Update On Avian Influenza

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Update On Avian Influenza

• Wallace Greene, PhD, ABMM
• Director, Diagnostic Virology Laboratory
• Department of Pathology
• M. S. Hershey Medical Center
• Hershey, Pennsylvania

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WHAT HAPPENS WHEN CHICKEN LITTLE GETS THE FLU?
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A Report from Secretary Michael O. Leavitt March
13, 2006 President Bush asked Congress for
7.1 billion to fund preparations, and in
December 2005 Congress appropriated 3.8 billion
to help the Nation prepare. Of that, 3.3 billion
was allocated to HHS. This report outlines how
that funding is being used to help achieve HHSs
five primary objectives.
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We are in a race. We are in a race against a
fast moving virulent virus with the potential to
cause an influenza pandemic. In November when
President Bush announced the National Strategy
for Pandemic Influenza, the highly pathogenic
H5N1 avian flu virus was confirmed in birds in 16
countries. It was known to have infected 122
people and 62 half of those infected died.
..To date, most of those people were exposed to
infected poultry. Fortunately, there has been no
sustained human-to-human transmission of the
disease, but the rapid spread of H5N1 is reason
for concern.
We are in a race, a race against a quick
changing virus, for H5N1 has not only spread, it
has evolved. There are now two main variants, or
clades, of H5N1 and it is this second, newer
clade that is spreading across western Asia into
Europe, the Middle East and Africa. This second
clade has killed over 60 percent of those it is
known to have infected.
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Assessment of Current Situation
Research suggests that currently circulating
strains of H5N1 viruses are becoming more capable
of causing disease (pathogenic) in animals than
were earlier H5N1 viruses. One study found that
ducks infected with H5N1 virus are now shedding
more virus for longer periods without showing
symptoms of illness. This finding has
implications for the role of ducks in
transmitting disease to other birds and possibly
to humans as well. Additionally, other findings
have documented H5N1 infection among pigs in
China and H5N1 infection in felines (experimental
infection in housecats in the Netherlands and
isolation of H5N1 viruses in tigers and leopards
in Thailand). In addition, in early March 2006,
Germany reported H5N1 infection in a stone marten
(a weasel-like mammal). The avian influenza A
(H5N1) virus that emerged in Asia in 2003
continues to evolve and may adapt so that other
mammals may be susceptible to infection as well.
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INFLUENZA TIMELINE
1890 first recorded influenza pandemic 1918
Spanish flu pandemic, caused by an H1N1 strain
kills more than 40 million people. Recently
shown to be due to a bird-human jump 1957
Asian flu pandemic kills 100,000 people, due to
H2N2 virus 1968 Hong Kong flu pandemic kills
700,000 people, due to H3N2 virus. Both H2N2
and H3N2 strains likely due to exchange of genes
between avian and human flu viruses May 21, 1997
Bird flu virus H5N1 is isolated for the first
time in a human in Hong Kong. The virus infects
18 people after close contact with poultry,
with six deaths. Within three days, Hong
Kongs entire chicken population is
slaughtered.
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INFLUENZA TIMELINE
Sept 1998 Two new influenza drugs are
announced Feb 2003 H5N1 infects two people in
Hong Kong, one dies Feb 28, 2003 Outbreaks of
H7N7 occur in the Netherlands. By April, it
has spread to 800 poultry farms, resulting in the
culling of 11 million chickens. The virus
infects 83 people with one death Dec 2003
South Korea has first outbreak of H5N1 virus Jan
2004 Japan has first outbreak on H5N1 since
1925 WHO confirms H5N1 infection in 11 people,
eight fatal, in Thailand and Vietnam. Virus
wrecks havoc in poultry industry in Thailand,
Vietnam, Japan, and South Korea and is found in
China WHO begins work on developing H5N1
vaccines in U.S. and U.K.
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INFLUENZA TIMELINE
March 2004 H5N1 flu virus becomes more
widespread among flocks in Asia, has caused 34
human cases, with 23 deaths July 2004 Several
countries, including Thailand, Vietnam,
China and Indonesia report new infections in
poultry with H5N1 August 2004 H5N1 is reported
to have killed 5 more people in Vietnam Chinese
scientists report H5N1 infections in pigs H5N1
has spread throughout most of SE Asia, resulting
in the culling of over 100 million chickens.
In Vietnam and Thailand, 37 people have been
infected, with 26 deaths October 2004 UK
authorities suspend manufacturing of flu
vaccine November 2004 WHO ramps up activities,
urges focus on vaccine development
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INFLUENZA TIMELINE
Jan/Feb 2005 13 additional human cases in
Vietnam, 12 fatal Feb 2005 First report on
H5N1 in Cambodia Probable person-to-person
transmission reported in Vietnam First
vaccines begin clinical trials March 2005 15
additional cases in Vietnam and one in
Cambodia Bird flu has spread to 10 countries
and killed around 50 million chickens May 2005
Reports of human deaths reported in China, and
over 1,000 dead migratory birds have been
identified. July 2005 Philippines report their
first case
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INFLUENZA TIMELINE
2005 Vietnam Transmission through consumption
of uncooked duck blood2006 Azerbaijan
children were found to be infected through
collecting feathers from dead swans.2006
Indonesia - WHO reported evidence of
human-to-human spread. In this situation, 8
people in one family were infected. The first
family member is thought to have become ill
through contact with infected poultry. This
person then infected six family members. One of
those six people (a child) then infected another
family member (his father). No further spread
outside of the exposed family was documented or
suspected.
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1918 Influenza Pandemic
One anectode shared of 1918 was of four women
playing bridge together late into the night.
Overnight, three of the women died from influenza
(Hoagg). Others told stories of people on their
way to work suddenly developing the flu and dying
within hours (Henig). One physician writes that
patients with seemingly ordinary influenza would
rapidly "develop the most viscous type of
pneumonia that has ever been seen" and later when
cyanosis appeared in the patients, "it is simply
a struggle for air until they suffocate," (Grist,
1979). Another physician recalls that the
influenza patients "died struggling to clear
their airways of a blood-tinged froth that
sometimes gushed from their nose and mouth,"
(Starr, 1976).
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Emergency hospital during 1918 influenza
epidemic, Camp Funston, Kansas (National Museum
of Health Medicine photo)
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An Emergency Hospital for US Influenza Patients
The influenza virus had a profound virulence,
with a mortality rate at 2.5 compared to the
previous influenza epidemics, which were less
than 0.1. The death rate for 15 to 34-year-olds
of influenza and pneumonia were 20 times higher
in 1918 than in previous years (Taubenberger).
People were struck with illness on the street and
died rapid deaths.
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1918
Half of the world became infected 25 of
Americans were ill 99 of excess deaths were
among those under 65 years old Mortality peaked
in 20 to 34 year olds Women under 35 accounted
for 70 of all female flu deaths In 1918, more
people died from influenza than the bubonic
plague killed in a century This virus killed more
people in 25 weeks than HIV has killed in 25
years
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1918
The virus first appeared March 4, 1918 in
soldiers at Camp Funston, Kansas and spread
rapidly to most American cities and was
relatively mild. In June, the Spanish news
reported A strange form of disease of epidemic
character has appeared in Madrid. The epidemic
is of a mild nature, no deaths having been
reported. In late August, a deadly variant
exploded simultaneously in the French port city
of Brest (a major disembarkation of American
soldiers), Boston (where troops returned from the
battlefield), and Freetown, Sierra Leone (where
British navy vessels were docked.
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1918

By Fall of 1918, the conditions in Camp Funston
were much worse. The commander wrote the
governor There are 1440 minutes in a day. When
I tell you there were 1440 admissions in a day,
you realize the strain put on our nursing and
medical forces. October 1918 became the
deadliest month in US history, and the last week
of October was the deadliest week from any cause
at any time. More than 20,000 Americans died in
that week alone. In New York City, over 21,000
children lost both parents to this disease.
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Flu Pandemics A Comparison
Year 1918 2000 World Population 1.8
Billion 5.9 Billion Primary Mode
of Troopships Jet Aircraft Transportation Railro
ad automobile Time for Virus to 4 months 4
days Circle the Globe Estimated Dead 50
Million ????? Worldwide
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Death toll in 20th century pandemics and
projections for the next pandemic Population
Death Toll per 100,000 people 1918 1.8
billion 50 million 2,777 1957 3.8 billion 1
million 26 1968 4.5 billion 1 million
27 Next 6.5 billion 1.7 million 26 Next
6.5 billion 180 million 2,777 According to
data from http//www.census.gov/ipc/www/world.html
http//www.prb.org/Content/NavigationMenu/PRB/E
ducators/Human_ Population/Population_Growth/Popul
ation_Growth.htm
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• Avian Influenza
• Where are we RIGHT NOW?

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Animal H5N1 Cases
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Europe Eurasia Albania Austria Azerbaijan
Bosnia Herzegovina Bulgaria Croatia Czech
Republic (H5) Denmark France Georgia Germany
Greece Hungary Italy Poland Romania Russia
Serbia Montenegro Slovak Republic Slovenia
Sweden Switzerland Turkey Ukraine United
Kingdom Updated April 7, 2006
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Human H5N1 Cases
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Cumulative Number of Confirmed Human Cases of
Avian Influenza A/(H5N1) Reported to WHO 16
October 2006
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In view of the immediacy of the threat, WHO
recommends that all countries undertake urgent
action to prepare for the pandemic. As the
present situation continues to evolve towards a
pandemic, countries, the international
community, and WHO have several phase-wise
opportunities to intervene, moving from a
pre-pandemic situation, through emergence of a
pandemic virus, to declaration of a pandemic and
its subsequent spread. Vaccines were
available for the 1957 and 1968 pandemic viruses,
but arrived to late. As a result, great social
impact and economic disruption, as well as loss
of life, accompanied the three pandemics of the
previous century. Evidence that the virus is
now endemic in wild bird populations means that
the present level of risk will not be easily
diminished.
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Risk of a pandemic is great Since 2003, the
world has moved closer to a pandemic than at any
time since 1968, when the last of the previous
centurys three pandemics occurred. All the
prerequisites for the start of a pandemic have
now been met save one the establishment of
efficient human-to-human transmission. During
2005, ominous changes have been observed in the
epidemiology of the disease in animals. Human
cases are continuing to occur, and the virus has
expanded its geographical range to include new
countries, thus increasing the size of the
population at risk. Outbreaks have recurred
despite aggressive control measures, including
the culling of more than 140 million poultry.
Wild migratory birds are now dying in large
numbers from highly pathogenic H5N1. Domestic
and wild ducks can excrete large quantities of
highly pathogenic virus without showing signs of
illness.
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Public Health Importance of Influenza Approxima
tely 40,000 deaths yearly Attack rates of 5 -
20 in general populations (normal flu) Nursing
home attack rates of 60 Over 85 mortality in
persons 65 and older
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Transmission Typical incubation - 2 days, range
1-4 days Viral shedding - can begin one day
before onset of symptoms peak
shedding first 3 days of illness subsides by
days 5-7 in adults, gt10 days in children
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Influenza A Viruses Subtyped based on surface
glycoproteins 16 hemagglutinins (HA) and 9
neuraminidases (NA) Current human subtypes -
H1N1, H3N2, H1N2
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Antigenic shift. Courtesy National Institute of
Allergy and Infectious Disease
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CURRENTLY CIRCULATING AVIAN INFLUENZA VIRUSES
THE NEXT PANDEMIC COULD COME FROM ANY OF THESE
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Low Pathogenic Strains vs. Highly Pathogenic
Strains
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Live Produce Markets
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Indonesian high school students are waiting for
health tests after a visit to a zoo affected by
bird flu
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New WHO Pandemic Phases
Interpandemic Period Phase 1 No new influenza
subtypes in humans, subtype that has
caused human infection may be present in
animals Phase 2 As above, but circulating
animal subtype poses substantial risk of
human disease Pandemic Alert Period Phase 3
Human infection with new subtype, no
human-to-human (HTH) spread Phase 4
Small clusters with limited HTH transmission,
highly localized spread, suggesting the
virus is not well adapted to humans Phase
5 Larger clusters, but HTH spread is still
localized, virus is increasingly better
adapted to humans, but not yet fully
transmissible Pandemic Period Increased and
sustained transmission in general
population
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Current WHO phase of pandemic alert
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What we all learned from Katrina is that
sometimes we have to think very clearly about the
unthinkable, because the unthinkable often
happens. Michael Leavitt Health and Human
Services Secretary
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http//pandemicflu.gov
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http//www.pandemicflu.state.pa.us
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http//pandemicflu.gov/plan/pdf/CIKRpandemicInflue
nzaGuide.pdf
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THE FUTURE?
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Will we be ready?
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