STATEMENT ON PEDIATRIC TRAVELLERS

*Members: Dr. P.J. Plourde (Chair); Dr. S. Houston; Dr. S. Kuhn; Dr. A. McCarthy; Dr. K.L. McClean; Dr. C. Beallor; Ms. A. Henteleff

Ex-Officio Representatives: Dr. M. Tepper; Dr. J. Given; Dr. R. Weinman; Dr. F. Hindieh; Dr. J.P. Legault; Dr. P. McDonald; Dr. N. Marano; Dr. P. Arguin; Dr. P. Charlebois; Dr. A. Duggan;

Liaison Representatives: Dr. C. Greenaway; Mrs. A. Hanrahan; Dr. C. Hui; Dr. P. Teitelbaum; Dr. Anita Pozgay

Member Emeritus: Dr. C.W.L. Jeanes.

Consultant: Dr. S. Schofield.

Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada (PHAC) with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. PHAC acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers.

Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.

Introduction

Children, defined by Statistics Canada as those < 15 years of age, comprise 7% of Canadians who travel internationally to destinations other than the United States (1). Although small in number compared to adult travellers, infants and children are an important group based on their unique challenges and the often greater complexity of their preparation for travel. They differ from older individuals in their risk profile, their manifestations and severity of travel-related illnesses as well as the tools available to help protect them from those risks. They also present additional challenges for both travel health professionals and parents in the availability and utilization of preventive and self-treatment measures. In addition, specific health information about travellers in the pediatric age group is limited.

Background: General Risks of Travel

Most of the published data examining travel health risks either exclude children or they comprise a small proportion of the total. In a prospective study of health problems in American travellers attending a travel medicine clinic, 8.3% were ≤ 19 years old, but children 0 – 9 years were more likely to report illness (77%) compared to most other age groups (2). In addition, children ≤ 12 years made up a disproportionate number of cases seeking medical care.

Studies of illness in returning travellers have found that fever is the most common reason to seek care at travel medicine clinics (3), with malaria being the most likely infection (35 – 40%) (3,4) followed by much smaller proportions due to dengue fever, rickettsia, and typhoid, although this varies considerably by region. One small pediatric-specific study identified a similar spectrum of etiologies (5). In another study of 153 children, the authors prospectively studied children up to 15 years old who were admitted with fever and a history of travel within the preceding 12 months (6). Final diagnoses included viral illness (34%), infectious diarrhea (27%), malaria (14%), with a variety of other tropical infections in 12% (6). Cosmopolitan infections, or those found around the world, and particularly viral ones, appear to be more frequent in children (48%) than adult travellers (34%) (4,6). Presumably pediatric morbidity is underestimated by hospital-based data, and little is known about the risk of non-infectious health conditions.

The Department of Foreign Affairs and International Trade Canada analyzed 1995 data from consular reports collecting data on cases of Canadian deaths abroad and determined that of 220 deaths, < 5% were ≤ 19 years of age (7). Trauma has repeatedly been shown to be the most likely cause of death in people < 50 – 60 years of age (7,8), including children (9). Although trauma is also the most common reason for a child to die in Canada (10), the risk appears to be higher in teens who travel than those who do not (8).

Infants and Children: High Risk Travellers?

Children do not usually participate in travel plans until they reach school age, and may have little or no prior international travel experience. Therefore, their reasons for travel as well as their awareness of the risks of travel usually depend upon those of the guardian or adult with whom they are travelling. Their travel is not restricted to that of the short term holiday at a sunny destination, but may also be comprised of prolonged trips, missionary postings, expatriate living, and even more adventurous or unconventional travel activities. Presumably, the greater the risk profile of the adult traveller, the higher the risk for the child. Hence, the risk profile for children born abroad or those born in Canada to immigrant parents and who return to their country of origin to visit friends and relatives (VFR), is thought to be higher than that of children who are not from immigrant families (11). Reasons for this include the observations that VFR travellers tend to travel longer, go to higher risk destinations, stay in rural areas, live with local people, and are less likely to seek pre-travel advice and vaccination, or to use malaria chemoprophylaxis (12).

Individual children differ not only from adults but also from each other as a result of variation in anatomical, physiological, immunological, developmental, and behavioural characteristics. These are discussed in terms of the different pediatric age categories below. While in most cases these factors increase the risk and / or complexity of managing these travellers, children may also benefit from better underlying health compared to some adult travellers.

Infants and Pre-school Age Children (0 – 5 yrs)

Infants and young children have unique characteristics that influence their risk. Short stature, low weight, and proportionally large head size put them at a greater risk of a variety of serious injuries. A large body surface area to weight ratio and immature thermoregulation mechanisms lead to increased susceptibility to temperature extremes (13). Although this is dramatic in the very young, older children and teenagers continue to be at higher risk compared to adults. Infants and pre-school age children have the least immunologic development and experience, and therefore are often more likely to develop an infection when an organism is encountered, be it travel-related or cosmopolitan (14). When infections do occur in the youngest children, their reserve is more limited than in adults and therefore they can progress from mild to severe illness in a short period of time. On the other hand, this age group is also the most challenging to assess medically. At this stage there are developmentally-appropriate behaviours such as putting objects in the mouth, crawling on the ground, limited ability to understand and communicate, short attention span, among others (15) that increase the likelihood of certain infections or incidents.

School-aged Children (6 – 12 yrs)

Arguably, children in this age group may make the easiest travellers. They have grown beyond some of the risks of the younger children, gaining in physical size and coordination as well as early development of judgment. However, their potential for seeking independence and being involved in riskier physical activities also increases, and with it increasing chance of trauma (9,16). They are also at higher risk than adults for some travel-related infections (see below).

Adolescents (13 – 18 yrs)

Youth travel has been recognized as the fastest growing market in the travel industry (17). Teenagers increasingly have opportunities to travel not only with their family, but also alone or with other groups where there may be more risks and less supervision (18). Over 50% of travelling 10 – 19 year olds report some form of health problem while travelling (2). Immunologic maturation probably decreases the risk of some infectious conditions while physical development improves their response to environmental extremes compared to younger children. However, there is also a rise in risk-taking behaviour that results from increasing autonomy with the inability to recognize future consequences, an inappropriate sense of omnipotence, an increasing identification with peers and conflict with parents, along with limited or evolving ability for abstract thinking (19). These characteristics may result in increasing risk of injuries from more adventurous activities, as well as illness resulting from sexual activity, body piercing, tattooing, and experimentation with drugs and alcohol (20,21). There is also the possibility of participation in illicit activities that may result in contact with local law enforcement; four percent of Canadians arrested and detained abroad in 1995 were 10 – 19 years of age (22). Unfortunate and even deadly practices of drug smuggling by pediatric body packing have been reported (23).

Assessment and Preparation

As a result of these differences from adults, children may have an increased risk of exposure to a hazard, an increased risk of contracting an infection or suffering from an illness, and developing more severe manifestations of various conditions. On the other hand there are fewer options in vaccinations and medications to use for prevention and/or self-treatment due to age limitations, and often greater challenges in their administration. As a result, the challenges tend to be inversely proportional to the size/age of traveller.

A travel health risk assessment similar to that for adult travellers should be conducted (24). However, greater time may be required to complete the consultation with children and should be taken into account when scheduling their visits. In some cases, multiple visits may be necessary in order to provide complete care, especially for longer or more adventurous trips. Consideration should be given to having a preliminary visit with the parent(s) alone, especially with pre-school-aged children, so that they can give you their full attention. However, it is also important to involve school-aged children and adolescents in order to ensure that the child has been given a feeling of ownership in the planning process. The whole-family visit allows for children to air concerns about the planning that the parents had not recognized, yet may be important to the success of the voyage. It is also important to allow for time to briefly consult with the adolescent in private in order to address issues related to more sensitive topics such as sexuality and substance abuse (18). Ideally, educational materials and websites should be available to appeal to different age groups. Given the complexities of travel medicine for a broad age spectrum across family members, it is not surprising that a centralized expert care delivery model has been shown to be more cost-effective than generalist-provided travel advice (25).

Travel health clinics should be organized to allow sufficient time and space to minimize the stress on the child, the parent(s), as well as other travellers within earshot. In particular, vaccinators should be comfortable dealing with children and the techniques that minimize emotional trauma. Multiple factors have been shown to impact on uptake of travel vaccines (26), but almost one-quarter of young adults admit to fear of injections, with 8% expressing unreasonably-intense fear (27). Experts argue that the anxiety exhibited by most children is not a phobia (unreasonable response to a benign stimulus) but an understandable anticipatory fear (28). Procedural distress occurs in >90% of toddlers, and almost half of 4 – 6 year olds receiving routine childhood vaccines (29), therefore this is an issue that must be anticipated. A review of different methods to reduce distress found that a topical anesthetic may prevent some pain, but is superficial and requires application in advance. Refrigerant topical anesthetics are immediate, but also only affect the skin. On the other hand, distractions such as light touch, blowing air or bubbles, and non-procedural chatter from the parent may all be effective, and do not require special materials or advance planning (29). A positive vaccination experience is particularly important in travel medicine due to the need for multiple visits for more vaccinations, and the known impact of a prior negative experience with needles (30). For older children, giving them some control over the circumstances of the vaccination may also be helpful.

General Travel Preparation

Travel Planning

Parents should be encouraged to closely examine their plans with the children in mind (31). Consultation with older children regarding the itinerary and activities is key, to ensure that the trip will appeal to everyone, at least some of the time. Flexibility should be built into the itinerary to allow for adjustment of plans. Activities should be age-appropriate and safe. Familiarize the children in advance with the food, customs and language of the destination (32). Families would be wise to start with simple itineraries and more amenities for a first trip, then gradually become more adventurous depending on the comfort of themselves and the child for future trips. If travelling with children, the Department of Foreign Affairs and International Trade recommends carrying documentation that proves your right to accompany them if you are not a guardian, or the other parent is not travelling with you (http://www.voyage.gc.ca/preparation_information/checklist_sommaire-eng.asp).

Child-Related Items

Special foods (formula, baby food) or favorite snacks (granola bars, peanut butter, and fruit leather) for unforeseen delays or dissatisfaction with local food may need to be carried. Disposable diapers may not be readily available or be very expensive, therefore cloth diapers may be a consideration for longer-stays. Sunscreen and repellents should be carried for similar reasons. Consider the conditions of the country being visited (rough streets, rural setting, simple accommodation) when selecting equipment, such as a backpack carrier rather than a stroller, playpen to use as a cot or play space outside, and permethrin-impregnated netting to fit over these for insect protection (see section on Malaria and Other Vector-borne Infections). A small pack can be carried by most children, which can fit some small favorite toys, drawing paper, books, and snacks especially during long journeys (32).

Safety and Security

In addition to the usual recommendations to all travellers around reasonable precautions with documents and personal safety, some special suggestions for children are included in Table 1. Parents should keep in mind that safety standards are not uniform around the world (hotel pools, balconies, local roadways, etc.), therefore the onus is on them to ensure that either they have maximized the safety of the surrounding environment (31) and / or maintain heightened vigilance. Despite the absence of laws requiring safety items (car seats, seat belts, bike helmets) in the country of travel, parents should make every effort to adhere to practices as recommended or legislated in Canada.

Table 1.

Safety and Security Tips

• label clothes of small children inside with name or other identification     • provide older children with accommodation and parent contact information     • establish an age-appropriate “game plan” if separated     • use child-carriers such as a backpack rather than strollers     • explain the reason for extra caution on the streets     • inspect and childproof the accommodation     • choose a family “secret word” to use as a signal to open the door if left alone     • bring or acquire safety equipment for activities (life jacket, helmet, car seat, etc.)     • consider local safety standards before participating in activity (e.g. amusement park rides, local beach, boating)     • warn about dangers of approaching animals     • attempt to find rental vehicles with seatbelts and tether points for car seat

Health Care

Young children may get ill whether they travel or not, therefore it is important that parents are able to deal with minor problems themselves, and know what to do and where to go in the case of more severe illness. For children with chronic diseases, a summary of their condition and possibly a medical contact in a major centre is ideal (33). Appropriate travel health and evacuation insurance is therefore an essential part of the health preparation (31). Sufficient supply of prescription medications should be carried, along with permission letters for controlled drugs and needles. A medical kit can be customized to the ages of the children travelling, but may include items as shown in Table 2.

Table 2.

Medical Kit for Children

• Antipyretic / analgesic     • Saline nasal drops (infant) or decongestant (oral / nasal)      • Antihistamine     • Antiemetic / medication for motion sickness     • Antibiotic for self-treatment of severe travellers’ diarrhea (fever over 38.5 degrees C or bloody diarrhea)     • Topical corticosteroid cream (hydrocortisone 0.5%)     • Topical antibiotic cream     • Band-Aids     • Loperamide (> 2 yrs) or bismuth subsalicyclate     • Thermometer

Medical Kit for Children (continued)

• Malaria medications (if prophylaxis needed)     • Insect repellent     • Sunscreen, at least SPF 30     • Oral Rehydration Solution

Specific Pre-Travel Preparation

Air Travel

Traditionally, it was thought that young infants should avoid air travel due to physiological differences in the first 12 months of life which increase their susceptibility to hypoxemia (34). However, although there is unpredictable hypoxemia in small percentages of infants exposed to 15% oxygen (35), aircraft used for commercial flights are equivalent to 1700 m and 2500 m altitude in newer and older planes respectively, therefore hypoxia is very unlikely. The Aerospace Medical Association recommends waiting only 1 -2 weeks after birth to ensure that a child is healthy before flying, and some airlines will not accept newborns (36). Children with an underlying condition that predisposes them for hypoxia should have a medical assessment to determine whether in-flight oxygen is required (36).

Barotrauma and ear pain can result from the differential pressure between the middle ear and the ambient surroundings during descent, and is more common in children than adults (37). There is some evidence that oral pseudoephedrine reduces ear pain in adults (38,39), but may not provide benefit in children (40). Health Canada issued an advisory in October 2007 warning about life-threatening adverse effects with pediatric cough and cold products, including unintentional overdose, particularly in children under 2 years of age (http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2007/2007_147_e.html). An update indicates that this medicine should not be used in children under 6 years old (http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php). Actions that equilibrate pressure can include bottle or breast feeding, chewing gum, yawning, and blowing with a plugged nose (32). Autoinflation using an Otovent treatment set has also been successful in children who otherwise have difficulty clearing their ears (41). Opinions vary on the timing of flights after diagnosis of acute otitis media and are not based on any studies. Recommendations to provide analgesia if travel with acute ear infection is unavoidable are reasonable. Regulations in Canada allow children < 2 years old to sit on their parents’ lap, but require an approved restraint device if they occupy their own seat. (www.seatguru.com/airlines/Air_Canada/infants.php) The American Academy of Pediatrics have released a policy stating that use of a child-restraint seat should be mandatory (42).

Jet Lag

The effects of jet lag increase with age among adults (43), therefore it is thought that children may be even less affected. However, young children often have a set sleeping schedule that will inevitably be disrupted by long journeys with irregular sleep times and varying locations. Advice for adjustment is similar to that given to adults. While melatonin is considered safe and effective for adults crossing multiple time zones (44), at this time medication should not play a role for most children. A meta-analysis of melatonin for secondary sleep disorders in children including jet-lag showed no evidence of benefit (45). Melatonin has been used in children with other forms of sleep disorders, but a recent commentary points out that concerns about the lack of availability of a regulated product in Canada, uncertainty about appropriate dosing, and limited safety data suggest that larger-scale trials in children are warranted (46). Medications to induce sleep are also not routinely advised due to a risk of over sedation (32) or in some cases paradoxical agitation (e.g. dimenhydrinate) (47).

Motion Sickness

Symptoms of motion sickness vary in frequency and type with age. Preschool children have ataxia with minimal autonomic nervous symptoms (48), while the latter increase and peak at approximately 12 – 21 years of age (49). Dimenhydrinate or similar medications can be considered when necessary but scopolamine is avoided < age 12 years due to increased risk of adverse effects (50). Anti-dopaminergic medications are avoided altogether due to central nervous system adverse effects. Preventive non-pharmacologic measures such as sitting in the most stable part of a vehicle, avoidance of reading or other activity in a moving vehicle, and effective postural support should be employed as much as possible (51,52).

Injuries

Although trauma is known to be the most common reason for a child to die abroad, there is little documented about the risk of non-fatal pediatric injuries when children travel. In many developing countries, however, it is expected that the risk is greater than in Canada due to fewer safety measures (lack of seatbelts and car seats, lack of regulation of sporting or adventure activities) and unfamiliarity of travellers with driving practices (53). Suggestions to minimize risk are similar to those for other travellers, such as avoiding use of motorbikes, wear seatbelts if available, avoid driving at night, and use of appropriately-fitting safety equipment for various activities. Manifestations of snake envenomations are more likely be more severe (54) due to a relatively high venom dose to body size ratio (55). Injury from other venomous creatures can also be more severe, especially in children < 2 years of age (56).

Environmental Extremes

Physical and physiological characteristics of children place them at greater risk than adults at environmental extremes, as they are more likely to adapt poorly and slowly in both hot and cold conditions. Multiple factors contribute to their immature thermoregulation including high body surface area to weight ratio, high metabolic rate: cardiac output, decreased capacity to sweat, higher body surface area to blood volume, and reduced ability to judge the need for fluids and adjustment of clothing (57). This requires close parental observation to ensure that they have appropriate coverage against sun and heat (long sleeves / pant-legs, loose clothing, wide-brimmed hats, sunglasses, sunscreen) as well as cold and / or wet (layered clothing, rain or snow protection). Given the expected delay in acclimatization to higher temperatures, strenuous physical activities should be delayed for several days and even weeks in a hot humid environment, and the hottest part of the day avoided. Voluntary dehydration may occur if children exercising in hot humid conditions are offered unflavoured or simple flavoured drinks, but sports beverages with additional carbohydrates and sodium has been shown to prevent dehydration (58). Parents should therefore offer liberal amounts of these safe fluids.

Altitude sickness

Diagnosis of acute altitude sickness (AMS) can be challenging in young children, therefore the Lake Louise Questionnaire has been adapted for use in pre-verbal children (59). Studies suggest that AMS is at least as common in children as in adults, with rates of 19 – 34% (60). However, a study in Chile showed that the risk of AMS may be inversely related to age, occurring in 100% of children < 4 yrs, 50% of teenagers, and 27% of adults (61). Although high altitude pulmonary edema (HAPE) is rare overall, children appear to be at increased risk if they have a pre-existing illness such as viral upper respiratory tract infection or otitis media (62). The signs of AMS (nausea, vomiting, and irritability) are very non-specific in young children, and could be mistaken for other conditions. Given the rapidity with which children can deteriorate and the limitations in being able to assess them, experts recommend ascending no higher than 2500m with children. If ascents higher than this are made particularly to sleep, slow graded ascent (300 m per day, with a rest day every 1000 m) is recommended (60). Children with medical conditions that increased their risk of hypoxia-related problems should probably avoid high altitude (34). Published data are limited, but most experts agree that pediatric doses of acetazolamide (2.5 mg/kg bid) can be considered for unavoidable ascents to higher altitudes (60).

Infectious Diseases

Enteric Food and Water-borne Diseases

Travellers’ Diarrhea (TD) – Specific pediatric data on travellers’ diarrhea is surprisingly limited. Studies from both Switzerland (63) and Portugal (64) suggest that the attack rate is highest for children under 3 years of age, in spite of the high rate (60%) of (parental) adherence to dietary preventive measures. The adherence rate was highest in pre-school children, then dropped steadily to a nadir in teenagers. TD was also most prolonged in infants and toddlers compared to older children and adolescents (median 18 vs. 3 days) (63).

The spectrum of causative organisms is presumed to be similar to adults (65). Organism-specific epidemiological studies in Swedish travellers found children 0 – 6 years of age to be at higher risk than older groups for non-typhoidal salmonella (66), shigellosis (67) and giardiasis (67,68). The highest risk destination for all of these infections was the Indian sub-continent, followed by East and West Africa. Children with ethnic roots in the country visited (VFRs) were over-represented compared to adults with the infection (68). Cholera is rare among pediatric travellers from developed countries.

The elevated risk in children of these bacterial and parasitic infections may be a result of poor hygiene (young children), risky eating habits (teenagers) (63), and / or a relative lack of gastrointestinal immunity (69).

Typhoid and paratyphoid – Children comprise the highest risk group for S. typhi among imported cases reported in both the US and in recent years in Canada (14,70); among children, the preschool age group appears to be at highest risk, similar to the epidemiology of endemic countries (71). In contrast, S. paratyphi may be more common in children 7 years and over (72), which has been postulated to result from food transmission (e.g. street vendors) rather than the person-to-person transmission which occurs more commonly with typhoid (73). See CATMAT Typhoid Guidelines. (http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/94pdf/cdr2008.pdf) (74).

Hepatitis A – Although this infection is usually asymptomatic < 2 years of age, moderate to severe illness can occur in those who are older. Overall, the incidence of imported hepatitis A appears to have decreased in the last two decades from a rate of 300/100,000 to 6 – 28 per 100,000 non-immune travellers to medium to high risk destinations (75). This is likely a combination of vaccination and improved sanitation in destination countries. However a relatively high risk remains for travellers to certain destinations (Indian subcontinent) (76), visiting friends and relatives (VFRs) (73,75-77), < 15 years of age (75). For children visiting the Indian subcontinent, VFRs are at an 8-fold risk compared to older tourists (78). Vaccination should be considered for all travellers, including those 1 – 2 years of age due to the risk of transmission to others at higher risk. See CATMAT Hepatitis Guidelines (http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/08vol34/acs-2/index-eng.php) (79).

Hepatitis E - Imported hepatitis E has a transmission pattern and clinical manifestations similar to hepatitis A, with most cases occurring in adult travellers (80). Pregnant adolescents and children with chronic liver disease are at increased risk for severe manifestations and death (81,82). Mother-to-child transmission has also been documented at a rate of 50% (83). There is currently no vaccination available and insufficient specific antibody in serum immune globulin in North America to provide passive protection.

Prevention of Enteric Food and Water-borne

Food and beverage precautions are the same as those for older travellers (84), with special attention to frequently-consumed products in childhood such as milk (85). Although the protective benefit of hand hygiene has not been proven in travellers (86), a systematic review including studies from various developing countries as well as the US demonstrated an approximately 45% risk reduction of diarrhea episodes (87).

Vaccination plays a role in protecting children depending on their itinerary, age and other risk factors. Vaccines are currently available for prevention of cholera and enterotoxigenic E. coli (combination oral vaccine ≥ 2 yrs) typhoid fever (injectable ≥ 2 yrs, oral ≥ 6 yrs), see CATMAT Travellers’ Diarrhea (84), and hepatitis A (injectable ≥ 1 year), see CATMAT Hepatitis statement (79). Please refer to Table 4 for additional information. Data suggest that efficacy is similar to that in older travellers within these age guidelines with the exception of the cholera component of the combined oral vaccine, with three doses required in children 2 – 6 years (vs. 2 doses) and a shorter duration of immunity (6 months vs. 2 yrs) compared to older children and adults.

Bismuth subsalicylate taken four times per day has been shown to be effective prophylaxis in adults, with a 60% risk reduction (88). Although bismuth has been shown to decrease severity and duration of symptoms in children with acute diarrhea (89,90), prophylaxis data are lacking. It should be avoided in conditions associated with Reye Syndrome (varicella and influenza infections), and is not licensed for children < 2 years (84).

Standby self treatment for Travellers’ Diarrhea

In contrast to adults (91), oral rehydration therapy is the cornerstone of treatment for young children with TD yet is often under-utilized (63). Symptomatic self-treatment for non-bloody diarrhea with loperamide can be considered for those > 2 yrs (92,93) along with azithromycin (10 mg/kg/d for 3 days) for presumed bacterial pathogens (94). The latter is effective against multiple bacterial enteric pathogens including Campylobacter spp (95). and has been shown to be comparable to quinolones in treatment of adult TD in Mexico (96). Azithromycin may be the preferred agent for most travellers to south and southeast Asia due to rising quinolone resistance rates in some organisms (97). Although quinolones such as ciprofloxacin and levofloxacin are licensed for use ≥ 16 yrs in Canada, there is no evidence of effects on bones or cartilage in juvenile humans (98) and pediatric practitioners recognize it can be used selectively in children as a result (99), particularly for a short (1 – 3 day) course. Therefore, these can be considered alternatives for children intolerant or allergic to azithromycin. Cefixime is a third option, although efficacy studies are limited to shigellosis (100) where it may be inferior to azithromycin (101). Rifaximin is a poorly-absorbed rifamycin-derivative which appears to have activity against a broad range of enteric organisms (102). Currently it is not available in Canada, but is marketed in the US for the treatment of travellers’ diarrhea due to non-invasive E. coli in those ≥ 12 years of age.

Respiratory Infections

Respiratory infections are prominent among travellers of all ages, although the upper respiratory tract was more commonly involved than the lower tract among young persons in a review by GeoSentinel in 2003 (103). Risk of some respiratory infections may be increased compared to non-travellers due to crowded conditions (e.g. pertussis) (104), different seasons of illness and/or mixing of populations (e.g. influenza) (105) or increased prevalence in the population visited (e.g. tuberculosis) (106,107). Infants and pre-school children are generally at increased risk of severe disease for all these infections.

Vaccination is available for pertussis, influenza, and in select cases for tuberculosis (see Immunization section). Children may also participate in adventure activities during the trip which may result in the risk of infections such as histoplasmosis (108).

Malaria and Other Vector-borne Infections

Malaria - In endemic populations, children are more frequently and severely infected due to lack of partial immunity. Although one might expect little difference across age groups in malaria-naive travellers, data compiled by the Canadian Malaria Network also shows an overrepresentation of children among severe imported cases requiring the use of intravenous quinine (A McCarthy, Personal communication). This suggests that increased severity is also more likely among pediatric compared to adult travellers. Their relatively small blood volume may work against them, potentially resulting in a higher parasitemia much more quickly than in adults. Manifestations of severe malaria in children include cerebral disease (reduced consciousness, seizures, permanent neurologic deficit), severe anemia, and shock (109). For unknown reasons, other manifestations such as renal failure are more likely seen in adults. See Malaria Guidelines for further details on the prevention and treatment of malaria in children (110). Table 3 provides a brief outline.

Table 3. Malaria Chemoprophylaxis.

Drug	Dose	Frequency	Comments*
Chloroquine	5 mg/kg (base; max 300 mg)	Weekly Start 1 wk prior to risk and continue until 4 wks after risk ends	1) 150 mg tabs (base = 250 mg salt). 2) Liquid formulations available in some countries.
Mefloquine	5 mg/kg (base; max 250 mg) 5 – <10 kg: 1/8 tab 10 – <20 kg: ¼ tab 20 – <30 kg: ½ tab 30 – <40 kg: ¾ tab	Weekly Start 1 – 2 wks prior to risk and continue until 4 wks after risk ends	250 mg tabs (base)
Doxycycline	2 mg/kg (max 100 mg)	Daily Start 1 d prior to risk and continue until 28 d after risk ends	100 mg tabs; ≥ 8 yrs
Atovaquone-Proguanil	5 – 8 kg: ½ peds tab > 8 – 10 kg: ¾ peds tab >10 – 20 kg: 1 peds tab >20 – 30 kg: 2 peds tabs >30 – 40 kg: 3 peds tabs >40 kg: 1 adult tab	Daily Start 1 d prior to risk and continue until 7 d after risk ends	Pediatric tab: 62.5 mg atovaquone / 25 mg proguanil Adult tab: 250 mg atovaquone / 100 mg proguanil
Primaquine	0.5 mg/kg base (max 30 mg)	Daily Start 1 d prior to risk and continue until 7 d after risk ends	15 mg tabs (base)

For details on contraindications and cautions, see 2009 CATMAT Malaria Guidelines (110)

Other Diseases

Rates of other vector-borne diseases among pediatric travellers have not been well-documented outside of endemic regions. These include dengue fever, Japanese encephalitis b virus (JEV), yellow fever, tick-borne encephalitis, tick typhus, among others. See Table 4 for vaccines available (Japanese encephalitis, yellow fever, tick-borne encephalitis). Dengue fever and JEV are principally diseases of childhood in endemic countries depending on intensity of transmission. Infants and young children with dengue usually have an undifferentiated febrile illness with maculopapular rash or an upper respiratory tract infection with pharyngitis, whereas older children and adolescents resemble adults with classic dengue (111). For this reason, it may be less likely to be identified in young travellers, yet may predispose them to more severe manifestations with subsequent infections. Dengue hemorrhagic fever (DHF) is principally seen < 15 yrs of age in hyperendemic populations (111), but has rarely been reported in pediatric travellers (112). However, DHF can also occur with primary infections, usually in infants < 1 yr (due to passively-transmitted heterotypic maternal antibody) or those infected with dengue serotypes 1 or 3 (113). See individual disease guidelines at www.catmat.gc.ca for more details on these diseases. Although dengue vaccines are under development, none are available commercially at this time. Japanese encephalitis is more common among children than adults in endemic areas, presumably due to immunity in older populations from prior exposure. Most cases are mild or inapparent, but among symptomatic cases, children have a high risk of developing generalized motor seizures (114). However, overall mortality with Japanese encephalitis increases with age. Manifestations of other vector-borne diseases are similar to non-elderly adults (See CATMAT Japanese Encephalitis statement for further information) (115).

Personal protective measures

For all vector-borne diseases, the first line of defense for children are personal protective measures (PPM (116). These are important to prevent insect bites during both the daytime (dengue, tick-borne infections, yellow fever, African Sleeping Sickness) and evening / nighttime (malaria, JEV, leishmaniasis, chagas disease). Avoidance of areas or activities that increase exposure to vectors and use of physical barriers (e.g. loose, long-sleeved shirts, long pants whenever possible) should be the first measures considered, followed by use of chemical barriers. A recent the CATMAT guideline addresses this topic in detail including the very low risk of serious adverse effects with appropriate use of agents including DEET (117,118). Children should receive the same protective measures that adults use in regions that have vector-borne diseases that pose a health risk. For this reason, CATMAT (110) and the Academy of Pediatrics (119) recommend the use of DEET products up to 30% in children ≥ 6 months of age when other measures are not sufficient. In Europe and the US, Bayrepel^®/Picaridin is another chemical repellent that shows long lasting protection against a variety of biting arthropods (120). Many “natural” products do not provide sufficiently long protection to be of practical use and in many cases have not been tested for activity against tropical mosquito species (117).

Permethrin-impregnated bednets are essential for travellers of all ages when travelling to areas endemic for malaria and other serious diseases transmitted by night-biting insects (121). For younger infants, permethrin-treated nets can also be used for cots, playpens, and strollers. Where available, permethrin can also be applied to clothing, and has been shown to reduce arthropod bites. Hence it is expected to provide some protection against associated diseases (122). Permethrin products and pre-impregnated clothing are available commercially in the US and some tropical destinations. Refer to CATMAT statement on personal protective measures (117) for full details on the prevention and protection against mosquitoes and other arthropod bites.

Malaria Chemoprophylaxis

Chloroquine remains the prophlyaxis of choice for regions with malaria susceptible to this drug, and can be used in infants and children of all ages. For chloroquine-resistant areas, options are the same as for adults with some age limitations. Mefloquine is recommended by the manufacturer for children > 5kg, but it should be considered in any child at sufficient risk, regardless of weight. Children may be at higher risk of emesis (123), but are less likely to suffer neuropsychiatric effects than adults (124). Atovaquone-proguanil is also safe and effective from early infancy; a recent review by experts provides prophylactic doses for infants ≥ 5 kg (125). Tetracyclines can stain teeth and affect bone growth in young children, but doxycycline can be safely used in children ≥ 8 years of age (126). Primaquine is an alternative if none of the other options can be used (127). See Table 3 for dosage recommendations. Non-age or weight-related contraindications for the above antimalarials are the same for children as for adults.

Compliance with antimalarials can be particularly challenging in young children due to the lack of liquid formulations in North America, and the unpalatability of the tablets when crushed. Tips to ensure appropriate dosing (e.g. portions of tablets), improved taste, as well as prevention of inadvertent and potentially fatal overdosing is an important part of malaria prevention for children. See the 2009 CATMAT Canadian Recommendations for the Prevention and Treatment of Malaria among International Travellers for details (110).

Vaccine-Preventable Diseases

Routine Immunizations

 

Review of immunization starts with assessment of routine vaccination status as with adult travellers. Given that some infections may be a concern due to reduced access to safe medical care (e.g. tetanus from injury during remote trip) or potentially higher risk abroad, all children should have their vaccine records inspected during a pre-travel assessment. Risk may be elevated due to increased circulation of infections (e.g. measles, diphtheria, polio, Hemophilus influenzae b, Streptococcus pneumoniae, Meningococcal infections, or Hepatitis B) or exposure to situations where transmission is increased (e.g. pertussis, influenza A/B, or meningococcal infection) during mass gatherings. Importation of some of these infections through travel is well-documented, such as diphtheria (128), polio (129), and measles (130). The consultation provides an important opportunity to catch-up on vaccinations missed or delayed, and where necessary initiate a rapid and/or early vaccination schedule. Measles vaccination can be given from age ≥ 6 months when going to endemic areas, but since efficacy is reduced should be repeated twice according to the routine schedule, starting at 12 months of age. Other vaccinations can be initiated starting at 6 weeks of age as outlined in the Canadian Immunization Guide (131).

Recommended and Required Travel Immunizations

 

Recommendations for children to be vaccinated will vary with their individual risk of exposure and the severity of potential infection. For some diseases of children, this risk may be greater than that of an adult on the same trip. On the other hand, there may be no products available that are known to be effective and/or safe in young children or infants. Age limitations are a consideration for most of these vaccines and exceptions should be rare except where noted below (see Table 4). For details on these and other travel-related vaccines, see specific guidelines at www.catmat.gc.ca.

Table 4. Travel Vaccines.

Vaccine(s)	Brand Name(s)	Age	Schedule(s)	Comments
Hepatitis A	Havrix (Jr) *	≥ 1 – 18yrs *	0, 6 – 12 mos	Products interchangeable
	Vaqta (Peds) #	≥ 1 – 17yrs #	0, 6 – 18 mos
	Avaxim (Peds) †	≥ 2 – 15 yrs; Adult product ≥12 yrs †	0, 6 – 12 mos
Hepatitis B	Engerix-B (Peds)	≥ birth – 19 yrs 1	0,1, 6 mos 0,1,2,12 mos	1 Engerix (Adult) for 11 – 15 yrs, 0 and 6 mos (provincial programs)
	Recombivax HB (Peds)	≥birth – < 11 yrs (.25 μg) 11 – 19 yrs 2 (.5 μg)	0,1, 6 mos 0,1, > 2 mos > 1 mo between doses	2 Adult formulation for 11 – 15 yrs, 0 and 4 – 6 mos (provincial programs)
Typhoid	Typhim Vi, Typherix (injectable)	≥ 2 yrs	Single dose
	Vivotif (oral – Ty21a)	≥ 6 yrs	Alternate days, 4 doses (capsule or suspension)
Typhoid / Hepatitis A	Vivaxim	≥ 16 yrs	Single dose
Japanese encephalitis	Je-vax	1 – < 3 yrs (0.5ml) ≥ 3 yrs (1.0 ml)	0, 7, 30 d alt: 0, 7, 14 d	No longer being produced. New vaccine (Ixiaro) – not yet approved for children.
Yellow fever	YF-Vax	≥ 9 months	Single dose	Encephalitis < 6 months
Meningococcal - conjugate	Menactra	≥ 2 yrs	Single dose	2 doses, 9 – 15 mos (see text)
Cholera + ETEC	Dukoral	≥ 2 yrs	0, 7 days	Children 2 – 6 yrs require additional dose at 14 d for cholera Booster at 3 mos for ETEC, 2 yrs (≥ 6 yrs old) or 6 mos (2-6 yrs old) for cholera

Some travel-related diseases are more likely to occur in children compared to adults. See Enteric Infections, above, for hepatitis A and typhoid. Higher rates of hepatitis B have been demonstrated among children of expatriates and missionaries (132,133), highlighting the importance of medical, horizontal and possibly maternal transmission. Children are at greater risk for rabies, suffering 40% of dog bites worldwide (134). In Nepal, pediatric animal bites were more likely among expatriates than travellers, and more often occur in the head and neck region (135). Children may not have the reasoning skills to avoid animals, or to report a potential exposure (such as a scratch or other minor wound) to their parents. Meningococcal infections are highest risk for children < 2 years during outbreaks, but spread to older children and adolescents in epidemics (136). A single dose of conjugated quadrivalent meningococcal vaccine (vs. serogroups A, C, Y, W135) has been found to be safe in children ≥ 2 years old and results in higher mean titres compared to the quadrivalent polysaccharide vaccine (137). A phase II study suggests that an additional dose 3 months after the initial one may be immunogenic in 9 – 15 month old children (138). Although BCG is rarely used for Canadian travellers, it may be considered for children who are travelling or living for a prolonged period of time in a high-prevalence country (131,139), particularly in infants and children ≤ 4 yrs due to their elevated risk of severe and/or disseminated disease with primary infection (139,140). Alternatively, Tuberculin Skin Testing can be used when appropriate to monitor for latent TB infection (LTBI) and consideration of treatment for LTBI.

Cases of vaccine-preventable vector-borne infections (Japanese encephalitis, tick-borne encephalitis, yellow fever) have been rarely reported among pediatric travellers (141), but the severity of the illnesses is well-recognized among endemic populations. In one study of children ≤ 15 years attending a travel clinic, yellow fever vaccination is administered less than the recommended 10 days before departure in about 20%, and may put these children at risk (142). Care must be taken to review contraindications to this vaccine, since most cases of vaccine-associated encephalitis in infants have been reported in those < 4 months of age, and only two cases 5 – 7 months of age (143). One vaccine is currently available in North America to prevent Japanese b encephalitis for children ≥ 1 year old. A vaccine for Tick-borne encephalitis is available in Canada which is licensed for children ≥ 16 years although products for younger children are available in Europe. See individual CATMAT Statements on these diseases and immunizations for details at www.catmat.gc.ca.

Conclusions

Children comprise a special group of travellers whose risk profile require special consideration for parents and travel health professionals alike, and may result in more challenges for preparation. Careful consideration of the trip from the child’s perspective and sufficient time to consult appropriate resources to aid preparation to maximize protective strategies are essential to providing their pre-travel care.

Table 5.

Recommendations for Pediatric Travellers / Recommandations à l’intention des jeunes voyageurs
	EBM Rating
Parents should consider what is appropriate and enjoyable for children when they plan, prepare, and embark on their trip.	CIII
Immigrant children or Canadian-born children of immigrants visiting friends and relatives are at increased risk of several infectious conditions relative to local children and warrant special effort to ensure appropriate education and other protective measures.	AII
Diarrhea must be treated with fluid and electrolyte replacement, especially in children and the elderly	AI
Antibiotic therapy with a fluoroquinolone or azithromycin is recommended as presumptive therapy of moderate to severe travellers’ diarrhea (with fever over 38.5 degrees C or bloody diarrhea)	AI
Immunization against Hepatitis A and / or typhoid should be advised for children who will be at significant risk.	AII
Children ≥ 6 mos old at risk of exposure to serious arthropod-borne infections should appropriately use insect repellent containing DEET - the preferred insect repellent, unless contraindicated (e.g. allergic reaction).	AI
Additional personal protective measures including permethrin-treated nets and clothing barriers should be used in children of all ages.	AII
Children should be administered the appropriate malaria chemoprophylaxis when travelling to malaria-risk regions.	AI
Distraction methods can be used to help young children cope with immunization pain and fear.	BI
Routine childhood immunizations should be up-to-date prior to international travel due to the elevated risk for many of the infections abroad.	AII
Children are at higher risk of animal bites with rabies risk, therefore rabies vaccination should be considered, particularly those in remote regions and areas without adequate post-exposure prophylaxis, or on prolonged visits abroad	AII
Meningococcal quadravalent vaccine should be administered to children entering a region with sufficient endemic or epidemic activity	AI
All travel-related vaccines, when indicated, should be administered according to the known age limitations for efficacy and safety.	AI