3. Avian Influenza 15 subtypes of influenza in birds most pathogenic H5, H7 waterfowl (wild duck) are the natural reservoir of avian influenza virus domestic poultry (chicken, turkey) are susceptible to epidemic fatal pigs can infected with avian and mammalian influenza virus

4. Influenza Virus Family Orthomyxoviridae Genus Influenzavirus A, B Avian influenza H115 N19 All highly pathogenic avian influenza is Influenza A; Subtype H5, H7 Human influenza H 1, 2, 3 N 1, 2

5. History of “Human Avian-Flu 1997 Hong KongH5N1 18/6 1999Hong KongH9N2 2/0 2003NetherlandH7N7 83/1 2003Hong KongH5N1 2/1 2004VietnamH5N1 18/6 2004ThailandH5N1 3/2 Year country strain outcome (case/death) 28 Jan 2004

6. Resistance to Physical and Chemical Action Temperature : Inactivate 56 ๐ c in 3 hours 60 ๐ c in 30 min pH : Inactivated by acid pH Chemicals : Inactivated by oxidizing agent Sod. Dodecyl sulfate Lipid solvents  propiolactone Disinfectant : Inactivated by formalin, lodine compound Survival : long period in tissus, feces, water

7. Transmission of Avian-Flu 1. Direct contact with secretion esp. feces of poultry 2. Indirect contact from feed, water, equipment clothing 3. Human-to-human :- possible but low risk (CID 2002; 34:558-564)

8. Clinical Forms of Human Avian-Flu 1. Asymptomatic 2. Mild URI 3. Severe pneumonia 4. Multiple organ failure (CID 2002; 34:558-564)

9. Clinical Features of Human Avian-Flu FeverConjunetivitis HeadacheDiarrhea Malaise MyalgiaSevere Pneumonia SorethroatARDS CoughOrgan failure Runny rose

10. Clinical Manifestations of Severe H5N1 Infection No predictor of progression of disease Bacterial superimposed pneumonia were unlikely to be the causes Manifestation of severe disease - primary viral pneumonia - lymphopenia - impaired liver function - impaired renal function - prolonged clotting time

11. H5N1 Infection in Hong Kong 1997 (18 cases) Mean age (yr)326 M : F 5 : 2 3 : 8 Pneumonia011 GI symptom2 8 mean WBC 11,200 3,900 Lymphocytopenia011 Pancytopenia0 2 Renal failure0 4 Characteristic Mild Severe (N=7) (N=11)

12. 18 Human Avian-Flu in HK 1997 18 cases Mild URIPneumonia 7 cases11 cases Surviveddied 5 cases6 cases (ARDS, organ failure)

13. Postmortem finding in 2 patients Both reactive hemophagocytic syndrome lung-hemorrhage, fibrinous exudate no viral inclusion renal tubular necrosis liver fatty change RT-PCR for H5N1 found in renal tissue, bone marrow, spleen, liver Cytokine-driven conditions reactive hemophagocytic syndrome

14. Lab. Diagnosis of “Human Avian- Flu” 1. Culture (Madin-Darby canine kidney cells) - Cytopathic effect prelim. using H5 specific RT-PCR or immunostaining with monoclonal antibody 2. H5 specific RT-PCR 3. Rapid test :- IFA from NP, endotracheal :- antigen detection 4. Serodiagnosis :- NT in paired serum

15. Treatment of Avian-Flu 1. Supportive care :- Ventilator support when needed 2. Antiviral agents eg. Amantadine, Rimantadine, Zanamivir, Oseltamivir etc (Antiviral agents is the most effective when given within 2 days of onset, but don’t know in Avian Flu)

16. Influenza Antiviral Medications Chemoprophylaxis :- Amantadine, Rimantadine, Oseltamivir 70-90% efficacy in healthy adult high risk group eg. nursing home, hospital Treatment :- (same as above), Zanamivir x 5 days treat within 2 days after onset reduce symptoms, shorten time by 1-2 days, less contagious to other

17. Antiviral Drug for Influenza Virus AA A and B A and B Administration Oral Oral Inhalation Oral Treatment >1 y of age >13 y of age >7 y of age >1 y of age indications 1 Prophylaxis >1 y of age >1 y of age Not licensed >13 y of age indications 1 Adverse effects Central nervous Central nervous Bronchospasm Nausea, system, anxiety system, anxiety vomiting Amantadine Rimantadine Zanamivir Oseltamivir 1 Licensed ages.

18. Daily Dosage Oseltamivir (Tamiflu ® ) in Children For Prophylaxis and Treatment Weight < 15 kg ; Oseltamivir 30 mg, bid x 5d. 16-23 kg ; Oseltamivir 45 mg, bid x 5d. 24-40 kg ; Oseltamivir 60 mg, bid x 5d. > 40 kg ; Oseltamivir 75 mg, bid x 5d.

19. Vaccine for Avian-Flu Influenza vaccine do not protection against H5N1 No H5N1 vaccine available Vaccine composition change every year (antigenic drift)

20. Prevention of Avian-Flu for Health Care Worker Same as SARS measure 1. Isolation room 2. PPE (as SARS is more than enough) 3. disinfectants of material

21. Risk of H5N1 Infection among HCWs Exposed to H5N1 patients, HK. Median age 30 29 0.1 No (%) of nurses,171 (79) 234 (76) 0.2 doctor No (%) with 121 (56) 190 (61) 0.2 poultry exposure No (%) H5N1 8* (4) 2 (0.7) 0.01 antibody-positive CharacteristicsExposedNon-Exposed P (N=217) (N=309) (JID 2000; 181:344-8) * all were contact without protection because late diagnosis and severe illness * 2 cases of seroconversion

22. Prevalence of H5 antibody-positive individuals in cohorts, stratified by poultry exposure Household contacts 45 a 5/24 (21) 1/21 (5).13 Tour group members 26 1/16 (6) 0/10 (0).62 Coworkers exposed 23 0/9 (0) 0/14 (0) NA Not exposed 24 0/3 (0) 0/21 (0) NA No. of antibody-positive individuals/total (%) Exposed Not exposed Cohort n to poultry to poultry P (JID 1999; 180:1763-70)

23. Factors Influenzing HCW Acquired H5N1 from Patient 1. Severity of patient - quantity of virus 2. No. of days from admission to diagnosis 3. Infection - control practice - droplet precaution (human to human unlikely to occur, if occur it is asymptomatic)

24. History of Human Influenza 1918195719681977 Spanish Flu Asian Flu Hong Kong Flu Russian Flu H1N1 H2N2 H3N2 H1N1 year

25. Influenza Pandemics :- could it occur ? Pandemic influenza 3-4 times/century (1 st 1918-1919 : 2 nd 1957-1958 : 3 rd 1968-1969) more human infected with human (H1, H2, H3) and avian influenza “mixing vessel”pandemic expert suspect pandemic occur soon

29. Thank you