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DIAGNOSIS DAN PENATALAKSANAAN
INFEKSI VIRUS DENGUE
PENDAHULUAN
INDONESIA ENDEMIS INFEKSI VIRUS DENGUE ( IVD )TIADA HARI TANPA KASUS IVD
SETIAP PROVIDER KESEHATAN HARUS DAPATMENGENALI IVDMENDIAGNOSIS IVDMELAKUKAN TATALAKSANA KASUS IVD
ANGKA KESAKITAN & KEMATIAN KASUS IVDDAPAT DITEKAN SERENDAH MUNGKIN
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Kabupaten dan kota terjangkit
T a h u n
Angka insidens (IR) dan jumlah kabupaten/kota terjagkit DBD di Indonesia, 1968-2002*
*Data tahun 2002: Tidak lengkap
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Transmission of Dengue Virusby Aedes aegypti
Viremia Viremia
Extrinsic incubation
period
DAYS0 5 8 12 16 20 24 28
Human #1 Human #2
Illness
Mosquito feeds /acquires virus
Mosquito refeeds /transmits virus
Intrinsicincubation
period
Illness
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Replication and Transmissionof Dengue Virus (Part 1)
1. Virus transmitted to human in mosquito saliva
2. Virus replicates in target organs
3. Virus infects white blood cells and lymphatic tissues
4. Virus released and circulates in blood
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4
1
2
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Replication and Transmissionof Dengue Virus (Part 2)
5. Second mosquito ingests virus with blood
6. Virus replicates in mosquito midgut and other organs, infects salivary glands
7. Virus replicates in salivary glands
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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
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DIAGNOSIS
KLINISHARUS DIKUASAI OLEH HEALTH PROVIDERKRITERIA WHO / MODIFIED
ETILOGIKOTABESAR PUNYA FASILITAS LABORATORIUM
SEROLOGIPCRVIROLOGI
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SYOK -
KLINIS INFEKSI VIRUS DENGUE
ASIMPTOMATIS S I M P T O M A T I S
UNDIFFERENTFEVER
DENGUEFEVER
DENGUEHEMORHAGICFEVER
PERDARAHAN+
PERDARAHAN-
SYOK +
11DENGUE FEVER
PANAS 2 - 7 HARI
SAKIT KEPALANYERI RETRO ORBITALMYALGIA / ARTHRALGIARUAMPERDARAHANLEUKOPENIA
AKUTLGSG TINGGIBERMAIN -
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DENGUE HEMORHAGIC FEVER
PERDARAHAN LEBIH PROMINENT
THROMBOSITOPENIA ( 100.000 )
PLASMA LEAKAGE
PCV MENINGKAT 20 %
EFFUSI PLEURA
ASCITES
GANGGUAN SIRKULASI
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DENGUE SHOCK SYNDROME
DENGUE HEMORHAGIC FEVER
GANGGUAN SIRKULASI
PRESYOK
SYOK
TTU DAN TTB
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PLASMA LEAKAGE
P E M B U L U H D A R A H
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1. PCV 20 % , TANPA GANGGUAN SIRKULASI
2. DENGAN GANGGUAN SIRKULASI PENYEMPITAN TEKANAN NADI
3. DENGAN GANGGUAN SIRKULASI SYOK
4. DENGAN GANGGUAN SIRKULASI SYOK BERAT ( TTU DAN TTB )
DAMPAK INTRA VASKULER
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DAMPAK EKSTRA VASKULER
1. EFFUSI PLEURA
2. ASCITES
Syndrome Clinical Hemorrhage Laboratory
Undifferentiated Fever
Fever, mild respiratory or GI symptoms
T.T. + or -; bleeding signs + or -
plt NLhct NL
Dengue Fever Fever, headache, myalgia, leukopenia, usually rash.
T.T. + or -; bleeding signs + or -
plt or NLhct NL
Dengue Hemorrhagic Fever
Grade I Fever, mild respiratory or GI symptoms
T.T. +; bleeding signs - plt hct
Grade II Fever, mild respiratory or GI symptoms
T.T. +; bleeding signs + plt hct
Dengue Shock Syndrome
Grade III As in grade I or II. Cool, clammy skin, enlarged liver, hypotension or narrow pulse pressure
T.T. + or -; bleeding signs + or -
plt hct
Grade IV As in grade III. Blood pressure unobtainable.
T.T. usually -; bleeding signs + or -
plt hct
MODIFIKASI KLASIFIKASI IVD (WHO)
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DIAGNOSIS LABORATORIS
1.ISOLASI & IDENTIFIKASI VIRUS
2.DETEKSI RNA VIRUS
3.DETEKSI ANTIBODI SPESIFIK
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DETEKSI ANTIBODI
1.HEMAGLUTINASI INHIBISI (HI test)
2.KOMPLEMEN FIKSASI (CF test)
3.NEUTRALISASI (NT test)
4.IgM Elisa
5.IgG Elisa
RESPONSEANTIBODI
INTERVAL
S1 dan S2TITERKONVALESEN
INTERPRETASI
Kenaikan 4 x
Kenaikan 4 x
Kenaikan 4 x
Kenaikan -
Kenaikan -
Kenaikan -
-
³ 7 hari
Berapa saja
£ 7 hari
Berapa saja
³ 7 hari
£ 7 hari
Hanya 1 serum
£ 1 / 1280
³ 1 / 2560
£ 1 / 1280
³ 1 / 2560
£ 1 / 1280
£ 1 / 1280
1 / 1280
Infeksi primer
Infeksi sekunder
Infeksi primer / sekunder
Diduga infeksi sekunder
Bukan infeksi dengue
Tidak dapat dinilai
Tidak dapat dinilai
INTERPRETASI UJI HEMAGLUTINASI INHIBISI, WHO ( 1986 )
Keterangan : S1 dan S2 adalah Serum pengambilan pertama dan pengambilan kedua
Interpretasi ELISA Dengue (Panbio)
Rasio Hasil Interpretasi
IgM < 0,9 negatif Tidak ada infeksi dengue
IgM 0,9-1,1 equivocal Perlu tes ulang
IgM >1,1 positif Dugaan infeksi baru dengue
IgG < 1,8 negatif Tidak ada infeksi sekunder
IgG 1,8-2,2 equivocal Perlu tes ulang
IgG > 2,2 positif Dugaan infeksi sekunder akut
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Risk Factors Reported for DHF• Virus strain• Pre-existing anti-dengue antibody
• previous infection, maternal antibodies in infants
• Host genetics, Age• Higher risk in secondary infections• Higher risk in locations with two or more
serotypes circulating simultaneously at high levels (hyperendemic transmission)
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Increased Probability of DHF
Hyperendemicity
Increased circulationof viruses
Increased probabilityof secondary infection
Increased probability ofoccurrence of virulent strains
Increased probability ofimmune enhancement
Increased probability of DHFGubler & Trent, 1994
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Hypothesis on Pathogenesisof DHF (Part 1)• Persons who have experienced a
dengue infection develop serum antibodies that can neutralize the dengue virus of that same (homologous) serotype
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Neutralizing antibody to Dengue 1 virus
1
1
Dengue 1 virus 1
Homologous Antibodies Form Non-infectious Complexes
Non-neutralizing antibody
1
1 Complex formed by neutralizing antibody and virus
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Hypothesis on Pathogenesis
of DHF (Part 2)
• In a subsequent infection, the pre-existing heterologous antibodies form complexes with the new infecting virus serotype, but do not neutralize the new virus
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Non-neutralizing antibody to Dengue 1 virus
Dengue 2 virus
2 2
2
2
2
Heterologous Antibodies Form Infectious Complexes
Complex formed by non-neutralizing antibody and virus
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Hypothesis on Pathogenesisof DHF (Part 3)
• Antibody-dependent enhancement is the process in which certain strains of dengue virus, complexed with non-neutralizing antibodies, can enter a greater proportion of cells of the mononuclear lineage, thus increasing virus production
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2
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2
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Heterologous Complexes Enter More Monocytes, Where Virus Replicates
Non-neutralizing antibody
Dengue 2 virus 2
Complex formed by non-neutralizing antibody and Dengue 2 virus
2
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Hypothesis on Pathogenesisof DHF (Part 4)
• Infected monocytes release vasoactive mediators, resulting in increased vascular permeability and hemorrhagic manifestations that characterize DHF and DSS
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Viral Risk Factorsfor DHF Pathogenesis
• Virus strain (genotype)• Epidemic potential: viremia level,
infectivity• Virus serotype
• DHF risk is greatest for DEN-2, followed by DEN-3, DEN-4 and DEN-1
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Patogenesis Demam Berdarah Dengue dan Sindroma Syok Dengue
TM
CD8 Mo
TM
CD4
DV
TM
CD4
TM
CD8
Mo
Mo
MoDV
DV
DV
DVDV
Endothelialcells
Plasmaleakage
Shock
Hemostaticsystem
Hemorrhage
IL-2other
lymphokines
Cytokines(eg. IL-1, TNF)
ChemicalMediators(eg. PAF)
ComplementActivation
T cell ActivationIFN
Lysis
FcRClass I Class II
Dengue virusinfection of
human monocytes
Dengue Virus-Antibody Complex
Antibody-dependent enhancement
TATA LAKSANA
PERIODE FEBRISSECARA UMUM ASSES SEBAGAI DENGUE FEVERFLUID TERAPI ORAL / INTRAVENA CAIRAN RUMATANHALIDAY SEGAR FORMULA
PERIODE AFEBRIS DENGUE FEVER DENGAN CAIRAN RUMATAN DENGUE HEMORHAGIC FEVER DENGAN CAIRAN RL , PLASMA , PLASMA PENGGANTI , DARAH
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TANPA PLASMA LEAKAGE INFUS DG CAIRAN RUMATAN DGFORMULA HALIDAY SEGAR :SOL D5 1/2 SALINE UMUR > 3 TAHUNSOL D5 1/4 SALINE UMUR 3 TAHUN
DENGAN PLASMA LEAKAGE INFUS DENGAN :SOL RINGER LAKTATPLASMAPLASMA PENGGANTIDARAH ( WHOLE BLOOD )
ATAU
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Berat Badan ( Kg )10 10 – 20> 20
Cairan Rumatan ( Volume )/ 24 jam100 CC / Kg BB1000 CC + 50 CC / Kg BB diatas 10 Kg1500 CC + 20 CC / Kg BB diatas 20 Kg
Setiap derajat C kenaikan temperatur, cairan dinaikkan 12 % dari kebutuhan rumatan
formula Halliday - Segar
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INFUS RL 7 ml/kg BB/jam
Follow Up PCV
Tanda Vital
MAJU BURUK PCV PCV
Tensi / Nadi stabil Nadi /p.p 20 mm Hg DIURESIS + DIURESIS –
INFUS MAJU INFUS
RL 5 ml/kg BB/jam RL 10 ml/kg BB/jam
INFUS INFUS RL 3 ml/kg BB/jam RL 15 ml/kg BB/jam
TETAP MAJU BURUK 24-48 JAM PCV PCV PCV, Tanda Vital Stabil INFUS INFUS DIURESIS BAGUS Colloid / Plasma Transfusi darah STOP MAJU
TERAPI CAIRAN DHF GRADE I/II
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INFUS RL 10-20 ml/kg BB
Grade III Grade IV 1 jam BOLUS
Follow Up Tanda Vital
PCV
MAJU BURUK PCV PCV PCV Tensi / Nadi stabil Tensi / nadi buruk Tensi / nadi buruk DIURESIS + DIURESIS - DIURESIS – INFUS INFUS INFUS
RL 5 ml/kg BB/jam Transfusi darah Colloid / plasma 10-20 ml/kg BB/jam
dst MAJU BURUK (Diagram 1) Ingat : Pasang CVP Urine Catheter Obat Inotropik Catatan :
Dalam penatalaksanaan DHF grade III / IV, jangan lupa melakukan koreksi gas darah dan
elektrolit.
TERAPI CAIRAN DHF GRADE III / IV
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plus
3MLarvasiding
Ikanisasi Obat Nyamuk SemprotObat Nyamuk Gosok
PencahayaanVentilasi
Kasa
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Dengue Vaccine?
• No licensed vaccine at present• Effective vaccine must be tetravalent• Field testing of an attenuated
tetravalent vaccine currently underway• Effective, safe and affordable vaccine
will not be available in the immediate future
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Hari sakit saat pengambilan sampel
Total
3 4 5 6
Jumlah kasus diperiksa
Positivitas Rate IgM (%)
Positivitas Rate IgG (%)
Positivitas Rate ELISA (%)
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16.7
83.3
83.3
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42.9
92.9
96.4
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54.5
86.4
95.5
9
77.8
100
100
65
49.2
90.8
95.4
*= gabungan IgM & IgG
POSITIVITAS HASIL PEMERIKSAAN IgM DAN IgG DIHUBUNGKAN DENGAN HARI SAKIT
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