Pandemic Influenza; A Harbinger of Things to Come Michael T Osterholm Ph. D, 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
Type A Influenza • 16 different hemagglutinin antigens (HA) and nine different neuraminidase (NA) antigens • Human disease historically been caused by three subtypes of HA (H 1, H 2, H 3) and two subtypes of NA (N 1 and N 2) • All known subtypes of influenza A can be found in birds, but only subtypes H 5 and H 7 have caused severe outbreaks of disease in birds
Influenza Virus Change and Pandemic Potential • Reassortment • Recombination: point mutations
Influenza Virus Change and Pandemic Potential • Reassortment • Recombination: point mutations
People, Pigs and Poultry in China 1968 2004 People 790 million 1. 3 billion Pigs 5. 2 million 508 million 12. 3 million 13 billion Poultry
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 -100, 000 deaths worldwide – 1830 -1832 was similarly severe in smaller population
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”
Comparison of Mortality Impact in the Three Influenza Pandemics of the 20 th Century in the United States Antigenic shift (pandemic event Antigenic shift (Pandemic event) Number of Excess Deaths in the pandemic season (All-cause deaths) Total Excess Mortality rate per 100, 000 population (crude) (All-cause deaths) 1918 -19 A(H 1 N 1) All novel? ~500, 000 530 1957 -58 A(H 2 N 2) H+N ~ 60, 000 40 1968 -69 A(H 3 N 2) H only ~ 40, 000 18 Simonsen et al
Pandemic Influenza • 1918 -1919 (Spanish flu) – H 1 N 1 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%
Understanding Pandemic Influenza • Recent studies in mice using genetically engineered influenza strains similar to the 1918 H 1 N 1 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 2004; 431: 703 • The clinical picture and epidemiology, as well as current studies of H 5 N 1 cases in SE Asia suggest a similar “cytokine storm” phenomena. Peiris et al; Lancet 2004; 363: 617
Projected Number of Deaths Due to Future Pandemic Influenza Based on the 1918 -1920 Pandemic Area No. Deaths Twin Cities SMA 18, 538 Minnesota 30, 498 United States 1, 763, 664 Worldwide 30, 000 - 384, 000
17 Human Cases 12 Deaths 94 Human Cases 42 Deaths 4 Human Cases 4 Deaths 4 Human case 3 Deaths CIDRAP, 8/2005
Influenza Pandemic Preparedness • Prevention – vaccine and antivirals • Treatment – health-care delivery system • “Collateral damage response” – global just-in-time economy
Prevention • Vaccination • Antiviral therapy and prophylaxis
Vaccination • Current “standard” vaccine reflects 1950’s 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
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 world’s influenza vaccine is produced in nine countries (12% of the world’s population) • Production capacity will NOT increase significantly in the next several years • New and more timely methods for production desperately needed
Influenza Antiviral Drugs Approved for Human Use Viral M 2 Protein Inhibitors • amantadine • rimantadine Selective Neuraminidase Inhibitors • oseltamivir phosphate • zanamivir
Treatment and Corpse Management • Facilities and staffing • Worker and patient protection • Medical devices and therapy • Ethical issues • Use of “recovered” volunteers • Corpse management
Collateral Damage Response • Implications of the global just-in-time economy – other pharmaceutical products – food – equipment parts • International security
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
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