Full Text Review
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
These recommendations were finalized by the Task Force in June 1993
Contents
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
Link to Structured Abstract of
this review
Link to Summary Table of this
review
Link to Selected References list of this review
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