Pandemic Influenza: A Zoonotic Infection Kathleen M. Neuzil, MD, MPH PATH University of Washington...
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Pandemic Influenza: A Zoonotic InfectionKathleen M. Neuzil, MD, MPH
PATH
University of Washington School of Medicine
April 27, 2009
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Questions
What is the epidemiology of human influenza?
What is the role of animals in influenza epidemiology?
When do we worry about a pandemic?
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Excess mortality: Hallmark of epidemic influenza
1837: Robert Graves, Dublin.
1847: William Farr, London.
1887-1956: Selwyn Collins, USA.
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Influenza: An epidemic respiratory disease associated with “excess” deaths
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“Conductor turns away man because he is not wearing his anti-flu mask.”
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“Hunt up your wood-workers and cabinet-makers and set them to making coffins. Then take your street laborers and set them to digging graves. If you do this you will not have your dead accumulating faster than you can dispose of them.”
Amer J Public Health 1918; 8: 787.
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20th Century Influenza Pandemics20th Century Influenza Pandemics
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Influenza pandemics: Mutations of animal viruses, or viral reassortants
1918 Spanish (H1N1)
Avian mutated H1N1
40-50 million deaths
1957 Asian flu(H2N2)
Human H1N1Avian H2N2
H1N1 disappeared
1968 Hong Kong (H3N2)
Human H2N2, avian H3Nx
H2N2 disappeared
1977 Russian(H1N1)
Virus identical to human strains
Benign —H1N1, H3N2circulate
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Surface antigens of the Influenza A virus
Hemagglutinin
Neuraminidase
M2
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HA NA M NS
NS PA HA NA M NS
PB2 PB1
PB2
PB2
NS PA
PB1
HA
M NS
NA
PA NSPB1
Epidemic human virus A(H2N2)
Avian virus A(H3N?)
New epidemic virusNew epidemic virus A( A(H3H3N2N2))
1968 Pandemic1968 Pandemic
Steinhoff MC. Epid and Prev of Influenza. In: Infectious Dis Epidemiology. Nelson et al.
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Incidents with limited spread before 1997
1976 Swine flu H1N1
NJ: Enzootic in swine herds.
One death in military camp.
1986 H1N1 Netherlands: Swine virus from avian source.
One adult with severe pneumonia.
1988 Swine flu H1N1
Wisconsin: Swine virus.
Pregnant woman died.
1993 H3N2 Netherlands: Swine — human H3N2, avian H1N2.
Two children; mild disease.
1995 H7N7 UK: Duck virus. One adult — conjunctivitis.
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What is the role of pigs?
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H5N1 – Where did it start?
1996: First detected in geese in Guangdong Province, China.
1997: First recognized in humans: Hong Kong,18 human cases, 6 fatal.
H5N1 viruses isolated from birds at wholesale and retail markets in Hong Kong.
No further cases following widespread culling of chickens.
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2003-2005 Avian Influenza A (H5N1) outbreak in humans
Vietnam, Thailand, Cambodia
55 cases, 42 deaths Predominantly children
and young adults. Rural Asia: Households
maintain free-ranging poultry for income, food.
Children play near poultry; families slaughter birds for food.
Pathogenesis: high and disseminated viral replication and intense inflammatory response.
N Engl J Med 2005: 353; 25
N Engl J Med 2004; 350: 1179
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H5N1: How did it spread?
1997-May 2005: largely confined to SE Asia.
Infected wild birds in Qinghai Lake, China; rapidly spread westward.
Death of swans and geese marked spread into Europe, India and Africa.
Ducks may be “stealth carriers.”
Wild mallard ducks do not always show signs of disease when infected with highly pathogenic H5N1 viruses.
N Engl J Med 2006; 355: 2174
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Number of confirmed human H5N1 cases by month as of 2009-01-27
Source: World Health Organization
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H5N1: Human-to-human transmission?
Infection after close contact with infected child leading to illness and death.
Evidence of antibodies to H5 in health care workers who cared for patients in Hong Kong in 1997.
Intensified surveillance (PCR) with contacts has led to detection of mild cases, more infections in older adults, and increased numbers of family clusters in Vietnam.
Family clusters in Indonesia.
NEJM 2005; 353;13.
NEJM 2006; 355: 2186.
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So…
H5N1 is a novel virus with ability to infect and cause disease in humans
Limited human to human transmission at present
Total number of cases small; case fatality rate high
Exposure and risk of future cases increasing with increasing spread of virus among birds
Is avian influenza worth the investment of resources, and if so, what can/should be done?
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WHO: Pandemic alert
Influenza A virus with a novel HA or novel HA and NA — substantial proportion of the population has little or no antibody to the novel virus.
Novel virus demonstrates ability to cause disease in humans.
Novel virus demonstrates ability to spread easily among humans.
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Updated WHO guidance will be available in 2009Revised Pandemic Phases
Source: World Health Organization
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WHO Strategic Actions
The objectives of the strategic actions correspond to the principal opportunities to intervene and are likewise phase-wise.
Phase: pre-pandemic
1. Reduce opportunities for human infection
2. Strengthen the early warning system
Phase: emergence of a pandemic virus
3. Contain or delay spread at the source
Phase: pandemic declared and spreading internationally
4. Reduce morbidity, mortality, and social disruption
5. Conduct research to guide response measures
www.who.int
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So what should be done,pre-pandemic (now!)?
Improve surveillance worldwide.
– All types of influenza.– All types of respiratory
disease.– Easier, more reliable, less
expensive diagnostics.– Year-round surveillance.– Clinical research on human
cases/ populations.
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Reduce opportunities for human infection
Education about human behaviors.
Control spread in birds/animals (collaboration between animal and public health sectors).
Improve approaches to environmental detection of virus.
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General emergency preparedness
Clearly-defined plans, leadership structure.
Responsibility/accountability.
Communications.
Surge capacity — Mass delivery mechanisms for drugs/vaccines/health services.
Stockpiles of essential medical supplies.
Table-top exercises.
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Preventing/minimizing morbidity and mortality
Pandemic vaccines – Supplies, equitable access, developing country manufacturers, novel ways to use less antigen (make limited supply go further).
Antivirals – International stockpiles, supplies, equitable access, developing country manufacturers, international clinical trials networks.
Community mitigation strategies – Quarantines/border or school closures.
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Flu vaccine supply: Inadequate, inequitable
>95% of world flu vaccine comes from 9 countries 4 European companies produce 65% of world supply
Fedson DS. Vaccine Development for an Imminent Pandemic. Human Vaccines 2006: 2(1)38-42.Dennis C. Flu-vaccine makers toil to boost supply. Nature 440:1099. Apr 2006.
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Near term strategy: Is real-time response viable?Real time response is not a viable solution in the near-term since existing infrastructure would only serve a small portion of the world’s population within 6 months of outbreak.
0.0 B
1.0 B
2.0 B
3.0 B
4.0 B
5.0 B
6.0 B
7.0 B
2007 2008 2009 2010 2011 2012 2013
Real-time Global Pandemic Capacity – “Best Case”
1.2 B
0.0 B
1.0 B
2.0 B
3.0 B
4.0 B
5.0 B
6.0 B
7.0 B
2007 2008 2009 2010 2011 2012 2013
1.2 B 1.2 B
1.8 B 1.9 B 2.0 B 2.0 B
2.8 B
0.0 B
1.0 B
2.0 B
3.0 B
4.0 B
5.0 B
6.0 B
7.0 B
2007 2008 2009 2010 2011 2012 2013
Global Demand = 6.8B
Availability Timeframe for Global Need
Pandemic Courses Filled in 6 Month Timeframe
~2yrs ~1.4yrs ~1.3yrs ~1.3yrs ~1.3yrs ~1yr~2yr