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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
“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
“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
February 1, 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
January 22, 2007
“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”
•The Virus
•The Disease
•Diagnosis
•Treatment
•Management
INFLUENZA
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
•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
SEASONAL 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.”
“AVIAN FLU”
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/RimantadineNot 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 AmericanJanuary, 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 H3N2virus. Both H2N2 and H3N2 strains likely due to exchangeof genes between avian and human flu viruses
May 21, 1997 Bird flu virus H5N1 is isolated for the first time in a humanin Hong Kong. The virus infects 18 people after close contact with poultry, with six deaths. Within three days, Hong Kong’sentire 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 industryin Thailand, Vietnam, Japan, and South Korea and is foundin 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 flocksin Asia, has caused 34 human cases, with 23 deaths
July 2004 – Several countries, including Thailand, Vietnam, Chinaand 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 millionchickens
May 2005 – Reports of human deaths reported in China, and over 1,000dead 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-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.
Flu Pandemics – A Comparison
Year 1918 2000
World Population 1.8 Billion 5.9 Billion
Primary Mode of Troopships Jet AircraftTransportation Railroad automobile
Time for Virus to 4 months 4 daysCircle the Globe
Estimated Dead 50 Million ?????Worldwide
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
1918The 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.
1918Half 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.