Statement on influenza vaccination for the 1995-96 season

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Contents

• Introduction
• Recommended recipients
• Recommended use
• Strategies for reducing the impact of influenza
• Recommendations for the use of amantadine
• References

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Introduction

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

• 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.[4]
• People of any age who are residents of nursing homes and other long-term care facilities. Such residents often have one or more of the medical conditions outlined for 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 in reducing the rates of hospital admission, pneumonia and death.[5,6]
• People 65 years of age and over. The risk of severe illness and death related to influenza is moderately increased in healthy people in this age group[7,8] but is not as great as in people with chronic underlying disease. Vaccination is effective in preventing hospital admission and death.[9,10]
• Adults and children with chronic conditions such as diabetes 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 (aged 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.[11]
• People infected with human immunodeficiency virus (HIV). Limited information exists regarding the frequency and severity of influenza illness among HIV-infected people, but reports suggest that symptoms may be prolonged and the risk for complications increased for some HIV-infected people. 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 people 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 people.

People capable of transmitting influenza to those at high risk

• Health care and other personnel who have significant contact with people in the high-risk groups previously described. The potential for infecting people at high risk, particularly those in institutions, may be reduced through vaccination programs aimed at health care personnel.
• 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., elderly people and those with immunodeficiency),[12] annual vaccination of their household contacts may reduce the risk of influenza exposure.

Other people

• People who provide essential community services may be considered for vaccination to minimize the disruption of routine activities in epidemics. Vaccine may also be administered to those who wish to reduce their chances of acquiring infection.
• Pregnant women. Vaccination is recommended for pregnant women in high-risk groups (see above). Vaccine is considered safe for pregnant women regardless of their stage of pregnancy.
• People at high risk of influenza complications embarking on foreign travel to destinations where influenza is likely to be circulating should be vaccinated with the most current available vaccine. 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.

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Recommended use

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

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 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

Storage

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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:

• Establishing standing-order policies in institutions allowing nurses to administer vaccine.
• Vaccinating people at high risk who are being discharged from hospital or are visiting the emergency room in the autumn.
• Promoting influenza vaccination in clinics that serve high-risk groups (e.g., cancer clinics, cardiac clinics and pulmonary clinics).
• Using community newspapers and flu-information lines and collaborating with pharmacists and specialist physicians to distribute positively framed information about the benefits and risks of vaccination.
• Issuing computer-generated reminders to physicians, mailing reminder letters to patients or using other recall methods to identify outpatients at high risk.
• Issuing patient-carried reminder cards.
• Increasing accessibility of vaccination clinics to staff in institutions and community-based elderly people.
• Organizing activities such as vaccination fairs and competitions between institutions.
• Working with multicultural groups to plan and implement effective programs.

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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

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" section). 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 people 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 care provider has been vaccinated.

Treatment

Dosage

Precautions

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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