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Name : Lie Khie Chen Birth : Jakarta Graduates
MD : FKUI 1994Internist : FKUI 2003Consultant : FKUI 2006
Occupation Internal Medicine DepartmentTropical Medicine and Infectious Diseases Division
Interest SepsisAntimicrobial TreatmentAntimicrobial ResistanceFungal InfectionHIV and opportunistic infections
Curriculum Vitae
Update on Pathogenesis and Update on Pathogenesis and Management of Typhoid fever Management of Typhoid fever
Khie Chen
Division of Tropical Medicine and Infectious DiseasesDepartement of Internal Medicine
Medical Faculty Univesity of IndonesiaDr. Cipto Mangunkusumo General Hospital
Jakarta
Typhoid FeverTyphoid Fever
l Typhoid fever is an acute systemic infection caused by Salmonella enterica serotype typhi or paratyphi which is also known as Salmonella typhi
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Epidemiologic Distribution of Typhoid Fever
Some example of commonlyOccuring Salmonella serotypes and groups
Group SerotypeA S. paratyphi AB S. paratyphi B
S. stanleyS. saintpaulS. agonaS. typhimurium
C S. paratyphi CS. choleraesuisS. virchowS. thompson
D S. typhiS. enteritidisS. dublinS. gallinarium
PathogenesisContaminated food of drinks Gastric acid
Bowel lumen
Mucosal defence
ColonizationAdhesion to mucose
Invation to Peyer Patch
Regional Lymphadenitis Thoracic duct
1st systemic bacteriemia
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PathogenesisInfection of RE system
Liver, Spleen2nd Bacteriemia
Gall bladder Lung, MyocardKidney, etc
Reinfection in bowel mucose Systemic manifestation
Hyperplasia Peyer Patch Inflammation, erosion
Feces
Bleeding, perforation
First : ATTACHMENTSecond : MUCOSAL INVASION
Jade 2008
Salmonella PathogenesisSalmonella Pathogenesis
AttachmentAttachment
l Type 1 Fimbriaefim
l Long Polar Fimbriaelpf
l Plasmid-Encoded Fimbriaepef
l Thin Aggregative Fimbriaeagf
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fim, lpf, pef genesfim, lpf, pef genes
l Type 1 fimbriae specifically bind -D-mannose receptors on various eucaryotic cell types
l LP fimbriae mediate adhesion to the cells of the Peyer's patches of the small intestine in a mouse model of infection
l S. typhimurium, S. enteritidis, S. choleraesuis, and S. paratyphi C, contain pef sequences . PE fimbriae can adhere to histological sections of murine small intestine more effectively
Jade 2008
Agf geneAgf genel Thin aggregative fimbriae (3 to
4 nm wide) (curli) were identified and purified from S. enteritidis
• Curli-producing bacteria tend to autoaggregate, a phenomenon which has been suggested to enhance the survival of salmonellae facing hostile barriers such as stomach acid or other biocides they may encounter
Mucosal Mucosal InvationInvationl The mechanisms of Salmonella
invasion, that is, the stimulation of nonphagocytic cells to internalize bacteria, are clearly complex.
l Salmonella pathogenicity island 1 (SPI1), is believed to have been acquired by horizontal transfer from another pathogenic bacterial species during its evolution
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Clinical Picture
• Fever• Headache• malaise• myalgia• nausea• abdominal dis-
comfort• constipation• diarrhea• dry cough• epistaxis
• confusion, delirium• psychosis• convulsion • coated tongue• bradicardia relative• tender abdomen• hepatomegaly• splenomegaly• rose spots• erythmatous muco
papular lesion
0 5 7 14
Fever pattern in Typhoid Fever
High feverHeadacheAbdominal discomfortDiarrhea or constipationRelative bradicardia
LeucopeniaMild thrombocytopeniaRelative neutrofiliaAneosinofilia
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Fever pattern : typhoid fever
Typhus Inversus PatternLowest early in the morning Highest about 5.30 to 6.30 pmCan be found in typhoid fever
tuberculosisPulse Temperature dissosiation
In normal temperature 37oC (99oF) pulse 80 beats/minIncreased 9 beats/min every 1oFRelative bradicardia can be found in
enteric/typhoid fevermycoplasma, malaria falciparum
Devervescence : 3-7 days after treatmentusually on 2nd or 3rd weeks
Female 31 yo, fever since 2 weeks agoHb 9.3 L 1600 Ht 28 Tr 107.000Diff -/1/4/62/31/2 ESR 60 CRP 68Widal ty O 1/160 H >1/640 ty B H 1/160Treatment : Ceftriaxone 3g/dayGall culture - PCR S typhi +
Clinical Presentation of Typhoid FeverClinical Presentation of Typhoid Fever
Headache 59 94.9Epigastric pain 57 94.7Nausea 108 90.7Anorexia 41 90.2Fever (>37.2) 118 89.8Muscular pain 14 78.6Rigor 37 78.4Coated tongue 84 41.8Vomiting 104 57.7Cough 91 46.2Relative bradicardia 117 34.2Diarrhea 109 32.1Constipation 109 33.9Hepatomegaly 117 12.3Splenomegaly 117 0.8
Clinical sign and symptom sum (n=119) %
Pohan HT, Indones J Int Med 2004;36(2)
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Clinical scoring scale for typhoid Clinical scoring scale for typhoid feverfever
Fever < 1 wk 1Headache 1 Weakness 1Nausea 1 Anorexia 1Abdominal pain 1Vomiting 1Disturb GI motility 1
Insomnia 1Hepatomegaly 1Spelenomegaly 1Fever > 1 wk 2Relative bradicardia 2Typhoid tongue 2Melena stools 2Impaired consciousness 2
Clinical typhoid fever if score > 13 of maximal 20
Adapted from : Nelwan RHH. Conns Current Traatment 2003
Laboratory Examination
Peripheral blood count leucopenia, leucocytosisnormal WBC countmild anemia thrombocytopeniaincreased ESR
Serum transaminase increased ALT and ASTAlbumin hypoalbuminemiaSerology Increased titer of
aglutinin O, H and ViBlood culture Salmonela typhiPCR positive
Seroprevalensi Uji Widal pada Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Komunitas Perkotaan di DKI Jakarta
Distribusi Seroprevalensi Uji Widal
55.7
6
71
6
78
64.3
78
23.6
0102030405060708090
S. typhi S. pth A S. pth B S. pth C
persentase Widal OWidal H
Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006
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Seroprevalensi Uji Widal pada Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Komunitas Perkotaan di DKI Jakarta
Distribusi Titer Widal S. Thypi O dan H (n : 300)
8.7
26
6
1 0 0 0.3
11.7
1715
5.7
1 1
13.7 14.312.3
0
5
10
15
20
25
30
20 40 80 160 320 640 1280 >1280
pers
enta
se
Widal S. Thypi OWidal S. Thypi H
Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006
Seroprevalensi Uji Widal pada Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Komunitas Perkotaan di DKI Jakarta
Distribusi Titer Widal S. parathypi A
5
10 0 0 0 0 0
21
4
17
7.79.3
4.3
0.7 0.30
5
10
15
20
25
20 40 80 160 320 640 1280 >1280
pers
enta
se
Widal S. parathypi A OWidal S. parathypi A H
Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006
Seroprevalensi Uji Widal pada Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI Jakarta Komunitas Perkotaan di DKI Jakarta
20
22.3
18.3
9
1.30 0 0
20.7
13
21.3
10 10.3
20.7
00
5
10
15
20
25
20 40 80 160 320 640 1280 >1280
Widal S. parathypi B OWidal S. parathypi B H
Distribusi Titer Widal S. parathypi B
Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006
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Seroprevalensi Uji Widal pada Seroprevalensi Uji Widal pada Komunitas Perkotaan di DKI JakartaKomunitas Perkotaan di DKI Jakarta
20 40 80 160 320 640 1280 >1280
3.3
7.7
1
4.7
1
6
0.7
2.3
0
5
00.3
00.3
0 00
1
2
3
4
5
6
7
8
pers
enta
se
Distribusi sebaran serologi Widal S. parathypi C (n : 300)
Widal S. parathypi C OWidal S. parathypi C H
Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006
Blood culture and PCR results in diagnosis of Blood culture and PCR results in diagnosis of Typhoid Fever Typhoid Fever
TreatmentTreatmentl Non Pharmacologic : Bed rest, Nutritionl Pharmacologic
SymptomaticAntibiotic : Ampicillin/Amoxicillin 2x750 or 3x500 mgChloramphenicol 4x500mgCephalosporin : Ceftriaxone 3-4 g/daysFluoroquinolones : Ciprofloxaxin 2x500 mg
Ofloxacin 2x400 mgPefloxacin 1x400 mgFleroxacin 1x500 mgLevofloxacin 1x500mg
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South East Asia J Trop Med Pub Health2006; 37 (1):126
ComplicationsIntestinal complication
intestinal perforationgastrointestinal hemorrhagehepatiitis, pancreatitis, paralytic ileus
ExtraintestinalCardiovascular : shock, myocarditisNeuropsychiatric : encephalopaty, delirium
psychosisRespiratory : bronchitis, pneumonia, pleuritisHematology : anemia, DICKidney : glemerulonephritis, pyelonephritisOthers : osteomyelitis, focal abscess
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Carrier State• Exist of S. typhi in feces or urine withoutclinical manifestation 1 year after recovery fromtyphoid fever
• S. typhi still be found in feces of urine2 or 3 months after recovery in 16% patients
• Impairment of host defence mechanism,gall and kidney stone, chronic gall andkidney infection contribute in pathogenesis of carrier state
Carrier State• Diagnosis of carrier state :feces and urine culture, Vi antibody
• Treatment : Without gall stone :Ampicillin, Amoxicillin, CotrimoxazoleWith gall stone :Cholecystectomi and treatment withCiprofloxacin or NorfloxacinWith Schistosomiasis :Eradication of schistosomiasis before treatment of carier state
Prevention
• Avoid risky food or drinks• Hand washing• Vaccination• Detection of carrier state in food handler
