The 1996-1997 Influenza Season - A View from
the Benches
Danny L. Wiedbrauk, Ph.D.
William Beaumont Hospital, Royal Oak, Michigan 48073
Influenza moves rapidly throughout the population
each winter, causing 10,000 to 40,000 excess deaths annually.1
In the virology laboratory, this observation means that
the influenza season can be easy or difficult, depending upon
a number of factors. My informal poll of selected laboratories
indicates that the 1996-97 influenza season ranks as one of the
ugliest in recent memory. In these laboratories, the influenza-associated
workload was higher than it has been for the past five years.
Virology laboratories were not the only ones who were caught
short. Becton Dickinson ran out of Directigen®
influenza A EIA kits again this year and some laboratories had
to wait 2-4 weeks for their order to be filled.
Several factors have apparently contributed to
the increased influenza workload. First, the A/Wuhan(H3N2)-like
strain currently circulating in North America is different-enough
from the A/Johannesburg(H3N2) vaccine strain that previous vaccinations
may not provide protection from significant disease. Second,
anecdotal information from several local physicians indicates
that the circulating influenza A strain is particularly aggressive,
causing significant and widespread illness. While the truth of
this observation remains to be determined, this observation is
circulating among local physicians and they are ordering more
influenza tests. Finally, the recent recall of the Fluogen®
trivalent vaccine has heightened the awareness of physicians and
the lay public. Only 5-7% of the influenza-vaccinated population
were given recalled vaccine lots.3
However, the publicity associated with this recall
has significantly increased laboratory orders for influenza testing.
With increased awareness of influenza and increased testing volumes
comes an increased number of questions about influenza. Several
of the most frequently asked questions (and our answers) are listed
below.
Just when we thought we had this season under
control, a number of laboratories began isolating influenza B.
Maybe this isn't over yet!
How is the influenza season progressing?
The Centers for Disease Control and Prevention
(CDC) report that regional influenza activity was first observed
in Maryland in mid-October. Data from the CDC collaborating laboratories
in the U.S. indicate that peak isolation rates were observed from
November 17 through December 7, 1996.2 At that time,
99% of influenza viruses isolates were type A and 1% were type
B. All the subtyped isolates were type A(H3N2) and were antigenically
similar to the H3N2 strain that was included in the current vaccine
(see below).2
What influenza strains are in the 1996-1997 vaccine?
The trivalent influenza vaccine prepared for the
1996-97 season included A/Texas/36/91-like (H1N1), A/Wuhan/359/95-like
(H3N2), and B/Beijing/184/93-like influenza strains. The 1996-97
vaccine differs from the previous vaccine in that A/Wuhan/359/95
strain replaced the A/Johanesburg/33/94(H3N2) strain. To further
confuse the issue, U.S. vaccine producers replaced the A/Wuhan/359/95-like
and the B/Beijing/184/93-like viruses with the antigenically equivalent
A/Nanchang/933/95/(H3N2) and B/Harbin/07/94 strains because these
strains were easier to propagate in vitro.4,5
This change has caused some confusion in the medical and lay
community.
Why was the influenza vaccine recalled? Which
vaccine did we get?
In November, 1996, Parke-Davis (Parke-Davis Division,
Warner Lambert Company, Morris Plains, NJ) voluntarily recalled
11 lots of Fluogen® trivalent influenza vaccine
because the monitored quality of the A/Nanchang/933/95/(H3N2)
hemagglutinin antigen had declined.3 The reason for
this decline was not known. In investigating this problem, the
CDC and the New York State Department of Health evaluated the
antibody responses to the 1996-1997 vaccine among 86 residents
of three nursing homes in New York who received the recalled vaccine
and 86 residents from three other nursing homes who received vaccine
produced by a different manufacturer. This investigation revealed
that the residents who were given the recalled vaccine had significantly
lower antibody titers to the A/Nanchang/933/95/(H3N2) strain than
nursing home residents who received vaccine from another manufacturer
3. In addition, significantly fewer residents who
received the recalled vaccine achieved hemagglutinin inhibition
assay titers of >1:40 to the A/Nanchang/933/95(H3N2) compared
with controls. The antibody titers to the A/Texas/36/91/(H1N1)
and the B/Harbin/07/94 vaccine components were similar in both
groups.
How effective is the influenza vaccine?
The protection offered by the influenza vaccine
correlates with the development of hemagglutinin antibodies.
In young adults, immunization provides 65 to 80% protection against
illness caused by an influenza virus when there is a good match
with the vaccine strain.5 Influenza vaccination is
30-70% effective in preventing hospitalization for pneumonia and
influenza among elderly individuals who do not live in nursing
homes or other long-term care settings. Unfortunately, the vaccine
may be only 30-40% effective in preventing clinical illness
in elderly residents of nursing homes. While the vaccine usually
does not prevent disease in these individuals, the vaccine lessens
the severity of disease and is 50-60% effective in preventing
hospital admissions and 80% effective in preventing death from
influenza-associated pneumonia5,6 Risk-benefit studies
have consistently shown that the risk of death from influenza
outweighs the potential for adverse vaccine reactions in all age
groups.7,8 Despite its known benefits, current levels
of immunization against influenza are approximately 30% for persons
65 years of age or older and 9-13% among adults who have high
risk conditions.6
Are there rapid tests for influenza?
Laboratory detection of influenza virus can be
accomplished using tube cultures, shell vial cultures, direct
fluorescent antibody (DFA) methods 9, enzyme immunoassays
(EIA) (influenza A only), and the polymerase chain reaction (PCR).
Tube and shell vial cultures are not considered rapid tests because
their turnaround times are 2-14 days and 1-2 days, respectively.
Likewise, PCR tests, which have mean turnaround times of 24-48
hours, cannot be classified as rapid diagnostic tests for influenza.
Although commercial DFA and EIA methods are very
specific (95-100% versus culture), they are not as sensitive as
culture methods. Most DFA reagents for influenza virus detection
have sensitivities of 85-95% compared with culture. DFA methods
can detect influenza type A and B while rapid membrane EIA tests
only detect influenza A. Rapid membrane EIA methods for influenza
A have somewhat lower (75-90%) sensitivities compared with culture.
Although membrane-based EIA tests are 5-15 times more expensive
than DFA procedures, these low complexity tests can be performed
by personnel who have significantly less training and expertise
than is required for DFA tests. For this reason, rapid membrane
assays are increasingly used in STAT laboratories, physician offices,
and in situations were point-of-care testing is desirable. Like
the rapid strep tests, EIA-negative specimens should be cultured
to maximize the influenza detection rates. Follow-up cultures
are important to minimize the spread of disease and its associated
complications. In addition, hospitals and nursing homes who exclusively
use rapid EIA methods to cohort patients with influenza and to
identify nosocomial infections10 may miss a significant
number of influenza infections.
Literature Cited
1. Gardner P, Schaffner W. Immunization of adults.
N Eng J Med 1993; 328:1252-1258.
by Dr.Richard L. Hodinka
Children's Hospital of
Philadelphia
The fields of clinical microbiology and virology
have suffered a great loss with the death of Philip A. Hanff
on Dec. 9, 1996 at age 48. Phil was diagnosed with esophageal
cancer in Nov. 1995 and succumbed to aggressive liver metastases
found in Nov. 1996.
He was a native of Los Angeles, CA and earned
an B.A. degree from the University of California, Riverside in
1970 and a Ph.D. from the University of California, Los Angeles
in 1980. From 1975-1982, he completed two research postdoctoral
fellowships at the University of California School of Medicine,
Los Angeles, and from 1982-1984, finished his clinical microbiology
postdoctoral fellowship in the clinical Microbiology-Immunology
Laboratories at North Carolina Memorial Hospital on the campus
of the University of North Carolina, Chapel Hill.
His career as a clinical microbiologist began
in 1984 as Scientific Director of the Clinical Microbiology Laboratories
at Beth Israel Deaconess Medical Center in Boston. He was an
instructor in Pathology at the Harvard Medical School from 1984-1989
and was promoted to an Asst Professor of Pathology in 1989.
Phil was a member of the American Society for
Microbiology since 1978 and was an active participant in the Pan
American Society for Clinical Virology for the past 10 years.
Phil also was an annual speaker for and helped initiate the panel
on "Clinical Case Presentation and Discussion" which
has been a successful component of the Clinical Virology Symposium
in Clearwater since 1993. He served on editorial boards and was
a guest reviewer for a number of journals. He was in constant
demand as an invited speaker for numerous microbiology meetings
and had many published contributions in clinical microbiology.
Phil directed an outstanding diagnostic microbiology
lab and trained and supervised many technologists and medical
scientists. He was an excellent researcher and clinical educator
and was held with great esteem by his students, colleagues and
peers. He had a quick wit, was always friendly and cooperative
in his approach, and was compassionate and sensitive to the needs
and emotions of people who worked with him. His informed opinions
and advise were well respected. His wisdom and intellect went
far beyond his chosen field of science. Phil was a tremendous
asset to the fields of clinical microbiology and virology.
On a more personal note, I will always remember
Phil through our annual gatherings at the Clinical Virology Symposium.
Although this meeting is a platform for science, it also allows
individuals to establish friendships that will remain forever.
Many of us enjoyed Phil's company, as we dined with him, shared
conversations during nightly beach walks, and played some "interesting"
games of volleyball as time permitted. Since his passing, I have
often reflected on the laughter and fun had by all.
Phil was a warm and caring person who was always
attentive to his family and friends. He will be remembered often
and will be dearly missed by his many colleagues, professional
acquaintances, and friends. My deepest sympathy goes to his family.
Phil is survived by his wife, Jeni Yamada, and
their three boys, Aaron, Jason and Adam. A memorial fund has
been established on behalf of his widow and children. Contributions
may be directed to:
2. Centers for Disease Control. Update: Influenza
activity - United States, 1996-97 season. MMWR 1996; 45:1102-1105.
3. Centers for Disease Control. Decreased antibody
response to influenza vaccine among nursing-home residents who
received recalled vaccine - New York, 1996. MMWR 1996; 45:1100-1102.
4. Centers for Disease Control. Update: Influenza
activity - United States and worldwide, 1995-96 season, and composition
of the 1996-97 influenza vaccine. MMWR 1996; 45:326-329.
5. Centers for Disease Control. Prevention and control
of influenza: Recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR 1996; 45:1-24.
6. American College of Physicians Task Force on Adult
Immunization, Infectious Disease Society of America. Guide for
adult immunization. Philadelphia, PA: American College of Physicians,
1990.
7. Office of Technology Assessment. Cost effectiveness
of influenza vaccination. Washington, DC: Government Printing
Office, 1981.
8. Nichol KL, Margolis KL, Wuorenma J, von Sternberg
T. The efficacy and cost effectiveness of vaccination against
influenza among elderly persons living in the community. New England
Journal of Medicine 1994; 33:1778-784.
9. Wiedbrauk DL, Johnston SLG. Manual of Clinical
Virology. New York, NY: Raven Press, 1993.
10. Serwint JR, Miller RM. Why diagnose influenza
infections in hospitalized pediatric patients? Pediatric Infectious
Disease Journal 1993; 12.
Deceased Member