WHO PANDEMIC PHASES

3. WHO PANDEMIC PHASES

4. INFLUENZA VIRUS

5. MILESTONES IN INFLUENZA 1933 Demonstration of virus transmission to ferrets Smith et al. 1933 1937 Growth of influenza virus in hens’ eggs Francis & Magill 1937 1941 Agglutination of erythrocytes by influenza Hirst 1941 1943 Extensive clinical trials in USA showed vaccine was 70% effective Francis 1943 1945 Vaccination of US Army showed consistent protection Francis et al. 1946 1945 Licence of first influenza vaccine in USA

6. I cannot forecast to you the action of Russia. It is a riddle wrapped in a mystery inside an enigma. Sir Winston Churchill Radio Broadcast, October 1, 1939 I cannot forecast to you the pandemic impact of this influenza virus. Influenza virus is a riddle wrapped in a haemagglutinin – neuraminidase encrusted envelope inside an enigma Barry D Schoub NICD, June 22, 2009

7. SPORADIC INFLUENZA • PANDEMIC INFLUENZA • SEASONAL INFLUENZA

8. NICD

9. SPORADIC INFLUENZA • PANDEMIC INFLUENZA • SEASONAL INFLUENZA

11. NICD

12. SPORADIC INFLUENZA • PANDEMIC INFLUENZA • SEASONAL INFLUENZA

16. NICD INFLUENZA PANDEMICS • 1510 • 1889 – 1890 H2N2 • 1899 – 1900 H3N2 • 1918 – 1919 H1N1 “Spanish flu” • 1957 – 1958 H2N2 “Asian flu” • 1968 – 1969 H3N2 “Hong Kong flu”

17. SPORADIC INFLUENZA • PANDEMIC INFLUENZA • SEASONAL INFLUENZA

18. NICD INFLUENZA PANDEMICS • 1510 • 1889 – 1890 H2N2 • 1899 – 1900 H3N2 • 1918 – 1919 H1N1 “Spanish flu” • 1957 – 1958 H2N2 “Asian flu” • 1968 – 1969 H3N2 “Hong Kong flu” • 1977 H1N1

19. RECOMMENDED VACCINE FORMULATION The following strains have been recommended by the WHO for the 2009 Southern Hemisphere influenza season:- • A/Brisbane/59/2007 (H1N1) - like virus * • A/Brisbane/10/2007 (H3N2) - like virus ** • B/Florida/4/2006 - like virus # * A/South Dakota/6/2007 (an A/Brisbane/59/2007-like virus) is a current vaccine virus used in live attenuated vaccines ** A/Brisbane/10/2007 and A/Uruguay/716/2007 (an A/Brisbane/10/2007-like virus) are current vaccine viruses # B/Florida/4/2006 and B/Brisbane/3/2007 (a B/Florida/4/2006-like virus) are current vaccine viruses

20. 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986 1985 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Jun Jul Apr May Aug Sep Epidemiological week Mean onset ONSET & DURATION OF INFLUENZA SEASON: 1985 - 2007 • Median onset: • Week 23 • Range 15-28 • Median peak: • Week 27 • Range 20-32 • Median duration: • 10 weeks • Range 7-17

21. INFLUENZA VIRUS

22. NICD (9 subtypes) (16 subtypes)

23. NICD HAEMAGGLUTININS H1 N1 NEURAMINIDASES H2 N2 H3 N3 H4 N4 H5 N5 H6 N6 H7 N7 H8 N8 H9 N9 H10 H11 H12 H13 H14 H15 H16 PANDEMICS 1918 H1N1 SPANISH PANDEMIC 1957 H2N2 ASIAN PANDEMIC 1968 H3N2 HONG KONG PANDEMIC H5N1 AVIAN INFLUENZA

24. NICD INFLUENZA PANDEMICS • 1510 • 1889 – 1890 H2N2 • 1899 – 1900 H3N2 • 1918 – 1919 H1N1 “Spanish flu” • 1957 – 1958 H2N2 “Asian flu” • 1968 – 1969 H3N2 “Hong Kong flu” • 2009 - ? H1N1 v “Swine flu”/pandemic 2009

25. 1957 1977 1998 2009 Ag drift Ag Stasis (sporadic human cases) Seasonal flu Ag drift Seasonal flu Triple reassortant Eurasian Influenza A (H1N1) v 2009 Pandemic H1N1 1918 1918/19 Pandemic

28. Positive samples by influenza types and subtypes : Viral Watch South Africa 2009 250 80 200 60 150 40 Number Percentage 100 20 50 0 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 Week A awaiting typing A H1N1 (seasonal) A H3N2 B Novel H1N1 Detection rate**

29. Diagnosed and reported H1N1 influenza statistics

30. Diagnosed and reported H1N1 influenza statistics Reported to surveillance authority Laboratory test reliable Adequate specimen reaches laboratory Doctor takes specimen Report to doctor Symptomatically infected Infected individuals

31. PANDEMIC H1N1 DEATHS(31ST August 2009) TOTAL = 27 A) PREGNANCY: 12 (44%) Stage: 1st trimester 1 3rd trimester 10 Puerperium 1 Co-morbidity None 5 (42%) Under investigation 1 HIV 4 TB (only) 1 Obese + substance abuse 1 Age distribution Range 16-37

32. B) NON-PREGNANT Total: 15 Age range: 0-53yr • Nil 3 (20%) b) Co-morbidities • HIV 2 (1 TB) • Obesity 7 (1 asthma, 2 cardiac, 1 diabetes) • Diabetes 4 (1 obesity, 1 hypertension) • TB 1 • Premature 1

33. WHO PANDEMIC PHASES

34. NICD CHARACTERISTICS OF PANDEMICS • Novel virus • Increased transmissibility • +/- increased virulence • Age shift • Relative non-seasonality • Geographic heterogeneity • Multiple waves • Human adaptation  seasonal influenza

35. NICD 3. VIRULENCE CFR: MEXICO 0.4% (0.3 – 0.6%) USA 0.2% SEASONAL 0.04-0.08% INFLUENZA 1918/1919 5.0% PANDEMIC H5N1 60%

37. 1977 H1N1 INFLUENZA PANDEMICS • 1510 • 1889 – 1890 H2N2 • 1899 – 1900 H3N2 • 1918 – 1919 H1N1 “Spanish flu” • 1957 – 1958 H2N2 “Asian flu” • 1968 – 1969 H3N2 “Hong Kong flu” DEATHS > 50 million > 1 million ~ 0.5 million MILD SEASONAL INFLUENZA 250 – 500,000

39. NICD

41. NICD INFLUENZA PANDEMICS NO. OF WAVES • 1889 – 1890 H2N2 • 1899 – 1900 H3N2 • 1918 – 1919 H1N1 2 or 3 • 1957 – 1958 H2N2 3 • 1968 – 1969 H3N2 2

42. … a lot of “known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don’t know we don’t know” Donald Rumsfeld US Secretary of Defense

43. NICD THE IMPONDERABLES - VIRAL • ? Further waves • ? Replace human seasonal H1N1 • ? Reassort with human seasonal H1N1 • ? Mutational resistance development • ? Reassort with human seasonal H3N2 • ? Reassort with avian H5N1

44. NICD THE IMPONDERABLES - HUMAN • Travel • Urbanization • Immunosuppression • Displaced persons • Medical and scientific advances

45. THANK YOU