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THE
INFLUENZA VACCINE
The
Influenza Vaccine is an annual vaccine to protect against
the highly variable influenza virus.
Purpose
and benefits of annual Flu vaccination
"Influenza
vaccination is the most effective method for preventing
influenza virus infection and its potentially severe
complications." An influenza epidemic emerges during
each winter's Flu season. In the United States alone
an estimated 36,000 people die each year from influenza
and accompanying opportunistic infections and complications.
The number of annual influenza-related hospitalizations
is many times the number of deaths. "The high costs
of hospitalizing young children for influenza creates
a significant economic burden in the United States,
underscoring the importance of preventive Flu shots
for children and the people with whom they have regular
contact..." In Canada, the National Advisory Committee
on Immunization, the group that advises the Public Health
Agency of Canada, currently recommends that everyone
aged 2 to 64 years be encouraged to receive annual influenza
vaccination, and that children between the age of six
and 24 months, and their household contacts, should
be considered a high priority for the Flu vaccine. In
the U.S., the CDC recommends to clinicians that In general,
anyone who wants to reduce their chances of getting
influenza can get vaccinated. Vaccination is especially
important for people at higher risk of serious influenza
complications or people who live with or care for people
at higher risk for serious complications. Vaccination
against influenza is recommended for most members of
high-risk groups who would be likely to suffer complications
from influenza. Specific recommendations include all
children and teenagers, from six months to 18 years
of age. In expanding the new upper age limit to 18 years,
the aim is to reduce both the time children and parents
lose from visits to pediatricians and missing school
and the need for antibiotics for complications ... An
added expected benefit would be indirect — to reduce
the number of influenza cases among parents and other
household members, and possibly spread to the general
community. In the event of exposure to H5N1-type (avian
influenza), seasonal Flu vaccine may also offer some
protection against H5N1 infection.
Efficacy
of vaccine
Flu
vaccines are available both as an injection of killed
virus (or Flu shot) and as nasal spray of live attenuated
influenza virus (LAIV) (sold as FluMist in the US).
Flumist is not recommended for individuals under age
2 or over age 50. Vaccine is effective against influenza,
but not perfect. A study led by Dr. David K. Shay in
February, 2008 reported that "full immunization against
Flu provided about a 75 percent effectiveness rate in
preventing hospitalizations from influenza complications
in the 2005-6 and 2006-7 influenza seasons." While no
statistically significant advantage emerged for either
LAIV (Flumist) or TIV (needle-injected vaccine) over
the other in two trials among adults noted by the CDC,
the benefit of influenza vaccination over non-vaccination
were clear: "One randomized, double-blind, placebo-controlled
challenge study among 92 healthy adults aged 18–41 years
assessed the efficacy of both LAIV and TIV in preventing
influenza infection when challenged with wild-type strains
that were antigenically similar to vaccine strains.
The overall efficacy in preventing laboratory-documented
influenza from all three influenza strains combined
was 85% and 71%, respectively. In a randomized, double-blind,
placebo-controlled trial, conducted among young adults
during an influenza season when the majority of circulating
H3N2 viruses were antigenically drifted from that season’s
vaccine viruses, the efficacy of LAIV and TIV against
culture-confirmed influenza was 57% and 77%, respectively.
Neither the comparative advantages of Flumist in the
first study nor the apparent advantages of needle-injected
vaccine in the second rose to statistical significance.
The added benefits of needle-injected vaccine in the
second study "was based largely upon a difference in
efficacy against influenza B." Flumist may be comparatively
more effective among children. In studies conducted
before final approval for two-year olds and older children,
Flumist demonstrated a definite immunological advantage
over Flu shots in this age group. These studies demonstrate
that vaccination can be a cost-effective counter-measure
to seasonal outbreaks of influenza. In most years (16
of the 19 years before 2007), the Flu vaccine strains
have been a good match for the circulating strains.
In other Flu seasons like that of 2007/2008, the match
was less useful. But even a mis-matched vaccine can
often provide some protection: ...Antibodies made in
response to vaccination with one strain of influenza
viruses can provide protection against different, but
related strains. A less than ideal match may result
in reduced vaccine effectiveness against the variant
viruses, but it still can provide enough protection
to prevent or lessen illness severity and prevent Flu-related
complications. In addition, it’s important to remember
that the influenza vaccine contains three virus strains
so the vaccine can also protect against the other two
viruses. For these reasons, even during seasons when
there is a less than ideal match, CDC continues to recommend
influenza vaccination. This is particularly important
for people at high risk for serious Flu complications
and their close contacts.
Annual
re-formulation of Flu vaccine
Each year the influenza virus changes and different
strains become dominant. Due to the high mutation rate
of the virus a particular vaccine formulation usually
works for only about a year. The World Health Organization
coordinates the contents of the vaccine each year to
contain the most likely strains of the virus to attack
the next year. The annually updated trivalent Flu vaccine
for the 2007–2008 season consists of hemagglutinin (HA)
surface glycoprotein components from influenza H3N2,
H1N1, and B influenza viruses.
History
of the Flu vaccine
Vaccines
are used in both humans and nonhumans. Human vaccine
is meant unless specifically identified as a veterinary,
poultry or livestock vaccine.
Influenza
The first influenza pandemic was recorded in 1580; since
this time, various methods have been employed to eradicate
its cause. The etiological cause of influenza, the orthomyxoviridae
was finally discovered by the Medical Research Council
(MRC) of the United Kingdom in 1933.
Known
Flu pandemics:
*
1889–90 — Asiatic (Russian) Flu, mortality rate said
to be 0.75–1 death per 1000 possibly H2N2
* 1900 — Possibly H3N8
* 1918–20 – Spanish Flu, 500 million ill, at least 20–40
million died of H1N1
* 1957–58 – Asian Flu, 1 to 1.5 million died of H2N2
* 1968–69 – Hong Kong Flu, 3/4 to 1 million died of
H3N2
Flu
vaccine origins and development
In the world wide Spanish Flu pandemic of 1918, "Physicians
tried everything they knew, everything they had ever
heard of, from the ancient art of bleeding patients,
to administering oxygen, to developing new vaccines
and sera (chiefly against what we now call Hemophilus
influenzae—a name derived from the fact that it was
originally considered the etiological agent—and several
types of pneumococci). Only one therapeutic measure,
transfusing blood from recovered patients to new victims,
showed any hint of success." In 1931, viral growth in
embryonated hens' eggs was discovered, and in the 1940s,
the US military developed the first approved inactivated
vaccines for influenza, which were used in the Second
World War (Baker 2002, Hilleman 2000). Greater advances
were made in vaccinology and immunology, and vaccines
became safer and mass-produced. Today, thanks to the
advances of molecular technology, we are on the verge
of making influenza vaccines through the genetic manipulation
of influenza genes (Couch 1997, Hilleman 2002).
Flu
vaccine acceptance
According
to the CDC: "Influenza vaccination is the primary method
for preventing influenza and its severe complications.
Vaccination is associated with reductions in influenza-related
respiratory illness and physician visits among all age
groups, hospitalization and death among persons at high
risk, otitis media among children, and work absenteeism
among adults. Although influenza vaccination levels
increased substantially during the 1990s, further improvements
in vaccine coverage levels are needed". The current
egg-based technology for producing influenza vaccine
was created in the 1950s. In the U.S. swine Flu scare
of 1976, President Gerald Ford was confronted with a
potential swine Flu pandemic. The vaccination program
was plagued by delays and public relations problems,
but about 24% of the population was vaccinated by the
time the program was canceled with much concern and
doubt about Flu vaccination.
Current
status
Influenza research includes molecular virology, molecular
evolution, pathogenesis, host immune responses, genomics,
and epidemiology. These help in developing influenza
countermeasures such as vaccines, therapies and diagnostic
tools. Improved influenza countermeasures require basic
research on how viruses enter cells, replicate, mutate,
evolve into new strains and induce an immune response.
The Influenza Genome Sequencing Project is creating
a library of influenza sequences that will help us understand
what makes one strain more lethal than another, what
genetic determinants most affect immunogenicity, and
how the virus evolves over time. Solutions to limitations
in current vaccine methods are being researched.
Today,
we have the capability to produce 300 million doses
of trivalent vaccine per year — enough for current epidemics
in the Western world, but insufficient for coping with
a pandemic.
Clinical
trials of vaccines
A vaccine is assessed in terms of the reduction of the
risk of disease produced by vaccination, its efficacy.
In contrast, in the field, the effectiveness of a vaccine
is the practical reduction in risk for an individual
when they are vaccinated under real-world conditions.
Measuring efficacy of influenza vaccines is relatively
simple, as the immune response produced by the vaccine
can be assessed in animal models, or the amount of antibody
produced in vaccinated people can be measured, or most
rigorously, by immunising adult volunteers and then
challenging with virulent influenza virus. In studies
such as these, influenza vaccines showed high efficacy
and produced a protective immune response. For ethical
reasons, such challenge studies cannot be performed
in the population most at risk from influenza – the
elderly and young children. However, studies on the
effectiveness of Flu vaccines in the real world are
uniquely difficult. The vaccine may not be matched to
the virus in circulation; virus prevalence varies widely
between years, and influenza is often confused with
other Flu-like illnesses.
Nevertheless,
multiple clinical trials of both live and inactivated
influenza vaccines have been performed and their results
pooled and analyzed in several recent meta-analyses.
Studies on live vaccines have very limited data, but
these preparations may be more effective than inactivated
vaccines. The meta-analyses examined the efficacy and
effectiveness of inactivated vaccines in adults, children,
and the elderly. In adults, vaccines show high efficacy
against the targeted strains, but low effectiveness
overall, so the benefits of vaccination are small, with
a one-quarter reduction in risk of contracting influenza
but no effect on the rate of hospitalization. In children,
vaccines again showed high efficacy, but low effectiveness
in preventing "Flu-like illness", in children under
two the data are extremely limited, but vaccination
appeared to confer no measurable benefit. In the elderly,
vaccination does not reduce the frequency of influenza,
but may reduce pneumonia, hospital admission and deaths
from influenza or pneumonia. The measured effectiveness
of the vaccine in the elderly varies depending on whether
the population studied is in residential care homes,
or in the community, with the vaccine appearing more
effective in an institutional environment. This apparent
effect may be due to selection bias affecting the analysis
of the data, or differences in diagnosis and surveillance.
Overall,
the benefit of influenza vaccination is clearest in
the elderly, with vaccination in children of questionable
benefit. Vaccination of adults is not predicted to produce
significant improvements in public health. The apparent
contradiction between vaccines with high efficacy, but
low effectiveness, may reflect the difficulty in diagnosing
influenza under clinical conditions and the large number
of strains circulating in the population.
Vaccination
recommendations
Various
public health organizations have recommended that yearly
influenza vaccination be routinely offered to patients
at risk of complications of influenza:
*
the elderly (UK recommendation is those aged 65 or above)
* patients with chronic lung diseases (asthma, COPD,
etc.)
* patients with chronic heart diseases (congenital heart
disease, chronic heart failure, ischaemic heart disease)
* patients with chronic liver diseases (including liver
cirrhosis)
* patients who are immunosuppressed (those with HIV
or who are receiving drugs to suppress the immune system
such as chemotherapy and long-term steroids) and their
household contacts
* all people who are institutionalized in an environment
where influenza can spread rapidly, such as in prisons
or nursing homes
* healthcare workers (both to prevent sickness and to
prevent spread to patients)
* pregnant women
In
the United States a person aged 50–64 is nearly ten
times more likely to die an influenza-associated death
than a younger person, and a person over age 65 is over
ten times more likely to die an influenza-associated
death than the 50–64 age group. Vaccination of those
over age 65 reduces influenza-associated death by about
50%. However, it is unlikely that the vaccine completely
explains the results since elderly people who get vaccinated
are probably more healthy and health-conscious than
those who do not. Elderly participants randomized to
a high-dose group (60 micrograms) had antibody levels
44 to 79 percent higher than did those who received
the normal dose of vaccine. Elderly volunteers receiving
the higher dose were more likely to achieve protective
levels of antibody
As
mortality is high among infants who contract influenza,
the household contacts and caregivers of infants should
be vaccinated to reduce the risk of passing an influenza
infection to the infant.
Data
from the years when Japan required annual Flu vaccinations
for school-aged children indicate that vaccinating children—the
group most likely to catch and spread the disease—has
a strikingly positive effect on reducing mortality among
older people: one life saved for every 420 children
who received the Flu vaccine. This may be due to herd
immunity or to direct causes, such as individual older
people not being exposed to influenza. For example,
retired grandparents often risk infection by caring
for their sick grandchildren in households where the
parents can't take time off work or are sick themselves.
Side
Effects
Side
effects of the inactivated/dead Flu vaccine injection
are:
* mild soreness
* redness
* swelling where the shot was given
* fever
* aches These problems usually begin soon after the
injection, and last 1–2 days.
Side
effects of the activated/live/LAIV Flu nasal spray vaccine:
Some children and adolescents 2–17 years of age have
reported mild reactions, including:
* runny nose, nasal congestion or cough
* fever * headache and muscle aches
* wheezing * abdominal pain or occasional vomiting or
diarrhea Some adults 18–49 years of age have reported:
* runny nose or nasal congestion
* sore throat
* cough, chills, tiredness/weakness
* headache
Flu
vaccine virus selection
Each
year, three strains are chosen for selection in that
year's Flu vaccination by the WHO Global Influenza Surveillance
Network. The chosen strains are the H1N1, H3N2, and
Type-B strains thought most likely to cause significant
human suffering in the coming season. "The WHO Global
Influenza Surveillance Network was established in 1952.
The network comprises 4 WHO Collaborating Centres (WHO
CCs) and 112 institutions in 83 countries, which are
recognized by WHO as WHO National Influenza Centres
(NICs). These NICs collect specimens in their country,
perform primary virus isolation and preliminary antigenic
characterization. They ship newly isolated strains to
WHO CCs for high level antigenic and genetic analysis,
the result of which forms the basis for WHO recommendations
on the composition of influenza vaccine for the Northern
and Southern Hemisphere each year." The Global Influenza
Surveillance Network's selection of viruses for the
vaccine manufacturing process is based on its best estimate
of which strains will be predominant the next year,
amounting in the end to well-informed but fallible guesswork.
Flu
vaccine manufacturing
Flu vaccine is usually grown in fertilized chicken eggs.
Both types of Flu vaccines are contraindicated for those
with severe allergies to egg proteins and people with
a history of Guillain-Barré syndrome.
On
October 5, 2004, Chiron Corporation, a corporation contracted
to deliver half of the expected Flu vaccine for the
United States and a significant portion to the UK, issued
a press release that stated it was unable to dispense
its stock for the 2004-2005 season, due to suspension
of the corporation's license to produce the vaccine
by the Medicines and Healthcare Products Regulatory
Agency. However, the Centers for Disease Control and
Prevention took swift action to enlist the help of other
companies such as MedImmune and Sanofi pasteur to supply
vaccine in high-risk populations in the United States.
Most
injection-based Flu vaccines intended for adults in
the United States still contain Thiomersal. Despite
some controversy, the World Health Organization has
concluded that there is no evidence of toxicity from
thimerosal in vaccines and no reason on grounds of safety
to change to more-expensive single-dose administration.
As
of November 2007, both the conventional injection and
the nasal spray are manufactured using chicken eggs.
The European Union has also approved OptaFlu, a vaccine
produced by Novartis using vats of animal cells. This
technique is expected to be more scalable and avoid
problems with eggs, such as allergic reactions and incompatibility
with strains that affect avians like chickens. A DNA-based
vaccination, which is hoped to be even faster to manufacture,
is currently in clinical trials, but has not yet been
proven safe and effective. Research continues into the
idea of a "universal" influenza vaccine (but no vaccine
candidates have been announced) which would not need
to be tailored to work on particular strains, but would
be effective against a broad variety of influenza viruses.
H5N1
Vaccines have been formulated against several of the
avian H5N1 influenza varieties. Vaccination of poultry
against the ongoing H5N1 epizootic is widespread in
certain countries. Some vaccines also exist for use
in humans, and others are in testing, but none have
been made available to civilian populations, nor produced
in quantities sufficient to protect more than a tiny
fraction of the earth's population in the event that
an H5N1 pandemic breaks out.
Three
H5N1 vaccines for humans have been licensed as of June
2008:
*
Sanofi Pasteur's vaccine approved by the United States
in April 2007,
* GlaxoSmithKline's vaccine Pandemrix approved by the
European Union in May 2008, and
* CSL Limited's vaccine approved by Australia in June
2008.
All
are produced in eggs and would require many months to
be altered to a pandemic version.
H5N1
continually mutates, meaning vaccines based on current
samples of avian H5N1 cannot be depended upon to work
in the case of a future pandemic of H5N1. While there
can be some cross-protection against related Flu strains,
the best protection would be from a vaccine specifically
produced for any future pandemic Flu virus strain. Dr.
Daniel Lucey, co-director of the Biohazardous Threats
and Emerging Diseases graduate program at Georgetown
University, has made this point, "There is no H5N1 pandemic
so there can be no pandemic vaccine." However, "pre-pandemic
vaccines" have been created; are being refined and tested;
and do have some promise both in furthering research
and preparedness for the next pandemic. Vaccine manufacturing
companies are being encouraged to increase capacity
so that if a pandemic vaccine is needed, facilities
will be available for rapid production of large amounts
of a vaccine specific to a new pandemic strain.
Problems
with H5N1 vaccine production include:
* lack of overall production capacity
* lack of surge production capacity (it is impractical
to develop a system that depends on hundreds of millions
of 11-day old specialized eggs on a standby basis)
* the pandemic H5N1 might be lethal to chickens
Cell
culture (cell-based) manufacturing technology can be
applied to influenza vaccines as they are with most
viral vaccines and thereby solve the problems associated
with creating Flu vaccines using chicken eggs as is
currently done.The US government has purchased from
Sanofi Pasteur and Chiron Corporation several million
doses of vaccine meant to be used in case of an influenza
pandemic of H5N1 avian influenza and is conducting clinical
trials with these vaccines. Researchers at the University
of Pittsburgh have had success with a genetically engineered
vaccine that took only a month to make and completely
protected chickens from the highly pathogenic H5N1 virus.
According
to the United States Department of Health & Human Services:
In
addition to supporting basic research on cell-based
influenza vaccine development, HHS is currently supporting
a number of vaccine manufacturers in the advanced development
of cell-based influenza vaccines with the goal of developing
U.S.-licensed cell-based influenza vaccines produced
in the United States. Dose-sparing technologies. Current
U.S.-licensed vaccines stimulate an immune response
based on the quantity of HA (hemagglutinin) antigen
included in the dose. Methods to stimulate a strong
immune response using less HA antigen are being studied
in H5N1 and H9N2 vaccine trials. These include changing
the mode of delivery from intramuscular to intradermal
and the addition of immune-enhancing adjuvant to the
vaccine formulation. Additionally, HHS is soliciting
contract proposals from manufacturers of vaccines, adjuvants,
and medical devices for the development and licensure
of influenza vaccines that will provide dose-sparing
alternative strategies
Chiron
Corporation is now recertified and under contract with
the National Institutes of Health to produce 8,000–10,000
investigational doses of Avian Flu (H5N1) vaccine. MedImmune
and Aventis Pasteur are under similar contracts. The
United States government hopes to obtain enough vaccine
in 2006 to treat 4 million people. However, it is unclear
whether this vaccine would be effective against a hypothetical
mutated strain that would be easily transmitted through
human populations, and the shelflife of stockpiled doses
has yet to be determined.
The
New England Journal of Medicine reported on March 30,
2006 on one of dozens of vaccine studies currently being
conducted. The Treanor et al. study was on vaccine produced
from the human isolate (A/Vietnam/1203/2004 H5N1) of
a virulent clade 1 influenza A (H5N1) virus with the
use of a plasmid rescue system, with only the hemagglutinin
and neuraminidase genes expressed and administered without
adjuvant. "The rest of the genes were derived from an
avirulent egg-adapted influenza A/PR/8/34 strain. The
hemagglutinin gene was further modified to replace six
basic amino acids associated with high pathogenicity
in birds at the cleavage site between hemagglutinin
1 and hemagglutinin 2. Immunogenicity was assessed by
microneutralization and hemagglutination-inhibition
assays with the use of the vaccine virus, although a
subgroup of samples were tested with the use of the
wild-type influenza A/Vietnam/1203/2004 (H5N1) virus."
The results of this study combined with others scheduled
to be completed by spring 2007 is hoped will provide
a highly immunogenic vaccine that is cross-protective
against heterologous influenza strains.
On
August 18, 2006. the World Health Organization changed
the H5N1 strains recommended for candidate vaccines
for the first time since 2004. "The WHO's new prototype
strains, prepared by reverse genetics, include three
new H5N1 subclades. The hemagglutinin sequences of most
of the H5N1 avian influenza viruses circulating in the
past few years fall into two genetic groups, or clades.
Clade 1 includes human and bird isolates from Vietnam,
Thailand, and Cambodia and bird isolates from Laos and
Malaysia. Clade 2 viruses were first identified in bird
isolates from China, Indonesia, Japan, and South Korea
before spreading westward to the Middle East, Europe,
and Africa. The clade 2 viruses have been primarily
responsible for human H5N1 infections that have occurred
during late 2005 and 2006, according to WHO. Genetic
analysis has identified six subclades of clade 2, three
of which have a distinct geographic distribution and
have been implicated in human infections:
* Subclade 1, Indonesia
* Subclade 2, Middle East, Europe, and Africa
* Subclade 3, China
On
the basis of the three subclades, the WHO is offering
companies and other groups that are interested in pandemic
vaccine development these three new prototype strains:
* An A/Indonesia/2/2005-like virus
* An A/Bar headed goose/Quinghai/1A/2005-like virus
* An A/Anhui/1/2005-like virus
Until
now, researchers have been working on prepandemic vaccines
for H5N1 viruses in clade 1. In March, the first clinical
trial of a U.S. vaccine for H5N1 showed modest results.
In May, French researchers showed somewhat better results
in a clinical trial of an H5N1 vaccine that included
an adjuvant. Vaccine experts aren't sure if a vaccine
effective against known H5N1 viral strains would be
effective against future strains. Although the new viruses
will now be available for vaccine research, WHO said
clinical trials using the clade 1 viruses should continue
as an essential step in pandemic preparedness, because
the trials yield useful information on priming, cross-reactivity,
and cross-protection by vaccine viruses from different
clades and subclades.
As
of November 2006, the United States Department of Health
and Human Services still had enough H5N1 pre-pandemic
vaccine to treat about 3 million people (5.9 million
full-potency doses) in spite of 0.2 million doses used
for research and 1.4 million doses that have begun to
lose potency (from the original 7.5 million full-potency
doses purchased from Sanofi Pasteur and Chiron Corp.).
The expected shelf life of seasonal Flu vaccine is about
a year so the fact that most of the H5N1 pre-pandemic
stockpile is still good after about 2 years is considered
encouraging.
Flu
seasons
2003–2004
season (Northern Hemisphere)
The production of Flu vaccine requires a lead time of
about six months before the season. It is possible that
by Flu season a strain becomes common for which the
vaccine does not provide protection. In the 2003–2004
season the vaccine was produced to protect against A/Panama,
A/New Caledonia, and B/Hong Kong. A new strain, A/Fujian,
was discovered after production of the vaccine started
and vaccination gave only partial protection against
this strain.
Nature
magazine reported that the Influenza Genome Sequencing
Project, using phylogenetic analysis of 156 H3N2 genomes,
"explains the appearance, during the 2003–2004 season,
of the 'Fujian/411/2002'-like strain, for which the
existing vaccine had limited effectiveness" as due to
an epidemiologically significant reassortment. "Through
a reassortment event, a minor clade provided the haemagglutinin
gene that later became part of the dominant strain after
the 2002–2003 season. Two of our samples, A/New York/269/2003
(H3N2) and A/New York/32/2003 (H3N2), show that this
minor clade continued to circulate in the 2003–2004
season, when most other isolates were reassortants."
According
to the CDC:
During
the 2003–2004 influenza season, influenza A (H1), A
(H3N2), and B viruses co-circulated worldwide, and influenza
A (H3N2) viruses predominated. Several Asian countries
reported widespread outbreaks of avian influenza A (H5N1)
among poultry. In Vietnam and Thailand, these outbreaks
were associated with severe illnesses and deaths among
humans. In the United States, the 2003–2004 influenza
season began earlier than most seasons, peaked in December,
was moderately severe in terms of its impact on mortality,
and was associated predominantly with influenza A (H3N2)
viruses
During
September 28, 2003 – May 22, 2004, WHO and NREVSS collaborating
laboratories in the United States tested 130,577 respiratory
specimens for influenza viruses; 24,649 (18.9%) were
positive. Of these, 24,393 (99.0%) were influenza A
viruses, and 249 (1.0%) were influenza B viruses. Among
the influenza A viruses, 7,191 (29.5%) were subtyped;
7,189 (99.9%) were influenza A (H3N2) viruses, and two
(0.1%) were influenza A (H1) viruses. The proportion
of specimens testing positive for influenza first increased
to >10% during the week ending October 25, 2003 (week
43), peaked at 35.2% during the week ending November
29 (week 48), and declined to <10% during the week ending
January 17, 2004 (week 2). The peak percentage of specimens
testing positive for influenza during the previous four
seasons had ranged from 23% to 31% and peaked during
late December to late February.
As
of June 15, 2004, CDC had antigenically characterized
1,024 influenza viruses collected by U.S. laboratories
since October 1, 2003: 949 influenza A (H3N2) viruses,
three influenza A (H1) viruses, one influenza A (H7N2)
virus, and 71 influenza B viruses. Of the 949 influenza
A (H3N2) isolates characterized, 106 (11.2%) were similar
antigenically to the vaccine strain A/Panama/2007/99
(H3N2), and 843 (88.8%) were similar to the drift variant,
A/Fujian/411/2002 (H3N2). Of the three A (H1) isolates
that were characterized, two were H1N1 viruses, and
one was an H1N2 virus. The hemagglutinin proteins of
the influenza A (H1) viruses were similar antigenically
to the hemagglutinin of the vaccine strain A/New Caledonia/20/99.
Of the 71 influenza B isolates that were characterized,
66 (93%) belonged to the B/Yamagata/16/88 lineage and
were similar antigenically to B/Sichuan/379/99, and
five (7%) belonged to the B/Victoria/2/87 lineage and
were similar antigenically to the corresponding vaccine
strain B/Hong Kong/330/2001.
H9N2
In December 2003, one confirmed case of avian influenza
A (H9N2) virus infection was reported in a child aged
five years in Hong Kong. The child had fever, cough,
and nasal discharge in late November, was hospitalized
for two days, and fully recovered. The source of this
child's H9N2 infection is unknown.
H5N1
During January–March 2004, a total of 34 confirmed human
cases of avian influenza A (H5N1) virus infection were
reported in Vietnam and Thailand. The cases were associated
with severe respiratory illness requiring hospitalization
and a case-fatality proportion of 68% (Vietnam: 22 cases,
15 deaths; Thailand: 12 cases, eight deaths). A substantial
proportion of the cases were among children and young
adults (i.e., persons aged 5–24 years). These cases
were associated with widespread outbreaks of highly
pathogenic H5N1 influenza among domestic poultry.
H7N3
During March 2004, health authorities in Canada reported
two confirmed cases of avian influenza A (H7N3) virus
infection in poultry workers who were involved in culling
of poultry during outbreaks of highly pathogenic H7N3
on farms in the Fraser River Valley, British Columbia.
One patient had unilateral conjunctivitis and nasal
discharge, and the other had unilateral conjunctivitis
and headache. Both illnesses resolved without hospitalization.
H7N2
During the 2003–2004 influenza season, a case of avian
influenza A (H7N2) virus infection was detected in an
adult male from New York, who was hospitalized for upper
and lower respiratory tract illness in November 2003.
Influenza A (H7N2) virus was isolated from a respiratory
specimen from the patient, whose acute symptoms resolved.
The source of this person's infection is unknown.
2004
season (Southern Hemisphere)
The
composition of influenza virus vaccines for use in the
2004 Southern Hemisphere influenza season recommended
by the World Health Organization was:
* an A/New Caledonia/20/99(H1N1)-like virus
* an A/Fujian/411/2002(H3N2)-like virus (A/Kumamoto/102/2002
and A/Wyoming/3/2003 were egg-grown A/Fujian/411/2002-like
viruses)
* a B/Hong Kong/330/2001-like virus (B/Shandong/7/97,
B/Hong Kong/330/2001 and B/Hong Kong/1434/2002 were
among those used at the time. B/Brisbane/32/2002 was
also available.)
2004–2005
season (Northern Hemisphere)
According
to the CDC: On the basis of antigenic analyses of recently
isolated influenza viruses, epidemiologic data, and
postvaccination serologic studies in humans, the Food
and Drug Administration's Vaccines and Related Biological
Products Advisory Committee (VRBPAC) recommended that
the 2004–05 trivalent influenza vaccine for the United
States contain A/New Caledonia/20/99-like (H1N1), A/Fujian/411/2002-like
(H3N2), and B/Shanghai/361/2002-like viruses. Because
of the growth properties of the A/Wyoming/3/2003 and
B/Jiangsu/10/2003 viruses, U.S. vaccine manufacturers
are using these antigenically equivalent strains in
the vaccine as the H3N2 and B components, respectively.
The A/New Caledonia/20/99 virus will be retained as
the H1N1 component of the vaccine
2005
season (Southern Hemisphere)
The
composition of influenza virus vaccines for use in the
2005 Southern Hemisphere influenza season recommended
by the World Health Organization was:
* an A/New Caledonia/20/99(H1N1)-like virus;
* an A/Wellington/1/2004(H3N2)-like virus;
* a B/Shanghai/361/2002-like virus (B/Shanghai/361/2002,
B/Jilin/20/2003 and B/Jiangsu/10/2003 were used at the
time)
2005–2006
season (Northern Hemisphere)
The
vaccines produced for the 2005–2006 season use:
*
an A/New Caledonia/20/1999-like(H1N1);
* an A/California/7/2004-like(H3N2) (or the antigenically
equivalent strain A/New York/55/2004);
* a B/Jiangsu/10/2003-like viruses.
In
people in the U.S., overall Flu and pneumonia deaths
were below those of a typical Flu season with 84% Influenzavirus
A and the rest Influenzavirus B. Of the patients who
had Type A viruses, 80% had viruses identical or similar
to the A bugs in the vaccine. 70% of the people testing
positive for a B virus had Type B Victoria, a version
not found in the vaccine. "During the 2005–06 season,
influenza A (H3N2) viruses predominated overall, but
late in the season influenza B viruses were more frequently
isolated than influenza A viruses. Influenza A (H1N1)
viruses circulated at low levels throughout the season.
Nationally, activity was low from October through early
January, increased during February, and peaked in early
March. Peak activity was less intense, but activity
remained elevated for a longer period of time this season
compared to the previous three seasons. The longer period
of elevated activity may be due in part to regional
differences in the timing of peak activity and intensity
of influenza B activity later in the season."
2006
season (Southern Hemisphere)
The
composition of influenza virus vaccines for use in the
2006 Southern Hemisphere influenza season recommended
by the World Health Organization was:
* an A/New Caledonia/20/99(H1N1)-like virus;
* an A/California/7/2004(H3N2)-like virus (A/New York/55/2004
was used at the time);
* a B/Malaysia/2506/2004-like virus
2006–2007
season (Northern Hemisphere)
The 2006–2007 influenza vaccine composition recommended
by the World Health Organization on February 15, 2006
and the U.S. FDA's Vaccines and Related Biological Products
Advisory Committee (VRBPAC) on February 17, 2006 use:
* an A/New Caledonia/20/99 (H1N1)-like virus;
* an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005
and A/Hiroshima/52/2005 strains);
* a B/Malaysia/2506/2004-like virus from B/Malaysia/2506/2004
and B/Ohio/1/2005 strains which are of B/Victoria/2/87
lineage.
2007
season (Southern Hemisphere)
The
composition of influenza virus vaccines for use in the
2007 Southern Hemisphere influenza season recommended
by the World Health Organization on September 20, 2006
was:
* an A/New Caledonia/20/99(H1N1)-like virus,
* an A/Wisconsin/67/2005(H3N2)-like virus (A/Wisconsin/67/2005
and A/Hiroshima/52/2005 were used at the time),
* a B/Malaysia/2506/2004-like virus
2007–2008
season (Northern Hemisphere)
The composition of influenza virus vaccines for use
in the 2007–2008 Northern Hemisphere influenza season
recommended by the World Health Organization on February
14, 2007 was:
* an A/Solomon Islands/3/2006 (H1N1)-like virus;
* an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005
(H3N2) and A/Hiroshima/52/2005 were used at the time);
* a B/Malaysia/2506/2004-like virus
In the US, the CDC reported in Feb 2008 that the H1N1
component was a good match (96%) to the infections occurring.
But 87% of the H3N2 are A/Brisbane/10/2007-like viruses,
which are a recent antigenic variant of the vaccine
strain, A/Wisconsin. And 93% of the B viruses are in
a B/Yamagata lineage that is relatively distinct from
the vaccine strain B/Victoria lineage. Only one of the
three components was a good match; A/Wisconsin is moderately
protective against the drifted A/Brisbane strain. 4.5%
of those viruses tested are resistant to Oseltamivir,
or TamiFlu—a significant increase over previous years.
This vaccine has been described as 40% effective compared
to other years that have been 85–95% effective.
2008
season (Southern Hemisphere)
The
composition of virus vaccines for use in the 2008 Southern
Hemisphere influenza season recommended by the World
Health Organization on September 17-19, 2007 was:
* an A/Solomon Islands/3/2006 (H1N1)-like virus;
* an A/Brisbane/10/2007 (H3N2)-like virus;
* a B/Florida/4/2006-like virus
2008-2009
season (Northern Hemisphere)
The
composition of virus vaccines for use in the 2008-2009
Northern Hemisphere influenza season recommended by
the World Health Organization on February 14, 2008[89]
was:
* an A/Brisbane/59/2007 (H1N1)-like virus;
* an A/Brisbane/10/2007 (H3N2)-like virus (A/Brisbane/10/2007
was used at the time);
* a B/Florida/4/2006-like virus (B/Florida/4/2006 and
B/Brisbane/3/2007 (a B/Florida/4/2006-like virus) were
used at the time).
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