INFEKSI VIRUS DENGUE

(IVD)
WIDODO DARMOWANDOWO

1

KOMPETENSI DOKTER INDONESIA

KOMPETENSI 3

MEMBUAT DIAGNOSIS
&
MEMBERIKAN TERAPI AWAL
&
MERUJUK BENAR

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Aedes aegypti Mosquito

EPIDEMIOLOGI 2. KLINIK DIAGNOSIS TATA LAKSANA 4 . MASALAH INFEKSI VIRUS DENGUE 1.

MASALAH EPIDEMIOLOGI 5 .

6 .

DB menyerang merata di seluruh kecamatan. Itu jika dibandingkan dengan dua bulan sebelumnya. Sedang sekitar 400 lainnya harus dirawat di rumah sakit. Tujuannya. menguras dan menutup tempat yang menjadi nyamuk bertelur.[ Minggu." ujarnya. dinkes kini menggalakkan ULV (Ultra Long Volume) atau penyemprotan cairan berbahan kimia. "Perkiraan sekitar 400 warga yang menderita DB. Jumlah persisnya sih belum tahu. 400 Dirawat TRENGGALEK . Terkhir masih merebak di Kecamatan Karangan dan Pule. 07 Maret 2010 ] Nyatakan KLB Demam Berdarah Renggut Lima Nyawa. (din/her) 7 ." ucapnya. memutus perkembangan jentik nyamuk Aedes Agepty. Karena di satu desa reda. "Sekarang kan curah hujan mulai turun. Karena itulah kini Trenggalek dinyatakan Kejadian Luar bisa (KLB) BD. Sebab. "Terpenting lagi. virus yang ditularkan nyamuk Aedes Aegepti tersebut tersebar di 14 kecamatan di Trenggalek. Seperti diungkapkan Kasi Pengedalian Penyakit Dinas Kesehatan (Dinkes) Trenggalek Suparman. Namun secara umum. eh warga desa lain banyak yang terjangkit. tren penderita DB semakin menurun. Dijelaskan dia. Hingga kini belum biasa didata secara keseluruhan. Untuk mengurai korban DB." tuturnya. peran serta masyarakat berperan aktif dalam Pemberantasan Sarang Nyamuk (PSN) dengan mengubur.Dalam kurun dua bulan terakhir deman berdarah (DB) telah merenggut lima nyawa warga Trenggalek.

00 200 20.00 350 Kabupaten dan kota terjangkit 35.00 50 0.00 0 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 0 1 2 Tahun *Data tahun 2002: Tidak lengkap 8 .00 100 10.00 300 IR per 100000 penduduk 30.00 5.00 150 15.00 250 25. 1968-2002* 40.Angka insidens (IR) dan jumlah kabupaten/kota terjangkit DBD di Indonesia.

9 .

TINGKAT ENDEMISITAS WHO 2011 10 .

COUNTRIES AND AREA AT RISK OF DENGUE TRANSMISSION WHO 2011 11 .

Transmission of Dengue Virus by Aedes aegypti Mosquito feeds / Mosquito refeeds / acquires virus transmits virus Extrinsic Intrinsic incubation incubation period period Viremia Viremia 0 5 8 12 16 20 24 28 Illness DAYS Illness Human #1 Human #2 12 .

Replication and Transmission of Dengue Virus (Part 1) 1. Virus infects white 3 blood cells and lymphatic tissues 4. Virus released and circulates in blood 13 . Virus replicates 4 in target organs 3. Virus transmitted 1 to human in mosquito saliva 2 2.

Replication and Transmission of Dengue Virus (Part 2) 5. Virus replicates in salivary glands 14 . Virus replicates in mosquito midgut 7 and other organs. infects salivary glands 5 7. Second mosquito 6 ingests virus with blood 6.

Aedes aegypti  Dengue transmitted by infected female mosquito  Primarily a daytime feeder  Lives around human habitation  Lays eggs and produces larvae preferentially in artificial containers 15 .

VIRUS DENGUE 16 .

Infect Did. J. 176:322-30 .Adapted from Figure 1 in Vaughn et al. 1997.

GENOME STRUCTURE .

MASALAH KLINIK DIAGNOSIS & TATALAKSANA 19 .

DIAGNOSIS DIAGNOSIS KLINIK DIAGNOSIS ETIOLOGI 20 .

DIAGNOSIS KLINIK KRITERIA WHO 21 .

SYOK SYOK + - DHF III &IV DHF I & II 13 .WHO 2011 CLINICAL MANIFESTATION EXPANDED DENGUE DENGUE VIRAL INFECTION UNUSUAL MANIFESTATION SEVERE BLEEDING SEVERE ORGAN INVOLVEMENT UNDIFFERENT DENGUE DENGUE FEVER FEVER HEMORHAGIC FEVER PERDARAHAN PERDARAHAN + .

GEJALA KLINIK

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WHO 2009
NAUSEA VOMITING

PANAS 2 - 7 HARI NYERI KEPALA
NYERI RETRO ORBITAL
AKUT NYERI OTOT / SENDI
LGSG TINGGI
BERMAIN - RUAM / FLUSHING

PERDARAHAN
(SPONTAN / ( RL + )

LEUKOPENIA

PROBABLE
DENGUE VIRAL
INFECTION 24

THE COURSE OF DENGUE VIRAL INFECTION WHO 2009

A F E B R I S
25

DIAGRAM PENURUNAN TEMPERATUR INFEKSI VIRUS DENGUE 40 39 INFEKSI VIRUS DENGUE 38 1 2 3 4 5 TEMP 37 36 SAAT KRITIS UNDIFERENTIATED FEVER / DENGUE FEVER / DENGUE HEMORHAGIC FEVER/UNUSUAL 1 2 3 4 5 6 7 HARI SAKIT 26 .

UNDIF FEVER /DENGUE FEVER VS DENGUE HEMORRHAGIC FEVER UNDIFF. FEVER / DENGUE FEVER KLINIS MEMBAIK NAFSU MAKAN MUNCUL BERMAIN / BACA / GAMBAR RASH KAKI DAN TANGAN BRADIKARDIA PADA SAAT PANAS TURUN / PERIODE AFEBRIS DENGUE HEMORRHAGIC FEVER KLINIS MEMBURUK PLASMA LEAKAGE GANGGUAN HEMOSTATIK 27 .

000 ) PLASMA LEAKAGE / KEBOCORAN PLASMA PCV MENINGKAT  20 % GANGGUAN SIRKULASI ASCITES EFFUSI PLEURA 28 .DENGUE HEMORHAGIC FEVER PERDARAHAN LEBIH PROMINENT THROMBOSITOPENIA (  100.

PLASMA LEAKAGE PEMBULUH DARAH PLASMA LEAKAGE 29 .

PLASMA LEAKAGE EFUSI PLEURA D E F I S I T C A I R A N PCV GANGGUAN SIRKULASI ASCITES 30 .

PCV   20 % . DENGAN GANGGUAN SIRKULASI SYOK ( DHF GRADE III ) 4. DENGAN GANGGUAN SIRKULASI SYOK BERAT ( TTU DAN TTB ) ( DHF GRADE IV ) 31 . DENGAN GANGGUAN SIRKULASI PENYEMPITAN TEKANAN NADI ( DHF GRADE III ) 3.DAMPAK INTRA VASKULER 1. TANPA GANGGUAN SIRKULASI ( DHF GRADE I & II ) 2.

ASCITES 32 .DAMPAK EKSTRA VASKULER 1. EFFUSI PLEURA 2.

WHO 2011 CLINICAL MANIFESTATION DENGUE VIRAL INFECTION EXPANDED DENGUE SY UNUSUAL MANIFESTATION SEVERE BLEDDING SEVERE ORGAN INVOLVEMENT UNDIFFERENT DENGUE DENGUE FEVER FEVER HEMORHAGIC FEVER SYOK SYOK + - DHF III IV DHF I & II 13 .

LIVER ENLARGEMENT 5. PERSISTENT VOMITING 3. LABORATORY HCT INCREASE PLATELET DECRASE 34 . PERIODE FEBRIS WHO 2009 WARNING SIGN SEVERE DVI 1. LETHARGY / RESTLESSNESS 4. ABDOMINAL PAIN / TENDERNESS 2.

DIAGNOSIS KLINIK UNDIF FEVER DENGUE FEVER DENGUE HEMORHAGIC FEVER ??? 35 .

clammy T. + or -. mild respiratory or GI T. bleeding signs + plt  unobtainable. hct  36 . bleeding signs + or plt  skin. hct  or narrow pulse pressure Grade IV As in grade III. bleeding signs + or plt NL Fever symptoms .T. usually -. enlarged liver. Blood pressure T. bleeding signs + plt  symptoms hct  Dengue Shock Syndrome Grade III As in grade I or II. + or -. +. . hypotension . mild respiratory or GI T.T.T. MODIFIKASI KLASIFIKASI IVD (WHO) WHO 1997 Syndrome Clinical Hemorrhage Laboratory Undifferentiated Fever. bleeding signs + or plt  leukopenia. T. hct NL Dengue Hemorrhagic Fever Grade I Fever. +. usually rash. mild respiratory or GI T. + or -.T. plt  symptoms hct  Grade II Fever.T. myalgia. or . headache. bleeding signs .T. hct NL Dengue Fever Fever. Cool.

INFEKSI VIRUS DENGUE EXPANDED DENGUE SYNDROME UNUSUAL CLINICAL MANIFESTATION 37 .

SYSTEM MANIFESTASI KLINIK Encephalopathy Encephalitis/aseptic meningitis Neurology Intracranial haemorhage/thrombosis Neuropathy Guilian-Bare syndrome Myelitis Hepatitis/fulminant hepatic failure Acalculus cholecystitis Gastrointestinal/hepatic Acute pancreatitis Acute parotitis Diarhea Renal Hemolytic uremic syndrome Renal failure Myocarditis Cardiac Conduction abnormalities Pericarditis Rrespiratory ARDS Pulmonary haemorhage Musculoskeletal Myositis rhabdomyolisis Lymphoreticular Spontaneous splenic rupture 38 Lymphnode infarction .

INFEKSI VIRUS DENGUE BAYI 39 .

Manifestasi klinik Jumlah ( % ) Panas 100 Pilek 30 Batuk 55 Muntah 60 Diare 40 Kejang 20 Petekiae 85 Epistaksis 5 Hematemesis 15 Melena 20 Hepatomegali 100 Effusi pleura 100 Ascites 60 Penurunan kesadaran 45 Renjatan 35 40 Trombositopeni 90 .

DIAGNOSIS ETIOLOGI 41 .

TAK MUNGKIN UTK SERVIS RUTIN 2. NS1 ANTIGEN. IgM DAN IgG. IMUNOGLOBULIN . MAHAL. KULTUR. RT – PCR. DETEKSI INFEKSI VIRUS DENGUE 1. DIAGNOSIS DINI (HARI 1 – 3 SAKIT) 42 . MAHAL TAK MUNGKIN UNTUK SERVIS RUTIN 3. LAKUKAN ≥ HARI KE 5 SAKIT 4.

IMUNOGLOBULIN ( IgM DAN IgG ) 43 .

HUBUNGAN VIREMIA – IgM – TEMPERATUR .

MUNCULNYA IgM DAN IgG PADA PASIEN YANG TERINFEKSI VIRUS DENGUE .

INTERPRETASI HASIL PEMERIKSAAN IgM dan IgG IgM IgG Interpretasi (+) (-) Infeksi primer (+) (+) Infeksi sekunder (-) (+) Tersangka infeksi sekunder (-) (-) Tidak ada infeksi .

NS1 ANTIGEN ( NS1-Ag ) 47 .

Specific Monoclonal Antibody-Based Antigen Capture Immunoassay for Detection of Circulating Nonstructural Protein NS1: Implicatons for Early Diagnosis and Serotyping of Dengue Virus Infections”. Aug.. Dengue NS1 Antigen Xu. et al (2006). Journal of Clinical Microbiology. 2872-2878 . “Serotype 1. H.

4 95. POSITIVITAS HASIL PEMERIKSAAN IgM DAN IgG DIHUBUNGKAN DENGAN HARI SAKIT Hari sakit saat pengambilan Total sampel 3 4 5 6 Jumlah kasus diperiksa 6 28 22 9 65 Positivitas Rate IgM (%) 16.3 92.5 77.3 96.5 100 95.2 Positivitas Rate IgG (%) 83.8 49.4 *= gabungan IgM & IgG 49 LIT IKA FK UNAIR / RS SOETOMO 1999 .9 86.7 42.9 54.4 100 90.8 Positivitas Rate ELISA (%) 83.

PATHOGENESIS 50 .

DENGUE VIRAL INFECTION UNDIFERENTIATED FEVER DENGUE FEVER DENGUE HEMORHAGIC FEVER DENGUE SHOCK SYNDROME UNUSUAL MANIFESTATION ? 51 .

maternal antibodies in infants  Host genetics.Risk Factors Reported for DVI  Virus strain  Pre-existing anti-dengue antibody  previous infection. Age  Higher risk in secondary infections  Higher risk in locations with two or more serotypes circulating simultaneously at high levels (hyperendemic transmission) 52 .

Hypothesis on Pathogenesis of DVI (Part 1)  Persons who have experienced a dengue infection develop serum antibodies that can neutralize the dengue virus of that same serotype ( HOMOLOG ) 53 .

Homologous Antibodies Form Non-infectious Complexes Dengue 1 virus Neutralizing antibody to Dengue 1 virus Non-neutralizing antibody Complex formed by neutralizing antibody and virus 54 .

but do not neutralize the new virus 55 . Hypothesis on Pathogenesis of DVI (Part 2)  In a subsequent infection. the pre- existing HETEROLOGOUS antibodies form complexes with the new infecting virus serotype.

Heterologous Antibodies Form Infectious Complexes Dengue 2 virus Non-neutralizing antibody to Dengue 1 virus Complex formed by non-neutralizing antibody and virus 56 .

can enter a greater proportion of cells of the mononuclear lineage. Hypothesis on Pathogenesis of DVI (Part 3)  Antibody-dependent enhancement is the process in which certain strains of dengue virus. thus increasing virus production 57 . complexed with non- neutralizing antibodies.

Heterologous Complexes Enter More Monocytes. Where Virus Replicates Dengue 2 virus Non-neutralizing antibody Complex formed by non-neutralizing antibody and Dengue 2 virus 58 .

Hypothesis on Pathogenesis of DVI (Part 4)  Infected monocytes release vasoactive mediators. resulting in increased vascular permeability and hemorrhagic manifestations that characterize DHF and DSS 59 .

60 .

infectivity  Virus serotype DHF risk is greatest for DEN-2 followed by DEN-3. DEN-4 and DEN-1 61 . Viral Risk Factors for DVI Pathogenesis  Virus strain (genotype)  Epidemic potential: viremia level.

PENATALAKSANAAN 62 .

TERAPI CAIRAN 63 .

PLASMA . PLASMA PENGGANTI . DARAH . PERIODE FEBRIS • SECARA UMUM ASSES SEBAGAI INFEKSI VIRUS DENGUE • FLUID TERAPI ORAL / INTRAVENA CAIRAN RUMATAN ( FORMULA HALIDAY SEGAR ) PERIODE AFEBRIS • DENGUE FEVER DENGAN CAIRAN RUMATAN • DENGUE HEMORHAGIC FEVER DENGAN CAIRAN RL .

ATAU TANPA PLASMA LEAKAGE INFUS DG CAIRAN RUMATAN DG FORMULA HALIDAY SEGAR : KRISTALOID SOL D5 1/2 SALINE UMUR > 3 TAHUN SOL D5 1/4 SALINE UMUR  3 TAHUN DENGAN PLASMA LEAKAGE INFUS DENGAN : KRISTALOID SOL RINGER LAKTAT / ASETAT KOLOID PLASMA. PLASMA PENGGANTI DARAH ( WHOLE BLOOD ) 65 .

TANPA PLASMA LEAKAGE 66 .

TERAPI CAIRAN RUMATAN formula Halliday .Segar Berat Badan ( Kg ) Cairan Rumatan ( Volume )/ 24 jam 10 100 CC / Kg BB 10 – 20 1000 CC + 50 CC / Kg BB diatas 10 Kg > 20 1500 CC + 20 CC / Kg BB diatas 20 Kg Setiap derajat C kenaikan temperatur. cairan dinaikkan 12 % dari kebutuhan rumatan 67 .

KALAU ADA PLASMA LEAKAGE 68 .

parenteral treatment is essential. In most DSS cases isotonic crystaloid solutions are as effective as colloid solutions. but in children with DSS . Wills B Adv Exp Med Biol 2008.Although no specific treatment is available at present. Very careful titration of fluid therapy is necessary combined with frequent reassessment for signs of worsening shock or the Development of fluid overload. but the question wether early intervention with colloid solutions improve outcome in more advance shock requires further investigation Moxon C.144 69 . with good supportive care. In patients without signs of shock. fluid replacement can be attempted orally. 609: 131 . mortality for children with DHFcan be reduced to well below 1 %.

T/N STABIL PCV ↑. T/N STABIL PCV ↑ DIURESIS (+) TRANSFUSI KOLOID / WHOLE BLOOD STOP PLASMA MEMBAIK 70 . RL 7 cc/kgBB/1 JAM PCV. N ↑. VS MEMBAIK TETAP BURUK/RESPON (-) PCV ↓. PP ≤20 mmHg DIURESIS (+) DIURESIS (-) RL 5 cc/kgBB/1 JAM MEMBAIK RL 10 cc/kgBB/1 JAM DBD DERAJAT I / II TETAP BURUK/RESPON (-) RL 3 cc/kgBB/1 JAM RL 15 cc/kgBB/1 JAM MEMBAIK TETAP BURUK/RESPON (-) 24-48 JAM PCV ↓ PCV ↓.

TERAPI CAIRAN DHF GRADE III & GRADE IV 71 .

KRISTALOID 20 cc/kgBB CEPAT MEMBAIK TETAP BURUK / RESPON (-) Protokol tata laksana KRISTALOID KOLOID DBD derajat III/IV dengan 10 cc/kgBB/1 JAM 20 cc/kgBB CEPAT perbaikan klinis (PROTAP RUMATAN) MEMBAIK MEMBAIK TETAP BURUK / RESPON (-) KOLOID KRISTALOID KRISTALOID 10 cc/kgBB/1 JAM 7 cc/kgBB/1 JAM 10 cc/kgBB/1 JAM KRISTALOID KRISTALOID MEMBAIK TETAP BURUK/ 5 cc/kgBB/1 JAM 7 cc/kgBB/1 JAM RESPON (-) KRISTALOID KRISTALOID KRISTALOID PERDARAHAN PERDARAHAN 3 cc/kgBB/1 JAM 5 cc/kgBB/1 JAM 10 cc/kgBB/1 JAM (+) (-) KRISTALOID KRISTALOID TRANSFUSI INOTROPIK 3 cc/kgBB/1 JAM 7 cc/kgBB/1 JAM WHOLE BLOOD KRISTALOID 5 cc/kgBB/1 JAM KRISTALOID 72 3 cc/kgBB/1 JAM .

KRISTALOID 20 cc/kgBB CEPAT MEMBAIK TETAP BURUK / RESPON (-) Protokol tata laksana DBD derajat III/IV dengan KRISTALOID KOLOID perburukan klinis 10 cc/kgBB/1 JAM 20 cc/kgBB CEPAT (PROTAP RESUSITASI LANJUTAN) MEMBAIK MEMBAIK TETAP BURUK / RESPON (-) KOLOID KRISTALOID KRISTALOID 10 cc/kgBB/1 JAM 7 cc/kgBB/1 JAM 10 cc/kgBB/1 JAM KRISTALOID KRISTALOID MEMBAIK TETAP BURUK/ 5 cc/kgBB/1 JAM 7 cc/kgBB/1 JAM RESPON (-) KRISTALOID KRISTALOID KRISTALOID PERDARAHAN (+) PERDARAHAN (-) 3 cc/kgBB/1 JAM 5 cc/kgBB/1 JAM 10 cc/kgBB/1 JAM KRISTALOID KRISTALOID INOTROPIK TRANSFUSI 3 cc/kgBB/1 JAM 7 cc/kgBB/1 JAM WHOLE BLOOD KRISTALOID 5 cc/kgBB/1 JAM KRISTALOID 73 3 cc/kgBB/1 JAM .

SETIAP PROVIDER KESEHATAN HARUS DAPAT MENGENALI MENDIAGNOSIS TATALAKSANA INFEKSI VIRUS DENGUE ANGKA KEMATIAN DAPAT DITEKAN SERENDAH MUNGKIN 74 .

TERIMA KASIH 75 .