FLU BURUNG

Ida Bagus Suta Devisi Paru, Bagian/SMF Ilmu Penyakit Dalam FK UNUD/RSUP Sanglah Denpasar, 2011

WHO Confirmed Human Cases of Avian Influenza H 5 N 1 28 July 2005

Indonesia
Thailand Viet Nam Cambodia

1
17 87 4

1
12 38 4

Total

109

55

27 December 2006
Country Vietnam Indonesia
Thailand Turkey

Patient 93 74
25 12

Death 42 57
17 4

% 45.16% 77.02%
68% 33.33%

China Cambodia Irak Azerbaijan

Egypt Djibouti

21 6 3 8
18 1

14 6 2 5
10 0

66.66% 100% 66.66% 62.5%

55.5% 0%

TOTAL

261

157

60.2%

23 Agustus 2007 (WHO)

Indonesia : 105/84
Egypt : 38 / 15 Nigeria : 1 / 1 Laos : 2 / 2 China : 25 / 16 Cambodia : 7 / 7 Vietnam : 95 / 42 Djibouti : 1 / 0 Irak : 3 / 2 Thailand : 25 / 17 Turki : 12 / 4 Azerbaijan : 18 / 5

Total sejak awal : 322/195

Case Demographics
(as of August 2007)

102 cases / 81 fatal (CFR: 79%) Average age: 20 years (range 1.5 67 years) Male to female ratio 1.1 : 1

Cases:
Rural = 51 (50%) Semi-urban = 21 (21%) Urban = 30 (29%)

MASA INKUBASI
3 hari (1-7) hari. Masa penularan pada manusia

adalah 1 hari sebelum sampai 3-5 hari setelah gejala timbul pada anak dapat sampai 21 hari

Clusters
Cluster definition: two or more epi-linked cases where:
At least one is a laboratory-confirmed H5N1 AND At least another case has some laboratory evidence of H5N1 infection.

Indonesia: 10 clusters meeting this definition. Cluster size:

Median: 3 people/cluster Range: 2 - 7 people per cluster

Common Findings from Clusters

Cluster #
1

Cases

Fatal

Mode of Transmission
Unknown

H2H

Type of cluster

3 (2 confirmed, 1 suspect) 2 (2 confirmed)

Cannot be ruled out Cannot be ruled out Unlikely

Blood-related family Blood-related family Blood-related family Blood-related family Blood-related family

Fertilizer

3 (3 confirmed)

Direct (sick chicken) Exposure (sick chicken) Direct (sick chicken)

2 (2 confirmed)

Unlikely

4 (2 confirmed, 2 suspect)

Unlikely

Case Timelines
Day 24: Recovery (hospital discharge) Day 10: Death Day 5: Hospitalization

Day 2: 1st visit to a health care facility

3 - 4 days Exposure Onset Day 5 Day 10 Day 15 Day 20 Day 25

Bagaimana GEJALAnya ?

Clinical Presentation
(N Engl J Med Sept 2005; 353:1374-85.)

Fever (temperature >38C) Headache Myalgia Diarrhea Abdominal pain Vomiting Cough Sputum Sore throat Rhinorrhea Shortness of breath Pulmonary infiltrates Lymphopenia Thrombocytopenia Increased aminotransferase0

WHO (2006 )
Initial symptoms include a high fever, usually temperature higher than 38oC, and influenza-like symptoms. Diarrhoea, vomiting, abdominal pain, chest pain, and bleeding from the nose and gums have also been reported as early symptoms in some patients.

Pemeriksaan Fisik
Keadaan umum buruk Pemeriksaan saluran napas bagian bawah Auskultasi : ronki Demam Frekuensi pernapasan meningkat Gagal napas

Laboratorium

Laboratorium
Leukosit (n:4000-11000)
2100 (1200 3400) 4900 (1200 13,600) 700 (250 1100) 1453 (454 3400)
0.7 91 & 201

Limfosit (n: 1500 4000)

CD4/CD8 (n:1.4-2.0)

Platelet (n:150-400)

Leukocyte January May 2007

11%

5% Leucopenia Normal unknown 84%

Definisi Kasus / Pasien

1. Investigasi 2. Suspek 3. Probabel 4. Konfirmasi

DEFINISI KASUS
1. Kasus dalam investigasi - Seseorang yg diputuskan oleh dr setempat untuk investigasi terkait kemungkinan infeksi H5N1 - Surveilens pada kasus ILI dan pneumonia di RS serta mereka yg kontak dgn pasien AI di RS

2. Kasus suspek AI Seseorang menderita demam/panas 380C disertai 1 atau lebih gejala di bawah ini: - batuk - sakit tenggorokan - pilek - sesak napas dan diikuti satu atau lebih pajanan ini dlm 7 hari sebelum mulainya gejala a. Kontak erat (dlm jarak 1 m): merawat, berbicara atau bersentuhan dgn pasien suspek, probabel atau kasus konfirmasi b. Terpajan (mis; memegang,menyembelih, mencabuti bulu, memotong, mempersiapkan untuk konsumsi) dgn ternak ayam, unggas liar, bangkai unggas atau terhadap lingkungan yg tercemar

c. Mengkonsumsi produk unggas mentah atau tidak dimasak dgn sempurna di wilayah yg dicurigai atau dipastikan terdapat hewan atau manusia yg terinfeksi H5N1 dlm 1 bulan terahkir d. Kontak erat dgn binatang lain (selain ternak unggas atau unggas liar) misal kucing atau babi yg telah dikomfirmasi terinfeksi H5N1 e. Memegang/menangani sampel (hewan atau manusia) yg dicurigai mengandung virus H5N1 dlm suatu lab atau tempat lainnnya f. Ditemukan leukopeni dibawah nilai normal h. Ditemukan titer antibodi terhadap H5 dgn uji H1 menggunakan eritrosit kuda atau uji ELISA untuk influenza A tanpa subtipe g. Foto toraks pneumonia yg cepat memburuk pada serial foto

3. Kasus Probabel AI Kasus suspek ditambah satu atau lebih keadaan di bawah ini: a. Kenaikan titer antibodi terhadap H5 minimal 4 kali dgn uj H1menggunakan eritrosit kuda atau uji ELISA b. Hasil lab terbatas untuk influenza H5 menggunakan uji netralisasi (dikirim ke lab rujukan) Atau Seseorang yg meninggal karena penyakit saluran napas akut yg tak dapat dijelaskan penyebabnya yang secara epidemiologis berkaitan dgn aspek waktu, tempat dan pajanan terhadap suatu kasus probabel atau suatu kasus H5N1 yg terkonfirmasi

4. Kasus konfirmasi Influenza A / H5N1 Kasus suspek atau probabel dgn satu atau lebih keadaan ini : a. Isolasi virus H5N1 positif b. Hasil PCR H5N1 positif c. Peningkatan 4 kali lipat titer netralisasi untuk H5N1 dari spesimen konvalesen dibandingkan dgn spesimen akut (diambil, 7 hari setelah awitan gejala penyakit) titer antibodi netralisasi konvalesen harus pula 1/80 d. Titer antibodi mikronetralisasi 1/80 H5N1 pada spesimen serum yg diambil pada hari 14 setalah awitan disertai hasil positif uji serologi lain, misal titer H1 sel darah kuda 1/160 atau WB spesifik H5 positif

Rontgen

FOTO RONTGEN 29 JUNI`05

07 JULI`05

10 JULI`05

Mrs RY:

6 -01-07

7-01-07

11-01-07

8-01-07

Ibu R

29 Des potong ayam 1 Jan 07 : demam 2 Jan : ke klinik 1 3 Jan : ke klinik 2 4 & 5 jan : alternatif 6 Jan : RS Tangerang 8 Jan : RSP 12 Jan : Meninggal

Foto serial JG
08 05-2006 10 -05-2006 13 05-2006 14 05-2006

15 05-2006

16 05-2006

17 05-2006

18 05-2006

19 05-2006

20 05-2006

21 05-2006

22 05-2006

22 January 2005
NEJM 353 - 22 Desember 2005

24 January 2005
NEJM 353 - 22 Desember 2005

25 January 2005

NEJM 353 - 22 Desember 2005

26 January 2005

28 January 2005
NEJM 353 - 22 Desember 2005

NEJM 353 -22 Desember 2005

Why such severe disease?

Disseminated diseases? High viral replication? Immunopathology? Host susceptibility..
to infection? to severe disease?

H5N1 RNA is frequently detectable in rectal swabs and blood

H5N1 RNA in H5N1 RNA in

rectal swab
(positive/ tested)

plasma/serum
(positive/ tested)

All tested Fatal only Non-fatal only

5/7
(71%)

9 / 16
(57%)

9 / 11
(82%)

0/5
(0%)

de Jong MD et al. Nat Med 2006

VIRUS DISSEMINATION

Horimoto & Kawaoka 2005; Nat Rev Microbiol

Why such severe disease?

Disseminated diseases? High viral replication? Immunopathology? Host susceptibility..
to infection? to severe disease?

Viral load in throat during avian and human influenza

AVIAN vs HUMAN
8

FATAL H5N1 vs NON-FATAL H5N1

p = 0.003
8 7 6 5 4 3 2 0 1 FATAL 2 NON-FATAL 3

p = 0.058

log cDNA copies/ml

7 6 5 4 3 2 0 1 H5N1 6 (4-8) 2 H3N2/H1N1 2 (2-3) 3

median illnessday (range)

6 (4-7)

7 (4-8)

de Jong MD et al. Nat Med 2006

Why such severe disease?

Disseminated diseases? High viral replication? Immunopathology? Host susceptibility..
to infection? to severe disease?

Cytokine levels in plasma during avian and human influenza

IFN-
5 4 3 2 1 0 -1 -2
p = 0.029 p = 0.42

IL-6
4
3 2 1 0 -1 1 0
p < 0.0001

IL-10
3 2
p = 0.002 p = 0.85

p = 0.001

p = 0.30

log pg/ml

p < 0.0001

-1 controls 3 2 1 0 -1

H5N1

H3/H1

controls

-2

p < 0.0001

H5N1

H3/H1

H5N1

H3/H1

controls

5 4 3 2 1 0 -1 -2

p = 0.20

p = 0.054

p = 0.60

3
2 1 0 -1 died survived H5N1 -2 died survived H5N1

log pg/ml

died

survived H5N1

de Jong MD et al. Nat Med 2006

PENGOBATAN

DOSIS OSELTALMIVIR
Dewasa : 2X75 mg/hari selama 5 hari Anak : usia >1 tahun (2mg/kg BB) Berat <15 kg : 2X30 mg/hari Berat 15-23 kg : 2X45 mg/hari Berat >23-40 Kg : 2X60 mg/hari Berat > 40 Kg : 2X75 mg/hari Diberikan selama 5 hari

Beberapa Obat Baru

Combination with amantadine Peramivir & Zanamivir IV Interferon Gamma&Alfa 2 ,

Etoposide, Molleluca, Herbal, anti-cytokine

The optimal dose & duration of oseltamivir

PENGOBATAN (WHO 15 AUG 07)

Antiviral : Oseltamivir Antibiotics : empiric CAP treatment Oxygen therapy : Sa O2 > 90 % IPPV : low TV & low pressure Steroid : low dose for respiratory septic shock Antipyretic : paracetamol Infection Control : PPE, negative pressure room

Pencegahan

Oseltamivir / Tamiflu :

Dosis 1 X 75 mg selama 7 hari Diberikan kepada yang jelas-jelas kontak dengan unggas sakit atau pasien

Mass Geographical Prophylaxis :

Satu desa diisolasi Secara praktis mungkin sulit dilakukan Vaksin Flu Burung masih sedang dikembangkan Dapat diberikan vaksin untuk mencegah flu biasa

Vaksiniasi :

PENCEGAHAN

Kalau anda sedang flu :

Jangan dekat-dekat orang lain Kalau mungkin istirahat di rumah Tutup mulut dan hidung ketika batuk & bersin Cuci tangan secara teratur Bila sakit berkepanjangan segera ke dokter

Pola Hidup Sehat :

Cuci tangan secara teratur Makan bergizi, olahraga teratur, jangan merokok

From birds to human

Migratory water birds Domestic birds
Hong Kong 1997, H5N1 HK, China 1999, H9N2 Netherlands 2003, H7N7 Hong Kong 2003, H5N1

Source: WHO/WPRO Communicable Disease Surveillance and Response, WHO

Reassortment (in human)

Migratory water birds

Source: WHO/WPRO Communicable Disease Surveillance and Response, WHO

Mode of Transmission
Inconclusive 17% 21 % Direct 47% 48 % Indirect 36% 31 %

Mode of Transmission
Slaughtered sick birds, 9, 9% Inconclusive, 21, 21% H5N1-positive poultry at home, 2, 2%

Healthy poultry in environment, 7, 7%

Handled sick/dead poultry, 22, 21%

Poultry deaths in home, 12, 12% Poultry deaths in environment, 23, 22% Handled poultry faeces, 1, 1% Food handler, 4, 4%

H5N1-positive poultry in environment, 1, 1%

P E N U L A R A N

PANDEMI

THE PROSPECT OF AN INFLUENZA PANDEMIC IS REAL. IT IS IMPOSSIBLE TO PREDICT WHEN A PANDEMIC MIGHT OCCUR. BUT IT IS CERTAINLY POSSIBLE TO BE PREPARED.