizen deaths from non-natural causes. Washington D.C.: U.S. Department of State. Available from: http://travel.state.gov/law/family_issues/death/death_600.html.)

Depending on travel destination, duration, and planned activities, other common injury and safety concerns include natural hazards and disasters, civil unrest, terrorism, hate crimes against Americans, falls, burns, poisoning, drug-related overdose, and suicide. If seriously injured, emergency care may not be available or acceptable by U.S. standards. Trauma centers which are capable of providing optimal trauma care are uncommon outside urban areas.

Males, compared with females, are more likely to die from injury causes while traveling internationally. Acquaintance rape and sexual assault are among the important risks to women travelers. Travelers should be aware of the increased risk of certain injuries while traveling abroad, particularly in low-income countries, and be prepared to take preventive steps to avoid them.

Road Traffic Injuries

Road traffic injuries are the leading cause of injury-related deaths worldwide. An estimated 3,000 people are killed each day around the world in road traffic crashes involving cars, buses, motorcycles, bicycles, trucks, or pedestrians. Each year another 20 to 50 million are seriously injured. In response to this crisis, in 2008 the United Nations General Assembly, passed resolution 62/244 ‘Improving global road safety” to strength international cooperation to develop policies and practices to reduce crash risks around the world.

According to U.S. Department of State data, road traffic crashes are also the leading cause of injury death to U.S. citizens while traveling internationally (see Figure 2-3). An estimated 768 Americans were killed in road traffic crashes in the period from 2003 to 2005. Approximately 13% of these road traffic deaths involved motorcycles and 7% were pedestrians. A study from Bermuda reported that tourists sustain a much higher rate of motorbike injuries than the local population, with the highest rate in persons aged 50–59 years. Loss of vehicular control, unfamiliar equipment, and inexperience with motorized two-wheelers contributed to crashes and injuries, even when traveling at speeds less than 30 mph. Road traffic crashes are also a leading cause of nonfatal injury among U.S. citizens requiring emergency transport back to the United States.

Road traffic crashes are common in foreign tourists for a number of reasons: lack of familiarity with the roads, driving on the opposite side of the road than in one's home country, poorly made or maintained vehicles, travel fatigue, poor road surfaces without shoulders, unprotected curves and cliffs, and poor visibility due to lack of adequate lighting, both on the road and on the vehicle. In many low-income areas of the world, unsafe roads and vehicles and an inadequate transportation infrastructure contribute to the traffic injury problem. A safety concern in low-income countries is the mixing of motor vehicles with vulnerable road users such as pedestrians, bicyclists, and motorbike users. It is common in low-income countries to have cars, buses, and large trucks all sharing the same road with pedestrians, motorbikes, bicycles, rickshaws and even animals. This mixing of road users all in the same travel lane increases the risk for crashes and injuries.

Sometimes travelers have few options in getting to remote areas, but if there are choices, they should look for better-maintained vehicles, daytime travel, seatbelts and a trained and licensed or hired driver.

Prevention of Road Traffic Injuries

Health advisors should counsel the traveler to:

• •Use safety belts and child safety seats whenever possible. Safety belts reduce the risk of death in a crash by 45%–60%, child safety seats by 54% and infant seats by 70%. When traveling, rent newer vehicles with safety belts and airbags and bring a child safety seat from home.
• •Rent larger vehicles if possible, because they provide more protection in a crash.
• •Try to ride only in taxis with functional safety belts and ride in the rear seat.
• •Wear helmets when riding motorcycles, motorbikes, and bicycles. If helmets are likely to be unavailable at the destination, they should be brought from home.
• •Avoid drinking alcohol and driving or biking. U.S. data show that an alcohol-impaired driver has a 17 times greater risk of being involved in a fatal crash.
• •Visit the websites of the Association for International Road Travel (ASIRT) (www.asirt.org) and Make Roads Safe (www.makeroadssafe.org), both NGOs, which have useful safety tips for international travelers, including road safety checklists and country specific driving risks.
• •Check the safety and security information from the U.S. Department of State (www.travel.state.gov).
• •Consider hiring a driver familiar with the destination, the language and an expert in maneuvering through local traffic.
• •Avoid riding on overcrowded, overweight, top heavy busses, or minivans, or riding with any driver who has consumed alcohol.
• •Be aware of pedestrians and be aware as a pedestrian of the dangers. Walk with a friend, rather than alone, as this helps with safety.

Water Injuries

Drowning accounts for 13% of deaths of Americans abroad. The risk factors have not been clearly defined, but are suspected to be related to unfamiliarity with local water currents and water conditions. Drowning was the leading cause of injury death to Americans visiting countries where exposure to water recreation was a major activity such as Fiji, Dutch Antilles, Aruba, and Costa Rica. Studies have found that young men are particularly at risk of head and spinal cord injuries from diving into shallow water, with alcohol a factor in some cases. In 2000, approximately 449,000 people drowned worldwide; the exact number of travelers who suffer from nonfatal drowning is not precisely known.

Alcohol is also a suspected contributing factor to both drowning and boating mishaps.

Scuba diving is a frequent pursuit of travelers in ocean destinations. Travelers should either be experienced divers, or dive with a reliable dive shop and instructors. They should be reminded not to dive on the same day they arrive by airplane. The fatality rate among all divers, worldwide, is thought to be 15 to 20 deaths per 100,000 divers per year.

Other Unintentional Injuries

From 2003 to 2005, other than drowning, airplane crashes, natural disasters, and other unintentional injuries accounted for over a third of all injury deaths to Americans in foreign countries (see Figure 2-3). Fires can be a substantial risk in low-income countries where building codes are not present or enforced, where there's an absence of smoke alarms, where there is no emergency access to 9-1-1 services, and where the fire department focus is on putting out fires rather than on fire prevention or victim rescue.

Preventing Other Unintentional Injuries

Health advisors should counsel the traveler on the following:

• •Travelers should consider purchasing special health and evacuation insurance if their destinations include countries where there may not be access to good medical care.
• •Because trauma care is poor in many countries, victims of injuries can die before ever reaching a hospital, and there may be no coordinated ambulance services. In remote areas, medical assistance, drugs and medicines may be unavailable and travel can take a long time to the nearest medical facility.
• •Where possible avoid using local unscheduled small aircraft. If available choose larger aircraft (greater than 30 seats) as they have undergone more strict and regular safety inspections. Larger aircraft also provide more protection in the event of a crash. From 2003 to 2005 an estimated 83 Americans were killed in airplane crashes in foreign countries (see Figure 2-3). For country-specific airline crash events, see www.airsafe.com.
• •To prevent fire-related injuries, select accommodations on the 6th floor or below (fire ladders generally cannot reach above the 6th). If possible, stay in hotels with smoke alarms and preferably sprinkler systems. Be alert for improperly vented heating devices which may cause poisoning from carbon monoxide (CO), a colorless odorless gas and by-product of all fossil fuel combustions. Some travelers choose to carry a personal CO detector. Travelers should identify two escape routes from buildings and remember to escape a fire by crawling low under smoke and by covering one's mouth with a wet cloth.

Violence-Related Injuries

Violence is a leading worldwide public health problem and a growing concern of travelers. In 2000, about 1.6 million persons lost their lives to violence and only one-fifth were casualties of armed conflicts. Rates of violent deaths in low- to middle-income countries are more than 3 times those in higher-income countries, although there are great variations within countries, depending on regional demographic differences.

Homicide was the second leading cause of injury death among American travelers in foreign countries accounting for almost 400 deaths from 2003 to 2005 (see Figure 2-3). For some low-income countries such as Honduras, Colombia, Guatemala, and Haiti homicide was the leading cause of injury death for Americans accounting for 43%–65% of all injury deaths.

Terrorism-related deaths among Americans in foreign countries, while alarming, are still relatively rare events and accounted for only 2% of all injury deaths (see Figure 2-3). The vast majority of terrorism deaths among Americans occurred in countries of the Middle East. According to data from the State Department, 2003–2005, 82% of the injury deaths among Americans in Saudi Arabia and 55% of injury deaths in Israel/West Bank/Gaza were from terrorism.

Suicide is the fourth leading cause of injury death to U.S. citizens traveling abroad (see Figure 2-3). Factors contributing to homicide and suicide may be different while traveling than at home. Unfamiliarity with a destination, not being vigilant to one's surroundings, and alcohol involvement may increase risk of assault and homicide. For longer-term travelers (e.g., missionaries and volunteers), social isolation and substance abuse, particularly in the face of living in areas of poverty and rigid gender roles, may increase the risk of depression and suicide.

If a traveler is the victim of a crime overseas, the nearest U.S. embassy, consulate, or consular agency for assistance should be contacted at www.travel.state.gov.

Prevention of Violence

U.S. travelers are viewed by many criminals as wealthy, naïve targets, who are inexperienced and unfamiliar with the culture and inept at seeking assistance once victimized. Traveling in high poverty areas, civil unrest, alcohol or drug use, and traveling in unfamiliar environments at night increase the likelihood that a U.S. traveler will be the victim of planned or random violence.

To avoid violence while traveling, limit travel at night, travel with a companion, and vary the routine travel habits. Travelers should wear locally available accessories that are more typical of a country-savvy expatriate community and avoid expensive or provocative clothing, or accessories. Accommodations on the ground floor of hotels or immediately next to the stairwell should be avoided. Criminals are less likely to victimize upper level floors. All doors and windows should be locked. Some carry a door intruder alarm, a smoke alarm, and a rubber door stop that can be used as a supplemental door lock. Persons unknown to the traveler should not be invited into one's accommodations as this can be misinterpreted or against local laws and customs.

The U.S. Department of State website (www.travel.state.gov) has useful information regarding safety and security.

Summary

Injuries and violence are as much a public health problem to travelers overseas as are infectious and chronic diseases—and they are in many ways more deadly. Injuries are still the most frequent cause of death abroad in developing countries. Effective prevention strategies are available, particularly for travelers who find themselves in new environments and who may be more likely to be unaware of risks or complacent in exotic surroundings. Despite greater understanding and increased research efforts in this field, data on the magnitude and severity of injuries is still incomplete or unreliable in many countries. Existing data indicate that injury and violence are among the most important causes of premature death and ill-health to U.S. travelers overseas. Travel health advisors and other health-care providers should alert the public to the known risks and especially about simple and effective preventive measures to implement during international travel.

NATURAL DISASTERS AND ENVIRONMENTAL HAZARDS

Josephine Malilay, Dahna Batts, Armin Ansari, Charles W. Miller, Clive M. Brown

Natural Disasters

Travelers should be aware of the potential for natural phenomena such as hurricanes, tornadoes, or earthquakes. Natural disasters can contribute to the transmission of some diseases, especially since water supplies and sewage systems may be disrupted, sanitation and hygiene compromised by population displacement and overcrowding, and normal public health services interrupted.

Disease Risks

• •
  The risk for infectious diseases is minimal unless a disease is endemic in an area prior to the disaster event, since transmission cannot take place unless the causative agent is present.

  • ○
    Although typhoid can be endemic in developing countries, natural disasters have seldom led to epidemic levels of disease.
  • ○
    Floods have been known to prompt outbreaks of leptospirosis in areas where the organism is found in water sources (see the Leptospirosis section in Chapter 5).
• •When water and sewage systems have been disrupted, safe water and food supplies are of great importance in preventing enteric disease transmission. If contamination is suspected, water should be boiled and appropriately disinfected (see the Water Disinfection for Travelers section earlier in this chapter).
• •Travelers who are injured during a natural disaster should have a medical evaluation to determine what additional care may be required for wounds potentially contaminated with feces, soil, or saliva or that have been exposed to fresh or sea water that may contain parasites or bacteria.
• •Tetanus booster status should always be kept current.

Injuries

• •When arriving at a destination, travelers should be familiar with local risks for seismic, flood-related, landslide-related, tsunami-related, and other hazards, as well as warning systems, evacuation routes, and shelters in areas of high risk.
• •After natural disasters, deaths are rarely due to infectious diseases but most often to blunt trauma, crush-related injuries, or drowning. Travelers should thus be aware of the risks for injury before, during, and after a natural disaster.
• •In floods, people should avoid driving through swiftly moving water.
• •Travelers should exercise caution during clean-up, particularly when encountering downed power lines, water-affected electrical outlets, interrupted gas lines, and stray or frightened animals.
• •During natural disasters, technological malfunctions may release hazardous materials (e.g., release of toxic chemicals from a point source displaced by strong winds, seismic motion, or rapidly moving water).

Environmental Risks

• •Natural disasters often lead to wide-ranging air pollution in large cities. Uncontrolled forest fires have caused widespread pollution over vast expanses of the world.
• •Natural or manmade disasters resulting in massive structural collapse or dust clouds can cause the release of chemical or biologic contaminants (e.g., asbestos or the arthrospores that lead to coccidioidomycosis).
• •Health risks associated with these environmental occurrences have not been fully studied.
• •Travelers with chronic pulmonary disease may be more susceptible to adverse effects from these exposures.

Event-Specific Information

Typically, following natural disasters of a magnitude that may impact travelers, current information about the disaster, as well as travel health information specific to those needing entry into such regions, is provided on the CDC Travelers' Health website (www.cdc.gov/travel). Recommendations may include specific immunizations or cautions regarding unique hazards in the affected area.

Environmental Hazards

Air

• •Air pollution may be found in large cities throughout the world; its sources are often attributed to automobile exhaust and industrial emissions and may be aggravated by climate and geography.
• •The harmful effects of air pollution are difficult to avoid when visiting some cities; limiting strenuous activity and not smoking can help.
• •Any risk to healthy short-term travelers to such areas is probably small, but persons with pre-existing health conditions (e.g., asthma or chronic obstructive pulmonary disease) could be more susceptible.
• •Avoidance of dust clouds and areas of heavy dust or haze may be wise.

Water

• •
  Rivers, lakes, and the ocean may be contaminated with—

  • ○
    organic or inorganic chemical compounds (e.g., heavy metals or other toxins);
  • ○
    harmful algal blooms (i.e., cyanobacteria) that can be toxic both to fish and to people who eat the fish or who swim or bathe in the water; and
  • ○
    pathogens from human and animal waste that may cause disease in swimmers.
• •Such hazards may not be immediately apparent in a body of water.
• •
  Extensive water damage after major hurricanes and floods increases the likelihood of mold contamination in buildings. U.S. residents may visit flooded areas overseas as part of emergency, medical, or humanitarian missions. Mold is a greater hazard for persons with conditions such as impaired host defenses or mold allergies. To prevent exposure that could result in adverse health effects from disturbed mold, persons should—

  • ○
    Avoid areas where mold contamination is obvious.
  • ○
    Use personal protective equipment (PPE) (e.g. gloves, goggles, tight-fitting NIOSH-approved N-95 respirator). Travelers should take sufficient PPE with them, as these may be scarce in the countries visited.
  • ○
    Keep hands, skin, and clothing clean and free from mold-contaminated dust.
  • ○
    The CDC MMWR guidance, “Mold Prevention Strategies and Possible Health Effects in the Aftermath of Hurricanes and Major Floods,” provides recommendations for dealing with mold in these settings.

Radiation

• •Natural background radiation levels can vary substantially from region to region, but these natural variations are not a health concern for either the traveler or resident population.
• •Travelers should be aware of regions known to have been contaminated with radioactive materials, such as the area surrounding the Chernobyl nuclear power station, 100 km (62 miles) northwest of Kiev, Ukraine. This unprecedented radiation emergency and subsequent contamination primarily affected regions in three republics—Ukraine, Belarus, and Russia—with the highest radioactive ground contamination within 30 km (19 miles) of Chernobyl.
• •In most countries, known areas of radioactive contamination are fenced or marked with signs. These areas should not be trespassed.
• •Any traveler seeking long-term (more than a few months) residence near a known or suspected contaminated area should consult with staff of the nearest U.S. Embassy and inquire about any applicable advisories in that area regarding drinking water quality or purchase of meat, fruit, and vegetables from local farmers.
• •
  Radiation emergencies are rare events. In case of such an emergency, however, travelers should:

  • ○
    Follow instructions provided by local emergency and public health authorities.
  • ○
    If such information is not forthcoming, U.S. travelers should immediately seek advice from the nearest U.S. embassy.
• •Natural disasters (such as floods) may also result in displacement of industrial or clinical radioactive sources. In all circumstances, travelers should exercise caution when they encounter unknown objects or equipment, especially if they bear the radioactive symbol. If a questionable object is encountered, appropriate authorities should be notified.

SCUBA DIVING

Daniel A. Nord

Scuba diving can present a variety of unique medical challenges for the traveling diver. Because diving injuries are generally rare, few health-care providers are trained in their diagnosis and treatment. Thus, the recreational diver must be able to recognize the signs of injury and ensure the availability of dive medicine help when needed.

Fitness to Dive

Planning for dive-related travel should take into account any changes in health status, recent injuries, or surgery. In general, respiratory disorders, as well as any disorders affecting higher function and consciousness (e.g., diabetes mellitus or seizures), respiratory function (e.g., asthma), psychological problems (e.g., anxiety), and pregnancy raise special concerns about diving fitness.

Diving Disorders

Barotrauma

Ear and Sinus

Ear barotrauma is the most common injury in divers. On descent, failure to equalize pressure changes within the middle ear space creates a pressure gradient across the eardrum, which can cause bleeding or fluid accumulation in the middle ear, as well as stretching or rupture of the eardrum and the membranes covering the windows of the inner ear. Symptoms can include—

• •pain
• •tinnitus (ringing in the ears)
• •vertigo (dizziness or sensation of spinning)
• •sensation of fullness
• •effusion (fluid accumulation in the ear)
• •decreased hearing

Paranasal sinuses, because of their relatively narrow connecting passageways, are uniquely susceptible to barotraumas, generally on descent. With small changes in pressure (depth), symptoms are usually mild and short lived, but can be exacerbated by continued diving. Larger pressure changes, especially with forceful attempts at equilibration (e.g., valsalva maneuver), can be more injurious. Additional risk factors for ear and sinus barotrauma include—

• •earplugs
• •medications
• •ear and/or sinus surgery
• •nasal deformity
• •disease

A diver who may have sustained ear or sinus barotrauma should discontinue diving and seek medical attention.

Pulmonary

It is critical for a scuba diver to exhale (or breathe normally) while ascending slowly. Overinflation of the lungs, which usually happens when a novice diver panics, can result as a scuba diver ascends toward the surface without exhaling. During ascent, compressed gas trapped in the lung increases in volume until the expansion exceeds the elastic limit of lung tissue, causing damage and allowing gas bubbles to escape into one or more of three possible locations, as follows:

• •Gas entering the pleural space can cause lung collapse or pneumothorax.
• •Gas entering the mediastinum (space around the heart, trachea and esophagus) causes mediastinal emphysema and frequently tracks under the skin (subcutaneous emphysema) or into the tissue around the larynx, sometimes precipitating a change in the voice characteristics.
• •Gas rupturing the alveolar walls can dissect into the pulmonary capillaries and pass via the pulmonary veins to the left side of the heart, where it is distributed according to relative blood flow, resulting in arterial gas embolism (AGE).

While mediastinal or subcutaneous emphysema usually resolves spontaneously, pneumothorax generally requires specific treatment to remove the air and reinflate the lung. AGE is a medical emergency requiring appropriate intervention, which includes recompression treatment with hyperbaric oxygen.

Lung overinflation injuries from scuba diving can range from dramatic and life threatening to mild symptoms of chest pain and dyspnea. Although pulmonary barotrauma is relatively uncommon in divers, prompt medical evaluation is necessary, and evidence for this condition should always be considered in the presence of respiratory or neurologic symptoms following a dive.

Decompression Illness

Decompression illness (DCI) is an all-inclusive term that describes the dysbaric injuries, AGE, and decompression sickness (DCS). Because the two diseases are considered to result from separate causes, they are described here separately. However, from a clinical and practical standpoint, distinguishing between them in the field may be impossible—and unnecessary, since the initial treatment is the same for both. DCI can occur even in divers who have carefully followed the standard decompression tables and the principles of safe diving.

Arterial Gas Embolism (AGE)

Gas entering the arterial blood through ruptured pulmonary vessels can distribute bubbles into the body tissues, including the heart and brain, where they disrupt circulation. AGE may cause minimal neurologic symptoms or dramatic symptoms that require immediate attention. These signs and symptoms include—

• •numbness
• •weakness
• •tingling
• •dizziness
• •visual blurring
• •chest pain
• •personality change
• •paralysis or seizures
• •loss of consciousness
• •death

In general, any scuba diver who surfaces unconscious or loses consciousness within 10 minutes after surfacing should be assumed to have AGE. Intervention with basic life support is indicated, including the administration of 100% oxygen, followed by rapid evacuation to a hyperbaric oxygen treatment facility.

Decompression Sickness

Breathing air under pressure causes excess inert gas (usually nitrogen) to dissolve in body tissues. The amount dissolved is proportional to and increases with depth and time. As the diver ascends to the surface, the excess dissolved gas must be cleared through respiration via the bloodstream. Depending on the amount dissolved and the rate of ascent, some gas can supersaturate tissues, where it separates from solution to form bubbles, interfering with blood flow and tissue oxygenation and causing signs and symptoms of decompression sickness. These symptoms include—

• •joint aches or pain
• •numbness and/or tingling
• •mottling or marbling of skin
• •coughing spasms or shortness of breath
• •itching
• •unusual fatigue
• •dizziness
• •weakness
• •personality changes
• •loss of bowel or bladder function
• • staggering, loss of coordination, and/or tremors
• •paralysis
• •collapse or unconsciousness

Serious permanent injury may result from either AGE or DCS.

Flying after Diving

The risk of developing decompression sickness is increased when divers are exposed to increased altitude too soon following a dive. The cabin pressure of commercial aircraft may be the equivalent of 8,000 ft (2,438 m). Thus, divers should avoid flying or an altitude exposure >2,000 ft (610 m) for—

• •a minimum of 12 hours after surfacing from a single no-decompression dive, or
• •after repetitive dives and/or multiple days of diving, wait a minimum of 18 hours before ascending to altitude, to reduce the risk of decompression sickness.

These recommended preflight surface intervals do not guarantee avoidance of DCS. Longer surface intervals will further reduce DCS risk.

Prevention of Diving Disorders

Recreational divers should dive conservatively and well within the limits of their dive tables or computers. Risk factors for DCI are primarily dive depth and bottom time; however, factors such as rapid ascent, repetitive dives, strenuous exercise, dives >60 feet, altitude exposure soon after a dive, and physiological variability also increase risk. Divers should be cautioned to stay well hydrated and rested, dive within the limits of their training, and follow established guidelines for dives unique to their travel destination. Diving is a skill that requires appropriate training and certification and should be done with a companion.

Treatment of Diving Disorders

Definitive treatment of DCI begins with early recognition of symptoms, followed by recompression with hyperbaric oxygen. A high concentration (100%) of supplemental oxygen is considered effective first aid in relieving the signs and symptoms of decompression illness and should be administered as soon as possible. Divers are often dehydrated, either because of incidental causes, immersion, or DCI itself, which can cause a capillary leak. Administration of isotonic glucose-free intravenous fluid is recommended in most cases. Oral rehydration fluids may also be helpful, provided they can be safely administered (e.g., if the diver is conscious). The definitive treatment of DCI is recompression and oxygen administration in a hyperbaric chamber.

The Divers Alert Network (DAN) maintains a 24-hour emergency consultation and evacuation assistance at 919-684-8111 or 919-684-4326 (collect calls are accepted). DAN will provide assistance with management of the injured diver, help in deciding if recompression is needed, the location of the closest recompression facility, and assistance in arranging patient transport. DAN can also be contacted for routine nonemergency consultation by telephone at 919-684-2948, ext. 222, or by accessing the website www.diversalertnetwork.org.

Travelers who plan to scuba dive may want to ascertain whether there are recompression facilities at their destination prior to embarking on their trip.

MEDICAL TOURISM

Christie M. Reed

Introduction

Travel for the purpose of obtaining health care abroad has received a great deal of attention in the popular media recently—even Wikipedia has recently devoted a section to the practice (http://en.wikipedia.org/wiki/Medical_tourism). However, it is not the only form of “medical tourism.” The term has also been applied to travel by health-care professionals for the purpose of providing health care. The extent of either form of travel is not well characterized, but the overarching issues for both types of travelers, their primary health-care providers, and travel medicine providers are outlined below.

Travel to Obtain Care

Data from the annual U.S. Department of Commerce in-flight survey during 2003–2006 show an overall annual increase in the number of trips taken by U.S. residents for which at least one purpose was health care. In 2006, there were approximately half a million overseas trips in which health treatment was at least one purpose of travel. Common cited procedures include:

• •Dentistry
• •Reproductive procedures
• •Surgeries (cosmetic, joint replacement, and cardiac)

Lower cost is often mentioned as the motivation for this type of medical tourism, and an entire industry has grown up around this phenomenon. One can search for a provider and research accreditation status of the facility online, opt for an online concierge service that will make all the arrangements or, more recently, find that health insurance coverage may include the option of “outsourced” health care.

The dynamic nature of the field was described in a recent roundtable discussion in Merrell et al.,

In recent years, standards have been rising in other parts of the world even faster than prices have surged in the U.S. Many physicians abroad trained in the U.S. and the Joint Commission International (JCI) applies strict standards to accreditation of offshore facilities. Those facilities use the same implants, supplies, and drugs as their U.S. counterparts. However, a heart bypass in Thailand costs $11,000 compared to as much as $130,000 in the U.S. Spinal fusion surgery in India at $5,500 compares to over $60,000 in the U.S.

However, the quality of facilities, assistance services, and care is neither uniform nor regulated; thus, in most instances, responsibility for assessing suitability of an individual program or facility lies solely with the traveler.

Guidelines for Travelers Seeking Care Abroad

Potential patients should consider that, whatever procedure is being contemplated, travelers undergoing medical treatment outside their accustomed environment are almost always at a disadvantage, particularly if there are complications. Concerns are—

• • Resolution of financial issues if costs escalate, such as in the case of complications.
• •Language and cultural differences may impede accurate interpretation of both verbal and nonverbal communication.
• •Religious and ethical differences may be encountered over issues such as heroic efforts to preserve life or limb or in care of the terminally ill.
• •Lack of familiarity with the local medical system, limited access to past medical history, unfamiliar drugs and medicines.
• •Legal recourse may be fairly limited, difficult to obtain, or nonexistent.
• •Follow-up care back in the United States may be more difficult to arrange and may be fraught with problems, should there be complications.

Potential patients should consider the guiding principles developed by the American Medical Association for employers, insurance companies, and other entities that facilitate or offer incentives for care outside the United States, although in some circumstances it is unclear how realistic they may be (see www.ama-assn.org/ama1/pub/upload/mm/31/medicaltourism.pdf). These principles stipulate that international care must be voluntary and provided by accredited institutions; financial incentives should not inappropriately limit or restrict patient options; there should be continuity of care, including coverage of costs upon return; patients should be informed of their rights and legal recourse before travel; patients should have access to licensing, outcome, and accrediting information when seeking care; medical record transfers should comply with Health Insurance Portability and Accountability Act (HIPAA) guidelines; and patients should be informed of potential risks of combining surgical procedures with long flights and vacation activities. The American Society for Plastic Surgery emphasizes plastic surgery is “real” surgery and outlines the issues every patient undergoing surgery should consider, whether at home or abroad, on their website at www.plasticsurgery.org/patients_consumers/patient_safety/Medical-Tourism.cfm. Several clusters of mycobacterial wound infections in travelers returning from cosmetic procedures abroad have been published. Similarly, the American Dental Association provides informational documents, including: “Traveler's Guide to Safe Dental Care” through the Global Dental Safety Organization for Safety and Asepsis Procedures at www.osap.org and “Dental Care Away from Home” at www.ada.org/public/manage/care/index.asp.

Individuals researching accreditation status should note that, although facilities may be part of a chain, they are surveyed and accredited individually. They should also check the duration of the accreditation and validate that the information is current by consulting the public portion of the appropriate accrediting agency website (see references below).

Pre-Travel Advice for the Medical Tourist

As discussed in the Planning for Healthy Travel section in Chapter 1, patients who do elect to travel should consult a travel health-care practitioner for advice tailored to individual health needs, preferably at least 4–6 weeks in advance of travel. This is particularly true for patients considering invasive procedures, who should consult as soon as travel is considered to allow for assessment of hepatitis B vaccination status (see the Hepatitis B section earlier in this chapter). Hepatitis B and C viruses and HIV are examples of blood-borne infections that can be transmitted via contaminated equipment, from infected health-care providers during invasive procedures, via transfusion of blood or blood products, or through transplantation of tissue or organs that have not been properly screened. Prevalence rates of these viruses vary considerably around the world and are generally higher in developing parts of the world than in the United States. U.S. policies address hepatitis B vaccination status of health-care workers, but these policies are not uniform worldwide and there are no currently licensed vaccines for hepatitis C and HIV. Blood transfusion programs in the United States and other developed areas rely on voluntary, nonremunerated donors; screen the donated blood for a variety of potentially blood-borne pathogens; and are closely regulated. Standards in other parts of the world vary. Based on data from 2000–2001, the latest available on the WHO Global Database on Blood Safety (www.who.int/bloodsafety/global_database/en/), 70 countries did not test all donated blood for the three major blood-borne viruses, HIV and hepatitis B and C.

Organ Transplantation

Organ transplantation in the United States is also a voluntary, closely monitored process coordinated by the United Network for Organ Sharing (www.optn.org). The need for transplantable organs, however, far exceeds the available supply worldwide. Travel to a country with less rigorous methods of distribution for the purpose of obtaining a transplant has been termed “transplant tourism” or “organ trafficking.” Recently, there have been reports in the media of investigations and arrests associated with “rings” that use unscrupulous methods to obtain organs. In 2004, the World Health Assembly Resolution 57.18 encouraged member countries to protect vulnerable populations. Some countries have begun experimenting with controlled programs to relieve the shortage, support the health of the donor, and remove incentives for clandestine operations. A revised set of eleven WHO Guiding Principles on Human Cell, Tissue and Organ Transplantation will be presented to the World Health Assembly in 2009 (www.who.int/transplantation/).

Travel for the Purpose of Delivering Health Care

There are many structured opportunities for health-care professionals, students, or trainees to participate in established programs in developing areas of the world that are mutually beneficial to both the local population and the traveler. Travel by health-care workers in their professional capacity should be governed by the principle of Primum non nocere, or “first, do no harm.” The traveling health-care worker should have sufficient experience or be at a stage in training to be able to contribute labor, knowledge, and skills to the host community. Benefits to the traveling health-care worker include exposure to patients with tropical diseases and conditions that are not commonly seen or are at a more advanced stage than in the country of residence; local diagnostic skills which are often less dependent on technology; and new cultures and new ways of thinking, in addition to any personal gratification. Many medical schools and universities have established reciprocal relationships with institutions in developing areas in which there is an exchange of students and faculty. A variety of organizations match volunteers with local needs for skills-building or to address specific problems. Doctors Without Borders/Médecins Sans Frontières (MSF), which received the Nobel Peace Prize in 1999 for humanitarian efforts around the world, requires a minimum 6-month commitment from physicians and a shorter commitment for surgeons. Interventional programs such as dentistry or surgery simultaneously provide reparative or reconstructive services to the population and train local staff to perform the procedures and provide follow-up care, often donating excess supplies. Other ongoing volunteer relationships exist between faith-based or service organizations and local communities. The involvement of the local health establishment is key to determining needs and maximizing benefit to the local population, as well as educating the visitors on local customs and medical issues and providing translation, if needed, to adequately assess the patients, obtain consent, and advise on postprocedure care.

These forms of international capacity-building should be differentiated from—

• •medicine that is practiced on local populations ad hoc by independent travelers to areas that seem to have no system of health care,
• •the development of adventure holidays sold to groups of doctors specifically for the purposes of research or providing health care in the absence of prior consultation, and
• •students or trainees who travel to “gain practical experience” beyond their training with minimal supervision or absence of structured learning, or practitioners performing outside the area of their expertise.

The acts performed in a life-threatening emergency are justified, but if a local health-care system exists there should still be follow-up with the nearest local provider. Health-care professionals contemplating an international clinical experience should also consult the Humanitarian Aid Workers section in Chapter 8 for a discussion of emotional and physical fitness to participate, preparation, and after-care issues.

The Primary Health-Care Provider

Primary health-care providers play a crucial role in several aspects of medical tourism. For un- or under-insured patients who cannot afford their prescribed course of treatment, the primary care provider may be asked to provide counsel regarding international treatment options, assist with vetting available options, optimize patient status prior to travel, or coordinate care on return. Each provider will need to assess individually his or her ability to address travel health issues or refer to a travel medicine provider.

Clinicians who care for immigrant populations should also be aware that the majority of health-seeking travelers in 2004 were current U.S. citizens born outside the United States, followed by non-U.S. citizens. Health-care needs, such as dentistry, are often included in visits home, due to familiarity with care in the country of origin, the high cost of health care in the United States, and lack of insurance coverage in these populations. There are also recent reports that patients on transplant waiting lists may also travel abroad for the procedure and return to the developed country of residence for continued care, often requiring immediate hospitalization and intense initial management with little documentation. Options for dialysis care are also increasing in developing areas; thus patients requiring this level of care may return home for visits and obtain local care. Acute hepatitis B infections have been diagnosed in patients returning to developed countries from both scenarios. Clinicians providing care to immigrant populations should consider routinely inquiring about future or recent travel home to visit friends and relatives, whether health care will be sought or occurred during travel and advise accordingly (see the VFR section in Chapter 8).

Travel Medicine Providers

Patients who plan to seek medical care abroad may not divulge this activity during the consultation. The desire for anonymity may be a reason for seeking procedures, such as cosmetic surgery or sex-change operations, abroad. As previously mentioned, cost is often an issue, and patients may be uncomfortable self-disclosing. Clinicians may find that routine discussion of hepatitis B vaccination with all patients in the context of risk due to tattoo, sex, emergency medical care, and invasive procedures offers an environment for patients to initiate further discussion.

Health-care providers may also find that the medical industry and associated resources that are rapidly expanding in the developing world related to medical tourism intersect directly with the medical care options for patients with pre-existing illness who travel, emergency care for travelers, and health-care options for expatriates (see the Obtaining Health Care Abroad for the Ill Traveler section later in this chapter).

Additional Resources for Medical Tourism and Accredidation

• •Joint Commission International (jointcommissioninternational.org/)
• •Trent International Accreditation Scheme (trentaccreditationscheme.org/)
• •Australian Council for Healthcare Standards International (www.achs.org.au/ACHSI/)
• •Canadian Council on Health Services (www.cchsa.ca/)
• •International Society of Plastic Surgery also certifies international surgeons who meet U.S. standards (www.isaps.org)

PERSPECTIVES: COUNTERFEIT DRUGS

Michael D. Green

GENERAL INFORMATION

Counterfeit and substandard drugs are an international problem contributing to morbidity, mortality, toxicity, and drug resistance. A counterfeit medicine is a compound that is not made by an authorized manufacturer but is presented to the consumer as if it were. Overall, global estimates of drug counterfeiting are somewhat ambiguous, depending on geographic region, but proportions range from 1% of sales in developed countries to >10% in developing countries. In specific regions in Africa, Asia, and Latin America, chances of purchasing a counterfeit drug may be higher than 30%. Although the availability of fake drugs is a worldwide occurrence, developing countries lacking adequate resources to effectively monitor and maintain good drug quality are most susceptible. These conditions allow for the proliferation of counterfeit as well as substandard medicines.

Since counterfeit drugs are not made by the legitimate manufacturer and are produced under unlawful circumstances, contaminants or lack of proper ingredients may result in serious harm to one's health. For example, the active pharmaceutical ingredient (API) may be completely lacking, present in small quantities, or substituted by another less-effective compound. In addition, the wrong inactive ingredients (excipients) can contribute to poor drug dissolution and bioavailability. As a result, a patient may not respond to treatment, or they may exhibit adverse reactions to unknown substituted ingredients.

Prior to international departure, travel clinics should alert travelers of the dangers of counterfeit and substandard drugs and provide suggestions on how to avoid them. Listed are main points of which to be aware.

HOW TO AVOID COUNTERFEIT DRUGS WHEN TRAVELING

The best way to avoid counterfeit drugs is to reduce the need to purchase medications abroad. Anticipated amounts of medications for chronic conditions such as hypertension, sinusitis, arthritis, hay fever, etc., medications for gastroenteritis (travelers' diarrhea), and prophylactic medications for infectious diseases such as malaria (depending on the destinations) should all be purchased at home prior to traveling.

To do before you leave:

• ¢ Make sure you have all your vaccinations before embarking. Immunizations provide the best protection against many serious diseases.
• ¢ Purchase in advance, in your home country, all the medicines you will need for the entire trip. Prescriptions from your doctor usually cannot be filled overseas, and over-the-counter medicines may not be available in many foreign countries. Checked baggage can get lost; therefore pack as much as possible in a carry-on bag. Bring along extra in case of travel delays.
• ¢ Make sure your medicines are in their original containers. If the drug is a prescription, make sure your name and dosage requirements are on the container.
• ¢ Bring your “Patient Prescription Information” sheet. This sheet provides information on common generic and brand names, usage, side effects, precautions, and drug interactions.

What to do if you run out and require additional medications:

• ¢ Purchase medicines from a legitimate pharmacy. In some places, it is difficult to know if a pharmacy has a genuine license. Your chances of receiving a counterfeit drug are less if you avoid buying from open markets, street vendors, or suspicious-looking pharmacies. Request a receipt when making the purchase. The U.S. Embassy may be able to assist you in finding a legitimate pharmacy in the area.
• ¢ Do not buy medicines that are significantly cheaper than the typical price. Although generics are usually less expensive, many counterfeited brand names are sold at prices significantly below the normal price for that particular brand.
• ¢ Make sure the medicines you purchase are in their original packages or containers. Many times medicines are sold to the pharmacy in bulk and the pharmacist will dispense the required amount of medicine into another container. If you receive medicines as loose tablets or capsules supplied in a plastic bag or envelope, ask the pharmacist to see the container from which it was originally dispensed. Record the brand, batch number, and expiration date. Sometimes a wary consumer will prompt the seller into making sure he or she supplies you with quality medicine.
• ¢ Be familiar with your medications. The size, shape, color, and taste of counterfeit medicines may be different from the authentic. Discoloration, splits, cracks, spots, and stickiness of the tablets or capsules are indications of a possible counterfeit. Keep examples of authentic medications available for comparison if you purchase the same brand.
• ¢ Be familiar with the packaging. Different color inks, poor-quality print or packaging material, and misspelled words are clues to counterfeit material. Also, keep an example of packaging for comparison. Observe the expiration date to make sure the medicine has not expired and the package contains the drug insert.

USEFUL WEBSITES ON COUNTERFEITS

• ¢
  General Information:

  • ○
    CDC:

    • □
      wwwn.cdc.gov/travel/contentCounterfeitDrugs.aspx
    • □
      www.cdc.gov/malaria/travel/counterfeit_drugs.htm
  • ○
    World Health Organization: who.int/mediacentre/factsheets/fs275/en
• ¢ U.S. Food and Drug Administration: www.fda.gov/counterfeit/
• ¢U.S. Pharmacopeia: www.usp.org/worldwide/dqi/drugQuality.html
• ¢Warnings and alerts: www.safemedicines.org/in_the_news/drug_alerts.php
• ¢
  What can you pack in your luggage (for travelers with disabilities and medical conditions):

  • ○
    Transportation Security Administration: www.tsa.gov/travelers/airtravel/specialneeds/editorial_1059.shtm
• ¢
  What can you bring back:

  • ○
    U.S. Customs and Border Protection: www.cbp.gov/xp/cgov/travel/clearing/restricted/medication_drugs.xml
• ¢Reporting counterfeit cases: www.who.int/medicines/services/counterfeit/report/en/

DRUG–VACCINE AND DRUG–DRUG INTERACTIONS

Elizabeth D. Barnett

The pre-travel travel medicine visit potentially exposes people to a number of different vaccines, prophylactic medications, and therapeutic drugs. In addition, the traveler may already be taking one or more medications on a regular basis. Travel medicine practitioners need to think about the possible interactions between all these products. Although a comprehensive list of interactions is beyond the scope of this section, some of the more significant interactions of commonly used vaccines and medications are discussed here.

Interactions between Travel Vaccines and Drugs

Oral Typhoid Vaccine

There is a concern that antibiotics or anti-malarials with antibiotic activity should not be taken at the same time as the oral typhoid vaccine (a live-bacteria vaccine) as they may be active against the vaccine strain and prevent an adequate immune response to the vaccine. These issues should be addressed separately.

Sulfonamides and antibiotics taken orally should not be taken at the same time as oral typhoid vaccine. Parenteral typhoid vaccine is a more appropriate choice for individuals taking antibiotics.

The current mefloquine (Lariam) product insert recommends vaccinations with attenuated live bacteria be completed at least 3 days before the first dose of Lariam. However, one study in humans failed to show any decrease in immunogenicity when the vaccine was given to those on mefloquine prophylaxis. Mefloquine can be given concurrently with the oral typhoid vaccine. Although the antibody response to oral typhoid vaccine was reduced by higher dose proguanil in one study examining the effects of concomitant use of oral typhoid vaccine and chloroquine, mefloquine, and proguanil, a second study using approved prophylaxis doses of atovaquone–proguanil showed no decrease in immunogenicity. Atovaquone–proguanil at prophylaxis doses can be given concurrently with the oral typhoid vaccine. However, since the oral typhoid vaccine should be completed 14 days prior to traveling, there should be no opportunity for concomitant administration with atovaquone/proguanil in most travelers. This same study also showed no decrease in immunogenicity with chloroquine. Chloroquine can be given concurrently with the oral typhoid vaccine.

Doxycycline is an antibiotic with both antibacterial and antimalarial activity. Thus it should not be given concurrently with oral typhoid vaccine. However, since the oral typhoid vaccine should be completed 14 days prior to traveling, there should be no opportunity for interaction with doxycycline in most travelers.

Rabies Vaccine

Concomitant use of chloroquine may reduce antibody response to intradermal rabies vaccine administered for pre-exposure prophylaxis. The intramuscular route should be used for persons taking chloroquine concurrently (the intradermal route is currently not approved for use in the United States); ideally, the rabies pre-exposure prophylaxis series should be completed before beginning chloroquine.

Corticosteroids and other immunosuppressive agents may interfere with response to rabies immunization; when these are used concurrently with rabies vaccine for postexposure prophylaxis, testing should be done to ensure adequate antibody response.

Interactions between Antimalarials and Other Drugs

Mefloquine

Mefloquine may interact with several categories of drugs, including other antimalarials, drugs that alter cardiac conduction, and anticonvulsants. Although the antimalarial halofantrine is not available in the United States, potentially fatal prolongation of the QTc interval of the electrocardiogram may occur if halofantrine is given after mefloquine. Halofantrine should not be given with or after mefloquine. If halofantrine is given for treatment of malaria, mefloquine for prophylaxis should not be resumed until at least 12 hours after the last halofantrine dose. However, no conclusive data are available with regard to coadministration of mefloquine and other drugs that may theoretically have an impact on cardiac conduction. These include anti-arrhythmic or beta-blocking agents, calcium-channel blockers, antihistamines, H1-blocking agents, tricyclic antidepressant, or phenothiazines. Use of these drugs along with mefloquine should be avoided, if possible.

Mefloquine used with the anticonvulsants valproic acid, carbamazepine, phenobarbital, or phenytoin may lower anticonvulsant plasma levels, thus lowering seizure threshold. Monitoring anticonvulsant levels would be appropriate in persons for whom mefloquine must be used concomitantly with these drugs.

Chloroquine

Chloroquine absorption may be reduced by antacids or kaolin; at least 4 hours should elapse between doses of these medications. Concomitant use of cimetidine and chloroquine should be avoided, as cimetidine can inhibit the metabolism of chloroquine and may increase drug levels. Chloroquine inhibits bioavailability of ampicillin; 2 hours should elapse between doses.

Atovaquone–Proguanil

Tetracycline, rifampin, and rifabutin may reduce plasma concentrations of atovaquone and should not be used concurrently with atovaquone–proguanil. Metaclopramide may reduce bioavailability of atovaquone; unless no other antiemetics are available, this antiemetic should not be used for treatment of the vomiting that may accompany use of atovaquone at treatment doses. Atovaquone–proguanil should not be used with other proguanil-containing medications. Patients on anticoagulants may need to reduce their anticoagulant doses or more closely monitor their prothrombin time while taking atovaquone proguanil.

Doxycycline

Doxycycline use theoretically may lead to decreased efficacy of oral contraceptives, although it has been difficult to quantify this effect in a way that is useful for counseling travelers. Changes in hormone levels in women taking oral contraceptives concurrently with doxycycline have not been demonstrated. Phenytoin, carbamazepine, and barbiturates may decrease the half-life of doxycycline. Patients on anticoagulants may need to reduce their anticoagulant doses while taking doxycycline because of its ability to depress plasma prothrombin activity. Absorption of tetracyclines may be impaired by bismuth subsalicyclate, iron-containing preparations, and antacids containing calcium, magnesium, or aluminum; these preparations should not be taken within 1–3 hours of doxycycline. Doxycycline absorption is not markedly affected by food or milk taken concurrently. Doxycyline may interfere with the bactericidal activity of penicillin, and these drugs should not be taken concurrently.

Interactions with Antidiarrheal Drugs

Fluoroquinolones

Increase in the international normalized ratio (INR) has been reported when levofloxacin and warfarin are used concurrently. Concurrent administration of ciprofloxacin and magnesium or aluminum hydroxide containing antacids may reduce bioavailability of ciprofloxacin significantly. Ciprofloxacin decreases clearance of theophylline and caffeine; theophylline levels should be monitored when ciprofloxacin is used concurrently. Ciprofloxacin should not be used with tazanidine.

Azithromycin

Close monitoring for side effects of azithromycin is recommended when azithromycin is used with nelfinavir. Increased anticoagulant effects have been noted when azithromycin is used with warfarin; monitoring of prothrombin time is recommended for such individuals.

Rifaximin

No clinically significant drug interactions have been reported to date with rifaximin. Although the drug induces cytochrome P450 3A4 (CYP3A4), studies of concurrent administration of rifaximin with midazolam and with a single dose of the oral contraceptive ethinyl etradiol and norestironate did not show changes in the pharmacokinetics of these drugs.

Interactions with Drugs Used for Travel to High Altitude

Acetazolamide

Acetazolamide produces alkaline urine that can increase the rate of excretion of barbiturates and salicylates and may potentiate salicylate toxicity. Decreased excretion of dextroamphetamine, anticholinergics, mecamylamine, ephedrine, mexiletine, or quinide may also occur. Hypokalemia caused by corticosteroids may be potentiated by concurrent use of acetazolamide.

Dexamethasone

Dexamethasone interacts with multiple classes of drugs. Use of this drug for treatment of altitude illness may, however, be lifesaving. Interactions may occur with the following drugs and drug classes: macrolide antibiotics, anticholinesterases, anticoagulants, hypoglycemic agents, isoniazid, digitalis preparations, oral contraceptives, and phenytoin.

PERSPECTIVES: PPD TESTING OF TRAVELERS

Philip LoBue

Screening travelers for asymptomatic tuberculosis (TB) infections should only be carried out among travelers who will be at significant risk of acquiring TB (see the TB section in Chapter 5). Screening with a tuberculin skin test (TST) in a very low-risk population may result in a false-positive test, leading to unnecessary further screening or unnecessary therapeutic treatment. Using even highly sensitive and specific tests in very low-prevalence populations will produce more false positives than true positives.

Therefore, the TST should be considered only for travelers anticipating an extended stay over a period of years in a country with a high risk of TB or for those who could be expected to come in contact routinely with hospital, prison, or homeless shelter populations. The general recommendation is that persons at low risk for TB, which includes the vast majority of travelers, do not need to be screened before or after travel.

For travelers who anticipate a long stay or contact with a high-risk population, careful pre-travel screening should be carried out. The two-step TST is recommended in this population, for the following reasons:

• ¢The use of two-step testing can reduce the number of positive TSTs that would otherwise be misclassified as recent skin test conversions during future periodic screenings.
• ¢Certain persons who were infected with Mycobacterium tuberculosis years earlier exhibit waning delayed-type hypersensitivity to tuberculin. When they are skin tested years after infection, they might have a false-negative TST result (even though they are truly infected). However, this first skin test years after the infection might stimulate the ability to react to subsequent tests, resulting in a “booster” reaction. When the test is repeated, the reaction might be misinterpreted as a new infection (recent conversion) rather than a boosted reaction.
• ¢For two-step testing, persons whose baseline TSTs yield a negative result are retested 1–3 weeks after the initial test. If the second test result is negative, they are considered not infected. If the second test result is positive, they are classified as having had previous TB infection.
• ¢Two-step testing should be considered for the baseline testing of persons who report no history of a recent TST and who will receive repeated TSTs as part of an ongoing monitoring of whether they have been exposed to TB.
• ¢ If the two-step TST result is negative, the traveler should have a repeat TST 8–10 weeks after returning from their trip, or as part of a periodic screening examination for those who remain at high risk.

Two-step testing is particularly important for travelers who will have potential prolonged TB exposure; it is particularly important among those going to areas where drug resistance is very high. Two-step testing prior to travel will detect boosting and potentially prevent “false conversions”-positive TST results that appear to be indicative of infection acquired during travel, but which are really the result of previous TB infection. This is particularly important if the traveler is going to a country where XDR TB is rampant. It would be critical to know whether the person's skin test had actually been positive before the travel.

Persons having repeat TSTs must be tested with the same commercial antigen, as switching antigens can also lead to false TST conversions.

An alternative to two-step TST is a single FDA-approved interferon-gamma release assay (IGRA), such as the QuantiFERON TB test (Gold or Gold In-Tube versions). IGRAs are about equally specific as TST in non-BCG-vaccinated populations and much more specific in BCG-vaccinated populations. For a traveler whose time before departure is short, a single-step TST would be an acceptable alternative if there were insufficient time for the two-step TST and the IGRA were not available.

In general it is best not to mix tests. There is about 15% discordance between TST and IGRA, usually with the TST positive and the IGRA negative. There are multiple reasons for the discordance, and in any individual it is often difficult to be confident about the reason for discordance. However, if the health-care provider decides to mix tests, it is better to go from TST to IGRA than the other way around, because the likelihood of having a discordant result, with the TST negative and the IGRA positive, is much lower. Such discordant results may become unavoidable as more medical establishments switch from TSTs to IGRAs.

The use of TST among those visiting friends and relatives in TB-endemic areas should take into account the high rate of TST positivity in this population. In a study among 53,000 adults in Tennessee, the prevalence of a positive TST among the foreign born was 10 times that of the U.S. born (34.2% vs. 3.2%). Confirming TST status prior to travel would prevent the conclusion that a positive TST after travel was due to recent conversion.

TRAVEL HEALTH KITS

Amanda D. Whatley, Deborah Nicolls Barbeau

The purpose of packing a travel health jit is to ensure travelers have supplies they need to—

• •manage pre-existing medical conditions and treat any exacerbations of these conditions,
• • prevent illness related to traveling, and
• •take care of minor health problems as they occur.

Traveling with Medications

When medications are necessary for travel, it is important to remember the following:

• • Original containers: All medications should be carried in their original containers with clear labels, so the contents are easily identified. Although many travelers like placing medications into small containers or packing them in the daily-dose containers, officials at ports of entry may require proper identification of medications.
• • Prescriptions: Travelers should carry copies of all prescriptions, including their generic names.
• • Physician notes: For controlled substances and injectable medications, travelers are advised to carry a note from the prescribing physician on letterhead stationery.
• • Restricted medications: Travelers should be aware that certain medications are not permitted in certain countries. If there is a question about these restrictions, particularly with controlled substances, travelers are recommended to contact the embassy or consulate of the destination country.
• • Availability: A travel health kit is useful only when it is available. It should be carried with the traveler at all times (e.g., in a carry-on bag). Due to airline security rules, sharp objects and some liquids and gels must remain in checked luggage.

Pre-Existing Medical Condition Supplies

Travelers with pre-existing medical conditions are advised to carry enough medication for the duration of their trip and an extra supply, in case the trip is extended for any reason. If additional supplies or medications are needed for the management of exacerbations of existing medical conditions, these should be carried as well. The health-care provider managing a traveler's pre-existing medical conditions should be consulted for the best plan of action (see the section Traveling with Chronic Medical Illnesses in Chapter 8).

Persons with pre-existing conditions, such as diabetes or allergies to envenomations or medications, should consider wearing an alert bracelet and making sure this information is on a card in their wallet and with their other travel documents.

General Travel Health Kit Supplies

A variety of health kits is available commercially and may even be purchased over the Internet (see below); however, similar kits can be assembled at home, often at lower cost. The specific contents of the health kit are based on destination, duration of travel, type of travel, and the traveler's pre-existing medical conditions.

Although this is not a comprehensive list, basic items that should be considered are listed below. See Chapters 7 and 8 for additional suggestions that may be useful in planning the contents of a kit for travelers with specific needs.

Medications

• •
  Destination-related, if applicable:

  • ○
    Antimalarial medications
  • ○
    Medication to prevent or treat high-altitude illness
• •
  Pain or fever (one or more of the following, or an alternative):

  • ○
    Acetaminophen
  • ○
    Aspirin
  • ○
    Ibuprofen
• •
  Stomach upset or diarrhea:

  • ○
    Over-the-counter antidiarrheal medication (such as loperamide or bismuth subsalicylate)
  • ○
    Antibiotic for self-treatment of moderate to severe diarrhea
  • ○
    Oral rehydration solution packets
  • ○
    Mild laxative
  • ○
    Antacid
• •
  Items to treat throat and respiratory symptoms:

  • ○
    Antihistamine
  • ○
    Decongestant, alone or in combination with antihistamine
  • ○
    Cough suppressant/expectorant
  • ○
    Throat lozenges
• •Anti-motion sickness medication.
• •Epinephrine auto-injector (such as an EpiPen), especially if history of severe allergic reaction. Smaller-dose packages are available for children.
• •Any medications, prescription or over the counter, taken on a regular basis at home.

Basic First Aid

• •Disposable gloves (at least two pairs)
• •Adhesive bandages, multiple sizes
• •Gauze
• •Adhesive tape
• •Elastic bandage wrap for sprains and strains
• •Antiseptic
• •Cotton swabs
• •Tweezers*
• •Scissors*
• •Antifungal and antibacterial ointments or creams
• •1% hydrocortisone cream
• •Anti-itch gel or cream for insect bites and stings
• •Aloe gel for sunburns
• •Moleskin or molefoam for blisters
• •Digital thermometer
• •Saline eye drops
• •First-aid quick reference card

Other Important Items

• •Insect repellent
• •Sunscreen (SPF 15 or greater)
• •Antibacterial hand wipes or an alcohol-based hand sanitizer containing at least 60% alcohol
• •
  Useful items in certain circumstances:

  • ○
    Extra pair of contacts or prescription glasses, or both, for people who wear corrective lenses
  • ○
    Mild sedative (such as zolpidem), other sleep aid, or anti-anxiety medication
  • ○
    Latex condoms
  • ○
    Water purification tablets
  • ○
    Commercial suture/syringe kits to be used by a local health-care provider. (These items will also require a letter from the prescribing physician on letterhead stationery.)

Contact Card

It is also important for travelers to locate and record important contact information, in case it is needed during their trip. Often this information is needed quickly; having a contact card with the following items will help save time in these urgent situations.

Items to include on a contact card should be the address and phone numbers of the following:

• •Family member or close contact still in the United States
• •Health-care provider at home
• •Area hospitals or clinics
• •U.S. Embassy or Consulate in the destination country or countries

See the next section in this chapter, Obtaining Health Care Abroad for the Ill Traveler, for information about how to locate local health care and embassy/consulate contacts.

Commercial Medical Kits

Commercial medical kits are available for a wide range of circumstances, from basic first aid to advanced emergency life support. Many pharmacy, grocery, retail, and outdoor sporting goods stores sell their own basic first-aid kits. Travelers who choose to purchase a health kit rather than assemble their own should be certain to review the contents of the kit carefully to ensure that it has everything needed; additional items may be necessary.

For more adventurous travelers, a number of companies produce advanced medical kits and will even customize kits based on specific travel needs.

In addition, specialty kits are available for managing diabetes, dealing with dental emergencies, and handling aquatic environments.

Below is a list of websites supplying a wide range of medical kits. There are many suppliers, and this list is not meant to be all-inclusive.

• •American Red Cross: www.redcrossstore.org
• •Adventure Medical Kits: www.adventuremedicalkits.com
• •Chinook Medical Gear: www.chinookmed.com
• •Travel Medicine, Inc.: www.travmed.com
• •Wilderness Medicine Outfitters: www.wildernessmedicine.com

OBTAINING HEALTH CARE ABROAD FOR THE ILL TRAVELER

Theresa Sommers, Gary W. Brunette

An important aspect of preparing for a trip abroad is to consider the possibility of becoming sick or injured during travel. The following resources and information will be useful to travelers, should they require medical assistance abroad.

Traveling While Ill

Health-care providers should advise their patients about the possible need to avoid traveling if they become ill during their trip. Those with certain health conditions may need to postpone their travel arrangements, including air and public ground transportation. In general, travelers who are ill with a communicable disease that is spread easily to other people should discuss the need for rescheduling travel with their provider.

Travelers should be aware that some airlines check for visibly sick passengers in the waiting area and during boarding. If a waiting passenger looks visibly ill, the airline may prohibit that person from getting on the airplane.

Locating a Health-Care Provider

Several resources are available to American citizens who require medical attention during their travels. The following resources can assist travelers in finding adequate care:

• •
  The U.S. Department of State:

  • ○
    A U.S. consular officer can assist in locating appropriate medical services, as well as in notifying friends, family, or employer of an emergency.
  • ○
    For more information, see http://travel.state.gov/travel/tips/brochures/brochures_1215.html.
• •
  The International Society of Travel Medicine (ISTM):

  • ○
    ISTM maintains a directory of health-care professionals with expertise in travel medicine in almost 50 countries worldwide.
  • ○
    To access the directory, see www.istm.org.
• •
  The American Society of Tropical Medicine and Hygiene (ASTMH):

  • ○
    ASTMH maintains a worldwide directory of providers specializing in tropical medicine, medical parasitology, and travelers' health.
  • ○
    To access the directory, see www.astmh.org.
• •
  International Association for Medical Assistance to Travelers (IAMAT):

  • ○
    IAMAT maintains an international network of physicians, hospitals, and clinics who have agreed to treat IAMAT members in need of medical care while abroad.
  • ○
    Membership is free, although a donation to support IAMAT efforts is suggested. Members receive a directory of participating physicians and medical centers and have access to a variety of travel-related informational brochures.
  • ○
    For more information, see www.iamat.org.
• •
  Travel Health Online:

  • ○
    This resource maintains a list of travel medicine providers worldwide. Information is obtained from a variety of sources, so the quality of services and the expertise of the providers cannot be guaranteed.
  • ○
    For more information, see https://www.tripprep.com.

Travelers may also get information about local health care from embassies and consulates of other countries, hotel doctors, credit card companies, and multinational corporations, which may offer health-care services for their employees. In addition, travelers who obtain evacuation insurance before travel will have access to a 24-hour hotline for help in any medical emergency.

Accreditation of International Health-Care Facilities

The quality of health care from foreign medical centers can be variable, particularly in developing countries. To ensure a higher quality of care abroad, Joint Commission International attempts to continuously improve the safety and quality of care in the international community through the provision of education and consultation services and international accreditation.

A list of accredited international health-care facilities is available at the Joint Commission International website (www.jointcommissioninternational.org).

Drugs/Pharmaceuticals Abroad

The quality of drugs and medical products abroad cannot be guaranteed, as they may not meet U.S. standards or could be counterfeit (see Perspectives: Counterfeit Drugs earlier in this chapter). Travelers are advised to—

• •Bring with them all the drugs and medicines that they think they will need, including pain relievers, antidiarrheal medication, and, if applicable, antimalarials.
• •Exercise caution when buying medications (especially those that do not require a prescription). In many developing countries, virtually any drug can be purchased without prescription.
• •Travelers who may require an injection(s) abroad should bring their own injection supplies (see the Travel Health Kits section earlier in this chapter).
• •Travelers who do not have their own injection supplies yet require an injection should ask if the equipment is disposable and insist that a new needle and syringe be used.

Emergency Care Abroad

The quality and availability of proper emergency medical care abroad may be variable and, in situations requiring a blood transfusion, the safety of blood products often cannot be guaranteed.

• •Not all countries have accurate, reliable, and systematic screening of blood donations for infectious agents, which increases the risk of transfusion-related transmission of disease.
• •
  The 2001–2002 WHO Global Database on Blood Safety report supports this view:

  • ○
    40 countries reported they did not test all donated blood for HIV, hepatitis B and C viruses, and syphilis.
  • ○
    39 countries reported that, due to unavailable testing supplies, blood was released for clinical use without testing for transfusion-transmissible infections.
• •Due to this increased risk, travelers in developing countries should only receive a blood transfusion in life-and-death situations for which there may be no other options.
• •When a situation requires blood transfusion, travelers should make every effort to ensure that the blood has been screened for transmissible diseases, including HIV.
• •
  All travelers should consider being immunized against hepatitis B virus before their trip, especially—

  • ○
    Those who travel frequently to developing countries
  • ○
    Travelers whose itinerary indicate spending a prolonged period of time in developing countries
  • ○
    Travelers whose activities put them at higher risk for serious injury (e.g., adventure travel).
• •There are no medical indications for travelers to take blood with them from their home countries.
• •The limited storage period of blood and the need for special equipment negate the feasibility of independent blood banking for individual travelers or small groups. The international shipment of blood for transfusion is practical only when handled by agreement between two responsible organizations, such as national blood transfusion services. This mechanism is not useful for the emergency needs of individual travelers and should not be attempted by private travelers or organizations not operating recognized blood programs.

TRAVEL INSURANCE AND EVACUATION INSURANCE

Theresa Sommers, Gary W. Brunette

It is important for travelers to consider the financial consequences of a severe illness or injury abroad. A growing number of people do not have health insurance at home. Those who do need to check their policies to determine if their care abroad will be covered and what limitations may apply. Those who have adequate health insurance may not be covered for medical evacuation from a resource-poor area to a hospital where definitive care can be obtained. Even if they have a policy that would reimburse evacuation costs, the health insurance company may not have the resources to help organize the evacuation. Evacuation-only policies are available to fill this gap. Evacuation by air ambulance can cost $50,000 to $100,000 and must be paid in advance by those who do not have insurance.

Paying for Health Services Abroad

Travelers who receive medical care in other countries will usually be required to pay in cash or with a credit card at the point of service, even if they have insurance coverage abroad. This could result in a large out-of-pocket expenditure of perhaps thousands of dollars for medical care.

• •Travelers with health insurance coverage should be sure to obtain copies of all bills and receipts from overseas medical care.
• •The U.S. consular office can assist travelers who are U.S. citizens with transferring funds from the United States.
• •In extreme circumstances, the U.S. consular office may be able to approve small government loans until private funds are available.
• •Medical evacuation insurance may only cover the cost to the nearest destination where definitive care can be obtained. Some policies will cover eventual repatriation to one's home country. The traveler should be sure to understand what coverage is purchased.

Health Insurance Abroad

• •Some health insurance carriers in the United States may provide coverage for emergencies that occur while traveling.
• •
  The first step for travelers is to examine their present coverage and planned itinerary. Determine exactly which medical services will be covered abroad and what supplemental insurance you will need. Things to look for include—

  • ○
    Exclusions for treatment of exacerbations of pre-existing medical conditions
  • ○
    The company's policy for “out-of-network” services
  • ○
    Coverage for complications of pregnancy
  • ○
    Exclusions for high-risk activities such as skydiving, scuba diving, and mountain climbing
  • ○
    Exclusions regarding psychiatric emergencies or injuries related to terrorist attacks or acts of war
  • ○
    Whether pre-authorization is needed for treatment, hospital admission, or other services
  • ○
    Whether a second opinion is required before obtaining emergency treatment
• •Medicare and Medicaid will not cover services outside the United States, except in very limited circumstances.

Travel Health and Medical Evacuation Insurance

Travelers need to evaluate their existing health insurance policies to see whether they already have adequate coverage. Short-term supplemental policies that cover health-care costs on a trip can be purchased. Evacuation coverage can be sold separately or in conjunction with overseas health insurance. Evacuation companies often have better resources and experience in some parts of the world than others. Travelers may want to check with them about their resources in a given area before making a purchase. In general, travelers should purchase a policy that provides the following:

• •Arrangements with hospitals to guarantee payments directly. Travelers may want to check on this possibility for the planned itinerary.
• •Assistance via a 24-hour physician-backed support center. This is critical if the traveler is going to pay for evacuation insurance.
• •Emergency medical transport, including repatriation. Medical evacuation can be costly, ranging from a few thousand dollars to over $100,000.

While travel health and medical evacuation insurance is a consideration for all travelers, it is particularly important for travelers who—

• •Will be outside the United States for an extended period of time.
• •Have underlying illnesses. These travelers should make certain that complications of the underlying condition will be covered by the chosen policy.
• •Participate in activities involving greater risk for injury.

Finding a Travel Health and Medical Evacuation Insurance Provider

The following list, while not all-inclusive, gives a sample of resources for travelers seeking to purchase travel health and medical evacuation insurance:

• •U.S. Department of State (www.travel.state.gov)
• •International SOS (www.internationalsos.com)
• •MEDEX (www.medexassist.com)
• •International Association for Medical Assistance to Travelers (www.iamat.org)

Special Considerations for Travelers with Underlying Medical Conditions

Travelers with underlying medical conditions may want to take extra precautions in preparing for travel.

• •Travelers should choose a medical assistance company that allows customers to store their medical history before departure, so it can be accessed from anywhere in the world, if needed.
• •Travelers should carry a letter from their physician listing underlying medical conditions and all current medications (including their generic names).
• •If possible, travelers may want to carry with them the name of their medical condition and medications written in the local language(s) of the areas they plan to visit.

Special Considerations for Medicare/Medicaid Beneficiaries

• •The Social Security Medicare program does not provide coverage for medical costs outside the United States, except under very limited circumstances.
• • Medicare beneficiaries can purchase supplemental travel health insurance to cover medical expenses outside of the United States.
• •Some Medigap plans available to people enrolled in the original Medicare plan provide limited coverage for emergency care abroad.
• •As with all travelers, Medicare beneficiaries should examine their present coverage carefully to know exactly what will be covered abroad and supplement with additional travel health insurance as appropriate.

MENTAL HEALTH AND TRAVEL

Victor Balaban

Description

Travel is undertaken for a number of reasons, such as adventure, pleasure, business, or personal growth. While most travelers complete their journeys with a manageable amount of stress, foreign travel can produce a wide range of psychiatric, behavioral, and neurologic issues in travelers. Any journey can produce challenges, but longer journeys to more remote and strange environments can increase the psychological stresses for travelers.

Risk Factors

Risk factors that have been identified for developing psychiatric and neurologic problems during and after travel include—

• •Pre-existing psychiatric issues: Stress can trigger or exacerbate psychiatric reactions in travelers with pre-existing psychiatric or behavioral conditions.
• •
  Side effects of mefloquine or other drugs:

  • ○
    People with underlying psychiatric disorders should not receive the antimalarial medication mefloquine. The neuropsychiatric side effects associated with mefloquine may become pronounced in these patients.
  • ○
    The neuropsychiatric side effects associated with mefloquine may also be compounded when administered concurrently with the antiretroviral medication efavirenz, which also carries the risk of neurologic toxicity.
  • ○
    Elderly travelers and travelers with memory or cognitive deficits may be more prone to develop delirium in flight, particularly when combined with dehydration, alcohol, or the use of sleep aids such as zolpidem.
  • ○
    The use of recreational drugs has also been found to be a trigger for psychiatric symptoms in travelers.
• •Stressful events during travel, such as loneliness, a feeling of loss of control, financial difficulties, or a traumatic event such as a serious illness or viewing disturbing sights, can have behavioral and psychosocial consequences for travelers.

Occurrence and Risk for Travelers

Data are limited on the prevalence of travel-related psychiatric and neurologic disorders:

• • A study of Israeli long-term travelers to Southeast Asia found that 11.3% reported psychiatric or neurologic symptoms during travel. The most common symptoms were sleep disturbances, fatigue, and dizziness. The majority of symptoms were short-lived and transient, but 2.5% of travelers reported severe psychiatric or neurologic symptoms, and 1.2% had symptoms lasting more than 2 months.
• •A study of urgent repatriation of British diplomats found that 41% of evacuations for nonphysical causes were due to depression.
• •Adventure travelers in extreme settings, such as polar expeditions, have been found to undergo psychiatric changes, including disturbed sleep, impaired cognitive ability, negative affect, and interpersonal tension and conflict; approximately 5% have been found to meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) or the International Classification of Diseases (ICD) criteria for psychiatric disorders (including substance-related and sleep disorders).

Pre-Travel Mental Health Evaluation

Pre-travel screening should assess risk factors that might indicate a need for a traveler to be referred to a mental health professional for evaluation, especially prior to travel that is likely to be stressful. Factors that should be assessed include—

• •pre-existing psychiatric diagnoses, such as depression or anxiety disorders
• •history of psychosis in the traveler or a close family member
• •history of suicide attempts
• •evidence of depressed mood at assessment
• •exposure to prior traumas (e.g., disasters, severe injury, abuse, assault, etc.), particularly prior to travel that could involve re-exposure to traumatic events or situations
• •recent major life stressors or emotional strain
• •use of medications that may have psychiatric or neurologic side effects
• •pre-travel anxieties and phobias that are severe enough to interfere with a patients' ability to function or to prepare for and enjoy their travel.

Long-term travelers, aid workers, military personnel and other travelers likely to be exposed to stressful situations should be advised that the stresses and challenges they may face, particularly if combined with long hours of work, lack of sleep, or fatigue, can contribute to stress and anxiety. Long-term travelers should be encouraged to—

• •learn how to recognize signs of stress, exhaustion, depression, and anxiety in themselves;
• •take care of themselves physically by eating and exercising regularly; and
• •use their full allotment of time off or annual leave, particularly if they recognize signs of stress or exhaustion in themselves.

During Travel

Severe mental illness occurring abroad can be extremely stressful for travelers, their families, and those who try to care for them. Acute psychosis leading to disruptive behavior can land a traveler in jail in a developing country. Inpatient psychiatric facilities may be either nonexistent or completely inadequate for a foreigner. It can be very difficult to repatriate a psychotic person until the symptoms have been brought under control with medication. Someone will most often have to accompany the person home. Many evacuation insurance plans specifically exclude psychiatric illness from their coverage.

Post-Travel Mental Health Evaluation

Returning travelers may have experienced physical illnesses, personal difficulties, or traumas that could result in psychiatric reactions. Travel-related injuries and diseases that affect quality of life can also have profound and long-term psychiatric impacts. Even in the absence of trauma, some returning long-term travelers report experiencing “reverse culture shock” after their return, characterized by feelings of disorientation, unfamiliarity, and loss of confidence. Approximately 36% of aid workers report depression shortly after returning home, and as many as 60% of returned aid workers have reported feeling predominantly negative emotions on returning home, even though many reported that their time overseas was positive and fulfilling.

Post-travel evaluations should assess—

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  Behavioral and psychiatric symptoms, including:

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    Experiences during or soon after travel, which have been painful, hard to reconcile or which still cause distress, anxiety, or avoidance.
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    Persistent sleep disturbance or unusual fatigue.
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    Excessive use of alcohol or drugs.
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    Behavioral or interpersonal difficulties in home, school, work, in friendships or relationships.
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  Somatic symptoms that can also be indications of distress, including:

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    Unexplained somatic symptoms, such as headaches, backaches, or abdominal pain; and somatic disorders such as fibromyalgia, chronic fatigue syndrome, temporomandibular disorder, and irritable bowel syndrome.
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    Rashes, itching, and skin diseases, such as psoriasis, atopic dermatitis, and urticaria, which can be exacerbated by stress.

Clinicians should be aware that some travelers may be reluctant to acknowledge psychiatric symptoms or distress. For example, many cultures have stigmas associated with experiencing or disclosing behaviors associated with mental illness, as well as different culturally appropriate ways of expressing grief, pain, and loss. In addition, some travelers may fear being penalized or stigmatized at work if they have psychiatric diagnoses noted on their medical records.

Regardless of the type or duration of travel, and whether or not travelers appear to meet criteria for a psychiatric diagnosis, returned travelers who are having difficulties functioning or who appear to be unduly depressed or distressed should be encouraged to seek appropriate treatment or counseling.