1. DR. JULIE LOUISE GERBERDING DIRECTOR CENTERS FOR DISEASE CONTROL AND PREVENTION CURRENT STATUS OF AVIAN INFLUENZA AND PANDEMIC THREAT PRESENTATION TO IOM, APRIL 2005

2. Influenza Pandemics Happen! H1 H3 H2 1918 Spanish Flu H1N1 1957 Asian Flu H2N2 1968 Hong Kong Flu H3N2 1915 1925 1935 1945 1955 1965 1975 1985 1995 2005

3. Human virus virus NewReassortedvirus Avianvirus Avian host Swine Mechanisms of Antigenic Shift Direct Avian – Human Infection

4. 0 200 400 600 800 1000 19001920194019601980 Year Mortality Rate per 100,000 Source: Armstrong et al., JAMA ;1999 Infectious Disease Mortality in the United States 1900 - 1996

5. Bacteriologic Findings among Patients with Influenzal Pneumonia 1918-1919 SputumBlood S. pneumoniae1230/1609 (76%)78/1507 (4.9%) S. aureus133/1485 (9%)0/1535 Beta-hemolytic strep254/2077 (12%)32/1587 (2%) H. Influenzae436/729 (60%)1/1400 (.1%) Stevens KM: NEJM 1976; 1363-66

6. Potential Causes of Influenza-related Shock and Death Exacerbation of undiagnosed underlying conditions Coincidental occurrence of an unrelated problem Influenza pneumonia Secondary bacterial pneumonia Toxic shock syndrome / endotoxemia Hypersensitivity response Myopericarditis Cytokine-induced shock syndrome

7. Avian Influenza is Emerging H1 H3 H2 H7 H5 H9 1918 Spanish Flu H1N1 1957 Asian Flu H2N2 1968 Hong Kong Flu H3N2 1980 1996 2003 1997 2003 2004 1998 1999 Avian Flu 1915 1925 1935 1945 1955 1965 1975 1985 1995 2005

8. Outbreaks of Highly Pathogenic Avian Viruses Before 2004 Avian subtypeCountryYear H5N3U.S.1983 H7N7Australia1985 H5N2Mexico1995/95 H7N3Pakistan1995 H5N1Hong Kong1997 H5N2Italy1997 H7N1Italy1999 H5N1Hong Kong2001-2003 H7N7Netherlands2003

9. Situation Report: Confirmed Human H5N1 Cases Updated April 3, 2005 CountryH5N1 cases DeathsCase fatality Thailand 171271% Vietnam 553564% Cambodia 22100% Total 744966%

10. Risk Factors for Human H5N1 Illness in 1997 Case control study primary risk factor for H5N1 illness Exposure to live poultry in poultry stall or market in the week prior to illness Studies on poultry workers in Hong Kong markets 20% chickens infected with H5N1 Seroprevalence for H5 antibody = 10% Seroprevalence in general population = 0% Occupational risk factors for poultry workers: Butchering Exposure to sick birds

11. 1997 H5N1 Field Studies Most cases likely contracted influenza after exposure to infected poultry Human-to-human transmission occurred but was uncommon Groups with greatest risk of H5-antibody Household contacts and poultry workers Although poultry workers had highest antibody rate, none found ill with H5 May have been protected based on prior exposures to avian H5

12. Avian Influenza Poultry Outbreaks, Asia, 2003-04

13. H5N1 enzootic of unprecedented size and complexity now established –Poultry outbreaks in 9 or more countries –Ongoing poultry outbreaks and human cases –Substantial economic and social impact –Continuing risk of emergence of a pandemic Situation Report: Avian Influenza 2005

14. H5N1 seasonal pattern for avian flu in Asia –Expect increased activity in winter months Ongoing human cases –Most in young and healthy –Extremely high apparent case-fatality –No sustained person-to-person transmission

15. Human isolates (Vietnam, Cambodia & Thailand and 1 group of Vietnamese avian isolates –Resistant to adamantane drugs –Sensitive to oseltamivir Probable human-to-human transmission in Thailand; family clusters in Vietnam – ? increasing Antigenic heterogeneity among current H5N1 viruses (unlike 2003 Hong Kong H5N1 virus) –How variable are the 2005 H5N1 viruses? –How immunogenic? –Must compare human and avian isolates Situation Report: Avian Influenza 2005

16. Countries containing at least 1 WHO influenza laboratory WHO Collaborating Centers - Atlanta, London, Melbourne, and Tokyo WHO Collaborating Centers for Influenza

17. HHS Response: Partnership with WHO Support Global Influenza Pandemic Preparedness Enhance Collaboration with Animal Influenza Health Authorities Enhance Global Influenza Surveillance Training - Laboratory, epidemiology, and biosafety

18. HHS / CDC Contributions to Preparedness and Response in Asia: HHS/CDC A $5.5 M initiative to build surveillance capacity –Surveillance networks with bilateral funding to 9 countries in Asia –WHO HQ and Western Pacific Regional Office –CDC’s IEIP in Thailand and NAMRU-2 in Jakarta –WHO’s Animal Influenza Network –Communications between public health and veterinary agencies –Shipment of isolates and specimens

19. Enhancing Influenza Surveillance: HHS/CDC Pakistan Malaysia Thailand India China Mongolia South Korea Philippines Indonesia

20. FY04 Quarantine Stations Field Epidemiology / Laboratory Training Programs CDC Field Stations International Business Connectivity New CDC Sentinel Sites New Quarantine Stations New International LRN Sites New CDC Sentinel Sites International Health Protection Network FY06 Global Biosurveillance: International Health Protection Network Global Health Protection Network Bio Sense & Biointelligence Center FY04 Laboratory Response Network (LRN) National Clinical Lab Orders DoD/VA Dx & Rx Records Biowatch Data OTC Drug Sales Private Clinical Care Expanded Real-Time LRN Data Expanded Quarantine Stations New Data Streams FY06 DATAEXCHANGEDATAEXCHANGE

21. Quarantine Authorization Public Health Service Act (Title 42 U.S. Code 264(b), Section 316 of the Public Health Services Act amended -- "(c) Influenza caused by novel or reemergent influenza viruses that are causing, or have the potential to cause, a pandemic.” Quarantine and isolation tools were last used during the SARS 2003 outbreak Quarantine duration of one incubation period

22. CDC’s Research Priorities Ggenetic determinants of pathogenicity and transmissibility Testing for antiviral resistance, receptor binding properties, etc. Tracking antigenic changes in the circulating viruses to facilitate appropriate vaccine development Epidemiology of the current H5N1 epizootic –Why did it spread so rapidly? –How many people have been infected? –What is the extent of asymptomatic infection? –What is the actual death rate?

23. Commitment Collaboration Coordination Compassion Communication Competency Candor Clinical Laboratories Consistency Community Common Sense

24. Complacency is the enemy of preparedness! www.cdc.gov