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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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IR p

er 1

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0 pe

ndud

uk

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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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5

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

3

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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7

5

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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

2

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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

2

2

2

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2

22

2

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 (%)

6

16.7

83.3

83.3

28

42.9

92.9

96.4

22

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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43

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