Clinical Outcomes of Clinical Outcomes of Influenza InfectionInfluenza Infection

• AsymptomaticAsymptomatic

• SymptomaticSymptomatic

Respiratory syndrome - mild to Respiratory syndrome - mild to severesevere

Involvement of major organs - brain,Involvement of major organs - brain, heart, etc.heart, etc.

DeathDeath

Factors Influencing the Factors Influencing the Response to InfluenzaResponse to Influenza

• AgeAge

• Pre-existing immunity (some Pre-existing immunity (some crossover)crossover)

• SmokingSmoking

• Concurrent other health conditionsConcurrent other health conditions

• ImmunosuppressionImmunosuppression

• PregnancyPregnancy

Virology of InfluenzaVirology of Influenza

Subtypes:Subtypes:

A - Causes outbreakA - Causes outbreak

B - Causes outbreaksB - Causes outbreaks

C - Does not cause outbreaksC - Does not cause outbreaks

Immunogenic Components Immunogenic Components of the Influenza Virusof the Influenza Virus

• Surface glycoproteins, 15 hemagglutinins Surface glycoproteins, 15 hemagglutinins (H(H11-H-H1515), nine neurominidases (N), nine neurominidases (N11-N-N99))

• HH11-H-H33 and N and N11NN22 established in humans established in humans

• Influenza characterized by combination of H Influenza characterized by combination of H and N glycoproteinsand N glycoproteins 1912 pandemic - H1912 pandemic - H11NN11

2004 avian influenza - H2004 avian influenza - H55NN11

• Antigenic mix determines severity of diseaseAntigenic mix determines severity of disease

• Human response specific to hemagglutinin Human response specific to hemagglutinin and neurominidase glycoproteinsand neurominidase glycoproteins

Spread of HSpread of H55NN11 Avian Avian InfluenzaInfluenza

12 14 16 18 20 22 24 26 28 30 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 12 14 16 18 20 22 24 26 28 30 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 231 2

December, 2003 January 2004 December, 2003 January 2004 Feb Feb

Sou

th K

ore

a

Vie

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mJa

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Ch

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Figure 1. Natural hosts of influenza viruses

Nicholson et al. Influenza. Lancet 362:1734, 2003

Nicholson et al. Influenza. Lancet 362:1735, 2003

Figure 2. Origin of antigenic shift and pandemic influenza. The segmented nature of the influenza A genome, which has eight genes, facilitates reassortment; up to 256 gene combinations are possible during coinfection with human and non-human viruses. Antigenic shift can arise when genes encoding at least the haemagglutinin surface glycoprotein are introduced into people, by direct transmission of an avian virus from birds, as occurred with H5N1 virus, or after genetic reassortment in pigs, which support the growth of both avian and human viruses.

Outbreaks of Avian Influenza A (H5N1)... MMWR 53(5):102, 2004Outbreaks of Avian Influenza A (H5N1)... MMWR 53(5):102, 2004

Intervention StrategiesIntervention Strategies

• Culling (killing of infected flocks)Culling (killing of infected flocks)

• Innovative surveillance strategies- Identification and analysis of human to

human clusters- Necessary for vaccine development

(Science 304:968-9, 5/2004)

• Vaccination of bird handlers (vaccine Vaccination of bird handlers (vaccine being developed)being developed)