Pandemic Influenza: A Zoonotic Infection

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Pandemic Influenza A Zoonotic Infection

• Kathleen 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
Pandemics
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Influenza pandemics Mutations of animal viruses,
or viral reassortants
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Surface antigens of the Influenza A virus
Hemagglutinin
Neuraminidase
M2
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PB2
1968 Pandemic
Epidemic human virus A(H2N2)
New epidemic virus A(H3N2)
HA
NA
M
NS

Avian virus A(H3N?)
Steinhoff MC. Epid and Prev of Influenza. In
Infectious Dis Epidemiology. Nelson et al.
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Incidents with limited spread before 1997
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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 35313. 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

• gt95 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 4401099. 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 worlds population within 6 months of
outbreak.