Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made.  (Formerly, these situations were captured under a "C Recommendation".)  This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade.  For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.

Prevention of Influenza

Prepared by R. Wayne Elford, MD, CCFP, FCFP, Director of Research and Faculty Development, Department of Family Medicine, and Michael Tarrant, MD, CCFP, FCFP, Associate Professor of Family Medicine, University of Calgary, Alberta



Objective
To make recommendations about the prevention of influenza among general, high-risk and health care provider populations in Canada. This updates a 1979 report.

Burden of Suffering
Influenza is the most important acute respiratory illness that causes adults to seek medical care. Influenza A and B viruses are responsible, but mutate with great regularity, resulting in new strains and subtypes of virus that cause new epidemics almost annually. Current theories of influenza viral epidemiology have not explained fully the persistence, seasonality, and explosiveness of outbreaks over large geographical areas. Excess mortality in the general population is one of the hallmarks of an influenza epidemic. The age group over 65 years accounts for over 95% of the mortality associated with influenza. The increased mortality and morbidity among persons over 65 years, is mostly due to the higher prevalence of chronic heart and lung diseases in the elderly. The peak occurrence of hospitalizations of persons with acute respiratory disease, usually pneumonia, coincides with the peak of influenza virus activity each year. The magnitude of the problem is compounded when the increase in sick-leave in health care providers coincides with peak periods of hospitalization. The excess cost of sick-leave among those of working age during influenza epidemic years exceeds that for all other acute illnesses.

Options
Early detection of viral infection using a rapid diagnostic kit ("Directigen Flu A test"). Other detection methods (clinical detection, isolation of the virus and serological testing of antibody response) were briefly described.

Preventive measures included public awareness, isolation (to reduce transmission), annual vaccination and chemoprophylaxis with amantadine.

Outcomes
Disease incidence, severity, duration, related mortality, clinical symptoms, serum or secretory antibody response, immunologic memory, vaccination rate, and positive and negative predictive values of the rapid diagnostic kit.

Evidence
A MEDLINE search of the years 1981 to 1992 using the MeSH headings influenza virus, influenza vaccination and influenza chemoprophylaxis identified 155 citations. Reviews, editorials, commentaries and animal studies were then excluded. Additional citations were identified from the bibliographies of articles. If multiple articles on the same topic were found, those most recently published and with the most rigorous designs were retained. Study results were synthesized in table or graphic format only.

Values
The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.

Benefits, Harms, and Costs
Positive predictive value of the "Directigen Flu A test" is 63% compared with virus isolation. Negative predictive value is 100%. Reliability of test results when conducted by non-laboratory trained persons is unknown.

Clinical trials show that vaccines are 70% to 80% effective in reducing disease occurrence and related mortality in normal subjects when the vaccine and viral strain are closely matched.

Data from cohort analytic studies support vaccination of elderly persons living in institutions, persons with chronic heart or pulmonary conditions, diabetes and those who are immunocompromised. In elderly persons, live-attenuated vaccines offer no advantages over inactivated vaccines in terms of antibody response or immunologic memory. Little evidence exists that adverse effects of vaccination affect patient compliance. An RCT of vaccination of health care providers reported a minimal reduction in symptoms. Although efficacious, vaccination of the general population is not thought to be cost-effective.

2 RCTs demonstrated that outreach strategies (reminders, letter or telephone contact) conducted in physicians’ offices increased the vaccination rate among non-institutionalized adults at high risk.

Evidence from an RCT shows that amantadine is effective in preventing influenza A illness, but not in preventing influenza B. It also shortens the course of influenza A illness by 50% if administered within 48 hours of symptom onset. Adverse effects, primarily gastrointestinal and central nervous system symptoms, occur in about 40% of elderly patients with congestive heart failure, high serum creatinine and multiple underlying diagnoses.

{3 studies have been published since this review which may have led to different recommendations. These show benefits from vaccination for healthy young adults [Nichol 1995], older adults [Govaert 1994], and, through immunization of health care workers, for older institutionalized adults [Potter 1997].}

Recommendations
Recommendation grade [A, B, C, D, E]  and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

Validation
This report was externally peer-reviewed. The National Advisory Committee of the Bureau of Communicable Disease Epidemiology, Department of Health and Welfare Canada (now Health Canada), the Immunization Practices Advisory Committee (ACIP) of the U.S. Department of Health and Human Services and the 1989 U.S. Preventive Services Task Force recommended immunization of persons at high risk. The National Advisory Committee and the ACIP also recommended amantadine to prevent illness and to reduce severity and duration of illness.

Sponsors
The Canadian Task Force on Preventive Health Care developed this guideline with funding from Health Canada.

Selected References

Source Document
Elford RW and Tarrant M. Prevention of influenza. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 744-51.

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