Avian Influenza Update

Clinician Update on Avian Influenza Scott F. Dowell, MD, MPH

Outline

Pandemic influenza versus seasonal flu

Clinical features of influenza A (H5N1)

Early recognition and containment of AI

Resources for clinicians

Recognizing Avian Influenza

Pandemic Influenza

US Infectious Disease Mortality: The Impact of Influenza and AIDS Armstrong. JAMA 1999;281:61

1918 Hemagglutinin Causes Severe Lung Damage M88 M88/H sp Kobasa et al. Nature 2004;431:703

Neuraminidase Sets Up Bacterial Pneumonia Peltola et al. JID 2005;192:249

Avian Influenza in Asia (22 August, 2005)

Human H5N1 Most Common in Children Chotpitayasunondh. MMWR 2004;53:100 Died Died Recovered Recovered Died Recovered Died Died Recovered Died Died Died Died Outcome Sick/dead fighting cock in backyard Dead fighting cock at neighbors Sick/dead fighting cocks, chicken in backyard Sick/dead fighting cocks in backyard Sick poultry in backyard Sick poultry in backyard Dead poultry in backyard Sick/dead fighting cocks, poultry in backyard Purchased, cooked chicken from affected area Sick poultry in backyard Sick poultry at neighbors Dead poultry at neighbors Dead poultry at neighbors Exposure 31 Aug M 18 1 Mar F 39 13 Feb M 29 3 Feb F 47 26 Jan M 13 25 Jan M 2 24 Jan M 6 21 Jan M 4 20 Jan F 27 19 Jan F 58 M M M Sex 7 Jan 6 Jan 3 Jan Onset 6 6 7 Age

Thai Children at Risk for H5N1 Infection * Before and after a public education campaign Olsen et al. EID 2005;11: 0.4 7 (4) 12 (6) Children in your household touched sick or dead poultry with bare hands 0.3 17 (9) 24 (12) Took dead chicken or poultry from your yard and prepared it to eat 9 (5) 27 (14) After <0.01 <0.01 p-value 45 (23) Thought it was safe for children to touch sick or dead poultry with bare hands 78 (40) Thought it was safe to touch sick or dead poultry with bare hands Before Knowledge, attitudes, and practices*

Chotpitayasunondh. MMWR 2004;53:100

Influenza A (H5N1) Pneumonia Hien. NEJM 2004;350:1179

Lymphopenia Predicts Mortality Chotpitayasunondh et al. EID 2005;11:201 WBC/ALC Count Platelet Count 12,000 1,500 3,000 4,500 6,000 7,500 9,000 10,500 13,500 15,000 50,000 100,000 150,000 200,000 250,000 300,000 350,000 400,000 450,000 500,000 ALC WBC Platelet Survived Died Survived Died Survived Died . . . . . . . . . . . . Legend: No ARDS ARDS Median value . . . . . . . . . . . . . . . .

Early Oseltamivir Associated with Survival Chotpitayasunondh et al. EID 2005;11:201 1 2 3 1 2 3 4 5 6 7 8 9 10 11 12 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Patient No. Days after onset of illness Legend: - Oseltamivir - Day Discharged - Day of Death Died Survived

H5 in 2004 is More Virulent and Requires More Oseltamivir

Mouse model of lethal H5 infection

’ 04 virus more lethal than ’97 virus

Oseltamivir was protective

Higher dosages needed

8-day regimen better than 5-day

Yen et al. JID 2005;192:665

Clinical Features of Avian Influenza

Persistent fever, lymphopenia

Severe pneumonia or ARDS

unusual presentations possible

Exposure to sick poultry

Exposure to affected areas or persons

Clustering may be an emergency

Investigating Person-to-Person Spread

Timeline of Exposures and Illness Ungchusak. NEJM 2005:352;333

Getting the Virus

Urgent effort to get specimens to WHO network

Index patient dead, cremated

Mother’s body embalmed

Lung and other tissues tested by RT-PCR and IHC

Aunt survived

NP and OP swabs tested by cell culture, RT-PCR

Acute and convalescent serum (neutralization, ELISA)

Containing Pandemic Influenza With Antiviral Agents

Theoretical models using Thailand data

Contacts of suspected cases take antiviral agents

Pandemic contained if R o low

Prophylaxis with quarantine more effective

Critical is speed of detecting cases and response

Longini IM et al. Science 2005 Ferguson et al. Nature 2005

No. of Cases Day of illness No. of Cases Baseline 8-week 80% TAP +2 +15 Outbreak Recognized ~Day 68 Typical “Large” Outbreaks (Hong Kong Calibration) +10

An Influenza Pandemic and the Clinician