IdaSafitriLaksono

Number of Typhoid fever cases yearly

275639
255817
201252
134065

136088

2000

2001

2002

2003

2004

Incidence rate per 10.000 people of

Typhoid fever cases yearly
13
12
9.5

Subdit Surveillance Epd

Ministry of Health

6.2

6.4

2000

2001

2002

2003

2004

Bulletin WHO 2008

Hostbarriers
Local:pH,GITmotility,intestinalfloraGeneral :

humoralandsellularimmunity

Organism
Numberofmicrobes
Virulence (serotype)

Antibioticresistance

Intestinal Epithel
Lamina propria
Multiplication

Plaque Payeri

phagocytocis
Inflamation response
endotoxin (local, systemic)
Local: inflamation
Systemic: cytokine

Thoracic Duct
Primary bakteremia

circulation
Target Organ RES (Liver, spleen, bone marrow)

Secundary bakteremia
Other organs (metastatic)

Incubation period
Asimptomatic

Invasive period

Typhoid phase

Convalescence

Intermittent fever
Headache
Malaise
Abdominal pain
Constipation
Diarrhea

Persistent fever
Bradicardia
Hepatomegaly
Splenomegaly
Constipation
Diarrhea
Rose spot

Carrier
Relapse

Complication
370C

Day -15

400C

Day 0

Fever

Day 7

Day 21

Notspecificsymptomsandsigns
Fever 7days
Gastrointestinal symptoms
Vomiting,
Diarrhea/obstipation,
Meteorismus

Delirium,decreasingconsciousness
Adolescent~adult
Toxicappearance,dehidrated,
Typhoidtongue
hepatomegaly,splenomegaly

Sri Rezeki H, Tumbelaka AR, Satari HI. Sari Pediatri 2001;4:182-7

Fever
Chilling
Abdominalpain
Nausea
Vomiting
Diarrhea
Obstipation
Raving
Unconsciousness
Typhoidtongue
Epigastricpain
Hepatomegaly
Splenomegaly
10

25

50

75

100

Laboratory scheme of typhoid fever

Bloodcounts
leucopenia,aneosinophilia,
relativelymphocytosis
thrombocytopenia

IncreasingBSR,
Increasing SGOT/SGPT
Serologicaltest: IgM&IgG
Cultureof Salmonellatyphi

Serologicaltest :Widal test,Tubex TF,etc

DNAprobe
IgGofoutercellsmembrane
Immunoblotting(Typhidot)
PCR(polymerasechainreaction)

Bhutta ZA.Currentconceptsinthediagnosisandtreatmentoftyphoidfever.BMJ2006;333:7882.

Widaltest,since1896
Oantibody,establishedearlierbutforshorttimeonly(4 6months),
Hantibody,laterandstaylonger(9months 2years),
Viantibody,late(persistincarriers)

InterpretationofWidaltestshouldbetakencarefully,dependon:
Diseasestadium
Laboratorymethods
Endemicityofdisease
Immunisationhistory
Nsutebu EF, Ndumbe PM, Koulla S. Trans R Soc Trop Med Hyg. 2002 Jan-Feb;96(1):64-7.

AdvantagesofWidaltest
Olopoenia LA, King, AL. Widal agglutination test - 100 years later: still
plagued by controversy. Postgrad Med J 2000;76:80-84.

GROUP

SEROTYPE

ANTIGEN O

ANTIGEN H
PHASE I

PHASE II

S. paratyphi A

1, 2, 12

S. paratyphi B

1, 4, 5, 12

1,2

S. typhimurium

1, 4, 5, 12

1,2

S. paratyphi C

6, 7

1,5

S. Cholerasuis

6, 7

1,5

S. typhi

9, 12, Vi

S. enteritidis

1, 9, 12

g, m

C
D

Outof103patients(clinicalandculturalproventyphoid),TUBEXposin
86.4%,Typhidot74.7%,andWidal69.9%
Innontyphoidgroup,Tubexposin25%,Typhidot3.8%andWidal26,9%
MaximumnumberofTubexandTyphidotwerepositiveinpatientswith7
14daysoffever,whileWidalwasmostlypositiveinchildrenwithfeverof
morethan14days
Sensitivity,specificity,PPVandNPVforthetests

Tubex

86.4

84.6

95.7

61.1

Typhidot

74.7

96.1

98.7

49.0

Widal

69.9

73.0

91.1

38.0

Jaffery G, Hussain W, Saeed, Anwer M and Maqbool S. Annual Pathology Conference, 2003, Pakistan
and 3rd Scientific Conference of Paediatric Association of SAARC Countries 2004, Lahore

TubexTFdibandingkandenganUjiWidalpada
pasiendenganbiakandarahdan/atauPCR

RSCM,RSPersahabatan,RSTangerang,Mei Oktober2006
Diperiksa52kasus,27laki2dan25wanitadenganusiatertua
20 30tahun(53.8%)
SemuapasientelahmemenuhiSkortifoidNelwan>=8dan
klinismemenuhisyaratdemamtifoid.
TubexTFdibandingujiWidalterhadapskoritumenghasilkan
Sensitifitas100%dan53.1%
Spesifitas90%dan65%
Nilaiprediksipositif94.1%dan70.8%,prediksinegatif100%dan46.4%
Ratiolikelihood(+)10dan1.51,Ratiolikelihood()0dan0.72
AUCROCTubex5.91danWidal0.591,sangatberbedabermakna
Surya H, Setiawan B, Shatri H, Sudoyo A dan Loho T. Diunduh
dari http:/pacbiotekindo.co.id/tubextf.html, 29.11.2009

Intraintestinaltract

peritonitis,
bleeding,
perforation

Outsideintestinaltract

encephalitis
pneumonia
meningitis
osteomyelitis
hepatitis

Onethirdof102casesdevelopcomplications
Anicterichepatitis,bonemarrowsupression,paralyticileus,

myocarditis,psychosis,cholesystitis,osteomyelitis,peritonitis,
pneumonia,hemolysis,andSIADH
Ifhepatitisisexcluded,therateofcomplicationsis11%.

Achildwithsplenomegalyorthrombocytopeniahad1.5
timeshigherrisk,whereasachildwithleucopenia has2
timesrisktohavecomplications.
Achildwithbothsplenomegalyandthrombocytopenia
orleukopeniahad2.5 timeshigherrisk.
Alam Sher Malik. J of Trop Ped 2002;48:102-8.

Irritability
Decreasingconsciousness (latestadium)
Abdominaldistension
Abdominalpain
Defansemusculaire
Loweringintestinalsounds
Disappearanceofhepaticdullness

Clinicallydifficulttodifferentiate
Needsupportivelabs
Nasogastricandanaltubeshouldbeinserted
Abdominalxray(3positions)
Unequalairdistribution
Airfluidlevel
Hepaticarea radiolucent
Freeairatabdominalwall

Supportive:
Fluidtherapy,dietetic
Electrolyte
Acidbase

Causal:
Medicamentous (antibiotics,steroid)
Surgery (complicationtherapy)

Fluid
Maintenance,D5:NaCl0.9%(3:1)
Additional 12.5%foreach10 Cincrement

Dietetic
Solidfoodscouldbegivenassoonaspossible,insteadof

conventionalstrainedfood
Lessfibersandstimulatingfood
Nottostrict

Acidbasecorrections
Electrolytecorrections

Bhutta ZA.Currentconceptsinthediagnosisandtreatmentoftyphoidfever.BMJ2006;333:7882.

Antibiotics

Sensitive

Interme
diate

Resistant

Ampicillin

34

10

54

Amoxycillin

28

66

Nalidixic acid

64

12

24

Chloramphenicol

46

40

24

Cefixime

80

14

Azithromycine

78

22

Cotrimoxazole

64

36

Ciprofloxacin

84

15

E Hartoyo, A Yunanto, L Budiarti. 3rd Congress of Pediatric

Infectious Diseases. Cebu City, Philippines, March 2006

Chloramphenicol
100mg/kgBW/day oral, max 2gram,10days
Notrecommendedforcaseswithleucocytecount <2000/Ul

Cotrimoxazole
6mg/kgBW/day,10days

Amoxicillin
100mg/kgBW/day,10days

Ceftriaxone (cephalosporin3rdgen)
50 80mg/kgBW/day ,5days

Cefixime (cephalosporin3rdgen)
10 20mg/kgBW/day ,10days
Oral

Azithromycin
20mg/kg/day

Fluoroquinolone
Notrecommendedfor <14yearsold

RCTcomparingCeftriaxone75mg/BWflexibledurationto
Chloramphenicol75mg/BW14daysgivemeandefervescenceof
5.4daysand4.2daysrespectively.NorelapsinCeftriaxonegroups,
but4casesinChloramphenicol.
Tatli MM, Aktas G, Kosecik M, Yilmaz A. Int J Antimicrobial Agents 2003;21:350-3

Ceftriaxone50mg/BWonceadayfor14days,givemean
defervescenceof5.31daysandconciousnessimprovingthefirst4
hourinallcasesexcept2.
Nathin MA, Hadinegoro SR. In RHH Nelwan, editor. Typhoid fever, profile, diagnosis
and treatment in the 1990s. FKUI Press, Jakarta, 1992:133-9

From24isolates,87%ofthemsensitivetoampicillin,96%to
chloramphenicolandcotrimoxazole.Allisolatesweresensitiveto
Cefixime.Sincefluoroquinoloneisnotrecommendedfor
children,cefiximecouldplayaroleasachoiceinendemicareas
withMDRST
Santillan RM, Garcia GR, Benavente IS, and Garcia.
Proc West Pharmacol Soc 2000;43:65-6

InFMUICHDJakarta,from25casesconfirmedtyphoidfever,
cefixime1015mg/BWgive84%curerate,withamean
defervescencetimeof6.0 3.1days.
Hadinegoro SR, Tumbelaka AR, Satari HI. Sari Pediatri 2001;2(4): 182-7

Asitromisin
Pada 149kasus anak dan remaja,yangmenderita demam
tifoid klinis diberikan asitromisin oral (20mg/kg/hari) atau
seftriakson iv(75mg/kg/hari) selama 5hari.
Ternyata 30(94%) kelompok asitromisin serta 35(97%) dari
kelompok seftriakson sembuh dan tidak berbeda bermakna.
Enam kasus dengan seftriakson mengalami relaps dan tidak
ada relaps pada kelompok asitromisin.Pengobatan 5hari
dengan asitromisin dinyatakan cukup efektif untuk
mengobati demam tifoid tanpa komplikasi pada anak dan
remaja.

Frenck RW, Mansour A, Nakhla I, Sultan Y, Putnam S, Wiezerba T et al.

Clin Infect Dis. 2004;38(7):951-7.

Feverdefervescence(days)
Ampicilin/Amoxicilin
Cotrimoxazole
Chloramphenicol
Ceftriaxone
Cefixime

5,2 3,2
6,5 1,3
4,2 1,1
5,4 1,5
5,7 2,1

Hadinegoro SR. Naskah lengkap PKB Ilmu Kesehatan Anak XLIV.

Jakarta: FKUI 2001 :105-16.

Encephalopaty
Dexametason13mg/BW/day, 35days
Fluidrestrictionto4/5
Acidbaseandelectrolytecorrection

Peritonitis,intestinalhemorrhage
Fasting,parenteral nutrition,bloodtransfusion (if

indicated)
parenteralantibiotic

Hospital

RSCM
RSHS
RSWS
RSK
RSMH

Mortality(%)
0
0
0
0
0

4,0
0,6
3,3
2,0
3,2

RSCMJakarta,RSHSBandung,RSWSMakasar,
RSKSemarang,RSMHPalembang,19911996

Typhoidfeverinchildren,mostly>5yearsofage
Clinicallymilderthanadultcases,
Clinicallynotspecificinyoungerchildren
Sensitivity,specificity,andlowcostlaboratory
supportneeded
Drugofchoice :chloramphenicol
Prevention:vaccineandgoodhygienesanitation