H5N1 avian and pandemic flu

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H5N1 avian and pandemic flu
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H5N1 H3N2
Humanised H5N?
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20thC pandemic influenza strains

• 1918 H1N1 20 million deaths
• 1957 H2N2 lt1 million deaths
• 1968 H3N2 lt1 million deaths
• 1918 flu bird derived higher mortality
• 1957 / 1968 reassortant viruses
• Nature 10/2005
• H5N1 not very infectious in pigs

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High pathogenicity of H5N1

• Grows in wide variety of tissues
• Specific LRT receptor
• Evades immune response (interferon)
• Increased cytokine levels
• Animal model data shows more virulence with time
  1997 to 2004

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BIRD FLU OUTBREAKS IN 2005 (H5N1 STRAIN)
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Cumulative Number of Confirmed Human Cases of
Avian Influenza A/(H5N1) Reported to WHO
Total number of cases includes number of
deaths.WHO reports only laboratory-confirmed
cases.
Cases to 20/7/06
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Nature 13/7/06
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Median age 20. Case fatality highest 10 - 19
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Clinical features Vietnam 2003

• Fever
• Hypotension
• Respiratory failure
• Diarrhoea
• Leukopenia
• Lymphopenia
• Neutropenia

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Outcome current infections
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Neuraminidase inhibitors the worlds salvation?
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Nature 2005

• 2/05 isolate Vietnamese girl
• ? titres in ferrets
• ? oseltamivir sensitivity zanamivir sensitivity
  preserved
• Infection resolved on oseltamivir

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? Impact of oseltamivir resistance
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? Reasons for oseltamivir failure

• Low drug levels 2o diarrhoea
• Late commencement
• Immune mediated disease
• Effect of resistance
• RCT higher dose underway in SE Asia

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Infection Prevention Surveillance Service

• Do you have an acute respiratory illness,
  characterised by -
• High fever (temp gt 38 ºC)
• Cough
• Sore throat
• Shortness of breath or difficulty in breathing?

• Have you traveled overseas in the past 7 days to
  an Avian Flu affected area?
• China Philippines
• Viet Nam South Korea
• ThailandIndonesia
• CambodiaHong Kong
• RussiaJapan
• LaosMalaysia
• KazakhstanTurkey
• MongoliaRomania
• AND
• One or more of the following
• Contact (within 1 metre) with live or dead
  poultry in any setting
• OR
• Contact (within touching or speaking distance)
  with a confirmed human case of influenza A (H5N1)
  
• OR
• Contact (within touching or speaking distance)
  with a person with an unexplained acute
  respiratory illness that later resulted in death

• Consider Influenza
• Provide patient with N95 mask
• Implement Droplet and Contact precautions (N95
  mask, gloves and gown for all direct patient
  care)

No
Yes
No

• Provide patient with a N95 mask
• Admit to isolation room and activate negative
  pressure
• Implement Airborne and Contact Precautions. (N95
  mask, gloves and gown for all direct patient
  care)
• Contact VIDs registrar on-call via Switch
• Contact IPSS via pager 700

Normal triage process
Yes
Avian Influenza Guidelines Updated 26 October 2005
For a current list of Avian Flu affected areas
visit http//www.oie.int/downld/AVIAN20INFLUENZA
/A_AI-Asia.htm
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Antiviral stockpile

• 3.8 million oseltamivir / 25,000 zanamivir doses
• Containment phase 10 therapy / ring
  prophylaxis of family HCWs
• Maintenance phase 70 prophylaxis HCWs
• Remainder essential services workers
• 2000 doses held in Victoria
• Stockpile to be increased

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Pandemic flu vaccine development

• H5N1 toxic to eggs
• H5N2 used to vaccinate animals
• Ultimate humanised pandemic strain unknown
  currently
• Reverse genetics process being used to develop
  recombinant vaccine strains
• Modified H5 added to seed N1 containing virus
• Time to new vaccine 1-3 months??
• CSL capacity now 1 million doses week

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Novel vaccine approaches H5 subunit vaccine
NEJM 3/06
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http//www.cdc.gov/ncidod/eid/vol12no01/pdfs/Vol12
No01.pdf