†Members: Dr. J. Langley (Chair), Dr. B. Warshawsky (Vice-Chair), Dr. S. Ismail (Executive Secretary), Dr. N. Crowcroft, Ms. A. Hanrahan, Dr. B. Henry, Dr. D. Kumar, Dr. S. McNeil, Dr. C. Quach-Thanh, Dr. B. Seifert, Dr. D. Skowronski, Dr. C. Cooper.
Liaison Representatives: Dr. B. Bell (U.S. Center for Disease Control and Prevention), Ms. K. Pielak (Canadian Nursing Coalition for Immunization), Dr. S. Rechner (College of Family Physicians of Canada), Dr. M. Salvadori (Canadian Pediatric Society), Dr. S. Pelletier (Community Hospital Infection Control Association), Dr. N. Sicard (Canadian Public Health Association), Dr. V. Senikas (Society of Obstetricians and Gynaecologists of Canada), Dr. P. Plourde (Committee to Advise on Tropical Medicine and Travel), Dr. P. Van Buynder (Council of Chief Medical Officers of Health).
Ex-Officio Representatives: Ms. M. FarhangMehr (Centre for Immunization and Respiratory Infectious Diseases), Dr. S. Desai (Centre for Immunization and Respiratory Infectious Diseases), Dr. B. Law (Centre for Immunization and Respiratory Infectious Diseases), LCol (Dr.) James Anderson (Department of National Defence), Dr. Ezzat Farzad (First National and Inuit Health Branch - Office of Community Medicine), Dr. J. Xiong (Biologics and Genetic Therapies Directorate), Dr. D. Elliot (Centre for Immunization and Respiratory Infectious Diseases), Dr. P. Varughese (Centre for Immunization and Respiratory Infectious Diseases).
Additional Influenza Working Group Members: Dr. G. DeSerres, Dr. I. Gemmill, Dr. S. Halperin, Dr. B. Cholin, Dr. L. Pelletier.
Preamble
The National Advisory Committee on Immunization (NACI) provides the Public Health Agency of Canada with ongoing and timely medical, scientific and public health advice relating to immunization and certain prophylaxis agents.
The Public Health Agency of Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and is disseminating this document for information purposes. People administering the vaccine should also be aware of the contents of the relevant product leaflet(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s)/leaflet(s) of the Canadian manufacturer(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of the Public Health Agency of Canada’s Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.
IMPORTANT note regarding antiviral guidelines and pandemic monovalent H1N1 vaccine recommendations:
Owing to the increasing complexity of antiviral issues, antiviral recommendations will be developed, updated, approved and posted through a separate national process.
Guidance on the use of monovalent H1N1 vaccine is not addressed in this NACI statement but is available at http://www.phac-aspc.gc.ca/alert-alerte/h1n1/vaccine_vaccin-eng.php.
I. Introduction
I.1. Overview and Summary of Changes
The purpose of this statement is to provide the NACI recommendations for immunization with the seasonal trivalent inactivated influenza vaccine (TIV) for the 2010-2011 season, based on evidence available at this time.
The seasonal trivalent vaccine for 2010-2011 incorporates the pandemic 2009 influenza A (H1N1) (pH1N1) component, a new influenza A (H3N2) component and the same B component as last year.
Immunization programs should focus on those persons at high risk of influenza-related complications, those capable of transmitting influenza to individuals at high risk of complications and those who provide essential community services. As circulation of pH1N1 is anticipated in the coming season, there is support to consider offering vaccine (2010-2011 TIV containing the pH1N1 strain) to healthy persons who might not be included in the usual provincial program as well as continuing to target those considered to be at high risk of serious outcomes from pH1N1. For 2010-2011, NACI recommends that three additional groups that experienced a higher incidence of severe outcomes during both waves of the pH1N1 pandemic be considered as priority recipients for influenza vaccine. These new groups are persons with morbid obesity, Aboriginal peoples and children 2 to 4 years of age.
The 2010-2011 statement also contains updated epidemiological information from the 2009 pH1N1 pandemic. There is updated product information on the available formulations, including Agriflu®, which was recently authorized in Canada for use in persons aged 6 months and older. The other newly authorized product, Intanza®, will be addressed by NACI at a later date. NACI continues to recommend two doses of TIV for children under age 9 with no prior TIV, and one dose of TIV per season for children who have previously received one or more doses of TIV. This recommendation applies whether or not the child received monovalent pH1N1 vaccine in 2009-2010.
I.2. Background
In Canada, two available measures can reduce the impact of influenza: immunoprophylaxis with trivalent inactivated influenza vaccine (TIV) and chemoprophylaxis, or therapy with influenza-specific antiviral drugs. Immunization is the cornerstone of influenza prevention and is the focus of this NACI statement. Antiviral recommendations are no longer within the purview of NACI and will be prepared through a separate national process.
Influenza A viruses are classified into subtypes on the basis of two surface proteins: hemagglutinin (H) and neuraminidase (N). Three subtypes of hemagglutinin (H1, H2 and H3) and two subtypes of neuraminidase (N1 and N2) are recognized among influenza A viruses that have caused widespread human disease. Since 1977 the human H3N2 and human H1N1 influenza A subtypes have contributed to influenza illness to varying degrees each year. It is not yet known if this pattern will be altered by the emergence of the 2009 pandemic virus [A/California/7/2009 (H1N1)]. Immunity to the H and N antigens reduces the likelihood of infection and lessens the severity of disease if infection occurs.
Influenza B viruses have evolved into two antigenically distinct lineages since the mid-1980s, represented by B/Yamagata/16/88-like and B/Victoria/2/87-like viruses. Viruses of the B/Yamagata lineage accounted for the majority of isolates in most countries between 1990 and 2001. Viruses belonging to the B/Victoria lineage were not identified outside of Asia between 1991 and 2001, but in March 2001 they re-emerged for the first time in a decade in North America (1). Since then, viruses from both the B/Yamagata and B/Victoria lineages have variously contributed to influenza illness each year.
TIV is reformulated annually to include standardized amounts of the H protein from representative seed strains of the two human influenza A subtypes (H3N2 and H1N1) and one of the two influenza B lineages (Yamagata or Victoria). H-based serum antibody produced to one influenza A subtype is anticipated to provide little or no protection against strains belonging to the other subtype. The potential for vaccine to stimulate antibody protection across B lineages requires further evaluation and may be dependent upon age and/or prior antigenic experience with both B lineages (2-6). Over time, antigenic variation (antigenic drift) of strains occurs within an influenza A subtype or B lineage. Despite this antigenic drift, some cross-protection among strains belonging to the same A subtype or B lineage is expected, depending on how different the strains are. Because of antigenic drift in one or more components of TIV, a new vaccine formulation must be considered each year.
For the 2010-2011 season in the Northern Hemisphere, the World Health Organization (WHO) recommends that the trivalent vaccine contain A/California/7/2009(H1N1)-like, A/Perth/16/2009(H3N2)-like, and B/Brisbane/60/2008(Victoria lineage)-like antigens (7). The B component is unchanged from the 2009-1010 seasonal TIV, the A (H1N1) component is derived from the 2009 H1N1 pandemic virus and the A (H3N2) component is new.
II. Epidemiology
II.1. National Influenza Surveillance in the 2009-2010 Season
II.1.1. Disease Distribution
National influenza surveillance is coordinated through the Centre for Immunization and Respiratory Infectious Diseases (CIRID), Public Health Agency of Canada (PHAC). The FluWatch program collects data and information from five different sources to provide a national picture of influenza activity. Detailed methodology for FluWatch has been described elsewhere (8). The information in this statement for the 2009-2010 season is based primarily on surveillance data from August 30, 2009, to April 3, 2010; however, some epidemiological information from the first wave of the 2009 H1N1 pandemic will also be provided or referenced. A more detailed epidemiological summary for the first pH1N1 wave can be found in the 2009-2010 NACI influenza statement (available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/acs-dcc-6/index-eng.php) (9).
The first wave of the 2009 H1N1 pandemic in Canada started in mid-April of 2009. It was marked by an increase in influenza activity (i.e. influenza-like illness, laboratory detections and outbreaks) around the time that influenza activity was expected to decline and the 2008-2009 influenza season was expected to come to an end. Influenza activity due to the pH1N1 virus continued to increase across the country and peaked in the first three weeks of June 2009. Influenza activity declined throughout summer 2009 and began to increase again across the country starting in mid-September, marking the start of the second wave of the 2009 H1N1 pandemic. The second wave peaked from late October to mid-November and decreased dramatically by mid-December. Overall influenza activity since the beginning of 2010 has been low and sporadic for most of the country. In comparing the differences in magnitude between the two pandemic waves, the second wave was substantially larger with four to five times more hospitalized and fatal cases than the first wave (9a).
Influenza A viruses predominated across the country in the 2009-2010 season comprising 99.95% of the 38,966 isolates from the period August 30, 2009 to March 19, 2010, with only two provinces (Quebec and Ontario) reporting influenza B detections (0.05% or 19). Subtype information was available for 86.2% of the 38,947 positive influenza A detections, and of those, 99.8% (33,494) were pandemic H1N1 2009 (pH1N1) viruses, 0.03% (11) were seasonal H1 viruses and 0.15% (52) were H3 viruses. The majority (84.6% or 44) of the influenza A (H3) detections were from Quebec.
The National Microbiology Laboratory (NML) has antigenically characterized 852 influenza viruses from the period August 30, 2009, to March 19, 2010, that were received from sentinel public health and hospital laboratories across Canada: 98.1% (836) were antigenically similar to the pandemic strain A/California/07/2009 (H1N1); 0.4% (three) were A/Brisbane/59/2007 (H1N1)-like (from Quebec and Alberta); 0.9% (eight) were A/Perth/16/2009 (H3N2)-like (from Quebec, Alberta and British Columbia); 0.2% (two) were A/Brisbane/10/2007 (H3N2)-like (from Quebec and British Columbia); 0.2% (two) were B/Brisbane/60/2008 (Victoria lineage)-like (from Ontario); and 0.1% (one) was B/Florida/04/2006 (Yamagata lineage)-like (from Quebec). The pH1N1 vaccine was a very good match to almost all of the influenza viruses that circulated this season.
Weekly influenza-like illness (ILI) consultation rates were above baseline levels for the time of the year from the beginning of September to late November 2009, peaking at 112 consultations per 1,000 patient visits in week 43 (late October). During non-pandemic seasons, the weekly peak in ILI consultation rates ranged from 31 to 149 per 1,000 patient visits. Since week 49 (early to mid-December), the rates have remained below baseline levels (from 10 to 21 per 1,000) except in week 51 (rate=28 per 1,000) where the rate was within the baseline level. For most of the weeks since the start of the season, the ILI consultation rates were highest among those in the 5 to 19 yearcage group and lowest for those aged 65 and older.
Of the 2,769 outbreaksa of influenza or ILI that were reported, 31 (1.1%) occurred in hospitals, 56 (2.0%) in long-term care facilities, 2,641 (95.4%) in schools and 41 (1.5%) in other facilities. (Note that the 2009-2010 season is the first season for which school-based ILI outbreaks have been reported by all provinces and territories.) Fifty-four percent (1,492 of 2,769) of the outbreaks occurred in a two-week period between late October to early November while 87% (2,422 of 2,769) of the outbreaks occurred in a five-week period between mid-October to mid-November.
For more detailed information on influenza epidemiology, see the weekly FluWatch reports at http://www.phac-aspc.gc.ca/fluwatch/index-eng.php.
Hospitals and residential institutions: two or more cases of ILI within a seven-day period, including at least one laboratory-confirmed case. Institutional outbreaks should be reported within 24 hours of identification. Residential institutions include but not limited to long-term care facilities (LTCF), prisons.
Other: two or more cases of ILI within a seven-day period, including at least one laboratory-confirmed case; i.e., workplace, closed communities.
II.1.2. Risk Factors for Severe Disease
In addition to the usual FluWatch indicators, the surveillance system was enhanced during the pandemic period. Hospital-based surveillance was put into place in all provinces and territories to collect case-based information on all hospitalized, intensive care unit (ICU)-admitted and fatal cases due to pH1N1. The main findings summarized below are based on data reported during the period April 12, 2009, to April 3, 2010, and capture both first and second wave pH1N1 information. Detailed information on risk of severe outcomes in the first wave has been previously published (10).
A total of 8,678 lab-confirmed pH1N1 hospitalizations were reported, of which 1,473 persons (17.0%) were admitted to ICU and 428 (4.9%) died. More detailed information on age, gender, ethnicity, underlying medical conditions and pregnancy status was obtained from 8,277 hospitalized cases and is summarized below (9a).
• The highest hospitalization rates in both pandemic waves were in children under 5 years of age. Within this age group, the hospitalization rate for children <2 years was more than two times higher than that for children 2 to 4 years of age. The highest crude ICU admission rates were in children <2 years (6.3 per 100,000 in the second wave). The highest crude death rates were in those 65 years and older (1.9 per 100,000 in the second wave), closely followed by those 45 to 64 years (1.7 per 100,000 in the second wave). See Table 1 for detailed rates of severe outcomes by age group and pandemic wave.
• The distributions were similar across genders, with the proportion among females as follows: hospitalizations (50.0%), ICU admissions (51.0%) and deaths (49.6%).
Table 1. Hospitalization, ICU Admissions and Death Rates (per 100,000) for Laboratory-Confirmed H1N1 Cases by Age Group, Canada (April 12, 2009, to April 3, 2010).
| Age groups (years) | First wave (April 12 to August 29, 2009) | Second wave and post-peak period (August 30, 2009, to April 3, 2010) | ||||
|---|---|---|---|---|---|---|
| Hospitalization rate | ICU rate | Death rate | Hospitalization rate | ICU rate | Death rate | |
| < 2 | 28.9 | 2.3 | 0.1 | 110.1 | 6.3 | 0.8 |
| 2 ‒ 4 | 9.5 | 1.2 | 0.0 | 55.3 | 3.4 | 0.2 |
| 5 ‒ 19 | 6.1 | 0.7 | 0.1 | 22.7 | 1.9 | 0.2 |
| 20 ‒ 44 | 3.2 | 0.8 | 0.2 | 13.6 | 2.8 | 0.6 |
| 45 ‒ 64 | 3.3 | 1.0 | 0.3 | 21.0 | 5.4 | 1.7 |
| 65+ | 2.5 | 0.6 | 0.4 | 15.2 | 3.0 | 1.9 |
| All ages | 4.4 | 0.9 | 0.2 | 21.3 | 3.5 | 1.0 |
• Information on underlying medical conditions was obtained from 4,673 hospitalized cases, 1,193 ICU admissions and 364 deaths. Of the hospitalized cases, 2,622 (56.1%) had at least one underlying medical condition compared with 845 (70.8%) among the ICU admitted cases and 302 (83.0%) of the deaths. The cumulative crude hospitalization (85.2 per 100,000), ICU (17.9) and death (6.1) rates among those with at least one underlying medical condition were higher than among those without underlying medical conditions (13.2, 1.5,and 0.3 per 100,000, respectively). The most commonly reported underlying medical conditions were respiratory diseases (e.g., asthma) followed by diabetes, heart diseases, immunosuppression, renal diseases and neurological diseases.
• Aboriginal status was identified in 607 hospitalized cases, of which 115 (18.9%) were admitted to ICU and 30 (4.9%) died. Approximately 71% of the cases were First Nations, 18% Inuit, 8% Metis and 3% of unknown Aboriginal origin. While the majority of Aboriginal cases in the first wave were from Manitoba and Nunavut, in the second wave cases were reported from 10 provinces and territories, with approximately 50% from Alberta. The cumulative crude hospitalization (69.3 per 100,000), ICU (12.7) and death (3.3) rates among those of Aboriginal origin were approximately two times higher than in non-Aboriginals (24.5, 4.1 and 1.2 per 100,000, respectively). This trend was seen in Aboriginals living both on and off reserve. It should be noted that the relative risk of having a severe outcome for Aboriginals decreased dramatically from the first to the second wave. Aboriginal status was not reported by two provinces (Ontario and Nova Scotia) where approximately 23% of the Aboriginal population resides. Therefore, the number of Aboriginal cases reported is an underestimate. Population-based rates and relative risks are based on the reporting provinces and territories only.
• There were 1,300 hospitalized cases, 257 ICU admissions and 50 deaths in women of child-bearing age (15 to 44 years). Of the hospitalized women of child-bearing age, 266 (20.5%) were pregnant. Trimester status that was available for 134 (50%) of the hospitalized pregnant women showed that 10% were in the first trimester, 26% second trimester, 61% third trimester and 3% postpartum. Among the 24 ICU admissions in pregnant women for whom trimester status was known, 4% were first trimester, 29% second trimester and 67% third trimester. While four deaths occurred among pregnant women in the first wave (all in their third trimester), none were reported during the second wave. The crude hospitalization rate among pregnant women was 91.7 per 100,000 compared with 16.5 among non-pregnant women of child-bearing age. The risks for pregnant women decreased considerably during the second wave compared with the first.
Between April 26, 2009, and May 15, 2010, a total of 1,322 influenza-associated pediatric hospitalizations were reported through the Immunization Monitoring Program, Active (IMPACT) network, 368 of which occurred in the first wave and 954 in the second wave. In total, 96.9% of the hospitalizations were due to pH1N1. Based on available data collected from 342 patients during the first wave (April 1, 2009, to August 29, 2009) the median length of stay (LOS) for those <5 years of age was three days compared with four days for those ≥5 years of age. During the first wave, antibiotic use was reported for 290 patients (85%) while antiviral use was reported for 163 patients (48%). A summary of first wave pediatric results has been published (11). Preliminary data for the second wave shows that antiviral use was much more frequent (89%) compared with the first wave (48%). Antibacterial use during the second wave was similar to the first wave (84%).
The Canadian Nosocomial Infection Surveillance Program (CNISP) conducted laboratory-confirmed influenza surveillance in hospitalized patients 16 years of age and older from selected sentinel tertiary care hospitals across the country. Between June 1, 2009, and February 5, 2010, CNISP obtained information on 385 hospitalized cases infected with pH1N1. Approximately 75% of all hospitalized cases were treated with antibiotics and 88% were treated with antivirals. The average LOS was nine days for all hospitalized cases, 16 days for those admitted to ICU and 13 days for persons who died.
In summary, while most illnesses caused by the 2009 H1N1 virus have been acute and self-limited, a number of severe outcomes were reported. Hospitalization rates were highest for children under age 5 years; however, the highest mortality rate occurred in adults aged 45 and older. Having at least one underlying medical condition significantly increased the risk of hospitalization, ICU admission and death. Being pregnant or of Aboriginal status were associated with an increased risk of hospitalization. These findings are in line with patterns and risk factors for severe disease observed in other countries (12).
For more detailed information on influenza epidemiology in Canada, see http://www.phac-aspc.gc.ca/fluwatch/index-eng.php.
II.2. International Influenza Surveillance
Between September 2009 and January 2010, influenza activity occurred worldwide. The predominant circulating virus was pH1N1, which had emerged in March 2009. However, seasonal influenza A (H1N1), A (H3N2) and B viruses circulated at very low levels in many countries between September 2009 and January 2010. In many regions widespread activity was reported outside the usual influenza season with much of the temperate Northern Hemisphere experiencing peak pandemic influenza activity in late October to late November 2009. Influenza activity remained active in several other areas, particularly North Africa, and parts of South and East Asia in late January. From February to June 2010, the most active areas of influenza transmission moved from East Asia to Central and West Africa, and finally to Central America, the tropical zone of South America and the Caribbean. As of June 2010 pH1N1 also continued to circulate actively in Malaysia, Singapore and to a much lesser extent in parts of India, Bangladesh and Bhutan.
While influenza B has been detected at low levels across parts of Asia and Europe and has now been reported in Central America, it was the predominant strain this season in East Asia. As of June 2010, seasonal influenza type B viruses continued to circulate at low levels across Asia and to a lesser extent across parts of Africa and South America.
Seasonal influenza H3N2 viruses have been detected in South and Southeast Asia, as well as sporadically in some countries of West and Central Africa and Eastern Europe. As of June 2010, they continued to circulate in East Africa (13).
II.2.1. Southern Hemisphere
Temperate countries of the Southern Hemisphere are of particular interest as they will be the first to enter a second winter influenza season following the emergence of pH1N1. Surveillance data from Australia, New Zealand and South America will be informative to Canada in preparation for the upcoming 2010-2011 influenza season. As of late June 2010, surveillance in Australia and New Zealand showed low levels of influenza activity with continuing reports of sporadic cases of pH1N1 but no evidence of sustained community transmission. Some influenza A/H3N2 and B isolates have also recently been detected in Australia (13-15). In South America, a number of countries including Peru, Brazil and Chile reported regional influenza activity as of late June and there have been small numbers of pH1N1 detections in Chile and Uruguay. Other countries are reporting increasing trends in acute respiratory disease; however, other respiratory viruses (mostly RSV) are known to be circulating in some countries (13,16). Ongoing monitoring of Southern Hemisphere epidemiology as their influenza season evolves is warranted.
II.2.2. Europe
In Europe, influenza activity (including laboratory detections and ILI/acute respiratory infection (ARI) consultation rates) peaked around mid- to late November 2009 and has remained low since February 2010. For most weeks since the start of the season, the highest consultation rates have been in the 0- to14-year age group. More than 99% of the influenza viruses isolated from severe acute respiratory infection (SARI) cases since the start of the season were pH1N1. Influenza A has been the dominant virus type circulating in Europe, comprising 99.5% of isolates, with influenza B comprising 0.5%. Of the influenza A viruses that were subtyped, 99.9% were pH1N1. Of the 3,228 influenza viruses where further strain characterization was performed by June 13, 2010, 3,172 (98.3%) were A/California/7/2009(H1N1)-like; 26 (0.8%) were A/Perth/16/2009(H3N2)-like; six (0.2%) were A/Brisbane/10/2007(H3N2)-like; 19 (0.6%) were B/Brisbane/60/2008-like (B/Victoria lineage); and five (0.1%) were B/Florida/4/2006-like (B/Yamagata lineage) (17).
II.2.3. United States
Influenza activity in the United States was above baseline levels at the start of the season (August 30, 2009) and steadily increased throughout September, peaked from mid- to late-October, and decreased thereafter, remaining low to date in 2010. Since the start of the season, pH1N1 has been the predominant influenza strain. Based on a sample of 1,895 isolates that were antigenically characterized, 97.5% were pH1N1 (A/California/07/2009-like), 0.1% were seasonal influenza A (H1N1), 0.7% were influenza A (H3N2) and 1.7% were influenza type B viruses. Both seasonal influenza A (H1) viruses were related to the influenza A (H1N1) component of the 2009-2010 influenza vaccine (A/Brisbane/59/2007) and all of the influenza A (H3) viruses were related to the A(H3N2) component of the 2010-2011 vaccine (A/Perth/16/2009).
Of the 32 B viruses tested, 84.4% belong to the B/Victoria lineage and were related to the 2009-2010 and 2010-2011 vaccine strain (B/Brisbane/60/2008) and 15.6% belong to the B/Yamagata lineage (18).
II.2.4. Avian Influenza
From September 1, 2009, to June 8, 2010, 59 human cases of influenza A (H5N1) (leading to 33 deaths) were confirmed in Egypt, Indonesia, Vietnam, Cambodia and China. The largest numbers of cases reported were from Egypt and Indonesia (24 each). Many of these people had exposure to sick or dead poultry. From 2003 to June 8, 2010, a total of 499 human cases and 295 deaths have been confirmed from 15 countries. To date, there has been no evidence of sustained human-to-human transmission due to avian influenza (19).
II.3. Antiviral Resistance
Details of antiviral resistance patterns of circulating influenza strains performed by the routine surveillance program at the National Microbiology Laboratory (NML) are reported by the FluWatch program. A brief summary of antiviral resistance for the 2009-2010 season is provided here.
From August 30, 2009, to May 6, 2010, the NML tested 1,165 influenza A isolates (24 H3N2 and 1,141 H1N1) for amantadine resistance. All A (H3N2) isolates and all pH1N1 isolates (n=1,136) were amantadine resistant. Most seasonal A (H1N1) isolates (80%, four out of five) were amantadine sensitive.
The NML tested 1,087 influenza isolates [six seasonal A (H1N1), 13 A (H3N2), four B and 1,079 pH1N1] for oseltamivir (Tamiflu®) resistance. All A (H3N2) and B isolates were sensitive to oseltamivir. All seasonal A (H1N1) isolates were resistant to oseltamivir. The majority of pH1N1 isolates (98.9%, or 1,067 of 1,079) were sensitive to oseltamivir. The 12 cases of oseltamivir-resistant pH1N1 originated from: British Columbia (one), Alberta (three), Manitoba (one), Ontario (four), Quebec (two) and New Brunswick (one). All resistant isolates were associated with oseltamivir treatment or prophylaxis. All 1,076 Canadian influenza isolates [1,057 pH1N1, two A (H1N1), 13 A (H3N2) and four B] tested to date have been sensitive to zanamivir.
In the United States, the majority of pH1N1 viruses (98.7%) tested were susceptible to oseltamivir; however, 67 cases of oseltamivir resistance were confirmed (18). Worldwide, there have been 298 cases of oseltamivir-resistant pH1N1 viruses reported to the WHO, including the 12 cases reported from Canada. All but one have the H275Y substitution and are assumed to remain sensitive to zanamivir (20).
III. Trivalent Inactivated Influenza Vaccine
III.1. Preparations Authorized for Use in Canada
There are currently five trivalent influenza vaccines authorized for use in Canada. This statement describes the four vaccines that are formulated for intramuscular use. A fifth product, Intanza® (sanofi pasteur), is a new intradermal preparation for adults and seniors that will be addressed in a supplementary statement at a later date.
Full details of the composition of each vaccine and a brief description of its manufacturing process can be found in the product monograph. However, some relevant details and differences between products are highlighted below. For each of the intramuscular products described, a 0.5 mL vaccine dose contains 15 μg of influenza hemagglutinin of each of the three virus strains (two type A strains and one B strain). None of the 2010-2011 trivalent vaccines contains an adjuvant. They are all manufactured by a process involving chicken eggs, which may result in the vaccine containing trace amounts of residual egg protein.
Two of the products (Fluviral®, Vaxigrip®) are split-virus inactivated vaccines that have reduced vaccine reactogenicity compared with the original whole virus influenza vaccines.
• Fluviral® (GlaxoSmithKline) is authorized for use in adults and children 6 months of age or older. It is available in five-mL, multidose vials and contains thimerosal as a preservative. Antibiotics are not used in the manufacture of Fluviral®.
• Vaxigrip® (sanofi pasteur) is authorized for use in adults and children 6 months of age or older. It is available in single-dose ampoules or pre-filled syringes and in five-mL multidose vials. The multidose presentation contains thimerosal as a preservative. Vaxigrip® contains trace amounts of neomycin.
Two products (Agriflu®, Influvac®) are surface antigen, inactivated subunit vaccines.
• Agriflu® (Novartis) was newly authorized for use in Canada in 2010. Agriflu® is authorized for use in adults and children 6 months of age or older. It is available in a single-dose, pre-filled syringe and is thimerosal-free. Kanamycin and neomycin are used in the manufacture of Agriflu®.
• Influvac® (Abbott) is authorized for use in persons ≥18 years of age. It is available in a single-dose, pre-filled syringe and is thimerosal-free. Influvac® contains trace amounts of gentamicin.
The publicly funded programs for 2010-2011 will use Fluviral® and Vaxigrip® vaccines.
III.2. Immunogenicity and Efficacy
Intramuscular administration of inactivated influenza vaccine results in the production of circulating IgG antibodies to the viral hemagglutinin and neuraminidase, as well as a more limited cytotoxic T lymphocyte response. Both humoral and cell-mediated responses are thought to play a role in immunity to influenza. The antibody response after vaccination depends on several factors, including the age of the recipient, prior and subsequent exposure to antigens and the presence of immunodeficiency states. Humoral antibody levels, which correlate with vaccine protection, are generally achieved by two weeks after immunization; however, there may be some protection afforded before that time.
Recipients of the adjuvanted pH1N1 vaccine generally mounted very high antibody titers. Complete data are not yet available, however, regarding the duration of protection following receipt of this adjuvanted vaccine.
Because influenza viruses change over time, immunity conferred in one season will not reliably prevent infection by an antigenically drifted strain. For this reason, the antigenic components of the vaccine change each year, and annual immunization is recommended.
Repeated annual administration of influenza vaccine has not been demonstrated to impair the immune response of the recipient to influenza virus.
Multiple studies show that influenza vaccine is efficacious, with higher efficacy demonstrated against laboratory-confirmed influenza than clinically defined outcomes without laboratory confirmation (21). With a good match, influenza vaccination has been shown to prevent influenza illness in approximately 70% to 90% of healthy children and adults (22-26) and by about half in the elderly (27,28). A recent meta analysis identified vaccine efficacy of 50% in healthy adults (95% CI: 27-65) during select seasons of vaccine mismatch, although mismatch is a relative term and the amount of cross-protection is expected to vary (26,29,30).
Systematic reviews have also demonstrated that influenza vaccine decreases the incidence of pneumonia, hospital admission and death in the elderly (31,32), and reduces exacerbations in persons with chronic obstructive pulmonary disease (33). In observational studies, immunization reduces the number of physician visits, hospitalizations and deaths in high-risk persons <65 years of age (34), reduces hospitalizations for cardiac disease and stroke in the elderly (35), and reduces hospitalization and deaths in persons with diabetes mellitus (36). Increasingly, the need for caution has been expressed in the interpretation of observational studies that use non-specific clinical outcomes and that do not take into account differences in functional status or health-related behaviours (37-42). More studies that assess vaccine protection against laboratory-confirmed influenza and its serious complications are needed.
The first time that children <9 years of age receive influenza immunization, a two-dose schedule is required to achieve protection (43-45). Several studies have looked at whether these two initial doses need to be given in the same season.
Allison et al. (46) assessed vaccine effectiveness against ILI outpatient visits during November and December 2003 among children 6 to 21 months of age given two separate-season doses of TIV (fall 2002 and fall 2003) or two same-season doses (fall 2003). There was no change in vaccine components between study years. Vaccine effectiveness against ILI was recorded as 62% (95% CI: 49-72) for the separate-season and 82% (95% CI: 77-86) for the same-season schedules respectively. Although significantly different from each other, these vaccine effectiveness estimates are high given that a non-specific ILI clinical outcome was used and that the vaccine was suboptimally matched to a circulating virus in 2003-2004. Results from this study are therefore difficult to interpret in relation to same-season versus separate-season scheduling of two-dose immunization.
Englund et al. (47) conducted a randomized study of children 6 to 23 months of age comparing a two-dose TIV schedule given during separate seasons with two doses given during the same season. The authors reported similar immunogenicity whether two doses were given in the same or separate seasons when there was no change in vaccine formulation between seasons. In a non-randomized trial (5), the same investigators again compared a two-dose TIV schedule in children 6 to 23 months of age given during separate seasons (Group 1: fall 2003 + fall 2004) with two doses given during the same season (Group 2: fall 2004 + fall 2004). Seroprotection rates were not significantly different between the two schedules for the H3N2 (minor vaccine strain change) and H1N1 (no vaccine change) components. However, only 27% of healthy infants/toddlers in Group 1 had a seroprotective antibody response to the 2004-2005 influenza B component compared with 86% in Group 2. There was a major antigenic (lineage) change in the B component of the TIV vaccine between the 2003-2004 (B/Victoria) and 2004-2005 (B/Yamagata) vaccine formulations. Similar findings were reported in a randomized trial involving children 6 to 23 months of age conducted by the same research group and using the same 2003-2004 and 2004-2005 vaccine formulations (4).
Previously these immunogenicity data have been interpreted in relation to whether doses were given in the same versus separate seasons. Another interpretation, however, is that children 6 to 23 months of age immunized against one B lineage may not be adequately primed to respond to a single dose of the other B lineage. On the basis of the sum total of evidence, NACI gives more weight to the latter interpretation, but further evaluation is required.
Vaccine efficacy may be lower in certain populations (e.g., immunocompromised persons, elderly persons) than in healthy adults. However, the possibility of lower efficacy should not prevent immunization in those at high risk of influenza-associated morbidity, since protection is still likely to occur. Influenza vaccination can induce protective antibody levels in a substantial proportion of immunosuppressed adults and children, including transplant recipients, those with proliferative diseases of the hematopoietic and lymphatic systems, and HIV-infected patients (48-52). Most studies have shown that administration of a second dose of influenza vaccine in elderly individuals or other individuals who may have an altered immune response does not result in clinically significant antibody boost (51,53-56).
III.3. Administration of Influenza Vaccine: Dosage and Schedule
As described earlier, this statement deals with the four currently authorized products that are administered by the IM route. Fluviral®, Vaxigrip® and Agriflu® are authorized for use in adults and children six months of age or older, and Influvac® is authorized for use in persons ≥18 years of age. A 0.5 mL dose of vaccine of each vaccine contains 15 μg of hemagglutinin of each antigen. The recommended dosage schedule is presented in Table 2.
Table 2. Recommended Influenza Vaccine Dosage, by Age, for the 2010-2011 Season.
| Age | Dosage (mL) | Number of doses required |
|---|---|---|
| 6-35 months | 0.25 | 1 or 2* |
| 3-8 years | 0.5 | 1 or 2* |
| ≥9 years | 0.5 | 1 |
Immunization with currently available influenza vaccines is not recommended for infants <6 months of age
The first time that children <9 years of age receive TIV, a two-dose schedule is required. This recommendation applies whether or not the child received monovalent pH1N1 vaccine in 2009-2010.
Because they are less likely to have had prior priming exposure to an influenza virus and will receive a lower per-injection dose of TIV, special effort is warranted to ensure that a two-dose schedule is followed for previously unvaccinated children 6 to 23 months of age.
Pending further evidence, eligible children <9 years of age who have properly received one or more doses of TIV in the past are recommended to receive one dose per season thereafter. NACI encourages further research in this area, especially with respect to response to the B component.
While data require further corroboration, recent studies suggest that when there is a major antigenic (B lineage) change in vaccine component (B/Victoria versus B/Yamagata) between sequential seasons, two doses may need to be considered in the second season for children 6 to 23 months of age (4), (5). Studies are needed to assess the extent to which this may also apply to older children.
Influenza vaccine should be administered intramuscularly. The deltoid muscle is the recommended site in adults and children ≥12 months of age. The anterolateral thigh is the recommended site in infants between 6 and 12 months of age.
*Previously unvaccinated children <9 years of age require two doses of TIV, with a minimum interval of four weeks between doses. Eligible children <9 years of age who have properly received one or more doses of TIV in the past are recommended to receive one dose per season thereafter. This recommendation applies whether or not the child received monovalent pH1N1 vaccine in 2009-2010.
III.4. Storage Requirements
Influenza vaccine should be stored at +2°C to +8°C and should not be frozen.
III.5. Simultaneous Administration with Other Vaccines
Influenza vaccine may be given at the same time as other vaccines, preferably in opposite limbs. If injections are given in the same limb, different sites on the limb should be chosen. Different administration sets (needle and syringe) must be used.
The target groups for influenza and pneumococcal polysaccharide vaccines overlap considerably. Health care providers should take the opportunity to vaccinate eligible persons against pneumococcal disease when influenza vaccine is given, according to the Canadian Immunization Guide (57).
III.6. Adverse Events
Influenza vaccination cannot cause influenza because the vaccine does not contain live virus. Soreness at the injection site lasting up to two days is common in adults but rarely interferes with normal activities. Healthy adults receiving the TIV show no increase in the frequency of fever or other systemic symptoms compared with those receiving placebo.
Influenza vaccines are safe and well tolerated in healthy children. Mild local reactions, primarily soreness at the vaccination site, occur in ≤7% of healthy children who are <3 years of age. Post-vaccination fever may be observed in ≤12% of immunized children 1 to 5 years of age.
Several influenza vaccines that are currently marketed in Canada contain minute quantities of thimerosal, which is used as a preservative (58,59). Large cohort studies of health databases have demonstrated that there is no association between childhood vaccination with thimerosal-containing vaccines and neurodevelopmental outcomes, including autistic-spectrum disorders (60). Similar large-scale studies have not specifically addressed prenatal exposure to thimerosal-containing vaccines in pregnancy. Despite the absence of data indicating any associated risk, influenza vaccine manufacturers in Canada are currently working towards production and marketing of thimerosal-free influenza vaccines. Three thimerosal-free influenza products are now available in Canada: Agriflu®, Influvac® and the single dose formulation of Vaxigrip®.
Allergic responses to influenza vaccine are a rare consequence of hypersensitivity to some vaccine components, such as residual egg protein, which is present in minute quantities.
Guillain-Barré syndrome (GBS) occurred in adults in association with the 1976 swine influenza vaccine, and evidence is consistent with a causal relation between the vaccine and GBS during that season (61). In an extensive review of studies since 1976, the United States Institute of Medicine concluded that the evidence was inadequate to accept or reject a causal relation between GBS in adults and influenza vaccines administered after the swine influenza vaccine program in 1976 (62).
In a Canadian study, the background incidence of GBS due to any cause was estimated at 2.02 per 100,000 person-years in Ontario and 2.30 per 100,000 person-years in Quebec (63). A variety of infectious agents, including Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumonia (64), and infrequently influenza itself (65) have been associated with GBS. A consistent finding in case series is the occurrence of an infection in the six weeks before GBS diagnosis in about two-thirds of patients (64).
A retrospective review of the 1992-1993 and 1993-1994 U.S. influenza vaccine campaigns found an adjusted relative risk of 1.7 (95% CI: 1.0-2.8; p=0.04) for GBS associated with influenza vaccination (66). This is consistent with a more recent Canadian study involving a self-matched case series from the Ontario health care database for the years 1992 to 2004. It found the estimated relative risk of hospitalization for GBS in the period two to seven weeks after influenza vaccination, compared with the period 20 to 43 weeks after influenza vaccination, to be 1.45 (95% CI: 1.05-1.99, p=0.02) (67). These studies suggest that the absolute risk of GBS in the period following seasonal influenza vaccination is about one excess case per 1 million vaccinees above the background GBS rate. Preliminary analysis of surveillance for GBS after pH1N1 vaccination in the United States results in a similar estimate: 0.8 excess GBS cases per million doses administered (68). The potential benefits of influenza vaccine must be weighed against this very low risk.
The Ontario study also looked at the incidence of GBS in the entire Ontario population since 2000, when a universal influenza immunization program was introduced in that province; no statistically significant increase in hospital admissions because of GBS was found. Two studies suggest that influenza vaccine may have a protective effect for GBS. Tam et al. (69) conducted a nested case-control study using data from the United Kingdom General Practice Research Database (GPRD) between 1991 and 2001. The authors found positive associations between GBS and infection with Campylobacter, Epstein-Barr virus and influenza-like illness in the previous two months, as well as evidence of a protective effect of influenza vaccination. Stowe et al. (70) used the self-controlled case series method to investigate the relation of GBS with influenza vaccine and influenza-like illness using cases recorded in the U.K.’s GPRD from 1990 to 2005. The authors found a reduced risk (non-significant) of GBS after seasonal influenza vaccine rather than an increased risk but a greatly increased risk after influenza-like illness, consistent with preceding respiratory infection as a possible trigger.
During the 2000-2001 influenza season, an increased number of reports of vaccine-associated symptoms and signs that were subsequently described as “oculorespiratory syndrome” (ORS) (71) were reported nationally. The case definition is as follows: the onset of bilateral red eyes and/or respiratory symptoms (cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness or sore throat) and/or facial swelling occurring within 24 hours of influenza immunization. The pathophysiologic mechanism underlying ORS remains unknown, but it is considered distinct from IgE-mediated allergy.
Approximately 5% to 34% of patients who have previously experienced ORS may have a recurrence attributable to the vaccine, but these episodes are usually milder than the original one, and vaccinees indicate willingness to be immunized in subsequent years (72,73). Persons who have a recurrence of ORS upon revaccination do not necessarily experience further episodes with future vaccinations. Data on clinically significant adverse events do not support the preference of one vaccine product over another when revaccinating those who have previously experienced ORS.
Recipients of the adjuvanted pH1N1 vaccine generally mounted very high antibody titers. Adult and pediatric studies on the immunogenicity and safety of TIV following a prior dose of adjuvanted pH1N1 vaccine are planned but results may not be available in time to inform the 2010-2011 fall immunization program. NACI will monitor results from these studies and from early pharmacovigilance reports so that additional guidance can be issued if needed.
Please refer to the Canadian Immunization Guide (57) for further details about administration of vaccine and management of adverse events.
III.7. Contraindications and Precautions
Influenza vaccine should not be given to people who have had an anaphylactic reaction to a previous dose or to any of the vaccine components. For more information on vaccine safety and anaphylaxis, please see the Canadian Immunization Guide at http://www.phac-aspc.gc.ca/publicat/cig-gci/p02-03-eng.php.
Persons with known IgE-mediated hypersensitivity to eggs (manifested as hives, swelling of the mouth and throat, difficulty in breathing, hypotension or shock) should not be routinely vaccinated with influenza vaccine. Egg-allergic individuals who are at risk of the complications of influenza should be evaluated by an allergy specialist, as vaccination might be possible after careful evaluation, skin testing and graded challenge or desensitization. If such an evaluation is not possible, the risk of an allergic reaction to the vaccine must be weighed against the risk of influenza disease. The Canadian Immunization Guide’s recommendations for those with a known hypersensitivity to eggs can be found at http://www.phac-aspc.gc.ca/publicat/cig-gci/p02-04-eng.php. The importance of being able to immunize egg-allergic individuals was highlighted during the 2009 H1N1 pandemic and modified protocols for their immunization are being studied (74,75). Studies with the adjuvanted monovalent H1N1 vaccine found that most egg-allergic persons could receive this vaccine safely; however, the quantity of antigen (3.8 μg) in that vaccine was much less than the 45 μg of antigen in a dose of TIV. Further assessments with TIV are underway. The Canadian Society of Allergy and Clinical Immunology published an updated approach for administration of H1N1 and seasonal influenza vaccine to egg-allergic individuals in fall 2009 to support vaccination efforts during the pandemic (76).
Expert review of the risks and benefits of vaccination should be sought for those who have previously experienced severe lower respiratory symptoms (wheeze, chest tightness, difficulty breathing) within 24 hours of influenza vaccination, an apparent allergic reaction to the vaccine or any other symptoms (e.g., throat constriction, difficulty swallowing) that raise concern regarding the safety of re-immunization. This advice may be obtained from local medical officers of health or other experts in infectious disease, allergy/immunology and/or public health.
Individuals who have experienced the oculorespiratory syndrome (ORS), including those with a severe presentation (bilateral red eyes, cough, sore throat, hoarseness, facial swelling) but without lower respiratory tract symptoms, may be safely re-immunized with influenza vaccine. Persons who experienced ORS with lower respiratory tract symptoms should have an expert review as described in the previous paragraph. Health care providers who are unsure whether an individual previously experienced ORS versus an IgE-mediated hypersensitivity immune response should seek advice. In view of the considerable morbidity and mortality associated with influenza, a diagnosis of influenza vaccine allergy should not be made without confirmation (which may involve skin testing) from an allergy/immunology expert.
Persons with serious acute febrile illness usually should not be vaccinated until their symptoms have abated. Those with mild non-serious febrile illness (such as mild upper respiratory tract infections) may be given influenza vaccine. Opportunities for immunization should not be lost because of inappropriate deferral of immunization.
It is not known whether influenza vaccination is causally associated with increased risk of recurrent GBS in persons with a previous history of GBS due to any cause. Avoiding subsequent influenza vaccination of persons known to have had GBS within eight weeks of a previous influenza vaccination appears prudent at this time.
Although influenza vaccine can inhibit the clearance of warfarin and theophylline, clinical studies have not shown any adverse effects attributable to these drugs in people receiving influenza vaccine.
Therapy with beta-blocker medication is not a contraindication to influenza vaccination. Individuals who have an allergy to substances that are not components of the influenza vaccine are not at increased risk of allergy to influenza vaccine.
IV. Recommendations for the 2010-2011 Seasonal Influenza Vaccine
IV.1. General Considerations
The national goal of the seasonal influenza immunization program in Canada is to prevent serious illness caused by influenza and its complications, including death (77). In keeping with this, NACI recommends that immunization priority for seasonal TIV be given to those persons at high risk of influenza-related complications, those capable of transmitting influenza to individuals at high risk of complications and those who provide essential community services. However, influenza vaccine is encouraged for all Canadians who have no contraindication.
The antigenic characteristics of current and emerging influenza virus strains provide the basis for selecting the strains included in each year’s vaccine. The World Health Organization (WHO) recommends that the trivalent vaccine for the 2010-2011 season in the Northern Hemisphere contain A/California/7/2009(H1N1)-like, A/Perth/16/2009(H3N2)-like and B/Brisbane/60/2008(Victoria lineage)-like antigens (7). Vaccine producers may use antigenically equivalent strains because of their growth properties.
All manufacturers of influenza vaccines in Canada have confirmed to the Biologics and Genetic Therapies Directorate of Health Canada that the vaccines to be marketed in Canada for the 2010-2011 influenza season contain the three WHO-recommended antigenic strains.
Several characteristics of the trivalent influenza vaccine recommended for 2010-2011 should be noted. The B component is the only vaccine component that is unchanged from the 2009-2010 seasonal TIV. The A (H1N1) component is derived from the 2009 H1N1 pandemic virus and the A (H3N2) component is new.
Annual immunization against influenza is recommended for optimal protection. Because of antigenic drift in one or more of the predominant influenza viruses, a new TIV formulation— updated yearly with the most current circulating strains— provides optimal protection against new infections. Protective antibody levels are generally achieved by two weeks following immunization. Although initial antibody response may be lower to some influenza vaccine components among elderly recipients, a recent literature review identified no evidence for subsequent antibody decline that was any more rapid in the elderly than in younger age groups (78).
An additional consideration for the 2010-2011 season is the concern that the pH1N1 virus will continue to circulate (79) and that its unique epidemiological features may still be present. Studies of previous pandemics have found that the shift in mortality from the elderly to younger adults that is a pandemic hallmark has persisted for several years following the initial introduction of the novel strain (80). This observation lends support to consider offering vaccine (2010-2011 TIV containing the pH1N1 strain) to healthy persons who might not be included in the usual provincial program as well as continuing to target those considered to be at high risk of serious outcomes from pH1N1. Modelling suggests that with the high levels of immunity achieved through both natural infection and mass vaccination programs, the reversion to normal seasonal patterns may occur more quickly than in the past, within a 12- to 24-month period (81). Public health officials should consult Canadian pH1N1 sero-survey results as they become available to identify age groups that may need special promotional efforts to ensure protection against pH1N1 should it present a recurrent threat.
Health care providers may offer the seasonal TIV when it becomes available, since seasonal influenza activity may start as early as November in the Northern Hemisphere. Decisions regarding the precise timing of vaccination in a given setting or geographic area should be made according to local epidemiologic factors (influenza activity, timing and intensity), opportune moments for vaccination, as well as programmatic issues. Further advice regarding the timing of influenza vaccination programs may be obtained through consultation with local medical officers of health. Although vaccination before the onset of the influenza season is preferred, vaccine may still be administered up until the end of the season. Health care workers (HCWs) should use every opportunity to give TIV to individuals at risk who have not been immunized during the current season, even after influenza activity has been documented in the community.
Risks and benefits of influenza vaccine should be discussed prior to vaccination, as well as the risks of not getting immunized.
IV.2. Recommended Recipients
Current influenza vaccines authorized for use in Canada are immunogenic, safe and associated with minimal side effects. Influenza vaccine may be administered to anyone ≥6 months of age without contraindications.
To reduce the morbidity and mortality associated with influenza, immunization programs should focus on those at high risk of influenza-related complications, those capable of transmitting influenza to individuals at high risk of complications and those who provide essential community services (see Table 3).
Table 3. Recommended Recipients of Influenza Vaccine for the 2010-2011 Season*.
| People at high risk of influenza-related complications or those more likely to require hospitalization |
|
| People capable of transmitting influenza to those at high risk |
|
| Others |
|
| Special consideration in 2010–2011 |
|
*Note: Healthy persons aged 5 to 64 years without contraindication are also encouraged to receive influenza vaccine even if they are not in one of the priority groups.
These groups remain the priority for influenza vaccination programs in Canada. However, significant illness and societal costs also occur with seasonal influenza in people who may not be considered at high risk of complications (i.e. healthy people aged 2 to 64 years). Therefore NACI also encourages influenza vaccine for all Canadians.
Several additional categories have been identified for special consideration this year. Persons with morbid obesity and Aboriginal peoples experienced higher rates of pH1N1-related hospitalization and severe outcomes during the 2009 pandemic. Their risks associated with seasonal influenza are less certain; however, the concerns about continuing circulation of pH1N1 in the 2010-2011 season warrant their inclusion in groups to be targeted this year. Children 2 to 4 years of age also experienced high rates of pH1N1-related hospitalization and are similarly identified for special consideration.
IV. 2.1 People at High risk of Influenza-Related Complications or Those More Likely to Require Hospitalization
• Adults (including pregnant women) and children with the following chronic health conditions. A number of chronic health conditions are associated with increased risk of influenza-related complications and/or can lead to exacerbation of the chronic disease. These conditions especially include cardiac or pulmonary disorders (including bronchopulmonary dysplasia, cystic fibrosis and asthma), but also diabetes mellitus and other metabolic diseases; cancer; immunodeficiency and immuno-suppression (due to underlying disease and/or therapy); renal disease; anemia or hemoglobinopathy; and conditions that compromise the management of respiratory secretions and are associated with an increased risk of aspiration. This category includes children and adolescents (aged 6 months to 18 years) with conditions treated for long periods with acetylsalicylic acid because of the potential increased risk of Reye’s syndrome associated with influenza.
• People of any age who are residents of nursing homes and other chronic care facilities. Such residents often have one or more chronic medical condition and live in institutional environments that may facilitate spread of the disease.
• People ≥65 years of age. Admissions attributable to influenza in this age group are estimated at 125 to 228 per 100,000 healthy persons (82), and death rates increase with age (83).
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• Healthy children 6 to 23 months of age. Children in this age group are at increased risk of influenza-associated hospitalization compared with healthy older children and young adults. Hospitalization is most frequent in those <2 years of age with rates estimated in a variety of North American studies to be from 90 to 1,000 admissions per 100,000 healthy children (84,85). Risk is greatest in the very young. These rates of hospitalization are similar to or greater than those of persons ≥65 years of age, although comparisons based on days of hospitalization and other severity indicators are not available and differences in the methods and setting for estimating influenza-attributable rates must also be taken into account. Influenza immunization of older children is efficacious (22-24), but few trials have specifically included children 6 to 23 months of age.
NACI recognizes that both the number of studies and the number of participants in trials of influenza vaccine in children of this age are limited, that there are unanswered questions (for example, the uncertain efficacy of vaccine in unprimed children who have not had experience with the vaccine or infection and who receive a lower dose per injection than older children), and that there is uncertainty about the cost-effectiveness of routine immunization programs in this age group (86), (87). NACI strongly encourages further research regarding these issues. However, on the basis of existing data indicating a high rate of influenza-associated hospitalization in healthy children <24 months, NACI recommends the inclusion of children 6 to 23 months of age among high-priority recipients of influenza vaccine.
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• Pregnant women. Women with the chronic health conditions indicated in Table 1 have a high risk of complications associated with influenza and are recommended by NACI as a high-priority group for immunization at any stage of pregnancy.
Several studies have described influenza-related risk in healthy pregnant women and summary reviews are available (88-94). Since surrogate outcomes for influenza (e.g. hospitalization for ILI and respiratory or cardiopulmonary outcomes) rather than laboratory-confirmed influenza have been reported, it is difficult to know the true influenza-attributable risk. In some studies, it is also difficult to assess the contribution of underlying co-morbidities, since these are not always presented separately. More evaluation of the impact of seasonal influenza on the healthy pregnant woman and her fetus would be helpful.
All studies that have stratified analysis according to gestational age show that influenza-related risk is not evenly distributed across all trimesters of pregnancy (95-97). In these studies, the rate of influenza-related hospitalization is not significantly increased during the first trimester of healthy pregnancy but, rather, increases later in pregnancy and is highest in the third trimester (95-97). In Neuzil et al.’s frequently cited 1997 publication spanning almost 20 influenza seasons, the risk of cardiopulmonary hospitalization during the influenza season rose significantly above the non-pregnant rate only beyond 21 weeks’ gestation (95). Both Dodds et al. (Canada) and Neuzil et al. (U.S.) reported excess influenza-related hospitalization rates of 40 and 100 per 100,000 women-months, respectively, in the third trimester, comparable to non-pregnant adults with co-morbidities (95,96). Differences in the methods and settings for estimating influenza-attributable rates should be taken into account in making these comparisons.
The most robust epidemiologic evidence for increased influenza-related fatality in pregnancy comes from the 1918, 1957 and 2009 pandemics (98-100). Canada experienced four fatalities in pregnant women (all in their third trimester) in the first wave of pH1N1 and, as described in Section II.1.2, the rates of hospitalization and ICU admission were much higher in pregnant women than in non-pregnant women of child-bearing age, particularly in the third trimester. Increased maternal mortality during the antigenic shifts in 1968 and 1977 has not been described. With the exception of case reports and a single ecologic study in a single season in Great Britain (101), epidemiologic evidence has not shown increased maternal mortality associated with seasonal influenza (88,95), (102-106).
The antibody response to TIV in pregnant women is not expected to differ from that of non-pregnant individuals.
Transplacental passage of maternal antibody is hypothesized to potentially protect the newborn. Several observational studies have assessed this epidemiologically with mixed results based on non-specific outcomes such as acute respiratory illness (88,107-109). In September 2008, Zaman et al. published the first randomized controlled trial (RCT) to assess effectiveness of influenza vaccine administered in the third trimester of pregnancy (110). In this study, 340 pregnant women in Bangladesh were randomized to receive either TIV or pneumococcal polysaccharide vaccine in the third trimester. A total of 300 mothers were followed from two weeks after antenatal immunization to delivery, and 316 were followed from delivery until their infants were 24 weeks of age. During the prolonged tropical influenza season described, TIV effectiveness against respiratory illness with fever was 36% (95% CI: 4-57) in mothers and 29% (95% CI: 7-46) in their infants. Vaccine efficacy against laboratory-confirmed influenza in the infants of immunized mothers followed for six months was 63% (95% CI: 5-85). This study provides the first RCT evidence for mother/infant protection from TIV administered in pregnancy. The extent to which these results may be extrapolated to seasons with a different mix of virus strains and vaccine components, to temperate rather than tropical activity, and to different household/infant care or breastfeeding patterns warrants further evaluation.
The antibody responses of the mothers and infants in this study were recently published (111). Maternal immunization resulted in the presence of antibody titers against influenza A subtypes in a high proportion of mothers and their new-borns. Six-month follow-up data show that passively acquired protective levels of serum antibody for influenza A subtypes may be significantly greater in the babies of vaccinees compared with babies of controls up to 20 weeks of age.
The safety of influenza vaccine during pregnancy has recently been reviewed (112). Passive surveillance has not identified concern related to serious adverse events following influenza immunization in pregnant women. The extensive 2009 pandemic experience has been reassuring in that no safety signals were found with use of both adjuvanted and unadjuvanted pH1N1 vaccine in >100,000 pregnant women in Canada and >488,000 pregnant women in Europe (113,114). Active studies to date have not shown evidence of harm to the mother or fetus associated with influenza immunization (91), but cumulative sample size to date has been small, especially during the first trimester (107,108,115-119) Further systematic evaluation would thus be informative.
Serious maternal morbidity (namely hospitalization) during seasonal influenza supports a recommendation for seasonal TIV vaccine for healthy pregnant women since rates of influenza-associated hospitalization increase with length of gestation after the first trimester.
IV.2.2. People Capable of Transmitting Influenza to Those at High Risk of Influenza-Related Complications or Hospitalization
People who are potentially capable of transmitting influenza to those at high risk should receive an annual vaccination, regardless of whether the high-risk person has been immunized. Immunization of care providers decreases their own risk of illness, as well as of death and other serious outcomes among the patients for whom they care (120-126). Immunization of care providers and residents is associated with decreased risk of ILI outbreaks (127). Individuals who are more likely to transmit influenza to those at risk of medical complications or hospitalization due to influenza include the following groups:
• Health care and other care providers in facilities and community settings. This group includes regular visitors, emergency response workers, those who have contact with residents of continuing care facilities or residences, those who provide home care for persons in high-risk groups and students of related health care services.
• Household contacts (adults and children) of individuals at high risk of influenza complications, whether or not the individual at high risk has been immunized. These individuals include household contacts of individuals at high risk of influenza-related complications or hospitalization, as listed earlier: household contacts of infants <6 months of age (who are at high risk of complications from influenza but for whom influenza vaccine is not authorized); and members of a household expecting a newborn during the influenza season.
• Those providing regular child care to children <24 months of age whether in or out of the home.
• Those who provide services within closed or relatively closed settings to persons at high risk (e.g., crews on ships).
IV.2.3. Others
• People who provide essential community services. Vaccination for these individuals should be encouraged in order to minimize the disruption of routine activities during annual epidemics. Employers and their employees should consider yearly influenza immunization for healthy working adults, as this has been shown to decrease work absenteeism due to respiratory and other illnesses.
• People in direct contact during culling operations involving poultry infected with avian influenza. These individuals may be at increased risk of avian influenza infection because of exposure during the culling operation (128-131). Influenza immunization on a yearly basis for these workers has been recommended in some countries (132) and provinces, based on the theoretical rationale that it may prevent the infection of these individuals with human influenza strains and thus reduce the potential for human-avian re-assortment of genes should such workers become co-infected with avian influenza (133). Direct involvement may be defined as sufficient contact with infected poultry to allow transmission of avian virus to the exposed person. The relevant individuals include those performing the cull, as well as others who may be directly exposed to the avian virus, such as supervising veterinarians and inspectors. Those who are immunized with influenza vaccine just before exposure to avian influenza will not produce protective antibodies against the human vaccine strains for approximately 14 days. For further information on human health issues related to domestic avian influenza outbreaks, see the PHAC guidance at http://www.phac-aspc.gc.ca/publicat/daio-enia/index.html.
IV.2.4. Special Considerations for the 2010-2011 Season
The following groups have been identified for special consideration this year because they experienced higher rates of pH1N1-related hospitalization and severe outcomes (in the case of morbid obesity and Aboriginal peoples) during the 2009 pandemic. These observations coupled with the concerns about continuing circulation of pH1N1 in the 2010-2011 season warrant their inclusion in groups to be targeted this year.
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• Persons with morbid obesity. Obesity has not been previously associated with increased risk of influenza-related complications. However, a potential association between severe pH1N1 illness and obesity was reported during the first wave of pH1N1 (134). Additional observational studies of cases in the United States, Mexico, Canada, Australia and New Zealand have subsequently reported excess cases with severe disease (i.e., admitted to ICU, requiring mechanical ventilation) in the obese, particularly among those with morbid obesity (BMI ≥40) (135-137).
A Canadian study by Kumar et al. (136) of 168 cases of pH1N1 admitted to 38 adult and pediatric ICUs between April 16 and August 12, 2009, found that 33.3% of these cases were obese while 23.7% were morbidly obese, compared with 23.1% and 2.7% respectively in the Canadian population (138). Median BMI among cases who survived (BMI=29) was lower than among non-survivors (BMI=31), but the comparison was not statistically significant (p=0.33). Based on these findings it appears that those who are morbidly obese, in particular, are over-represented among severe cases.
In a study by Morgan et al. (139) of hospitalizations and deaths during the first wave of pH1N1 in the United States, morbid obesity was the only BMI category statistically associated with hospitalization among those ≥20 years of age with or without an Advisory Committee on Immunization Practices (ACIP)-recognized chronic condition. In patients with morbid obesity and a chronic condition, the odds ratio (OR) for hospitalization was 4.9 (95% CI: 2.4-9.9, p<0.001). BMI category was not associated with death among adults who had an ACIP-recognized chronic medical condition but in adults without an ACIP-recognized chronic medical condition, death was associated with obesity (OR=3.1, 95% CI: 1.5-6.6, p<0.001) and morbid obesity (OR=7.6, 95% CI: 2.1-27.9, p<0.001). Adults without chronic conditions who were morbidly obese did appear to be at increased risk of both hospitalization (OR=4.7, 95% CI: 1.3-17.2) and death (OR= 7.6, 95% CI: 2.1-27.9) as a result of pH1N1 in this study. Among critically ill patients in general, obesity has been shown to be a risk factor for increased morbidity, and all-cause hospitalization, but not consistently for mortality (140-142), while morbid obesity is associated with complications in ICU-admitted patients, including prolonged stay, prolonged ventilation and death (143,144).
Fewer data are available on the relationship between obesity and influenza outcomes in children. In the Morgan study (139), 2- to 19-year-olds who were obese had an elevated, but not statistically significant, risk of hospitalization due to pH1N1 and no increased risk of death. However, the numbers of children were small, the confidence limits wide and in addition underweight children had an elevated significant risk of hospitalization.
While the above findings provide important preliminary information, the precise relationship between degree of obesity and influenza-related complications requires further study as does the question of whether or not obesity is a risk factor independent of other chronic health conditions such as diabetes and cardiopulmonary disorders, which are more prevalent among those who are obese.
NACI recognizes that information on the association between obesity and influenza-related complications continues to evolve. In particular, data that establish risk gradient by degree of obesity, obesity as an independent risk factor for influenza-related complications, and obesity as a risk factor in children and for seasonal influenza are limited. NACI strongly encourages further research regarding these issues. However, on the basis of preliminary data indicating a high rate of pH1N1-associated hospitalization and death among those who are morbidly obese, as well as the concerns of circulating pH1N1 during the 2010-2011 influenza season, NACI recommends the inclusion of those who are morbidly obese (BMI ≥40) among high-priority recipients of influenza vaccine. Offering vaccine to other obese adults may also be considered. NACI notes that it is not an expectation that a person’s weight or BMI be measured in order to implement this recommendation.
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• Aboriginal peoples. Historically, Aboriginal status has been associated with increased risk of influenza-related complications including death (145,146). Similar findings were identified during the 2009 influenza A (H1N1) pandemic. Aboriginal populations from Canada, Australia and New Zealand were noted to have a three- to eight-fold higher rate of hospitalization and death associated with pH1N1 infection compared to the overall population (147).
Death rates related to pH1N1 among American Indian and Alaska Natives (AI/AN) were reported for 12 states populated with half of all AI/AN in the U.S (148). Approximately 3% of the total populations in these 12 states are AI/AN. Death rates by race/ethnicity were age adjusted to the 2000 U.S. standard population. A total of 426 pH1N1 deaths were reported by the 12 states between April 15 and November 13, 2009, of which 9.9% (n=42) occurred in AI/AN. The overall AI/AN pH1N1-related death rate was 3.7 per 100,000 population compared to 0.9 per 100,000 for all other racial/ethnic populations combined, resulting in a mortality rate ratio of 4.0. Age group-specific pH1N1-related death rates were 3.5 for those aged 4 years and under, 1.1 for those aged 5 to 24 years, 4.2 for those aged 25 to 64 years, and 7.2 for persons aged 65 and older. In all age groups, AI/AN death rates were higher than in the other populations combined.
In a case control study of Manitoba-based individuals with pH1N1 infection, Aboriginals were more likely to suffer more severe disease than non-Aboriginals (OR=6.52, 95% CI: 2.04-20.8) when comparing patients admitted to the ICU (i.e., with severe disease) and those cared for in the community (149). Similar higher risk for severe disease in Aboriginals was identified for admitted patients (OR for ICU admission= 3.23, 95% CI: 1.04-10.1). This analysis was controlled for age, sex, urban versus rural status and income. A Canadian study by Kumar et al. (136) of 168 cases of pH1N1 admitted to 38 adult and pediatric ICUs between April 16 and August 12, 2009, did not identify a statistically significant difference in survival based on Aboriginal status. However, an increased proportion of the Aboriginal community was noted to present with severe pH1N1 illness during the period of evaluation.
It has been proposed that the increased risk of severe outcome in the Aboriginal population is a consequence of multiple factors including high prevalence of chronic health conditions (e.g., diabetes, chronic lung disease, end-stage kidney disease) (148), obesity, delayed access to health care and increased susceptibility to disease because of poor housing and overcrowding (150-152). Research into an underlying biological mechanism for severe disease in Aboriginals has generated hypotheses but is not conclusive (149,153).
Based on the body of evidence indicating a higher rate of influenza-associated hospitalization and death among Aboriginals, NACI recommends the inclusion of Aboriginal peoples, both on and off reserve, among high-priority recipients of influenza vaccine. Special consideration to socioeconomic challenges and geographical isolation is required to overcome the logistical challenges faced to achieve this objective (145).
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• Healthy children 2 to 4 years of age. As shown in Table 1, children aged 2 to 4 experienced the second highest hospitalization rate of all age groups during the 2009 pandemic. The majority of these outcomes were in children with an underlying chronic condition (personal communication, PHAC, 2010). However, when only healthy persons are considered, the hospitalization rate for children 2 to 4 years of age still exceeded that of all other age groups except for children <2 years of age.
Children aged 2 to 4 also experience a significant burden of disease from seasonal influenza, primarily related to outpatient visits to a physician or emergency department (ED), which are 250 times more common than influenza-related hospitalizations in children of this age (154). In a U.S. study conducted over two influenza seasons, the rate of clinic visits for influenza was estimated to be 53 to 88 per 1,000 children 2 to 4 years of age, and the rate of ED visits was estimated to be 7 to 23 per 1,000 children (154). Other retrospective studies have demonstrated similar rates of illness among children <5 years of age in other influenza seasons (155-157).
In 2006 ACIP included children 24 to 59 months of age in the high-risk recipient list for influenza vaccine on the basis of their increased risk of influenza-related clinic and emergency department visits (154,158).
IV.2.5. Further Comments Regarding Influenza Immunization
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• Immunization of healthy persons 5 to 64 years of age. Individuals in this age group are encouraged to receive the vaccine, even if they are not in one of the aforementioned priority groups. Systematic reviews of randomized controlled trials in healthy children and adults show that inactivated influenza vaccine is about 70% to 90% effective in preventing laboratory-confirmed influenza infection (22-26). A recent meta analysis of randomized controlled trials since 1966 found a vaccine efficacy in young adults of 80% (95% CI: 56-91) against laboratory-confirmed influenza when measured during select seasons of vaccine match and 50% (95% CI: 27-65) during select seasons of vaccine mismatch to circulating virus, although the amount of protection conferred is anticipated to vary with the degree of mismatch, the mix of circulating viruses and other factors (26).
Prior to the American universal recommendation described later, the American Academy of Family Physicians and the ACIP recommended routine annual influenza vaccination of adults ≥50 years of age. The prevalence of high-risk conditions increases at age 50 years, while the influenza immunization rate among U.S. adults with high-risk chronic medical conditions in this age group has been low. Age-based influenza guidelines may be more successful in reaching individuals with chronic medical conditions; in one analysis, this approach has been considered cost-effective (159).
• Travellers. Travellers with a chronic health condition or other factors that would make them recommended recipients of influenza vaccine should be immunized (see Table 3), and healthy travellers are also encouraged to receive vaccine. Vaccine products/formulations prepared specifically for use in the Southern Hemisphere are not currently available in Canada, and the extent to which recommended vaccine components for the Southern Hemisphere may overlap with those in available Canadian formulations will vary. For further information on advising travellers about influenza prevention, consult the Committee to Advise on Tropical Medicine and Travel (CATMAT) statement (available at http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/05pdf/acs-dcc3102.pdf) (160).
V. Strategies for Reducing the Impact of Influenza
Vaccination is recognized as the cornerstone for preventing or attenuating influenza for those at high risk of serious illness or death from influenza infection and related complications. In addition to the direct protection of vaccine recipients, there is emerging evidence that vaccination may provide indirect protection to others in the household or in the community. A recent cluster randomized trial was conducted among Hutterite communities in Canada. It compared laboratory confirmed influenza among unvaccinated persons in Hutterite communities where children were given influenza vaccine (coverage=83% among children aged 3 to 15) with communities where children received hepatitis A vaccine. Influenza vaccine effectiveness in preventing influenza in unvaccinated persons was 61% (95% CI: 8-81) (161). School-based trials and observational studies suggest that immunization of healthy children may reduce influenza transmission (162-168) and a systematic review concluded that there was evidence that vaccinating healthy children and adolescents has the potential for reducing the impact of influenza epidemics, although limitations in study design or execution make community benefits hard to quantify (169). Studies that looked at indirect protection of patients when health care workers are immunized are described in section VI.
Despite the known benefits of vaccination, influenza immunization rates among recommended recipients are suboptimal. The 2005 Canadian Community Health Survey (CCHS) reports coverage rates of influenza vaccination in the previous year of only 30.3% (95% CI: 29.7-30.9, n=22,693) for adults aged 18 to 64 years with a chronic medical condition (170). Results from the 2006 Adult National Immunization Coverage Survey on coverage for adults 18 to 64 years of age with a chronic medical condition are similarly low at 38.2% (95% CI 33.3-43.1, n=395) (unpublished data, Immunization and Respiratory Infections Division, PHAC). Results from the latter survey also show that non-institutionalized seniors (≥65 years) have higher coverage, with 69.9% (95% CI: 64.1-75.7, n=287) receiving influenza vaccine in the previous year. The results for this senior age group have not changed since 2001 (69.1%).
Kwong et al. compared influenza vaccine rates in Ontario with those in other provinces in relation to introduction of the Universal Influenza Immunization Program (UIIP) in Ontario in 2000 (171). Vaccination rate data were obtained from the 1996-1997 cycle of the National Population Health Survey (NPHS) and the 2000-2001, 2003 and 2005 cycles of the CCHS. Between the pre-UIIP 1996-1997 estimate and the mean post-UIIP vaccination rate, influenza vaccination rates for the house-hold population aged ≥12 years increased 20 percentage points (from 18% to 38%) for Ontario, compared with 11 percentage points (13% to 24%) for other provinces (p=0.001). For those <65 years of age, the vaccination rate increases were greater in Ontario than in other provinces, while for those ≥75 years of age, the increase was smaller in Ontario.
Kwong et al. also studied health outcomes in Ontario compared with other provinces without a universal immunization program (171). The authors found that influenza-associated mortality, hospitalizations and doctors’ office visits decreased more in Ontario than in other provinces. The universal program was also associated with a 64% larger reduction in influenza-associated antibiotic prescriptions than in other provinces that maintained targeted programs (172). An economic appraisal of the Ontario program found an incremental cost-effectiveness ratio of $10,797/quality-adjusted life year (QALY) gained and concluded that universal immunization against seasonal influenza is an economically attractive intervention (173).
In February 2010 the ACIP voted to recommend a universal influenza immunization policy for seasonal influenza vaccine for all Americans aged 6 months and older, to be implemented for the 2011-2012 season (174,175). Reasons cited for the program expansion include supporting evidence that annual influenza vaccine is a safe and effective preventive health action with potential benefit in all age groups, existing recommendations that already cover 85% of the population, the lack of awareness of many higher risk persons of their risk factor and the occurrence of complications in some adults without previously recognized risk factors. There was also concern that pH1N1 will continue to circulate in the 2010-2011 season and that a substantial proportion of young adults do not yet have immunity to this virus, which produced higher risk of complications in this age group than is typical for seasonal influenza.
Before making expanded recommendations that may influence Canadian immunization programs nationally, NACI is committed to careful systematic review of the required and available evidence and interpretation in the context of goals and objectives previously established in Canada by a consensus process (77). As with other new vaccines, this process will be followed in considering population-based indications for expansion of influenza immunization programs. A summary of that analysis in relation to pediatric or other program expansion will be made available when concluded. Until then, NACI continues to encourage influenza vaccine for all Canadians.
Low rates of utilization of influenza vaccine may be due to failure of the health care system to offer the vaccine and refusal by persons who fear adverse reactions or mistakenly believe that the vaccine is either ineffective or unnecessary. HCWs and their employers have a duty to actively promote, implement and comply with influenza immunization recommendations in order to decrease the risk of infection and complications among the vulnerable populations for which they care. Educational efforts aimed at HCWs and the public should address common doubts about disease risk for HCWs, their families and patients, vaccine effectiveness and adverse reactions.
The advice of a health care provider is a very important factor affecting whether a person accepts immunization. Most people at high risk are already under medical care and should be vaccinated during regular fall visits. Strategies to improve coverage include, but are not limited to, the following:
• Standing-order policies in institutions allowing nurses to administer vaccine and simultaneous immunization of staff and patients in nursing homes and chronic care facilities. In these settings, increased vaccination rates are associated with:
• a single, non-physician staff person organizing the program;
• having program aspects covered by written policies; and
• instituting a policy of obtaining consent on admission that is durable for future years.
• Vaccinating people at high risk who are being discharged from hospital or visiting the emergency department.
• Promoting influenza vaccination in clinics in which high-risk groups are seen (e.g., cancer clinics, cardiac clinics, pulmonary clinics, obstetrics clinics).
• Using community newspapers, radio, television, other media and influenza information lines, and collaborating with pharmacists and specialist physicians to distribute information about the benefits and risks of influenza immunization.
• Issuing computer-generated reminders to HCWs, mailing reminder letters to patients or using other recall methods to identify outpatients at high risk.
• Issuing patient-carried reminder cards.
• Increasing the accessibility of immunization clinics for staff in institutions and for community-based elderly (e.g., mobile programs).
• Organizing activities such as vaccination fairs and competitions between institutions.
• Working with multicultural groups to plan and implement effective programs.
• Incorporating influenza vaccination within the provision of home health care.
VI. Immunization of Health Care Workers
Influenza vaccination provides benefits to health care workers (HCWs) and to the patients they care for. Unfortunately vaccine uptake in HCWs often falls short of expectations. Coverage rates for residents of long-term care facilities (LTCFs) range from 70% to 91% (176-178). Studies of HCWs in hospitals and LTCFs reveal influenza vaccination coverage rates of 26% to 61%. According to the 2006 Adult National Immunization Coverage Survey, coverage rates are higher among those in close contact with patients (69.7%, 95% CI: 66.8-72.6, n=727) (unpublished data, Immunization and Respiratory Infections Division, PHAC).
Transmission of influenza between infected HCWs and their vulnerable patients results in significant morbidity and mortality. Studies have demonstrated that HCWs who are ill with influenza frequently continue to work, thereby potentially transmitting the virus to both patients and co-workers. In one study, 59% of HCWs with serologic evidence of recent influenza infection could not recall having influenza, suggesting that many HCWs experience subclinical infection (179). These individuals continued to work, potentially transmitting infection to their patients. In two other studies, HCWs reported four to ten times as many days of respiratory illness as days absent from work due to respiratory illness, suggesting that many HCWs worked while they were ill and were potentially able to transmit infection (126,180). In addition, absenteeism of HCWs who are sick with influenza results in excess economic costs and, in some cases, potential endangerment of health care delivery because of the scarcity of replacement workers.
Four randomized controlled trials conducted in long-term care settings have demonstrated that vaccination of HCW staff is associated with substantial decreases in mortality in the residents. Potter et al. (121) found that vaccination of HCWs in geriatric medical long-term care sites was associated with reductions of total patient mortality from 17% to 10% (OR 0.56, 95% CI: 0.40-0.80) and in influenza-like illness (OR 0.57%, 95% CI: 0.34-0.94) Vaccination of patients was not associated with significant effects on mortality. Carman et al. (123) studied 20 long-term elderly-care hospitals and found 13.6% patient mortality in hospitals where influenza vaccine was given to staff compared with 22.4% in no-vaccine hospitals (OR 0.58, 95% CI: 0.40-0.84, p=0.014). Hayward et al. (120) found significant decreases in resident mortality in the first study year in U.K. care homes where influenza vaccine was offered to staff compared with non-intervention homes (rate difference: -5.0 per 100 residents, 95% CI: -7.0 to -2.0) and in influenza-like illness (ILI) (p=0.004), GP ILI consultations (p=0.008) and in hospital admissions with ILI (P=0.009). No differences were found during periods of no influenza activity or in a second study year. Lemaitre et al. (124) studied 40 nursing homes and found 20% lower resident mortality (p=0.02) in homes where influenza vaccine was provided to staff compared with control homes, and a strong correlation was observed between staff vaccination coverage and all cause mortality in residents (correlation coefficient=0.42, p=.007). In the vaccination arm, ILI in residents was 31% lower (p=.007) and staff sick leave was 42% lower (p=.03). A Cochrane review of studies in long-term care settings reported that pooled data from three cluster randomized controlled trials showed that vaccination of health care workers in long-term care facilities for the elderly reduced influenza-like illness (OR 0.71, 95% CI: 0.55-0.90, p=.005) and all cause mortality (OR 0.68, 95% CI: 0.55-0.84, p<.001) (181). The review also mentions that no effect was shown in the eldery for other outcomes such as laboratory-proven influenza and death from pneumonia.
For the purposes of this document, we define a HCW as a person who provides direct patient care or indirect health services. The term “direct patient contact” is defined as activities that allow opportunities for influenza transmission between HCWs and a patient.
NACI considers the provision of influenza vaccination for HCWs who have direct patient contact to be an essential component of the standard of care for the protection of their patients. HCWs who have direct patient contact should consider it their responsibility to provide the highest standard of care, which includes annual influenza vaccination. In the absence of contraindications, refusal of HCWs who have direct patient contact to be immunized against influenza implies failure in their duty of care to patients.
In order to protect vulnerable patients during an outbreak, it is reasonable to exclude from direct patient contact HCWs with confirmed or presumed influenza and unvaccinated HCWs who are not receiving antiviral prophylaxis. Health care organizations should have policies in place to deal with this issue.
Footnotes
Definitions of ILI/Influenza outbreaks for the 2009-2010 season Schools: greater than 10% absenteeism on any day most likely due to ILI.
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