Not All Pandemics Are Created Equal

1. Not All Pandemics Are Created Equal Arnold S. Monto University of Michigan School of Public Health Ann Arbor, Michigan USA

2. Questions for Discussion • Is there a clear definition of an influenza pandemic? • It does not involve severity • It involves only influenza type A viruses • How well can we use history to describe past pandemics • Until recently no virologic data before 1930’s • Molecular data from 1918

3. Effects of Past Pandemics on the US Source: NVPO

4. Pneumonia and Influenza Mortality in Influenza Pandemics *Modified from Dauer & Serfling, Am Rev Resp Dis. 1961; 83:15-28.

5. Impact of the 1889-1892 Pandemic Greenwood (1920) considers that approximately 25 percent of deaths from influenza in London in 1890 occurred in those aged 20-40 (1918 … nearly 50 percent occurred in those 20-40) Influenza, CH Stuart Harris 1953

6. 1918

7. Pneumonia and Influenza Mortality in Influenza Pandemics *Modified from Dauer & Serfling, Am Rev Resp Dis. 1961; 83:15-28.

8. The 1918 Pandemic in Asia and Africa Influenza-Associated Deaths • Asia • India: 12.5 million deaths (higher than bubonic plague). • Japan: 257,000 deaths. • Rest of Asia: 3,000,000 deaths. • Africa • Union of South Africa: 139,471 deaths out of 6,100,00 population. • Madagascar: 114,000 deaths out of 3,250,000 population. Jordan, ED. Epidemic Influenza, AMA, Chicago, 1927.

9. Age-Specific Influenza Death Rates Among Females in England and Wales, 1918  Nguyen-Van-Tam, JS, et al. Vaccine, 2003; 21:762-68.

10. Sex and Age-Specific Mortality Rates (annualized from 4-month rates?) for Influenza and Pneumonia (Primary Cause), Philadelphia (from US Bureau of the Census, Special Tables for Mortality from Influenza and Pneumonia, September 1 to December 31, 1918)

11. Age-Specific Excess (1918 versus 1917) Total Mortality Rates among Working Class Persons Covered by “Industrial Policies” of the Metropolitan Life Insurance Co. from Craig & Dublin. Trans Actuarial Soc Am. 1919; 20:134.

12. Epidemic Crest in Cities of the United States with Over One Hundred Thousand Population, 1918 Jordan, Epidemic Influenza. 1927; 105

14. Distribution of Day of Death from Influenza, ( 90 to 120 cases) as Recorded at US Army General Hospitals #1 and #25 during Autumn Pandemic Roberts. Am J Med Sci 1919; 158:397.

15. Total Puerperal Disease and Conditions with a Death Rate per Hundred Thousand White Women, Ages 15-44 Years Death Rate per 100,000 110 100 90 80 70 60 50 0 1911 ‘12 ‘13 ‘14 ‘15 ’16 ’17 ’18 ’19 ’20 ’21 ’22 ’23 1924 Jordan EO. Epidemic Influenza. 1927; 274.

16. Markedly diminished inhibition of post-1943 viruses with antisera to A/Weiss/43, A/Marton/43 and Huston/43 viruses Kilbourne et al. Proc Natl Acad Sci U S A. 2003;100:764

17. 1957

18. Status of Asian Influenza in the United States and Major Routes of Spread through July 22, 1957                           Arrows indicate probable spread from Foci of infection. Military Civilian   Confirmed Sporadic Cases   Confirmed Outbreaks   Suspect Outbreaks Langmuir AD,Am Rev Resp Dis. 1961; 83:5.

19. Weekly Incidence of Respiratory Illnesses (all ages) Per 100,000, July, 1957-June 1958 6,000 5,000 4,000 3,000 2,000 1,000 0 Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun 1958 1957 Langmuir AD,Am Rev Resp Dis. 1961; 83:8.

20. Influenza Attack Rates by Age in Tangipahoa Parish, Louisiana – August, 1957 Langmuir AD,Am Rev Resp Dis. 1961; 83:5.

21. Pneumonia and Influenza Mortality in Influenza Pandemics *Modified from Dauer & Serfling, Am Rev Resp Dis. 1961; 83:15-28.

22. 1968

23. June July Aug. Sept. Weekly Incidence of Influenza-like Diseases in Hong Kong, June to September 1968 Week Ending *Cockburn et al. Origin and progress of the 1968-69 Hong Kong Influenza Epidemic. Bull. Wld Hlth Org. 1969;41:345-8.

24. Oct. Nov. Dec. Jan. Feb. Peak Influenza Activity in the USA by State and Week, 1968-69 Week Ending *Sharrar RG. National Influenza Experience in the USA, 1968-69. Bull. Wld Hlth Org. 1969;41:361-6.

25. Pneumonia-Influenza Deaths in 122 US Cities, 1967-69 1968-1969 Epidemic Threshold 1,600 1,500 1,400 1,300 1,200 1,100 1,000 900 800 700 600 500 400 300 Epidemic Threshold Expected Number Expected Number 1967-1968 All Cities 1966-1967 Wk Ended 8 5 3 31 28 25 25 22 20 17 15 12 9 7 4 2 30 27 24 23 20 18 15 13 10 7 5 2 30 28 25 22 22 19 17 14 12 9 6 Month O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S Sharrar RG, WHO Bull. 1969; 41:365.

26. Influenza A Pandemics 1918 H1N1 1957 H2N2 1968 H3N2 1977* H1N1 *Affected mainly young people born after 1957.

27. Avian Influenza Credit: WHO Viet Nam Communicable Disease Surveillance and Response, WHO

28. Cough/Dyspnea 100% Diarrhea 70% Rash 0% Conjunctivitis 0% Fever 100% Characteristics of 10 Patients with Avian A(H5N1) Influenza in Vietnam Age: 5-24 years (mean 13.7 years) Leukopenia 100% Thrombocytopenia 90% Markedly Abnormal X-rays 100% Death 80% Oseltamivir used 50% Tran, TH, et al. N Eng J Med. 2004; 350:1179-88

30. 2009

31. Important Underlying Developments • International Health Regulations (2005) now in force • Provides over-arching international framework • Covers all critical aspects for responding to global threats • Reporting • Communications • Decision making • Response • Capacities

32. 2005 PhasesStructure & Pandemic Disease "Risk" Pandemic Phase 6 Pandemic Alert Phases 3-5 Post Pandemic Interpandemic Period Phases 1-2 Time

33. Revised Phases (Applied in 2009) Geographic spread Phases 5-6 Post Peak 5 - 6 Predominantly animal infections; Limited infections of people Post Pandemic 4 Sustained H-2-H transmission 1 - 3 Time

34. WHO Pandemic Phase Changes • April 25, 2009 - Invoking International Health Regulations, D-G declare a “Public Health Emergency of International concern” • April 27, 2009 – Phase 4 – Sustained Human to human transmission • April 29, 2009 – Phase 5 – Transmission in more than one country in one WHO region • June 11, 2009 – Phase 6 – Transmission in more than one WHO region • August 10, 2010- Post pandemic

35. Issues in the United States • Planning was based on unstated assumption that there would be time to prepare and a possibility of containment • Introductions from Mexico were rapid and widespread throughout Canada and the United States • Only in the first days were cases concentrated on the Mexican border • Migrants not clearly involved. Introductions more related to holiday travel by air

36. Challenges in Categorizing Severity • Without a severity index, it is difficult to know how to respond consistently • The US categories based on history and on case fatality • Calculation of case fatality proportions was not possible – denominators impossible to estimate during pandemic-possible retrospectively • WHO used terms, not numbers, to describe severity • Basic challenge is the unusual and unpredicted occurrence of disease & fatality

38. CDC estimates of 2009 H1N1 cases from April-April 10, 2010, by age group

39. CDC estimates of 2009 H1N1 related hospitalizations and deaths from April 2009- April 10, 2010, by age group

40. Type A Influenza Recycling Theory Summarized C.W.Potter, Textbook of Influenza

41. Conclusions • The definition of a pandemic has varied over time. Severity has never been part of that definition. • Two additional events took place in the 20th century which could have been considered pandemics. Both involved A(H1N1). • Epidemiologic characteristics of past pandemics suggest at least partial protection from past exposures. • The 2009 A(H1N1) virus emerged suddenly , was novel and of animal origin, thus fulfilling the current definition of a pandemic virus. • Its impact has been similar in many ways to past pandemics, conditioned by residual immunity in older individuals.