Avian Influenza Epidemiologi & Penularan pada Manusia

Sri Rezeki S Hadinegoro Divisi Infeksi & P.Tropis Dep Ilmu Kesehatan Anak FKUI-RSCM

Avian influenza
(bird flu, flu burung)

Virus avian influenza (H5N1) berasal dari burung liar (wild birds) menyerang unggas (burung, ayam), babi, kuda Menyebar cepat diantara populasi unggas dengan kematian tinggi Dapat menyebar antar peternakan Penularan melalui udara, air tercemar, berasal dari tinja unggas sakit Dapat menyerang manusia (penyakit zoonosis)

Avian influenza
(bird flu, flu burung)

Secara epidemiologi
Low pathogenic avian influenza (LPAI) Highly pathogenic avian influenza (HPAI)

Perbedaan pada susunan genetik virus HPAI

sangat virulen menyebabkan kematian ternak ayam 90-100%

LPAI
infeksi ringan atau tidak tampak sakit

Wabah Avian Influenza

1997, avian influenza A (H5N1), Hongkong, menyerang ayam dan manusia 1999
Hongkong: avian flu A (H9N2), 2 kasus anak, hidup Cina: H9N2

2003
Hongkong: avian flu A (H5N1), 2 kasus, 1 meninggal, riwayat perjalanan ke Cina Netherland: avian flu A (H7N7), 83 kasus pekerja peternakan, 1 meninggal Hongkong : avian flu A (H9N2), 1 kasus hidup

Situasi Virus Influenza H5N1 di Asia

6 Februari 2004

Penyebab wabah flu di Hongkong, Vietnam, Thailand, dan Jepang Dilaporkan 20 kasus pada manusia
Vietnam 15 Thailand 5

Kematian 16 kasus
Vietnam 11 Thailand 5

CFR 80%

Situasi Virus Influenza H5N1 di Asia

21 Juli 2005

Kasus avian influenza A (H5N1) pada manusia 109 orang

Vietnam 87 Thailand 17 Kamboja 4 Indonesia 2 (WHO), 1 belum ada hasil Kematian 55 orang (50,45%)
http://www.who.int/csr/disease/avian_influenza/en/

Situasi di Indonesia 2004

Virus menyerang ternak ayam sejak bulan Okt 2003-Feb 2004 4,7 juta ayam mati Belum ada laporan menyerang manusia Serosurvai virus influenza A(H5N1) terhadap peternak semua negatif, dari 2 daerah
Bali 102 sera, 28 kontrol, 8 swab hidung Tangerang: 100 sera, 25 kontrol, 6 swab hidung

Daerah tertular Avian Flu di Indonesia

September 2003-Desember 2004 17 provinsi, 108 kabupaten/kota

P Sumatera: 5 prop, 17 kab/kota P Jawa: 6 prop, 71 kab/kota P Kalimantan: 3 prop, 5 kab/kota Nusa Tenggara: 2 prop, 7 kab/kota
Sumber: Dirjen Peternakan, Deptan; Kompas 31 Juli 2005

Analisis Epidemiologi

Outbreak of highly pathogenic avian influenza A (H5N1)

2003-2004 wabah di 8 negara Asia : Kamboja, Cina, Indonesia, Jepang, Laos, Korea Selatan, Thailand, Vietnam >100 juta burung mati/ dimusnahkan Des 2003-Maret 2004: 12 confirmed human avian influenza A di Thailand, 23 Vietnam, kematian 23 orang Tidak ada laporan penularan manusia ke manusia

Analisis Epidemiologi

Akhir Juni 2004: epizootic outbreak of new lethal avian influenza (H5N1) pada ayam di Kamboja, Cina, Indonesia, Malaysia, Thailand, & Vietnam Agustus Oktober 2004: kasus pada manusia secara sporadis di Vietnam, Thailand Sept 2004: probable limited human to human transmission (Thailand) Des 2004: ayam & manusia (Vietnam) Feb 2005: infeksi pada manusia (Kamboja) Juli 2005 : infeksi pada manusia (Indonesia)
www.cdc.gov/flu/avian.htm

Penularan dari binatang ke manusia

Infeksi virus influenza A spesifik

manusia : H3N2, H2N2, H1N1 babi : H7N7 kuda : H3N8

AS, tahun 1998 ditemukan

H1N1 pada babi H3N2 dari manusia terdapat pada babi

Masa inkubasi 1-3 hari Penularan ke manusia melalui 2 cara

langsung dari unggas atau lingkungan yang tertular virus melalui host perantara, misalnya babi

Host distribution of influenza A subtypes

HA subtypes
Man

NA subtypes
+ +
+ + + + + + + + + + + + + + + + + + + + N1 N2 N3N4N5N6N7N8 N9

+ + +

Swine + + Horse + + Seal + + Turkey + + + + + + + Duck + + + + + + + + + + + + H1 H2 H3 H4 H5 H6H7H8H9H10H11H12

H1N1, H2N2, H3N2 and H5N1, H1N2 subtypes have been isolated in humans Today, H1N1 and H3N2 and H1N2 (less) subtypes of influenza A co-circulate No subtypes exist for B or C viruses

Masalah yang akan timbul

Epizootic outbreak merupakan ancaman kesehatan masyarakat Imunitas alami infeksi H5N1 pada manusia rendah
Mengakibatkan pandemi avian influenza (H5N1) pada manusia

Penularan dari manusia ke manusia terbukti (jaringan autopsi, nasofarings, usapan tenggorok dg RT-PCR) pada 3 kasus dalam 1 keluarga di Thailand Kasus Vietnam & Thailand resistans terhadap antivirus amantadine & rimantadine (sensitif thd antivirus lain oseltamivir & zanamivir) Belum ada vaksin avian influenza (H5N1) untuk manusia

INFLUENZA

a devastating AIRBORNE infectious disease

"Flu spreads across the world and ages"

Epidemic recorded by Hippocrates

412 B.C

1977 "Russian" flu 1968 "Hong Kong" flu A (H3N2) 1957 "Asian flu A (H2N2) 1933 First human influenza virus isolated 1918 "Spanish influenza" killed 20-40 million people
A(H1N1)

1781 & 1830 Epidemics spread across Russia from Asia Middle ages Numerous episodes described
Murphy B.R., Webster R.G., Virology, IInd edition, New York, 1990, 1091-2 Ghendon Y. Introduction to pandemic influenza through history Eur Jour of Epid, 1994;10: 451-453

Epizootic outbreak

Recent research: circulating strain H5 viruses are becoming more capable of causing diseases (pathogenic) for mammals (pig, cat, tiger, leopard) than earlier H5 viruses and more widespread in birds (ducks) in the region Reassortment of avian influenza genomes is most likely to occur when these viruses demonstrate a capacity to infect multiple species, as is now the case in Asia
www.cdc.gov/flu/avian.htm

Antigenic variation : intelligence of influenza viruses

Frequent with Influenza A, less for type B, never for type C To escape population immunity Involves the external antigens : HA and NA Two types of mutations depending on whether the RNA segment variation is small or great Antigenic drift Antigenic shift

Each year, evolution can induce a different virus

Betts FR, Douglas RG, Mandell G.L., Douglas R. G., Bennett J.E., Principles and practice of infectious diseases, 3rd ed., 1990;39:1306-25

Antigenic drift minor changes in HA or NA

Betts FR, Douglas RG, Mandell G.L., Douglas R. G., Bennett J.E., Principles and practice of infectious diseases, 3rd ed., 1990;39:1306-25

Affects Influenza A and B viruses Occurs every year or every few years within an influenza subtype Mutations affecting RNA amino acids Does not result in new subtype Can result in significant epidemics
one or more amino acids change A/H3N2 Viral population

RNA point mutations

RNA segment

A/H3N2

Infected host cell

DRIFT

Historical antigenic drifts for H3N2 and H1N1 subtypes

A/Hong Kong/68
A/England/72 A/Port Chalmers/73 A/Scotland/74 A/Victoria/75 A/Texas/77 A/Bangkok/79 A/Philippines/82 A/Brazil/78 A/Shangha/87 A/England/80 A/Beijing/89 A/India/80 A/Shangdong/93 A/Chile/83 A/Johannesburg/94 A/Mississipi/85 A/Wuhan/95 A/Singapore/86

H3N2 A/USSR/77

H1N1

Assaad F, Bektirimov T, Ljungars-Esteves K. influenza- world experience. In: Stuart-Harris C, Potter CW eds. The molecular virology andepidemiology of influenza London, New York and Orlando, Academic Press 1984- 5-15

Antigenic shift emergence of a "new" virus worldwide

Affects only Influenza A virus Major and sudden genetic variations in HA and/or NA No immunity in population Results in pandemics every 10 to 40 years
Infected host cell

RNA recombination human strain RNA avian strain RNA "New" virus

Genetic reassortment hybrid strain RNA

SHIFT

Result in new subtypes: "new" HA and/or "new" NA

Influenza viruses: two ways of avoiding population immunity

antibody (ab) to former (H2) virus

H3

H3 H3'

H3' H3'' anti-H3 ab

anti-H3' ab

anti-H3 ab

PANDEMIC INTRODUCTION

INTERPANDEMIC PERIOD

Shift

Drifts

Kilbourne ED Inactivated influenza vaccines. In: Vaccines IInd edition Re 59; 1994:565-81

H9 H5
Russian Influenza

H7 H5

H1
Spanish Influenza

H3 H2
Hong Kong Influenza

H1

Asian Influenza

1998/9
1997 2003
Ellina, 2004

1918

1957 1968 1977

Regular vaccines

Pandemic vaccines

Influenza Pandemics

Avian Influenza

Seasonal occurrence of influenza

Southern hemisphere Tropical Northern hemisphere

M A

Summary of influenza activity and occurrence in different climates

Reichelderfer PS, Kendal AP, Shortridge KF, Hampson A. and al. Influenza surveillance in the pacific In: Current topics in medical virology 1988:412-38

International surveillance network

Hannoun C. Role of international networks for the surveillance of influenza. Eur Journal of Epidemiol 1994;10:459-61

Choice of vaccine strains procedure Sentinel Doctors National influenza Centers (110 national laboratories in over 80 countries) Collaborating Reference Centers for Research against influenza (London, Atlanta, Melbourne and Tokyo) World Health Organisation (WHO - Geneva)

Vaccine Manufacturers

Influenza vaccines in practice

ACIP Recommendations

Age group 6-35 mos 3-8 yrs 9-12 yrs >12 yrs

Product

Dosage No. of doses

0.25 ml 0.50 ml 0.50 ml 0.50 ml 1 or 2* 1 or 2* 1 1

Split or subunit Split or subunit Split or subunit Split, subunit or whole

*at least 1 month apart for children receiving vaccine for the first time

Whole virus vaccine is prohibited for subjects under 13 years

MMWR, ACIP 1996

Rekomendasi WHO
Vaksinasi Influenza

Vaksinasi influenza untuk kelompok risiko tinggi (populasi yang berhubungan dengan peternakan ayam) Awam perlu dilindungi terhadap virus influenza manusia Tidak melindungi virus influenza A (H5N1) Mengurangi kesempatan terjadinya viral shift (subtipe baru yang dapat menyebab kan pandemi)
http://www.who.int/csr/disease/avian_influenza/en/

Travel Warning Before any international travel

Always educate yourself and others who may be traveling with you about any disease risks in areas you plan to visit http://www.cdc.gov/flu/avian/index.htm
Be sure you are up to date with all your shots, and see your doctor or health-care provider, ideally 46 weeks before travel to get any additional shots, medications, or information you may need http://www.cdc.gov/travel/seasia.htm

Travel Warning Before any international travel

Assemble a travel health kit containing basic first aid and medical supplies. Be sure to include a thermometer and alcohol-based hand rub for hand hygiene. http://www.cdc.gov/travel/other/travelershealth-kit.htm Identify in-country health-care resources in advance of your trip Check your health insurance plan or get additional insurance that covers medical evacuation in case you become sick. www.travel.state.gov/medical.html

Travel Warning
During Travel

Avoid places such as poultry farms and bird markets where live poultry are raised or kept , and avoid handling surfaces contaminated with poultry feces or excretions. Frequent handwashing. Influenza viruses are destroyed by heat; all foods from poultry, including eggs and poultry blood, should be thoroughly cooked. If you become sick with symptoms such as a fever, difficulty breathing, cough, or any illness that requires prompt medical attention, and informing your family or friends. http://www.cdc.gov/travel/other/illness-abroad.htm.

Travel Warning
After your return
Monitor your health for 10 days If you become ill with fever, difficulty breathing, cough, or any illness during this period, consult a health-care provider

Before you visit a health-care setting, tell the provider about your symptoms, if you have had direct poultry contact, and where you traveled. This way he or she can be aware you have traveled to an area reporting avian influenza

Avian influenza- situation in Indonesia 29 July 2005

Laboratory evidence now shows that the 8-year-old girl from Tangerang, Banten Province, is a probable avian influenza A/H5 case, based on analysis of serological samples. She was the daughter of the confirmed case reported previously
Two WHO Reference Laboratories at the University of Hong Kong and the Centers for Disease Control and Prevention USA, detected high positive rising microneutralisation titres specific for H5N1 in 2 samples taken 3 days apart
www.who.int/disease/avian_influenza/html

Avian influenza- situation in Indonesia 29 July 2005

Laboratory results for the 1-year-old daughter are still pending. Genotyping of the PCR-amplified isolate from the confirmed case (father) shows high homogeneity with other H5N1 isolates from poultry in Java, and no evidence of reassortment. Extensive epidemiological and environmental studies are ongoing around this family cluster.

Avian influenza- situation in Indonesia 29 July 2005

The Minister of Agriculture stated that laboratory results detected H5-infected bird faeces in a bird cage opposite side of the road of the family's house; cloacal and throat swabs of the pet bird inside the cage were negative for H5. This is the first, and thus far, the only indication of a possible source of exposure. Other environmental sampling was negative.

Avian influenza- situation in Indonesia 29 July 2005

The Ministry of Health is continuing to monitor over 300 contacts. None of the contacts have shown any symptoms to date. Seroprevalence results are still pending.
Surveillance has been intensified in affected areas and throughout the country.

The Ministries of Health and Agriculture are monitoring the situation in close collaboration with the World Health Organization.

Rekomendasi Depkes

Kerjasama antara Depkes & Deptan Survailans (seroepidemiologi) Biosecurity Deteksi dini kasus, spesimen Perawatan kasus Imunisasi (terutama terindikasi pada orang yang berhubungan dengan peternakan) Tim SARS diaktifkan kembali

Bacaan

www.cdc.gov/flu : basic information www.cdc.gov/flu/han020302.htm : updating www.who.int/csr/disease/avian_influenza/avianfaqs/en/html: frequently asked questions www.who.int/csr/disease/influenza/vaccinerecomm endations1/en/print.html: influenza vaccine www.cdc.gov/flu/avian/outbreaks/asia.htm: influenza antiviral drugs Depkes RI 2004. Pedoman penanggulangan Avian flu