Departement Gesondheidswetenskappe •

Faculty of Health Sciences

Influenza viruses and influenza pandemics: virological and human aspects

Wolfgang Preiser

Discipline of Medical Virology, University of Stellenbosch; NHLS Tygerberg

Public Health Forum: How serious is the flu pandemic threat?Faculty of Health Sciences, Tygerberg Hospital

30th November 2005

15 HA types: H1 - H15

9 NA types: H1 - H9

–ssRNA in 8 segments

Hydrolysis of sialic acid

Receptor binding to sialic acid(N-acetyl-neuraminic acid)

Neuraminidase

Release of newly synthesised virions

Haemagglutinin

Antigenic drift ⇒ annual seasonal epidemicsH3N2 strain

Recommended composition of influenza virus vaccines for use in the 2006 southern hemisphere influenza season — an A/New Caledonia/20/99(H1N1)-like virus;— an A/California/7/2004(H3N2)-like virus;— a B/Malaysia/2506/2004-like virus.

all causes

Influenza pandemic

non-infectious causes

infectious diseases

United States of AmericaAntigenic shift ⇒ sporadic pandemicssubtype strain

H1, H2, H3N1, N2

H1, H3N1, N2

H3, H7N7, N8

H1 - H15

N1 - N9

H1N1

PB2

PA

NA

NP

M

HA

NS

PB1

H1N1

PB2

PA

NA

NP

M

HA

NS

PB1

8 segments

"Spanish"1918: 40 mio.

H2N2

PB2

PA

NA

NP

M

HA

NS

PB1

H2N2

PB2

PA

NA

NP

M

HA

NS

PB1

3 segments

"Asian"1957: 1 mio.

5 seg.

H3N2

"Hongkong"1968: 1 mio.

2 segments

H3N?

PB2

PA

NA

NP

M

HA

NS

PB1

H3N2

PB2

PA

NA

NP

M

HA

NS

PB1

6 seg.

1950

"Russian"1977:

lab isolate?

H1N1

mammalian influenza A virus

avian influenza A virus

α(2,6)

α(2,3)

"mixing vessel": α(2,6) und α(2,3)Reassortment ⇐

α(2,3), α(2,6): binding between sialic acid and galactoseAmino acids at positions 226 / 228 of HA: leucin / serin ⇒ α(2,6); glutamin / glycin ⇒ α(2,3)

Prerequisites for an influenza pandemic

1. new viral subtype ⇒ no population immunity

2. high pathogenicity and virulence for humans

3. efficient human-to-humantransmission

Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO

25 November 2005

Country Total cases * DeathsViet Nam 93 42Thailand 21 13Cambodia 4 4Indonesia 11 7China 3 2Total 132 68

* Total number of cases includes number of deaths.WHO reports only laboratory-confirmed cases.

Reasons for concern

1. widespread epizootic⇒ increased human contact

Reasons for concern

2. highly pathogenic H5 and H7 types:several basic amino acids before HA cleavage site into HA1 and HA2 ⇒ ↑ tissue tropism ⇒ ↑ virulence

142 of 242 human infections with avian influenza viruses since 1959, and all but 1 of 70 human deaths,were due to H5N1!

1. new viral subtype ⇒ no population immunity

2. high pathogenicity and virulence for humans

3. efficient human-to-humantransmission

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√

X

Prerequisites for an influenza pandemic

WHO global influenza preparedness plan

Interpandemic periodPhase 1: No new influenza virus subtypes in humansPhase 2: circulating animal influenza virus subtype poses a

substantial risk of human diseasePandemic alert periodPhase 3: human infection(s) with a new subtype, but no human-to-

human spread, or at most rare instances of spread to a close contact.

Phase 4: small cluster(s) with limited human-to-human transmission but spread highly localized (virus not well adapted to humans)

Phase 5: larger cluster(s) but human-to-human spread still localized (virus becoming increasingly better adapted to humans)

Pandemic periodPhase 6: pandemic: increased and sustained transmission in general

population

WHO Department of Communicable Disease Surveillance and Response –Global Influenza Programme

WHO global influenza preparedness plan

Interpandemic periodPhase 1: No new influenza virus subtypes in humansPhase 2: circulating animal influenza virus subtype poses a

substantial risk of human diseasePandemic alert periodPhase 3: human infection(s) with a new subtype, but no human-to-

human spread, or at most rare instances of spread to a close contact.

Phase 4: small cluster(s) with limited human-to-human transmission but spread highly localized (virus not well adapted to humans)

Phase 5: larger cluster(s) but human-to-human spread still localized (virus becoming increasingly better adapted to humans)

Pandemic periodPhase 6: pandemic: increased and sustained transmission in general

population

WHO Department of Communicable Disease Surveillance and Response –Global Influenza Programme

WHO Epidemic and Pandemic Alert and Response (EPR) – 14 October 2005

1. Pandemic influenza is different from avian influenza2. Influenza pandemics are recurring events3. The world may be on the brink of another pandemic4. All countries will be affected5. Widespread illness will occur6. Medical supplies will be inadequate7. Large numbers of deaths will occur8. Economic and social disruption will be great9. Every country must be prepared10. WHO will alert the world when the pandemic

threat increases