Transcript Slide 1

Update On Avian Influenza
Wallace Greene, PhD,
ABMM
Director, Diagnostic
Virology Laboratory
Department of Pathology
M. S. Hershey Medical
Center
Hershey, Pennsylvania
“We’re all holding our breaths.
H5N1 is the most important threat
the world is facing.”
“People who fail to prepare for a flu
pandemic are going to be tragically
mistaken.”
Julie Gerberding, Head of the CDC
“Get rid of ‘if’. This is going to occur.”
–Anthony Fauci, NIH Director
“The world is now in the gravest
danger of a pandemic. It is coming.”
“There is no disagreement that this
is just a matter of time”
Director-General of the World Health
Organization
February 1, 2007
“There is a credible risk that the spread
of avian influenza and resulting disease
in the future constitute a public health
emergency.”
Official declaration of a potential
pandemic emergency by the federal
government.
Mike Leavitt - U.S. Secretary of Health
and Human Services
January 22, 2007
“More deaths occurred in 2006 than in
previous years combined. The fatality
rate for H5N1 rose to 70% last year, 10
points higher than the average since
the current series of outbreaks began
in 2003. The message is straight
forward: we must not let down our
guard.”
Margaret Chan, Head of the World
Health Organization
“This virus is particularly nasty. We
have never seen any influenza virus
like it before”
Nancy Cox, Chief Influenza Scientist
at the CDC
“I’ve never experienced anything like
it in terms of its destructive power. It
is staggering in terms of how much
lung tissue is destroyed.”
Director of Oxford University’s Clinical
Research Unit”
INFLUENZA
•The Virus
•The Disease
•Diagnosis
•Treatment
•Management
Influenza A Viruses
Subtyped based on surface glycoproteins:
16 hemagglutinins (HA) and
9 neuraminidases (NA)
Current human subtypes - H1N1, H3N2,
H1N2
CURRENTLY CIRCULATING AVIAN INFLUENZA VIRUSES
THE NEXT PANDEMIC COULD COME FROM ANY OF THESE
Viral evolution can not be predicted.
Reassortment - rapid development of a new variant
explosive spread
Adaptive mutations - more gradual development,
limited transmission
in the beginning
SEASONAL FLU
•Acute febrile illness
•Usually self-limiting
•Can be problematic in children and elderly
•Characterized by:
–“Generic” symptoms
–Fever, Chills, Myalgia, Cough, Headache,
Malaise
–Symptoms typically last 3 days, up to 8
days
–Complications – secondary pneumonia
“AVIAN FLU”
•
H5N1 is the only avian flu virus to repeatedly cause
severe disease in humans
•
Initial symptoms same as seasonal influenza
•
Watery diarrhea may proceed respiratory symptoms
• Abnormal chest radiographs include interstitial
infiltration, patchy lobar infiltrates in a variety of patterns
progressing to diffuse bilateral ground-glass appearance
with clinical features of ARDS
•
Median time from fever to ARDS is 6 days (range of
4-13 days)
•
Multi-organ failure occurs with liver, kidneys and
brain all affected.
•
Bacterial secondary infections not seen
•
“Cytokine storm” Nature (January 18, 2007, 319-323)
“Aberrant innate immune response in lethal infection of
macaques with 1918 influenza virus”
“AVIAN FLU”
Multi-organ failure occurs with liver, kidneys
and brain all affected.
Bacterial secondary infections not seen
“Cytokine storm”
Nature (January 18, 2007, 319-323)
“Aberrant innate immune response in lethal infection of
macaques with 1918 influenza virus”
•WHO recommends that infection control
precautions for adults remain in place for 7 days
after resolution of fever, 21 days for children
• “Family members should be educated in
personal hygiene and infection control
measures.”
Public Health
Importance of Influenza
Approximately 40,000 deaths yearly
Over 85% mortality is in persons 65 and older
Attack rates of 5 - 20% in general populations
(normal flu)
Nursing home attack rates of 60%
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,
>10 days in children
Treatment
• Supportive
• Antiviral Therapy
– Amatidine/Rimantadine
Not recommended due to resistance
– Neuraminidase Inhibitors
Neuraminidase Inhibitors
• Relenza ® (Zanamivir)
– Glaxo Wellcome
– Inhaled
• Tamiflu™ (Oseltamivir phosphate)
– Roche
– Oral
• Mode of action - inhibition of replication by
interference with neuraminidase activity
Viral Inhibitors
Scientific American
January, 1999
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 Kong’s
entire chicken population is slaughtered.
INFLUENZA TIMELINE
Sept 1998 – Two new influenza drugs are announced
Feb 2003 – H5N1 infects two people in Hong Kong, one dies
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.
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
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
INFLUENZA TIMELINE
2005 – Vietnam – Transmission through consumption of
uncooked duck blood
2006 – Azerbaijan – children were found to be infected
through collecting feathers from dead swans.
2006 – Indonesia - WHO reported evidence of human-tohuman 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.
Flu Pandemics – A Comparison
Year
1918
2000
World Population
1.8 Billion
5.9 Billion
Primary Mode of
Transportation
Troopships
Railroad
Jet Aircraft
automobile
Time for Virus to
Circle the Globe
4 months
4 days
Estimated Dead
Worldwide
50 Million
?????
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/Educators/Human_
Population/Population_Growth/Population_Growth.htm
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.
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
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.