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WHO Draft Rapid Response + Containment, May 2006. Projected Outbreak of H5N1 in Thailand. R 0 = 1.5. Red = new cases. Green = areas where the epidemic has finished. Ferguson et al. Nature 437:209, 2005. - PowerPoint PPT Presentation
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WHO Draft Rapid Response + Containment, May 2006
Projected Outbreak of H5N1 in Thailand
Red = new cases. Green = areas where the epidemic has finished.
Ferguson et al. Nature 437:209, 2005
R0 = 1.5
Left: uncontrolled outbreak. Red = new cases. Green = areas where the epidemic has finished.
Above: Controlled outbreak. Red = areas of infection. Blue = areas where a combination of control measures implemented.
http://www.nigms.nih.gov/news/releases/08032005.html
Projected Outbreak of H5N1 Influenza in Thailand
Elimination of a pandemic virus at its source?
• Ring chemoprophylaxis feasible if:– Geographically targeted in non-urban setting
– Early intervention within 1-3 wks
– Virus of low-moderate transmissibility (R0 < 1.8)
– Chemoprophylaxis of 80 - 90% of population
– High compliance
– Movement restrictions; social distancing
• Maximum of 1-3 million courses needed– 300,000 may be sufficient
Ferguson et al. Nature 437:209, 2005
Rapid Response: Antiviral Deployment
• Rapid use of antiviral prophylaxis is key component.• Mass targeted antiviral prophylaxis:– Goal of 90% coverage– Geographic radius of 5-10 km from each detected case
OR– Administrative area of “at-risk” population of 10-50,000
• Multiple logistical hurdles– WHO donation of 3.0 M courses– 440 courses = 7.8 kg– 100,000 courses = 19 shipping pallets– Start dispensing within 12 hrs of receipt
WHO Draft Rapid Response + Containment Document, May 2006
Antiviral Resistance in Influenza Viruses
• M2 inhibitors:– Primary resistance in epidemic (>90% of recent H3N2)
or pandemic virus possible; frequent with Rx– Confers cross-resistance to entire class– Resistant variants virulent and transmissible
• NA inhibitors:– No primary resistance; active for all 9 NA types– Inhibitory for M2 resistant-variants– Variable NAI cross-resistance depending on
type/subtype and drug– Most NAI resistance causes infectivity and virulence in
animals
NISN. Weekly Epi Record 33:306, 2004
Detection Of Antiviral Resistant Influenza During Treatment
Frequency of resistance
Oseltamivir M2 inhibitor
Out-patient adults
Out-patient children
0.4%
5.5%
~30%
~30%
Inpatient children 18% 80%
Immunocompromised
? >33%
Roberts N. Phil Trans R Soc Lond 356:1895, 2001
Kiso et al. Lancet 364: 759, 2004
Pharyngeal Viral Loads during Oseltamivir Treatment of H5N1
de Jong et al. NEJM 353:25, 2005
Neuraminidase Inhibitor Treatment : Antiviral Resistance
• Emergence of oseltamivir-resistant variants may be associated with prolonged viral detection in A/H3N2-infected children and in H5N1-infected patients. – Resistance due to H274Y mutation may
compromise clinical efficacy in some H5N1 patients.
• No transmission of oseltamivir-resistant variants detected in house-hold based studies or in prophylaxis failures to date.– Some resistant variants are transmissible in ferret
model (including H274Y mutation in N1)
Influenza Prevention In Households: PEP
Antiviral (Study)
No. Contacts
(age)
Reduction in 2° influenza illness
Reduction in influenza infection
Oseltamivir (Welliver et al, 2000)
955(13+ yr)
89% 49%
Oseltamivir* (Hayden et al, 2004)
792(1+ yr)
73% 35%(Index +)
Zanamivir* (Hayden et al, 2000)
837(5+ yr)
79% 62%
Zanamivir (Monto et al, 2002)
1,291(5+ yr)
82% 59%
*Index case given treatment
Interval from PEP Initiation to Secondary Illness Onset in Household Contacts (N = 1,291)
Note: zanamivir PEP started < 36 hr of index illness onset
Monto et al. JID 186:1582, 2002
Influenza Post-exposure Prophylaxis (PEP) with Neuraminidase Inhibitors: Summary
• Socially targeted antiviral prophylaxis (PEP) is highly effective in protecting contacts in households during seasonal influenza.– Reductions in illness > infection.
– Secondary cases occur early, often in first few days after index case recognition.
– Rapid initiation is essential.
• Inhaled zanamivir is also effective for prevention.– Unstudied in human H5N1 infections to date.
Rapid Response: Antiviral Deployment
• Mass targeted antiviral prophylaxis:– Goal of 90% coverage– Geographic radius of 5-10 km from each detected case
OR– Administrative area of “at-risk” population of 10-50,000– Minimal duration of 10 days
• Multiple logistical hurdles– 100,000 courses = 19 shipping pallets– Start dispensing within 12 hrs of receipt
WHO Draft Rapid Response + Containment Document, May 2006