Statement on influenza vaccination for the 1995-96 season

Canadian Medical Association Journal 1995; 153: 591-604
Health Canada, 1995
Reproduced with permission of the Minister of Supply and Services Canada, 1996
Copies of the original report (Canada Communicable Disease Report 1995; 21: 105-113) can be obtained from Eleanor Paulson, editor, CCDR, Bureau of Communicable Disease Epidemiology, Laboratory Centre for Disease Control, Tunney's Pasture, Ottawa, ON K1A 0L2.
The antigenic components of influenza vaccine have been updated for the 1995-96 season. Recommendations for use of the vaccines are unchanged from the 1994-95 season. The present statement includes recommendations for people infected with HIV and provides background information about influenza immunization in general. The present statement is more explicit than previous statements about possible serious side effects of amantadine. As well, the table showing recommended dosage of amantadine according to age and renal function has been reformatted to improve clarity.


Contents


Introduction

In Canada, two measures are available that 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 people 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 hemagglutinin -- reduces the likelihood of infection and lessens the severity of disease when infection does occur. 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 among these viruses as well. 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 1994-95 influenza season was characterized by moderate activity that commenced relatively late. Influenza activity began to increase in January 1995 and was associated with both influenza A (H3N2 was the most common subtype recorded) and influenza B viruses. In the period from October 1994 to June 1995 influenza A virus reports totalled 1063, with peak activity in late February. A total of 358 influenza B virus identifications were recorded during the same period. Although reporting peaked in mid-March, influenza B virus reporting continued relatively steadily until late April.

A summary of influenza activity in Canada during the 1994-95 season will appear in an upcoming issue of the Canada Communicable Disease Report.

Completed strain characterization of influenza isolates submitted to the Laboratory Centre for Disease Control between Oct. 1, 1994, and June 15, 1995, indicated the following. Of the 93 influenza A (H3N2) isolates, especially those reported in February, 30 resembled A/Beijing/32/92; the other 63 were 46 A/Shang-dong/09/93-like viruses and 17 A/Johannesburg/33/94-like strains, for the most part isolated later in the season. Of the influenza B isolates 49 were antigenically distinguishable from the B/Panama/45/90-like virus and more closely resembled B/Beijing/184/93 and B/Harbin/07/94-like strains; 6 were A/Texas/36/91 (H1N1)-like strains.

Globally, influenza A (H3N2), A (H1N1) and B viruses also continued to circulate.[1] Many recent isolates of influenza A (H3N2) viruses from outbreaks or sporadic cases were antigenically distinguishable from the 1994-95 vaccine strain A/Shangdong/9/93 and similar to the recent reference strain A/Johannesburg/33/94. Influenza B viruses circulated widely and the majority of strains were antigenically distinguishable from the B/Panama/45/90 strain in the 1994-95 vaccine and more closely resembled the recent reference strains B/Beijing/184/93 and B/Harbin/07/94. Influenza A (H1N1) isolates were antigenically closely related to the current vaccine component. Vaccines containing A/Shangdong/9/93 (H3N2)-like viruses or B/Panama/45/90-like viruses induced protective hemagglutination-inhibiting antibody responses to A/Johannesburg/33/94-like and B/Beijing/184/93 (H3N2)-like strains, respectively, at a lower frequency or lower geometric mean titre than to the vaccine viruses.

The National Advisory Committee on Immunization therefore recommends that the trivalent influenza vaccine for the 1995-96 season contain an A/Johannesburg/33/94 (H3N2)-like strain, an A/Texas/36/91 (H1N1)-like strain and a B/Beijing/184/93-like strain. However, the actual influenza B strain used by North American vaccine manufacturers may be B/Harbin/07/94 because of its growth properties.

Annual vaccination is required because there is always a change in the vaccine in response to antigenic drift. As well, immunity declines in the year following vaccination. Each 0.5 mL of vaccine will contain 15 µg 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 vaccination and may last 6 months or longer. However, in elderly people, antibody levels fall below protective levels in 4 months or less. Although the annual vaccination program should begin as soon as vaccine is available (i.e., late September or early October) to ensure high coverage before a significant circulation of influenza occurs, the preferred time for vaccination of residents in long-term care facilities is November.

The following are recommendations for the prevention and control of influenza during the 1995-96 influenza season.

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Recommended recipients

People at high risk

Vaccination of people at high risk is the single most important measure for reducing the impact of influenza.[2-4] Priority should be given to ensuring annual vaccination of people in the following groups:

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.

Other people

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Recommended use

The recommended dosage schedule and type of vaccine are presented in Table 1. Whole-virus and split-virus vaccines, both available in Canada, are similar with respect to immunogenicity, although whole-virus vaccines may be more immunogenic in elderly people.[13] The split-virus vaccine is generally associated with fewer side effects in children.[14,15] Either the split-virus or the whole-virus vaccine may be used in people 13 years of age or older. Only split-virus vaccines are recommended for those less than 13 years of age. Children under 9 years require two doses separated by 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, as data relating to influenza vaccine may generally have been obtained after such administration. The deltoid muscle is the recommended site in adults and older children, and the anterolateral thigh in infants and young children.

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. 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 use of acetaminophen may decrease the frequency of some side effects in adults.[16] 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 less than 24 months of age fever occurs more often but is seldom severe.

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

Unlike the 1976-77 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.

Contraindications and precautions

Influenza vaccine should not be given to people with known anaphylactic hypersensitivity to eggs manifested as hives, swelling of the mouth and throat, difficulty breathing, hypotension and shock. Adults with acute febrile illness usually should not be vaccinated until their symptoms have abated.

Influenza vaccine is considered safe in pregnancy.

In infants less than 6 months of age influenza vaccine is less immunogenic than in infants and children aged 6 to 18 months. Therefore, vaccination with currently available influenza vaccines is not recommended for infants less than 6 months of age.[17]

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.

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 people 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 given only once, whereas influenza vaccine is given annually. Children at high risk may receive influenza vaccine at the same time as routine pediatric vaccines but at a different site from that used for routine pediatric vaccinations.

Storage

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

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Strategies for reducing the impact of influenza

The effectiveness of influenza vaccine varies, depending on the age and immunocompetence of the vaccine recipient and the degree of similarity between the virus strain included in the vaccine and the strain of virus circulating during the influenza season. With a good match influenza vaccination has been shown to prevent illness in approximately 70% of healthy children and adults. Studies have also shown influenza vaccination under these circumstances to be approximately 70% effective in preventing hospital admission because of pneumonia and influenza among elderly people living in the community. Studies involving elderly people residing in nursing homes have shown influenza vaccination to be 50% to 60% effective in preventing hospital admission 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 frail elderly people.

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 vaccination programs should aim to vaccinate at least 90% of residents in long-term care facilities and 90% of adults and children with the cardiac or pulmonary disorders previously listed. Nevertheless, only about 45% of this population receive vaccine annually.

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.[18-20] 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, the 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 vaccinated 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:

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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 people 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:

Treatment

Amantadine has been shown to reduce the severity and shorten the duration of influenza A infection in healthy adults. Although there have been no well-controlled studies to demonstrate its efficacy in preventing complications in people at high risk, amantadine may, because of the potential benefits, be considered for those at high risk who have suspected influenza A infection. 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 consequences 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 older people 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 concentrations of the drug. These have been observed most often among people who have renal insufficiency, seizure disorders or certain psychiatric disorders, and among elderly people who have been taking amantadine prophylactically at a dosage of 200 mg/day. Lowering the dosage for these patients is effective in combating the severity of such side effects.

Amantadine is not metabolized but is excreted in the urine. Therefore, in those with reduced renal function, particularly elderly people, 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.

The safety of amantadine use in pregnancy has not been established; therefore, the drug is not recommended for use by women who are or could be pregnant. Because the drug is secreted in breast milk, it should not be administered to lactating mothers.

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References

  1. Recommended composition of influenza virus vaccines for use in the 1995-1996 season. WHO Wkly Epidemiol Rec 1995; 70: 53-56
  2. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1994; 43 (RR-9): 1-13
  3. Douglas RG Jr: Prophylaxis and treatment of influenza. N Engl J Med 1990; 322: 443-450
  4. 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: 550-555
  5. 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: 732-740
  6. 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: 1136-1139
  7. 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: 562-565
  8. Barker WH, Mullooly JP: Influenza vaccination of elderly persons -- reduction in pneumonia and influenza hospitalizations and deaths. JAMA 1980; 244: 2547-2549
  9. Fedson DS, Wajda A, Nicol JP et al: Clinical effectiveness of influenza vaccination in Manitoba. JAMA 1993; 270: 1956-1961
  10. 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: 778-784
  11. Committee on Infectious Diseases, American Academy of Pediatrics: The Red Book: Report of the Committee on Infectious Disease, 22nd ed, American Academy of Pediatrics, Elk Grove, Ill, 1991: 274-281
  12. 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: 383-388
  13. McElhaney JE, Meneilly GS, Lechelt KE et al: Antibody response to whole-virus and split-virus vaccines in successful ageing. Vaccine 1993; 11: 1055-1060
  14. Al-Mazrou A, Scheifele DW, Soong T et al: Comparison of adverse reactions to whole-virion and split-virion influenza vaccines in hospital personnel. CMAJ 1991; 145: 213-218
  15. 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
  16. Aoki FY, Yassi A, Cheang M et al: Effects of acetaminophen on adverse effects of influenza vaccination in health care workers. CMAJ 1993; 149: 1425-1430
  17. 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: 823-828
  18. McDowell I, Newell C, Rosser W: Comparison of three methods of recalling patients for influenza vaccination. CMAJ 1986; 135: 991-997
  19. 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: 616-625
  20. Frank JW, Henderson M, McMurray L: Influenza vaccination in the elderly: 1. Determinants of acceptance. CMAJ 1985; 132: 371-375

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Source: National Advisory Committee on Immunization: Members: Dr. David Scheifele (chairman), director, Vaccine Evaluation Centre, Vancouver; Dr. John Spika (executive secretary), director, Bureau of Communicable Disease Epidemiology, Health Canada, Ottawa; Nicole Armstrong (administrative secretary), Bureau of Communicable Disease Epidemiology, Health Canada, Ottawa; Drs. Fred Aoki, Department of Medical Microbiology, University of Manitoba, Winnipeg; Stephen Corber, medical officer of health, Ottawa-Carleton Health Department, Ottawa; Philippe DeWals, directeur, Département des Sciences de la santé communautaire, Centre hospitalier de l'Université de Sherbrooke, Sherbrooke, Que; Scott A. Halperin, associate professor, Department of Pediatrics and Microbiology, Dalhousie University, Halifax; Barbara Law, Department of Medical Microbiology, University of Manitoba, Winnipeg; Monika Naus, senior medical consultant, Disease Control Service, Ontario Ministry of Health, Toronto; Yves Robert, Direction de la santé publique de la région des Laurentides, Saint-Jérome, Que.; and Brian Ward, director, Parasitology Laboratory, McGill Centre for Tropical Diseases, Montreal. Liaison members: Lt.-Cndr. David Carpenter, Directorate of Health Protection and Promotion, Department of National Defence, Ottawa; Drs. Anne Carter, associate director, Department of Health Care and Promotion, CMA, Ottawa; Philippe Duclos, chief, Childhood Immunization Division, Bureau of Communicable Disease Epidemiology, Health Canada, Ottawa; Tom Freeman, assistant professor, Department of Family Medicine, University of Western Ontario, London, Ont.; Steve Hadler, National Immunization Program, US Centers for Disease Control and Prevention, Atlanta; J.H. Victor Marchessault, executive vice-president, Canadian Paediatric Society, Ottawa; Laszlo Palkonyay, chief, Viral Products Division, Bureau of Biologics, Health Canada, Ottawa; Hilary Robinson, epidemiologist, Indian and Northern Health Services, Medical Services Branch, Health Canada, Ottawa; May Smith, chief, Bacterial Products Division, Bureau of Biologics, Health Canada, Ottawa; and John Waters, director, Communicable Disease Control and Epidemiology, Alberta Health, Edmonton.


Disclaimer

This guideline is for reference and education only and is not intended to be a substitute for the advice of an appropriate health care professional or for independent research and judgement. The CMA relies on the source of the CPG to provide updates and to notify us if the guideline becomes outdated. The CMA assumes no responsibility or liability arising from any outdated information or from any error in or omission from the guideline or from the use of any information contained in it.
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