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GIDSAS JIT Influenza: An Impending Pandemic Rashid A. Chotani, MD, MPH Assistant Professor, School of Medicine, School of Public Health Director, Global Infectious Disease Surveillance & Alert System Johns Hopkins School of Medicine & Public Health 410-502-3116 [email protected] Chotani, GIDSAS – JHU 2005 GIDSAS Influenza Virus Three types A, B, C Surface antigens H (haemaglutinin) N (neuraminidase) Influenza A has subtypes H3N2, H1N1 (common human) H7N7 (avian 2003, The Netherlands) H5N2 (avian vaccine) H9N2 (human case in Hong Kong, SAR China, 2003) H5N1 (current avian strain of concern) Chotani, 2005 Credit: L. Stammard, 1995 GIDSAS Chotani, 2005 Influenza Virion Natural hosts of influenza viruses GIDSAS Haemagglutinin subtype H1 H2 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 H13 H14 H15 Chotani, 2005 Neuraminidase subtype N1 N2 N3 N4 N5 N6 N7 N8 N9 GIDSAS “Spanish Flu” A(H1N1) 1918 -19 Two European women wearing flu masks during the 1918-19 Spanish flu epidemic. Approximately 20 million people died worldwide, and 500,000 in US. Chotani, 2005 GIDSAS Chotani, 2005 The big pandemic of 1918 GIDSAS Images from the 1918 Influenza Epidemic National Museum of Heath and Medicine Chotani, 2005 GIDSAS “Asian Flu” A(H2N2) 1957-58 During the 1957-59 Asian flu epidemic, a school child in Islington, London, gargles to keep the virus at bay. More than a million people died worldwide and about 70,000 in US. Chotani, 2005 GIDSAS Chotani, 2005 GIDSAS “Hong Kong Flu” A(H3N2) 1968-69 Members of the Red Guard in China covered their mouths against flu germs in 1968 on the orders of Chairman Mao. The Hong Kong flu of 1968-69 killed more than 1 million people worldwide, and 34,000 in US. Chotani, 2005 GIDSAS Chotani, 2005 Recorded Influenza Pandemics GIDSAS Definitions Epidemic – a located cluster of cases Pandemic – worldwide epidemic Antigenic drift Changes in proteins by genetic point mutation & selection Ongoing and basis for change in vaccine each year Antigenic shift Changes in proteins through genetic reassortment Produces different viruses not covered by annual vaccine Chotani, 2005 GIDSAS Reassortment (in humans) Migratory water birds Source: WHO/WPRO Chotani, 2005 GIDSAS Reassortment (in pigs) Migratory water birds Source: WHO/WPRO Chotani, 2005 GIDSAS From birds to humans Migratory water birds Domestic birds • Hong Kong, SAR China 1997, H5N1 • Hong Kong, SAR China 1999, H9N2 • The Netherlands 2003, H7N7 • Hong Kong, SAR China 2003, H5N1 Source: WHO/WPRO Chotani, 2005 GIDSAS Chotani, 2005 GIDSAS Mutation (in humans) Migratory water birds Source: WHO/WPRO Chotani, 2005 GIDSAS Avian Influenza A(H5N1), 1998 Avian Influenza A(H5N1) caused 18 cases of influenza with 6 deaths in the Hong Kong area. Experts are concerned that the virus may acquire a mutation encouraging human-to-human transmission. Source: C. Goldsmith and J. Katz. Chotani, 2005 GIDSAS Home to roost: cormorants crowd the treetops at the Mai Po marshes nature reserve. Experts are beginning tests on birds attracted to the marshes to find out whether they could be spreading the bird flu virus. Picture by Oliver Tsang Poultry chief wants to know if ducks a threat Health officials say traces of the H5N1 virus have been found in duck samples taken from markets. Chotani, 2005 GIDSAS Typically, an avian flu virus has to go first to pigs, then on to humans, but the Hong Kong strain appears to be jumping directly from birds to people. Chotani, 2005 GIDSAS The H5N1 Influenza Pandemic Threat • Avian infection in 9 countries • 34 human cases and 23 deaths (68%) • Culled >100 m chickens • Avian infection in Hong Kong • 18 human cases and 6 deaths (33%) • Culled poultry • Avian infection in 4 countries • 7 human cases and 6 deaths (86%) • Person-to-person? • Ongoing avian H5N1 infections 1997 Chotani, 2005 1998 1999 2000 2001 2002 2003 2004 GIDSAS Chotani, 2005 GIDSAS Chotani, 2005 GIDSAS Chotani, 2005 GIDSAS Chotani, 2005 GIDSAS Current Situation of Avian Influenza and human cases related to the H5 virus subtype Source: European Commission http://europa.eu.int/comm/health/ph_threats/com/Influenza/ai_current_en.htm Chotani, 2005 GIDSAS Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) since 26 December 2003 to 9 November 2006 No. of Reported Cases 125 Cases 64 Deaths 92 100 80 60 42 40 20 20 4 4 9 13 5 0 Cambodia Indonesia Thailand Viet Nam Countries Source: WHO Source: WHO Chotani, 2005 GIDSAS Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) since 26 December 2003 to 10 October 2006 TOTAL HUMAN CASES 125 Deaths: 60 (51%) Survived: 57 (49%) Source: WHO Chotani, 2005 GIDSAS Current Situation of Avian Influenza and human cases related to the H5 virus subtype Source: European Commission http://europa.eu.int/comm/health/ph_threats/com/Influenza/ai_current_en.htm Chotani, 2005 GIDSAS Global avian Influenza (all types) human cases Source: European Commission http://europa.eu.int/comm/health/ph_threats/com/Influenza/images/influenza.jpg Chotani, 2005 GIDSAS Animal & Human Cases 2003 - 2005 Source: European Commission http://europa.eu.int/comm/health/ph_threats/com/Influenza/ai_recent_en.htm Chotani, 2005 GIDSAS Chotani, 2005 GIDSAS Chotani, 2005 Possible Spread of HPAI Along Major Flyways of Migrating Birds GIDSAS Influenza Vaccine Development Source: WHO Global Influenza Program Chotani, 2005 GIDSAS Influenza Pandemic Vaccine Source: WHO Global Influenza Program Chotani, 2005 GIDSAS Key “bottlenecks” Source: WHO Global Influenza Program Chotani, 2005 GIDSAS Vaccine Production Capacity Source: WHO Global Influenza Program Chotani, 2005 GIDSAS Vaccine Consumption - 2000 Source: WHO Global Influenza Program Chotani, 2005 GIDSAS Chemotherapy Prevent membrane fusion Amantidine (Symmetrel) Remantidine (Flumadine) Neuraminidase inhibitors Zanamivir (Relenza) • US buying $2.8 million (could treat 84,300 people) Oseltamivir (Tamiflu) Peramivir (more potent in vitro)??? Chotani, 2005 GIDSAS Vaccine September 16, 2005 – HHS News Headlines US buying $100 million of avian vaccine Vaccine has not been approved by FDA Proper dosage being determined • Protection for 2 to 20 million Americans Chotani, 2005 GIDSAS Chotani, 2005 Culling Quarantine Disinfection Vaccination against circulating flu H5N1 vaccine development Stockpiling of antivirals GIDSAS Chotani, 2005 GIDSAS Chotani, 2005 CURRENT WHO PHASE of PANDEMIC ALERT GIDSAS THE NEXT PANDEMIC? Potential impact of next pandemic (CDC) 2-7.4 million deaths globally In high income countries: • 134-233 million outpatient visits • 1.5-5.2 million hospitalizations • ~25% increase demand for ICU beds, ventilators, etc. Chotani, 2005 GIDSAS Take-home messages The threat to public health will remain so long as the virus continues to cause disease in domestic poultry The outbreaks in poultry are likely to take a very long time to control Should the final prerequisite for a pandemic be met, the consequences for human health around the world could be devastating Regardless of how the present situation evolves, the world needs to be better prepared to respond to the next influenza pandemic Chotani, 2005 GIDSAS Timing has a lot to do with the outcome of a rain dance “The only thing more difficult than planning for an emergency is having to explain why you didn’t.” Be Proactive NOT Reactive!!!! We have to prepare for the next pandemic!!! Chotani, 2005 IL BIOSCUDO (The Bio-shield) Daniore, Chotani et al.