Pandemic Influenza; A Harbinger of Things to Come

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Pandemic Influenza A Harbinger of Things to Come

• Michael T Osterholm PhD, MPH
• Director, Center for Infectious Disease Research
  and Policy
• Associate Director, DHS National Center for Food
  Protection and Defense
• and
• Professor, School of Public Health
• University of Minnesota

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Type A Influenza

• 16 different hemagglutinin antigens (HA) and nine
  different neuraminidase (NA) antigens
• Human disease historically been caused by three
  subtypes of HA (H1, H2, H3) and two subtypes of
  NA (N1 and N2)
• All known subtypes of influenza A can be found in
  birds, but only subtypes H5 and H7 have caused
  severe outbreaks of disease in birds

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Influenza Virus Change and Pandemic Potential

• Reassortment
• Recombination point mutations

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Influenza Virus Change and Pandemic Potential

• Reassortment
• Recombination point mutations

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People, Pigs and Poultry in China
1968 2004 People 790 million 1.3
billion Pigs 5.2 million 508
million Poultry 12.3 million 13 billion
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Understanding Pandemic Influenza

• Pandemic An epidemic that becomes very
  widespread and affects a whole region, a
  continent or the world.
• Definition of pandemic influenza somewhat fuzzy
• Influenza pandemics
• at least 10 pandemics recorded in last 300 years
• 1918-1920 50,000,000-100,000,000 deaths
  worldwide
• 1830-1832 was similarly severe in smaller
  population

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Understanding Pandemic Influenza

• Pandemics occur when a novel influenza strain
  emerges that has the following features
• readily transmitted between humans
• genetically unique (i.e., lack of preexisting
  immunity in the human population
• increased virulence
• Pandemics have differed in terms of
  population-specific mortality rates and can not
  be characterized by a single risk predictive
  model

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Comparison of Mortality Impact in the Three
Influenza Pandemics of the 20th Century in the
United States
Simonsen et al
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Pandemic Influenza

• 1918-1919 (Spanish flu)
• H1N1 strain
• 200 million to 1 billion people were infected
  more than 50-100 million died
• killed a disproportionate number of healthy young
  adults (W curve)
• A summary of 13 studies in 1918-19 involving
  pregnant women demonstrated that the
  case-fatality rate ranged from 23 to 71

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Understanding Pandemic Influenza

• Recent studies in mice using genetically
  engineered influenza strains similar to the 1918
  H1N1 pandemic strain suggest that macrophage
  activities with high levels of cytokine
  production maybe a factor in the lung and other
  organ damage (cytokine storm). Kobasa et al
  Nature 2004431703
• The clinical picture and epidemiology, as well as
  current studies of H5N1 cases in SE Asia suggest
  a similar cytokine storm phenomena. Peiris et
  al Lancet 2004363617

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Projected Number of Deaths Due to Future Pandemic
Influenza Based on the 1918-1920 Pandemic
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17 Human Cases 12 Deaths 94 Human Cases 42
Deaths 4 Human Cases 4 Deaths 4 Human
case 3 Deaths
CIDRAP, 8/2005
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Influenza Pandemic Preparedness

• Prevention
• vaccine and antivirals
• Treatment
• health-care delivery system
• Collateral damage response
• global just-in-time economy

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Prevention

• Vaccination
• Antiviral therapy and prophylaxis

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Vaccination

• Current standard vaccine reflects 1950s
  technology
• grown in chicken eggs
• takes 6 months or more to produce
• use of reverse genetics to develop prototype
  vaccine virus
• Recent approval of live, attenuated vaccine
• Need an immediate and comprehensive international
  program to develop a cell culture system for
  vaccine production with surge capacity

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Influenza Vaccine Crisis

• Current annual international capacity for
  influenza vaccine production using egg culture is
  approximately 300 million trivalent doses (900
  million monovalent)
• Almost all of the worlds influenza vaccine is
  produced in nine countries (12 of the worlds
  population)
• Production capacity will NOT increase
  significantly in the next several years
• New and more timely methods for production
  desperately needed

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Influenza Antiviral Drugs Approved for Human Use

• Viral M2 Protein Inhibitors
• amantadine
• rimantadine
• Selective Neuraminidase Inhibitors
• oseltamivir phosphate
• zanamivir

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Treatment and Corpse Management

• Facilities and staffing
• Worker and patient protection
• Medical devices and therapy
• Ethical issues
• Use of recovered volunteers
• Corpse management

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Collateral Damage Response

• Implications of the global just-in-time economy
• other pharmaceutical products
• food
• equipment parts
• International security

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What Do We Do?

• Pray, plan and practice (In that order)
• Not a matter of if, just when and where
• Lack of international political will and support
• At minimum, assume we will virtually no vaccine
  for the first 6-8 months and then supplies will
  remain limited
• The 1918-20 experience provides many important
  lessons