WHO PANDEMIC PHASES INTERPANDEMIC PERIOD Phase 1 Phase 2 PANDEMIC ALERT PERIOD Phase 3 Phase 4 Phase 5 PANDEMIC PERIOD Phase 6 POSTPANDEMIC PERIOD

INFLUENZA VIRUS

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

I cannot forecast to you the action of Russia 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

SPORADIC INFLUENZA PANDEMIC INFLUENZA SEASONAL INFLUENZA

NICD

SPORADIC INFLUENZA PANDEMIC INFLUENZA SEASONAL INFLUENZA

HUMAN CASES OF AVIAN INFLUENZA Year Subtype No. of Cases Location 1997 H5N1 18 (6 deaths) Hong Kong 1999 H9N2 2 (children ages 4 yr, 13 mo) 2002 H7N2 1 United States (Virginia) 2003 2 (1 death) H7N7 89 (1 death) The Netherlands New York 1 (child) 2003- (ongoing) 262/440 (60%) Vietnam, Thailand, Cambodia, Indonesia, China, Turkey, Iraq, Azerbaijan, Egypt etc 2004 H7N3 2 Canada (British Columbia) H10N7 2 (infants) Egypt NICD

SPORADIC INFLUENZA PANDEMIC INFLUENZA SEASONAL INFLUENZA

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” NICD

SPORADIC INFLUENZA PANDEMIC INFLUENZA SEASONAL INFLUENZA

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 NICD

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

ONSET & DURATION OF INFLUENZA SEASON: 1985 - 2007 Epidemiological week 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 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 Mean onset 2007 Apr May Jun Jul Aug Sep Median onset: Week 23 Range 15-28 Median peak: Week 27 Range 20-32 Median duration: 10 weeks Range 7-17

INFLUENZA VIRUS

(9 subtypes) (16 subtypes) NICD

HAEMAGGLUTININS H1 N1 NEURAMINIDASES H2 N2 H3 N3 H4 N4 H5 N5 H6 N6 PANDEMICS 1918 H1N1 SPANISH PANDEMIC 1957 H2N2 ASIAN PANDEMIC 1968 H3N2 HONG KONG PANDEMIC H5N1 AVIAN INFLUENZA 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 NICD

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

Positive samples by influenza types and subtypes : Viral Watch South Africa 2009 50 100 150 200 250 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 Number 20 40 60 80 Percentage A awaiting typing A H1N1 (seasonal) A H3N2 B Novel H1N1 Detection rate**

Diagnosed and reported H1N1 influenza statistics

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

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

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

WHO PANDEMIC PHASES INTERPANDEMIC PERIOD Phase 1 Phase 2 PANDEMIC ALERT PERIOD Phase 3 Phase 4 Phase 5 PANDEMIC PERIOD Phase 6 POSTPANDEMIC PERIOD

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

INFLUENZA PANDEMICS 1977 H1N1 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 1977 H1N1 SEASONAL INFLUENZA 250 – 500,000

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 NICD

Donald Rumsfeld US Secretary of Defense … 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

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 NICD

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

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