WHO PANDEMIC PHASES INTERPANDEMIC PERIOD Phase 1 Phase

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

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

A. SPORADIC INFLUENZA B. PANDEMIC INFLUENZA C. SEASONAL INFLUENZA

NICD

A. SPORADIC INFLUENZA B. PANDEMIC INFLUENZA C. SEASONAL INFLUENZA

HUMAN CASES OF AVIAN INFLUENZA Year Subty pe No. of Cases Location 1997 H 5 N 1 18 (6 deaths) Hong Kong 1999 H 9 N 2 2 (children ages 4 yr, 13 mo) Hong Kong 2002 H 7 N 2 1 United States (Virginia) 2003 H 5 N 1 2 (1 death) Hong Kong 2003 H 7 N 7 89 (1 death) The Netherlands 2003 H 7 N 2 1 New York 2003 H 9 N 2 1 (child) Hong Kong 2003(ongoin g) H 5 N 1 262/440 (60%) Vietnam, Thailand, Cambodia, Indonesia, China, Turkey, Iraq, Azerbaijan, Egypt etc 2004 H 7 N 3 2 Canada (British Columbia) 2004 H 10 N 7 2 (infants) Egypt NICD

A. SPORADIC INFLUENZA B. PANDEMIC INFLUENZA C. SEASONAL INFLUENZA

INFLUENZA PANDEMICS q 1510 q 1889 – 1890 q 1899 – 1900 q 1918 – 1919 q 1957 – 1958 q 1968 – 1969 flu” H 2 N 2 H 3 N 2 H 1 N 1 H 2 N 2 H 3 N 2 “Spanish flu” “Asian flu” “Hong Kong NICD

A. SPORADIC INFLUENZA B. PANDEMIC INFLUENZA C. SEASONAL INFLUENZA

INFLUENZA PANDEMICS 1510 q 1889 – 1890 H 2 N 2 q 1899 – 1900 H 3 N 2 q 1918 – 1919 H 1 N 1 q 1957 – 1958 H 2 N 2 q 1968 – 1969 H 3 N 2 q 1977 H 1 N 1 q “Spanish flu” “Asian flu” “Hong Kong flu” NICD

RECOMMENDED VACCINE FORMULATION The following strains have been recommended by the WHO for the 2009 Southern Hemisphere influenza season: q A/Brisbane/59/2007 (H 1 N 1) - like virus * q A/Brisbane/10/2007 (H 3 N 2) - like virus ** q 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 n Median onset: n n 2005 2004 2003 2002 2001 2000 1999 Median peak: n n Week 23 Range 15 -28 2006 1998 1997 1996 Week 27 Range 20 -32 1995 1994 1993 1992 Median duration: n n 1991 1990 1989 1988 1987 10 weeks Range 7 -17 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 Apr May Jun Jul Aug Epidemiological week Mean onset Sep

INFLUENZA VIRUS

(9 subtypes) (16 subtypes) NICD

HAEMAGGLUTININS H 1 N 1 H 2 N 2 H 3 N 3 H 4 N 4 H 5 N 5 H 6 N 6 H 7 N 7 H 8 N 8 H 9 NEURAMINIDASES H 10 H 11 H 12 H 13 H 14 PANDEMICS 1918 H 1 N 1 SPANISH PANDEMIC H 15 1957 H 2 N 2 ASIAN PANDEMIC H 16 1968 H 3 N 2 HONG KONG PANDEMIC H 5 N 1 AVIAN INFLUENZA NICD

INFLUENZA PANDEMICS q 1510 q 1889 – 1890 H 2 N 2 q 1899 – 1900 H 3 N 2 q 1918 – 1919 H 1 N 1 “Spanish flu” q 1957 – 1958 H 2 N 2 “Asian flu” q 1968 – 1969 H 3 N 2 “Hong Kong flu” q 2009 - ? H 1 N 1 v flu”/pandemic 2009 “Swine NICD

H 1 N 1 1918/19 Pandemic Ag drift 1957 Seasonal flu Ag Stasis (sporadic human cases) 1977 Ag drift 1998 2009 Seasonal flu Triple reassortant Influenza A (H 1 N 1) v 2009 Pandemic Eurasian

Positive samples by influenza types and subtypes : Viral Watch South Africa 2009 250 80 60 150 40 100 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 H 1 N 1 (seasonal) A H 3 N 2 B Novel H 1 N 1 Detection rate** Percentage Number 200

Diagnosed and reported H 1 N 1 influenza statistics

Diagnosed and reported H 1 N 1 influenza statistics Reported to surveillance authority Laboratory test reliable Adequate specimen reaches laboratory Doctor takes specimen Report to doctor Symptomatically infected Infected individuals

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

B) NON-PREGNANT Total: 15 Age range: 0 -53 yr a) Nil 3 (20%) b) Co-morbidities 1. HIV 2 (1 TB) 2. Obesity 7 (1 asthma, 2 cardiac, 1 diabetes) 3. Diabetes 4 (1 obesity, 1 hypertension) 4. TB 1 5. 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 1. Novel virus 2. Increased transmissibility 3. +/- increased virulence 4. Age shift 5. Relative non-seasonality 6. Geographic heterogeneity 7. Multiple waves 8. Human adaptation seasonal influenza NICD

3. CFR: VIRULENCE MEXICO 0. 4% (0. 3 – 0. 6%) USA 0. 2% SEASONAL INFLUENZA 1918/1919 PANDEMIC H 5 N 1 0. 04 -0. 08% 5. 0% 60% NICD

INFLUENZA PANDEMICS Ø Ø Ø 1510 1889 – 1890 1899 – 1900 1918 – 1919 1957 – 1958 1968 – 1969 Ø 1977 DEATHS H 2 N 2 H 3 N 2 H 1 N 1 H 2 N 2 H 3 N 2 “Spanish flu” > 50 million “Asian flu” > 1 million “Hong Kong flu” ~ 0. 5 million H 1 N 1 MILD SEASONAL INFLUENZA 250 – 500, 000

NICD

INFLUENZA PANDEMICS NO. OF WAVES Ø 1889 – 1890 H 2 N 2 Ø 1899 – 1900 H 3 N 2 Ø 1918 – 1919 H 1 N 1 2 or 3 Ø 1957 – 1958 H 2 N 2 3 Ø 1968 – 1969 H 3 N 2 2 NICD

… a lot of “knowns; there are things 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 also unknowns – the ones we don’t know” Donald Rumsfeld US Secretary of Defense

THE IMPONDERABLES - VIRAL 1. ? Further waves 2. ? Replace human seasonal H 1 N 1 3. ? Reassort with human seasonal H 1 N 1 4. ? Mutational resistance development 5. ? Reassort with human seasonal H 3 N 2 NICD

THE IMPONDERABLES - HUMAN 1. Travel 2. Urbanization 3. Immunosuppression 4. Displaced persons 5. Medical and scientific advances NICD

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