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.
Overview
In 1979, the Canadian Task Force on the Periodic
Health Examination reviewed the evidence then available and concluded that
there was good evidence for high-risk groups such as persons over 65 years
of age or those with a chronic debilitating disease to receive yearly vaccinations
for influenza (A Recommendation).< 1> There was fair evidence for not
vaccinating the general population who are not at risk (D Recommendation).
Review of new evidence has moderated the strength of these earlier recommendations. Nevertheless, there is still fair evidence for annual vaccination of selected high-risk populations and health care providers but insufficient evidence to recommend for or against vaccination of the general population under 65 years of age. There is good evidence, however, to provide outreach to high-risk groups and to use amantadine chemoprophylaxis among high-risk individuals in contact with an index case.
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.<2>
Maneuver
The proper use of inactivated (killed-virus)
vaccine is the mainstay of prophylaxis. The traditional intramuscular routes
of vaccination may soon be replaced by less invasive approaches. Ingestion
of subunit-killed influenza vaccine in the form of enteric-coated capsules
stimulates local synthesis of secretory IgA antibody. A comparative study
suggests that protection against mucosal infection by respiratory viruses
correlates better with level of surface IgA antibody than with serum antibody.
From a prevention viewpoint, the value of early detection is primarily for the purpose of surveillance and the resulting ability to implement intervention maneuvers in high-risk populations, thereby reducing the explosiveness of epidemic outbreaks in local regions.
Clinical Detection
Practically, whenever the epidemiological evidence
suggests a high prevalence of influenza virus in the community, any febrile
(>38°C) respiratory illness accompanied by prostration, myalgia, headache
and cough is likely to be diagnosed as influenza by community practitioners.<3>
Isolation of the Virus
Inoculation of cell cultures with nasopharyngeal
washes, throat/nasopharyngeal swabs and daily observation for cytopathic
effects remains the gold standard for detection of influenza.<4>
Serological
Over a two week interval, a fourfold rise in
antibody titre following natural influenza virus infection and/or artificial
induction with vaccine can be detected with a complement fixation test
using nucleoprotein or a haemaglutination inhibition (HAI) test. Because
most laboratories stock only "generic" strains of the group A and B influenza
virus antigens, the antibody response for specific strains of naturally
occurring virus is detected variably from season to season.
Rapid Diagnostic Kit
Smears of nasopharyngeal secretions can now be
examined for respiratory viruses using rapid immunofluorescence techniques.
A positive result on a "Directigen Flu A test" has a positive predictive
value of 62.6% compared to virus isolation and a negative predictive value
of 100% when used in a controlled laboratory setting (if the rapid diagnostic
kit is negative, virus isolation culture is negative 100% of the time).<4>
The test produces results in less than 15 minutes and is available in community
(non-laboratory) centre environments as an adjunct to clinical diagnosis.
However, the reliability of the test in the hands of non-laboratory trained
personnel in the community environment is still unknown.
Effectiveness of Prevention
On the basis of clinical trials, vaccines have
been shown to be 70-80% effective in reducing both the occurrence of the
disease and the associated mortality in normal subjects when the vaccine
and the epidemic strain are closely matched.<5> Because efficacy of
the vaccine is proven, it would be unethical to withhold the vaccine pending
further clinical trials. Therefore, grade I evidence for high risk populations
will never be obtained. There is fair (grade II-2) evidence for providing
annual influenza vaccination for high-risk population groups such as the
institutionalized elderly, persons with chronic heart and or pulmonary
conditions,<6> diabetics,<7> and immunocompromised individuals including
HIV infected.<8> Directing the use of the vaccine to those most likely
to have fatal complications of influenza is the most effective way to diminish
mortality.<9,10>
Public Awareness
Surveillance permits the correct virus strains
to be incorporated annually into each new vaccine. The World Health Organization
(WHO) utilizes two reference laboratories, in Atlanta and London, to monitor
global patterns and receive reports of influenza activity through surveillance
systems developed in collaboration with regional and local health departments
in countries world wide. The wide fluctuation in vaccine use from year
to year suggests that increasing public awareness through community health
education could improve herd immunity among the general population. A number
of well designed field trials have demonstrated that the influenza vaccination
rate in non-institutionalized high risk patients can be significantly increased
by introducing outreach strategies in the primary care physician’s office.<11,12>
These study findings have led to specific proactive health education programs
that encourage vaccination of high risk patients and health care providers
in many acute care hospitals, ambulatory care settings, and chronic care
facilities. However, minimal reduction in clinical symptoms was documented
in a randomized trial of vaccination of health care providers.<13>
Isolation
Crowding, as occurs in institutionalized populations,
greatly enhances the spread of the influenza virus. Early detection and
protocol-directed isolation approaches to reduce transmission will ameliorate
a more severe outbreak of influenza. This process has limited practicability
in real institutional management other than restricting visitation to high-risk
individuals during periods of epidemic activity.
Annual Vaccination
Even in high-risk populations the benefit from
influenza vaccination is highly variable, because of poor vaccine antigenic
match, poor compliance with obtaining vaccination and poor antibody response
rates among the elderly. In both Canada and the U.S., the public health
services have established a policy objective of immunizing 60% of high
risk persons with influenza vaccine annually and make the vaccine available
for this group free of charge.<14> Split vaccines have been chemically
treated to reduce pyogenic components and are the type that should be used
in children under 13 years. In the elderly, however, live-attenuated vaccines
have not been shown to offer an advantage over inactivated vaccines in
terms of inducing serum or secretory antibodies or immunologic memory.
There is a paucity of evidence suggesting that the frequency of adverse
reactions to vaccination should constitute a deterrent to patient compliance
with influenza vaccination.<15> The chief problem associated with the
influenza vaccine is the failure to use it.
Antiviral Prophylaxis/Pharmacotherapy
Randomized trials have proven the efficacy of
amantadine in the prevention of influenza illness by restricting the replication
of the influenza A virus.<16> It, however, is not effective against
influenza B virus which is responsible for approximately 20% of epidemics.
Used therapeutically within 48 hours of onset of symptoms, it usually shortens
the course of influenza A illness by up to 50%.<17> Elderly patients
with congestive heart failure, high serum creatinine, and multiple underlying
diagnoses have a significant incidence (40%) of attributable adverse reactions
to amantadine. The most common gastrointestinal and central nervous symptoms
are dose-related and disappear promptly when the drug is discontinued.
Amantadine is best considered as a supplement to vaccination for the prophylaxis
of influenza A. Studies have shown that when unvaccinated high-risk patients
are encountered after an index case of acute influenza has been identified
in the community, the most appropriate management is to vaccinate and then
administer amantadine for two weeks so as to provide protection while antibody
production is induced.
Recommendations of Others
The National Advisory Committee of the Bureau
of Communicable Disease Epidemiology, Department of Health and Welfare
Canada recommends that intramuscular administration of split or whole-virus
vaccines be given annually to: 1) people at high risk; 2) people capable
of transmitting influenza to those at high risk; and 3) other people who
provide essential community services. Additionally they recommend amantadine
prophylaxis for the control of influenza A outbreaks among residents of
institutions, and as an adjunct to late vaccination in people at high risk.
Amantadine is also recommended for treatment in order to reduce the severity
and shorten the duration of influenza A in healthy adults.<18>
The Immunization Practices Advisory Committee (ACIP) of the U.S. Department of Health and Human Services strongly recommends the use of influenza vaccine for any person greater than 6 months who – because of age or underlying medical condition – is at increased risk for complications of influenza. After underscoring that chemoprophylaxis is not a substitute for vaccination, they recommend the use of amantadine for preventing illness and for the symptomatic treatment in order to reduce the duration and severity of systemic symptoms.<9>
In 1989, the U.S. Preventive Services Task Force<19> also recommended vaccinating high-risk groups (A Recommendation); this recommendation is currently being reviewed. The U.S. Public Health Service has established a policy objective of vaccinating 60% of high risk persons with influenza vaccine annually. A 1991 consensus conference in Canada established the goal of vaccinating 70% of high-risk persons. Both countries now make the vaccine available for this group free of charge.
Conclusion and Recommendations
Even though good (grade I) evidence exists for
the efficacy of influenza vaccination in the general population, directing
the use of the vaccine to those who are most likely to have fatal complications
of influenza is the most effective way to diminish mortality. There is
fair (grade II-2) evidence for providing annual influenza vaccination for
high-risk population groups such as the institutionalized, elderly, persons
with chronic heart and/or pulmonary conditions, diabetics or the immunocompromised
(B Recommendation). There is fair evidence to immunize health care providers
(B Recommendation). There is also good (grade I) evidence that the influenza
vaccination rate in the non-institutionalized high-risk patients can be
increased significantly by introducing outreach strategies (A Recommendation).
There is fair (grade II-1) evidence from studies performed in controlled
laboratory settings that the use of a rapid diagnostic kit for diagnosis
of influenza A virus infections has high specificity and negative predictive
value, and therefore could be useful in the early detection of influenza
A infections. There is good (grade I) evidence that early daily administration
of amantadine to high risk persons and to unvaccinated persons exposed
to influenza A virus during an outbreak of influenza reduces the spread
of the infection (A Recommendation).
Unanswered Questions (Research
Agenda)
The epidemiology of patterns of spread of the
influenza virus over large geographical areas remains enigmatic. The pathogenesis
(e.g. serum sickness vs. viremia) of clinical prostration manifestations
of influenza illness is still unclear. In the elderly, there is considerable
room for improvement of vaccine efficacy, possibly through different modes
of administration and/or enhancement of antibody response rates. There
is a need for field trials using "Rapid Diagnostic Kit" detection in order
to determine the reliability of out-of-laboratory use in community office
setting, and the effectiveness of early treatment with amantadine.
Evidence
The MEDLINE search strategy for this review identified
articles for the years 1981-1992 using the following MESH headings: influenza
virus, influenza vaccination, influenza chemo-prophylaxis and produced
115 citations. The list of citations was refined by excluding reviews,
editorials, commentaries and animal studies, and expanded by the addition
of key references contained in the bibliography of the medline articles.
In the situation where multiple articles on the same topic existed, the
more recent articles and those with the most rigorous design were retained
in the selected bibliography.
This review was initiated in April 1992 and recommendations were finalized by the Task Force in June 1993.
Full Citation
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.