Avian Influenza

15 subtypes of influenza in birds mostpathogenic H5, H7

waterfowl (wild duck) are the naturalreservoir of avian influenza virus

domestic poultry (chicken, turkey)are susceptible to epidemic fatal

pigs can infected with avian and mammalianinfluenza virus

Influenza VirusFamily Orthomyxoviridae

Genus Influenzavirus A, B

Avian influenzaH1 15N1 9

All highly pathogenic avian influenzais Influenza A; Subtype H5, H7

Human influenzaH 1, 2, 3N 1, 2

History of “Human Avian-Flu

1997 Hong Kong H5N1 1861999 Hong Kong H9N2 2/02003 Netherland H7N7 831/2003 Hong Kong H5N1 21/2004 Vietnam H5N1 186/2004 Thailand H5N1 32/

Year country strain outcome(case/death)

28 Jan 2004

Resistance to Physical and Chemical Action

Temperature : Inactivate 56๐c in 3 hours 60๐c 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

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)

Clinical Forms of Human Avian-Flu

1. Asymptomatic

2. Mild URI

3. Severe pneumonia

4. Multiple organ failure

(CID 2002; 34:558-564)

Clinical Features of Human Avian-Flu

Fever ConjunetivitisHeadache DiarrheaMalaiseMyalgia Severe PneumoniaSorethroat ARDSCough Organ failureRunny rose

Clinical Manifestations of Severe H5N1 Infection

No predictor of progression of disease

Bacterial superimposed pneumonia wereunlikely to be the causes

Manifestation of severe disease- primary viral pneumonia- lymphopenia- impaired liver function- impaired renal function- prolonged clotting time

H5N1 Infection in Hong Kong 1997 (18 cases)

Mean age (yr) 3 26

M : F 5 : 2 3 : 8

Pneumonia 0 11

GI symptom 2 8

mean WBC 11,200 3,900

Lymphocytopenia 0 11

Pancytopenia 0 2

Renal failure 0 4

Characteristic Mild Severe (N=7) (N=11)

18 Human Avian-Flu in HK 1997

18 cases

Mild URI Pneumonia7 cases 11 cases

Survived died5 cases 6 cases

(ARDS, organ failure)

Postmortem finding in 2 patients

Both reactive hemophagocytic syndrome

lung-hemorrhage, fibrinous exudate no viralinclusion

renal tubular necrosis

liver fatty change

RT-PCR for H5N1 found in renal tissue, bone marrow, spleen, liver

Cytokine-driven conditions reactivehemophagocytic syndrome

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

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)

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

Antiviral Drug for Influenza

Virus A A 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

indications1

Prophylaxis >1 y of age >1 y of age Not licensed >13 y of age

indications1

Adverse effects Central nervous Central nervous Bronchospasm Nausea,

system, anxiety system, anxiety vomiting

Amantadine Rimantadine Zanamivir Oseltamivir

1 Licensed ages.

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.

Vaccine for Avian-Flu

Influenza vaccine do not protection against H5N1

No H5N1 vaccine available

Vaccine composition change every year(antigenic drift)

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

Risk of H5N1 Infection among HCWs Exposed to H5N1 patients, HK.

Median age 30 29 0.1

No (%) of nurses, 171 (79) 234 (76) 0.2doctor

No (%) with 121 (56) 190 (61) 0.2poultry exposure

No (%) H5N1 8* (4) 2 (0.7) 0.01antibody-positive

Characteristics Exposed Non-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

Prevalence of H5 antibody-positive individuals in cohorts, stratified

by poultry exposure

Household contacts 45a 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)

Factors Influenzing HCW AcquiredH5N1 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)

History of Human Influenza

1918 1957 1968 1977

Spanish Flu

Asian Flu

Hong Kong Flu

Russian Flu

H1N1

H2N2

H3N2

H1N1

year

Influenza Pandemics :-could it occur ?

Pandemic influenza 3-4 times/century(1st 1918-1919 : 2nd 1957-1958 : 3rd 1968-1969)

more human infected with human (H1, H2, H3) and avian influenza

“mixing vessel” pandemic

expert suspect pandemic occur soon

Thank you