FARIDA OESMAN DEPARTMENT OF CLINICAL PATHOLOGY FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA

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1 FARIDA OESMAN DEPARTMENT OF CLINICAL PATHOLOGY FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA

2 TYPHOID FEVER DENGUE FEVER MALARIA LEPTOSPIROSIS

3 NOT SPECIFIC DEFINITIVE HOST RESPONSE HEMATOLOGY ACUTE PHASE PROTEIN SEROLOGY SPECIFIC ANTIBODY ANTIGEN DETECTION MICRO- ORGANISM CULTURE PCR COMPLICATION SCREENING CONFIRMED DIAGNOSIS

6 GRAM NEGATIVE BACTERIA >1700 SEROTYPES 100 ARE PATHOGENIC TO HUMAN MOST COMMON IS S.typhi

8 SERO SERO O H Ag H Ag GROUP TYPE ANTIGEN PHASE 1 PHASE 2 A S paratyphi A 1, 2,12 a 1, 5 B C D S paratyphi B S paratyphi C S typhi 1, 4, 5, 12 6, 7 9, 12 b c d 1, 2 1, 5 -

9 SECONDARY BACTEREMIA PRIMARY BACTEREMIA

10 COMPLETE BLOOD COUNT HEMOGLOBIN NORMAL, ANEMIA LEUCOPENIA, LEUCOCYTOSIS THROMBOCYTE NORMAL, THROMBOCYTOPENIA BLOOD FILM NEUTROFILIA

11 GOLD STANDARD IN BLOOD, BM, URINE, STOOL POSITIVE CONFIRMED DIAGNOSIS NEGATIVE NOT EXCLUDE DIAGNOSIS LOW SENSITIVITY TIME SPECIMEN COLLECTION PRESENCE OF ANTIBIOTIC

12 LOW SPECIFICITY CRUDE ANTIGEN WIDAL HIGH SPECIFICITY PURIFIED ANTIGEN TYPHI DOT (OMP) ELISA (LPS) TUBEX (LPS O9)

13 SOMATIC (O) FLAGELLA (H) APPEAR DAY 6-8 APPEAR DAY DISAPPEAR WITHIN 6-12 MONTHS PERSIST SEVERAL YEARS

14 POSITIVE TYPHOID/PARATYPHOID INFECTION PREVIOUS IMMUNIZATION REPEATED EXPOSURE TO S.typhi IN ENDEMIC AREA CROSS REACTION WITH ENTEROBACTERIACEA ANAMNESTIC REACTION

15 NEGATIVE NOT EXCLUDE TYPHOID FEVER EARLY ANTIBIOTIC TREATMENT IMMUNOSUPRESSIVE DRUG DEFECT OF ANTIBODY SYNTHESIS MALNUTRITION IMMUNODEFICIENCY MALIGNANCY EARLY SPECIMEN COLLECTION

16 SINGLE SERA PAIRED SERA ENDEMIC AREA DAYS ESTABLISHED TITER IN POPULATION INCREASED TITER 2-4 TIMES

17 TO LPS T INDEPENDENT TO LPS-PEPTIDE T DEPENDENT

18 SENSITIVE IMMUNODOMINANT & ROBUST IMMUNOGENIC IN INFANT EARLY DETECTION POTENT B CELL MITOGEN T INDEPENDENT SPECIFIC ONLY IN GROUP D SALMONELLA

19 % positive BLOOD AGLUTININ STOOL URINE Week

22 GENUS FLAVIVIRUS 4 SEROTYPE DENV 1-4

ACTIVATION INCREASED PERMEABILITY CAPILER PLATELET AGGREGATION

24 DENGUE VIRUS SECONDARY INFECTION HETEROLOG DENGUE VIRUS IMMUNE COMPLEXES HETEROLOG DENGUE VIRUS NON NUTRALIZING Ab COMPLEMENT ACTIVATION INCREASED PERMEABILITY CAPILER PLATELET AGGREGATION ENDOTHELIAL CELL DAMAGED PLASMA LEAKAGE DSS DECREASED PLATELET COAGULATION ACTIVATION DIC

27 COMPLETE BLOOD COUNT HEMOGLOBIN NORMAL, ANEMIA LEUCOPENIA TO MILD LEUCOCYTOSIS THROMBOCYTOPENIA INCREASED HEMATOCRIT 20% BLOOD FILM NEUTROPENIA ATYPICAL LYMPHOCYTE COAGULATION POSITIVE RUMPELL LEEDE, D-DIMER PROLONGED BT, PT & APTT DECREASES FIBRINOGEN

28 PRIMARY INF SECONDARY INF

29 POSITIVE PRIMARY/SECONDARY INFECTION CROSS REACTION WITH OTHER FLAVIVIRUS NEGATIVE NO INFECTION EARLY INFECTION IMMUNOCOMPROMISED

30 IgG(-)IgM(+) IgG(+)IgM(+) IgG(+)IgM(-) ACUTE PRIMARY INFECTION ACUTE PRIMARY INFECTION ACUTE SECONDARY INFECTION SECONDARY INFECTION CROSS REACTION WITH OTHER FLAVIVIRUS

31 POSITIVE PRIMARY INFECTION SECONDARY INFECTION NEGATIVE NO INFECTION LATE INFECTION (>5 DAYS)

34 SUSPECT DENGUE INF UNKNOWN 5 DAYS NS1 Ag DAYS AFTER ONSET OF FEVER IgM & IgG > 5 DAYS POS CONFIRMED EARLY ACUTE INF NEG IgM POS DENGUE INF OTHER FLAVI- VIRUS INF NEG DENGUE INF UNLIKELY IMMUNOCOMPROMISED POS PRESUMABLY EARLY ACUTE INF NEG EARLY ACUTE INF IS UNLIKELY

38 COMPLETE BLOOD COUNT HEMOLYTIC ANEMIA LEUCOPENIA THROMBOCYTOPENIA BLOOD FILM RELATIVE MONOCYTOSIS CHEMISTRY MODERATE INCREASED AST, ALT

39 LOW SENSITIVITY MICROSCOPIC PARASITEMIA <0.01% SEROLOGY ANTIGEN DETECTION POLIMERASE CHAIN REACTION

40 Indeks Spesimen vs Angka Postip S P ECIMEN P OSITIV E S P ECIMEN P OSITIV E

43 HISTIDINE RICH PROTEIN 2 (HRP 2) PRODUCE BY TROPHOZOIT & GAMETOCYTE OF P. FALCIPARUM DETECT ON DAY 7 STILL PRESENT ON DAY 28 (27% CASES) PARASITE LACTATE DEHIDROGENASE (pldh) PRODUCE BY PARASITE (ASEXUAL & SEXUAL PHASE) OF P. VIVAX AND PAN MALARIA (VIVAX, FALCIPARUM, MALARIAE, OVALE)

44 P. FALCIPARUM HISTIDINE RICH PROTEIN2 (HRP2) P. VIVAX P. VIVAX SPECIFIC pldh PLASMODIUM LAIN PAN MALARIA SPECIFIC pldh

46 L. INTERROGANS RAT, MICE PRIMARY HOST DOG, DEER, RABIT, COW, SHEEP SECONDARY HOST

47 FEVER RENAL IMPAIRMENT JAUNDICE PRESENCE OF LEPTOSPIRA PRESENCE OF ANTIBODY

48 COMPLETE BLOOD COUNT LEUCOCYTOSIS BLOOD FILM NEUTROPHILA CHEMISTRY INCREASED UREUM, CREATININE INCREASED BILIRUBIN, AST, ALT

49 DARK FIELD MICROSCOPE DIRECT IFA CULTURE POLIMERASE CHAIN REACTION

50 REFERENCE METHOD MAT ELISA CRUDE ANTIGEN LIVE LEPTOSPIRA PURIFIED ANTIGEN Ig TOTAL PAIRED SERA IgG & IgM SINGLE SERA

51 SINGLE SERA PAIRED SERA NEGATIVE EARLY INFECTION SEROCONVERSION INCREASED TITER 2-4 X HIGH TITER CURRENT INFECTION CURENT INFECTION

52 SUGGESTIVE OF LEPTOSPIROSIS < 7 DAYS 7 DAYS MAT BLOOD CULTURE PCR NEG ELISA POS POS NEG REPEAT POS NEG REPEAT >3 DAYS SEROCON VERSION CONFIRMED DIAGNOSIS BLOOD CULTURE NOT EXCLUDE DIAGNOSIS HIGH TITER LOW TITER REPEAT RISING TITER

53 BACTERIA /VIRAL/PARASITE DETECTION CONFIRMED INFECTION ANTIBODY DETECTION CAREFULL INTERPRETATION DIAGNOSIS BASED ON CLINICAL & LABORATORY FINDING

4/16/2013 FARIDA OESMAN DEPARTMENT OF CLINICAL PATHOLOGY FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA TYPHOID FEVER DENGUE FEVER MALARIA LEPTOSPIROSIS

4/16/2013 FARIDA OESMAN DEPARTMENT OF CLINICAL PATHOLOGY FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA TYPHOID FEVER DENGUE FEVER MALARIA LEPTOSPIROSIS FARIDA OESMAN DEPARTMENT OF CLINICAL PATHOLOGY FACULTY OF MEDICINE, UNIVERSITY OF INDONESIA TYPHOID FEVER DENGUE FEVER MALARIA LEPTOSPIROSIS NOT SPECIFIC DEFINITIVE HOST RESPONSE HEMATOLOGY ACUTE PHASE