Canada Communicable Disease Report
Vol. 23 (ACS-2)
1 July 1997

An Advisory Committee Statement (ACS)
National Advisory Committee on Immunization (NACI)*

STATEMENT ON INFLUENZA VACCINATION FOR THE 1997-98 SEASON

PREAMBLE

The National Advisory Committee on Immunization (NACI) provides Health Canada with ongoing and timely medical, scientific, and public-health advice relating to immunization. Health 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. Persons administering or using the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian licensed manufacturer(s) of the vaccine(s). Manufacturer(s) have only sought approval of the vaccine(s) and provided evidence as to its safety and efficacy when used in accordance with the product monograph(s).

INTRODUCTION

The antigenic components of the influenza vaccine have been updated for the 1997-1998 season. The present statement has a new section, entitled "Recent Developments in Influenza Immunization," as well as updated sections concerning people infected with HIV, and health-care and other personnel who have significant contact with high-risk people, and a section on adverse events.

In Canada, two available measures can reduce the impact of influenza: immunoprophylaxis with inactivated (killed-virus) vaccine, and chemoprophylaxis or therapy with an influenza-specific antiviral drug (amantadine). Vaccination of persons at high risk each year before the influenza season is currently the most effective measure for reducing the impact of influenza.

Influenza A viruses are classified into subtypes on the basis of two surface antigens: 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. Immunity to these antigens - especially to the hemagglutinin - reduces the likelihood of infection and lessens the severity of disease if infection occurs. Infection with a virus of one subtype confers little or no protection against viruses of other subtypes. Furthermore, over time, antigenic variation (antigenic drift) within a subtype may be so marked that infection or vaccination with one strain may not induce immunity to distantly related strains of the same subtype. Although influenza B viruses have shown more antigenic stability than influenza A viruses, antigenic variation does occur. For these reasons, major epidemics of respiratory disease caused by new variants of influenza continue to occur. The antigenic characteristics of current and emerging strains provide the basis for selecting the virus strains included in each year's vaccine.

The 1996-1997 influenza season was characterized by a primary peak in early January attributable to influenza A and a secondary peak in early March attributable to influenza B.  As of 2 May 1997, 261 influenza isolates had been characterized by LCDC; 202 (77%) were influenza A, 201 of which were A/Wuhan/359/95 (H3N2)-like and one was A/Johannesburg/33/94 (H3N2)-like.  All 59 (23%) influenza B isolates were identified as B/Beijing/184/93-like.

In the northern hemisphere, many countries reported moderate to severe influenza epidemics.  Globally, influenza A viruses were predominantly H3N2-like, and most were closely related to the current vaccine strain, A/Wuhan/359/95.  H1N1-like viruses were isolated sporadically, and were closely related to A/Bayern/7/95. The majority of influenza B isolates, internationally, were antigenically close to the B/Beijing/184/93 vaccine virus.

In adults, the current vaccine induced HI antibodies to recent representative strains of influenza A H3N2-like and influenza B viruses.  Geometric mean titres induced by the 1995-1996 vaccine strain were 50% lower for A/Bayern/7/95 H1N1-like than they were for the 1995-1996 vaccine strain.

NACI, therefore, recommends that the trivalent vaccine for the 1997-1998 season contain an A/Wuhan/359/95 (H3N2)-like strain, an A/Bayern/7/95 (H1N1)-like strain, and a B/Beijing/184/93-like strain.

The actual influenza strain used by North American vaccine manufacturers will likely be A/Nanchang/933/95 (H3N2)-like, A/Johannesburg/82/96 (H1N1)-like, and B/Harbin/7/94 because of their growth properties.

Annual immunization is required because one or more of the vaccine components is changed each year. As well, immunity declines in the year following vaccination. Each 0.5 mL of vaccine will contain 15 mg of hemagglutinin of each antigen. The vaccine will be available as either a whole-virus or a split-virus (chemically disrupted) preparation. Protection from the vaccine generally begins about 2 weeks after immunization and may last 6 months or longer. However, in the elderly, antibody levels fall below protective levels in 4 months or less. Thus, November is the preferred time for immunization of elderly individuals. Nevertheless, annual vaccination programs, such as those for residents of long-term care facilities, should begin as soon as vaccine is available in September or early October to ensure high coverage prior to significant circulation of influenza. Finally, no opportunity should be missed to give vaccine to any individual at risk who has not been immunized during the current season.

RECENT DEVELOPMENTS IN INFLUENZA IMMUNIZATION

This section provides a brief review of interesting developments in influenza immunization since the last NACI statement.  Where applicable, elements from this section have been applied to the following section, "Recommended Recipients." In some cases, topics are discussed, but no formal recommendations are made.

• Immunization of HIV-infected individuals: A randomized, placebo-controlled trial evaluated the effect of influenza immunization on HIV-1 virus load (i.e. plasma virus concentration) in HIV-infected adults in a Baltimore outpatient clinic.  At 30 days post-immunization, there was no difference in HIV-1 load between recipients of vaccine and placebo⁽¹⁾.  A non-controlled, descriptive report in 53 HIV-infected children revealed no significant difference in pre- and post-influenza immunization HIV-1 load⁽²⁾.
• Immunization of pregnant females without risk factors: A currently unpublished, case-control study done in the United States showed that females after week 21 of pregnancy were more likely to be hospitalized for a range of acute cardiopulmonary events than their non-pregnant counterparts, during the influenza season.  The study did not show that the excess hospitalizations were due to influenza, nor did it demonstrate that they would be prevented by immunization.  Although this is an interesting development in an area where further research is warranted, NACI concluded that the evidence provided by this study was insufficient to broaden the current recommendations for immunizing pregnant women.  NACI does recommend influenza immunization for all pregnant women with risk factors, regardless of the stage of pregnancy.
• Immunization to prevent acute otitis media: A prospective, controlled study compared the occurrence of respiratory tract infections and clinical otitis media in a group of immunized and non-immunized children attending day-care centres in Finland⁽³⁾.  Although there was no difference between the groups in the number of respiratory tract infections, there was a significant reduction in cases of otitis media in vaccine recipients compared to controls.  Randomization of children was by day care, and the study was neither blinded nor placebo controlled.  This study does not provide sufficient evidence to support a recommendation for routine use of influenza vaccine to prevent otitis media, and further research is warranted.  Individual children with recurrent otitis media may benefit from influenza immunization given the excellent safety profile of split-virus vaccines.

The following are recommendations for the prevention and control of influenza during the 1997-1998 influenza season.

RECOMMENDED RECIPIENTS

People at high risk

Vaccination of people at high risk is the single most important measure for reducing the impact of influenza^(4-6).  Priority should be given to ensure annual vaccination of people in the following groups.

• Adults and children with chronic cardiac or pulmonary disorders (including bronchopulmonary dysplasia, cystic fibrosis and asthma)severe enough to require regular medical follow-up or hospital care. Chronic cardiac and pulmonary disorders are by far the most important risk factors for influenza-related death⁽⁶⁾.
• People of any age who are residents of nursing homes and other chronic care facilities. Such residents often have one or more of the medical conditions outlined in the first group. In addition, their institutional environment may promote spread of the disease. Studies have shown that the use of vaccine in this setting will decrease the occurrence of illness, and has an even greater impact on reducing the rates of hospital admission, pneumonia, and death^(7,8).
• People ³ 65 years of age. The risk of severe illness and death related to influenza is moderately increased in healthy people in this age group^(9,10), but is not as great as in people with chronic underlying disease. Vaccination is effective in preventing hospital admission and death^(11,12).
• Adults and children with chronic conditions, such as diabetes mellitus and other metabolic diseases, cancer, immunodeficiency, immunosuppression, renal disease, anemia, and hemoglobinopathy. The degree of risk associated with chronic renal and metabolic diseases in children is uncertain, but this uncertainty should not preclude consideration of vaccination.
• Children and adolescents (age 6 months to 18 years) with conditions treated for long periods with acetylsalicylic acid. This therapy might increase the risk of Reye's syndrome after influenza⁽¹³⁾.
• Persons infected with HIV. Limited information exists regarding the frequency and severity of influenza illness among HIV-infected persons, but reports suggest that symptoms may be prolonged and the risk for complications increased for some HIV-infected persons. Because influenza can result in serious illness and complications, vaccination is a prudent precaution and will result in protective antibody levels in many recipients. However, the antibody response to vaccine may be low in persons with advanced HIV-related illnesses; giving a second dose of vaccine 4 or more weeks after the first does not improve the immune response for these persons. HIV load does not increase with influenza immunization according to a randomized placebo-controlled trial⁽¹⁾.
• People at high risk of influenza complications embarking on foreign travel to destinations where influenza is likely to be circulating. These individuals should be vaccinated with the most current available vaccine. Immunization may be considered for all individuals who wish to avoid influenza while travelling to such areas. In the tropics, influenza can occur throughout the year. In the southern hemisphere, peak activity occurs from April through September. In the northern hemisphere, peak activity occurs from November through March. The effectiveness of the influenza immunization for travellers may vary depending on differences between influenza strains encountered abroad and those included in the current vaccine.

People capable of transmitting influenza to those at high risk

People who are potentially capable of transmitting influenza to those at high risk should receive annual vaccination.

• Health-care and other personnel who have significant contact with people in the high-risk groups previously described. A reduction in mortality and influenza-like-illness was reported among patients in chronic-care facilities when staff were also immunized⁽¹⁴⁾.  Every effort should be made to immunize both residents and staff in this setting.
• Household contacts (including children) of people at high risk who either cannot be vaccinated or may respond inadequately to vaccination. Because low antibody responses to influenza vaccine may occur in some people at high risk (e.g. the elderly, people with immunodeficiencies⁽¹⁵⁾), annual vaccination of their household contacts may reduce the risk of influenza exposure.

Other people

• People who provide essential community services. Vaccination may be considered to minimize the disruption of routine activities in epidemics. Employers and their employees should consider yearly influenza immunization for healthy working adults as this has been shown to decrease work absenteeism because of respiratory and other illnesses⁽¹⁶⁾.
• Pregnant women. Vaccination is recommended for pregnant women in high-risk groups (see "Recommended Recipients" above).  Influenza vaccine is considered safe for pregnant women at all stages of pregnancy. Although recent data (unpublished observations) suggest that women in their second and third trimesters of pregnancy are at increased risk of hospitalization during the influenza season (see "Recent Developments in Influenza Immunization" above), further research is warranted before recommendations can be made about immunizing otherwise healthy pregnant women.
• Breast-feeding mothers. Influenza immunization does not adversely affect the health of breast feeding mothers or their infants. Breast feeding is not a contraindication for influenza immunization.

RECOMMENDED USE

The recommended dosage schedule and type of vaccine are presented in Table 1. Both whole-virus and split-virus vaccines are available in Canada. Split-virus and whole-virus vaccines are similar with respect to immunogenicity, although whole-virus vaccines may be more immunogenic in the elderly⁽¹⁷⁾. The split-virus vaccine is generally associated with fewer side effects in children^(18,19) and young adults⁽²⁰⁾. Either the split-virus or the whole-virus vaccine may be used in people ³ 13 years of age. Only split-virus vaccines are recommended for those < 13 years of age. Children < 9 years of age require two doses, with an interval of 4 weeks; the second dose is not needed if the child received one or more doses of vaccine prepared for a previous season.

Intramuscular administration is preferred because data relating to influenza vaccine have generally been obtained after such administration. The deltoid muscle is the recommended site in adults and older children, the anterolateral thigh in infants and young children.

Table 1 Recommended influenza-vaccine dosage, by age, 1997-1998

Adverse reactions

Influenza vaccination cannot cause influenza because the vaccine does not contain live virus. Soreness at the injection site lasting up to 2 days is common, but rarely interferes with normal activities. Fever, malaise, and myalgia may occur within 6 to 12 hours after vaccination and last 1 to 2 days, especially in young adults who have received the whole-virus vaccine and those receiving vaccine for the first time. Prophylactic acetaminophen may decrease the frequency of some side effects in adults⁽²⁰⁾. Adults receiving the split-virus vaccine showed no increase in the frequency of fever or other systemic symptoms compared to those receiving placebo⁽²¹⁾. In children aged 2 to 12 years, fever and local reactions are no more frequent after administration of split-virus vaccine than after placebo injections. In those < 24 months of age, fever occurs more often but is seldom severe.

Allergic responses are rare and are probably a consequence of hypersensitivity to some vaccine component, most likely residual egg protein, which is present in minute quantities.

Unlike the 1976-1977 swine influenza vaccine, subsequent vaccines prepared from other virus strains have not been clearly associated with an increased frequency of Guillain-Barré syndrome. Influenza vaccine is not known to predispose to Reye's syndrome.

Please refer to the Canadian Immunization Guide⁽²²⁾ for further details about administration of vaccine and management of adverse reactions.

Contraindications and precautions

Influenza vaccine should not be given to people who had an anaphylactic reaction to a previous dose or with known anaphylactic hypersensitivity to eggs manifested as hives, swelling of the mouth and throat, difficulty in breathing, hypotension, and shock.

Individuals with acute febrile illness usually should not be vaccinated until their symptoms have abated.

Influenza vaccine is considered safe in pregnancy.

In infants < 6 months of age, influenza vaccine is less immunogenic than in infants and children aged 6 to 18 months. Therefore, immunization with currently available influenza vaccines is not recommended for infants < 6 months of age⁽²³⁾.

Although influenza vaccination 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.

False-positive HIV antibody tests were reported after immunization with the 1991-1992 influenza vaccines. The incidence of false-positive tests declined with the development of different tests so that such false-positive HIV antibody tests are not likely to be a problem now⁽²⁴⁾.

Simultaneous administration of other vaccines

The target groups for influenza and pneumococcal vaccination overlap considerably. Health-care providers should take the opportunity to vaccinate eligible persons against pneumococcal disease during the same visit at which influenza vaccine is given. The concurrent administration of the two vaccines at different sites does not increase the risk of side effects. Pneumococcal vaccine, however, is usually given only once, whereas influenza vaccine is given annually. Children at high risk may receive influenza vaccine at the same time but at a different site from that used for routine pediatric vaccines.

Storage

Influenza vaccine should be stored at 2^o C to 8^o C and should not be frozen.

STRATEGIES FOR REDUCING THE IMPACT OF INFLUENZA

The effectiveness of influenza vaccine varies depending upon the age and immunocompetence of the vaccine recipient, the degree of similarity between the virus strain included in the vaccine, and the strain of circulating virus during the influenza season. With a good match, influenza vaccination has been shown to prevent illness in approximately 70% of healthy children and adults. Under these circumstances, studies have also shown influenza vaccination to be approximately 70% effective in preventing hospitalization for pneumonia, and influenza among elderly persons living in the community. Studies among elderly persons residing in nursing homes have shown influenza vaccination to be 50% to 60% effective in preventing hospitalization and pneumonia, and up to 85% effective in preventing death, even though efficacy in preventing influenza illness may often be in the range of 30% to 40% among the frail elderly.

Vaccination is recognized as the single most effective way of preventing or attenuating influenza for those at high risk of serious illness or death. Influenza vaccine programs should aim to vaccinate at least 90% of eligible recipients.  Nevertheless, only 70% of long-term care facility residents and 20% to 40% of adults and children with medical conditions listed previously receive vaccine annually^(25,26).

It is not known how much of this low rate of utilization is due to failure of the health-care system to offer the vaccine or to refusal by those for whom vaccine is recommended because they fear adverse reactions or believe that the vaccine is either ineffective or unnecessary^(27-29). Educational efforts aimed at physicians and the public should address common concerns about vaccine effectiveness and adverse reactions. These include the beliefs of patients at risk that they hardly ever get influenza, fear of side effects from the vaccine, and doubt about the efficacy of the vaccine.

The advice of a health-care provider is often a very important factor affecting whether a person is immunized or not. Most people at high risk are already under medical care and should be vaccinated during regular fall visits. Strategies to improve coverage include the following:

• standing-order policies in institutions allowing nurses to administer vaccine
• simultaneous immunization of staff and patients in nursing homes and chronic-care facilities
• vaccinating people at high risk who are being discharged from hospital or visiting the emergency room in the autumn
• promoting influenza vaccination in clinics which see high-risk groups (e.g. cancer clinics, cardiac clinics, and pulmonary clinics)
• using community newspapers, flu-information lines, and collaborating with pharmacists and specialist physicians to distribute positively-framed information about the benefits and risks of immunization
• issuing computer-generated reminders to physicians, mailing reminder letters to patients, or using other recall methods to identify outpatients at high risk
• patient-carried reminder cards
• increased accessibility of immunization clinics to staff in institutions and community-based elderly
• organized activities, such as vaccination fairs and competitions between institutions
• working with multicultural groups to plan and implement effective programs.

RECOMMENDATIONS FOR THE USE OF AMANTADINE

Amantadine hydrochloride is an antiviral agent that interferes with the replication cycle of type A (but not type B) influenza viruses. The following are recommendations for its use in prophylaxis and treatment.

Prophylaxis

The only drug currently approved in Canada for the specific prophylaxis of influenza virus infections is amantadine hydrochloride. It is 70% to 90% effective in preventing illness caused by type A influenza viruses but is ineffective against type B strains. Because antiviral agents taken prophylactically may prevent illness but not subclinical infection, some persons who take these drugs may still develop immune responses that will protect them when they are exposed to antigenically-related viruses in later years. However, amantadine prophylaxis should not replace annual influenza vaccination in groups for whom vaccine is recommended.

Amantadine prophylaxis may be used as follows:

• For the control of influenza A outbreaks among high-risk residents of institutions. Amantadine should be given to all residents, whether previously vaccinated or not, and to unvaccinated staff (see "Precautions" below). Consultation with the local medical officer of health to confirm that the circulating influenza strain is type A is essential.
• As the sole agent for prophylaxis in people at high risk during an outbreak when vaccine is unavailable, contraindicated, or unlikely to be effective due to a shift in the antigenic composition of the outbreak strain. In this case, prophylactic amantadine must be taken each day for the duration of influenza A activity in the community.
• As an adjunct to late vaccination of people at high risk.  Amantadine should be continued for 2 weeks after appropriate vaccination is completed; that is, for those receiving two doses of vaccine, amantadine should be continued for 2 weeks after the second dose.
• As a supplement to vaccination in people at high risk expected to have an impaired immune response to vaccine.This includes persons with HIV infection, especially those with advanced HIV disease. No data are available on possible interactions with other drugs used in the management of patients with HIV infection. Such patients should be monitored closely if amantadine is administered.
• For unvaccinated people who provide home care for people at high risk during an outbreak. Amantadine prophylaxis should be continued until 2 weeks after the home-care provider has been vaccinated.

Treatment

Amantadine has been shown to reduce the severity and shorten the duration of influenza A in healthy adults. There have been no well-controlled studies to demonstrate its efficacy in preventing complications in people at high risk; however, because of the potential benefits, amantadine may be considered for those at high risk who have suspected influenza A. The drug should be administered within 24 to 48 hours after the onset of illness and continued until 2 days after its resolution. Amantadine-resistant influenza viruses may emerge during treatment but there is no evidence that these viruses are more virulent or transmissible than amantadine-sensitive influenza viruses. However, the conse- quences of widespread therapeutic use of amantadine are not known. Studies to assess this issue are required.

Dosage

Recommendations for dosage are presented in Table 2, but the package insert should be read for complete information. Any adjustments for renal function should be made in addition to adjustments for age.

Precautions

In otherwise healthy young adults given amantadine prophylactically, 5% to 10% report difficulty concentrating, insomnia, light-headedness, and irritability. These side effects are usually mild and cease shortly after the prophylaxis is stopped; however, they can be more frequent in the older population unless a reduced dosage is used.

Serious side effects (e.g. marked behavioural changes, delirium, hallucinations, agitation, and seizures) have been associated with high-plasma drug concentrations. These have been observed most often among persons who have renal insufficiency, seizure disorders, or certain psychiatric disorders, and among elderly persons who have been taking amantadine as prophylaxis at a dose of 200 mg/day. Lowering the dosage among these persons is effective in combatting the severity of such side effects.

Amantadine is not metabolized but is excreted in the urine.  Therefore, in people with reduced renal function, particularly the elderly, toxic levels can occur if the dosage is not reduced.  Recommended dosage by age and renal function is shown in Table 2. The dosage should be reduced in people with a seizure disorder to avoid the risk of increased frequency of seizures. The patient's age, weight, and renal function and the presence of other underlying conditions should be considered and the dosage adjusted accordingly. In addition, patients should be carefully monitored for side effects.

Table 2 Recommended amantadine hydrochloride dosage by age and renal status

References

1. Glesby MJ, Hoover DR, Farzadegan H et al.  The effect of influenza vaccination on human immunodeficiency virus type 1 load: a randomized, double-blind, placebo-controlled study.  J Infect Dis 1996;174:1332-36.

2. Jackson CR, Vavro CL, Valentine ME et al.  Effect of influenza  immunization on immunologic and virologic characteristics of pediatric patients infected with human immunodeficiency virus.  Pediatr Infect Dis 1997;16:200-04.

3. Keikkinen T, Ruuskanen O, Waris M et al.  Influenza vaccination in the prevention of acute otitis media in children. Am J Dis Child. 1991;145:445-48.

4. CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1994;43(No. RR-9):1-13.

5. Douglas RG Jr. Prophylaxis and treatment of influenza. N Engl J Med 1990;322:443-50.

6. Glezen WP, Decker M, Perrotta D. Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houston, 1978-1981. Am Rev Respir Dis 1987;136:550-55.

7. Patriarca PA, Arden NH, Koplan J et al. Prevention and control of type A influenza infections in nursing homes. Benefits and cost of four approaches using vaccination and amantadine. Ann Intern Med 1987;107:732-40.

8. Patriarca PA, Weber JA, Parker RA et al. Efficacy of influenza vaccine in nursing homes: reduction in illness and complications during an influenza A (H3N2) epidemic. JAMA 1985;253:1136-39.

9. Gross PA, Quinnan G, Rodstein M et al. Association of influenza immunization with reduction in mortality in an elderly population. A prospective study. Arch Intern Med 1988;148:562-65.

10. Barker WH, Mullooly JP. Influenza vaccination of elderly persons - reduction in pneumonia and influenza hospitalizations and deaths. JAMA 1980;244:2547-49.

11. Fedson DS, Wajda A, Nicol JP et al. Clinical effectiveness of influenza vaccination in Manitoba. JAMA 1993;270:1956-61.

12. Nichol KL, Margolis KL, Wuorenma J et al. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med 1994;331;778-84.

13. American Academy of Pediatrics.  Influenza. In: Peter G. Ed. 1994 Red book: report of the Committee on Infectious Diseases. 22nd ed. Elk Grove Village, IL: American Academy of Pediatrics, 1991:275-83.

14. Potter J, Stott DJ, Roberts MA et al.  Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients.  J Infect Dis.  1997;175:1-6.

15. Nelson KE, Clements ML, Miotti P et al. The influence of human immunodeficiency virus (HIV) infection on antibody responses to influenza vaccines. Ann Intern Med 1988;109:383-88.

16. Nichol KL, Lind A, Margolis KL et al. The effectiveness of vaccination against influenza in healthy working adults. N Engl J Med 1995;333:889-93.

17. McElhaney JE, Meneilly GS, Lechelt KE et al. Antibody response to whole-virus and split-virus vaccines in successful ageing. Vaccine 1993;11:1055-60.

18. Al-Mazrou A, Scheifele DW, Soong T et al. Comparison of adverse reactions to whole-virion and split-virion influenza vaccines in hospital personnel. Can Med Assoc J 1991;145:213-18.

19. Gruber WC, Taber LH, Glezen WP et al. Live attenuated and inactivated influenza vaccine in school-age children. Am J Dis Child 1990;144:595-600.

20. Aoki FY, Yassi A, Cheang M et al. Effects of acetaminophen on adverse effects of influenza vaccination in health care workers. Can Med Assoc J 1993;149:1425-30.

21. Nichol K, Margolis KL, Lind A et al.  Side effects associated with influenza vaccination in healthy working adults.  Arch Intern Med.  1996:156;1546-50.

22. National Advisory Committee on Immunization.  Canadian immunization guide. 4th ed. Ottawa, Ont: Health Canada, 1993. (Supply and Services Canada, Cat. No. H49-8/1993E.)

23. Groothuis JR, Levin MJ, Rabalais GP et al. Immunization of high-risk infants younger than 18 months of age with split-product influenza vaccine. Pediatrics 1991;87:823-28.

24. Simonsen L, Buffington J, Shapiro CN et al. Multiple false reactions in viral antibody screening assays after influenza vaccination. Am J Epidemiol 1995;141:1089-96.

25. Duclos P, Arruda H, Dessau JC et al.  Immunization of non-institutionalized adults - Quebec (as of May 30, 1996).  CCDR 1996;22:177-82.

26. DeWals P, Carbonneau M, Payette H, Niyonsenga T.  Influenza and pneumococcal vaccination in long term care facilities in two regions of Quebec.  Can J Infect Dis 1996:7;296-300.

27. McDowell I, Newell C, Rosser W. Comparison of three methods of recalling patients for influenza vaccination. Can Med Assoc J 1986;135:991-97.

28. Williams WW, Hickson MA, Kane MA et al. Immunization policies and vaccine coverage among adults: the risk for missed opportunities. Ann Intern Med 1988;108:616-25.

29. Frank JW, Henderson M, McMurray L. Influenza vaccination in the elderly: 1. Determinants of acceptance. Can Med Assoc J 1985;132:371-75.

Supplementary References

Ho DD. HIV-1 viremia and influenza. Lancet 1992;339:1549. Letter.

O'Brien WA, Grovit-Ferbas K, Namazi A et al. Human immunodeficiency virus-type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination. Blood 1995;86:1082-89.

World Health Organization. Recommended composition of influenza virus vaccines for use in the 1996-1997 season. Wkly Epidemiol Rec 1996;71:57-61.

* Members: Dr. D. Scheifele (Chairman); Dr. J. Spika (Executive Secretary); N. Armstrong (Advisory Committee Secretariat Officer); Dr. P. DeWals; Dr. S. Halperin; Dr. B. Law; Dr. M. Naus; Dr. B. Ward; Dr. I. Gemmill; Dr. W Schlech III; Dr. P. Orr; Dr. G. DeSerres; Dr. J. Carsley.

Liaison Members: Dr. D. Carpenter (ND); Dr. A. Carter (CMA); Dr. T. Freeman (CFPC); Dr. S. Hadler (CDC); Dr. V. Marchessault (CPS); Dr. J. Waters (ACE); Dr. J. Levingood.

Ex-Officio Members: Dr. P. Duclos (LCDC); Dr. L. Palkonyay (DD); Dr. D Kurtesz (LCDC).

[Canada Communicable Disease Report]