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IdaSafitriLaksono

Number of Typhoid fever cases yearly


275639 255817 201252 136088 134065

2000

2001

2002

2003

2004

Incidence rate per 10.000 people of Typhoid fever cases yearly


13 12 9.5 6.4 6.2

Subdit Surveillance Epd Ministry of Health

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 Thoracic Duct Primary bakteremia circulation

phagocytocis Inflamation response endotoxin (local, systemic)


Local: inflamation Systemic: cytokine

Target Organ RES (Liver, spleen, bone marrow) Secundary bakteremia Other organs (metastatic)

Incubation period
Asimptomatic

Invasive period
Intermittent fever Headache Malaise Abdominal pain Constipation Diarrhea

Typhoid phase
Persistent fever Bradicardia Hepatomegaly Splenomegaly Constipation Diarrhea Rose spot

Convalescence
Carrier Relapse

Complication 370C 400C

Day -15

Day 0

Day 7

Day 21

Fever

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 S. paratyphi A S. paratyphi B S. typhimurium S. paratyphi C S. Cholerasuis S. typhi S. enteritidis

ANTIGEN O 1, 2, 12 1, 4, 5, 12 1, 4, 5, 12 6, 7 6, 7 9, 12, Vi 1, 9, 12

ANTIGEN H PHASE I PHASE II 1,2 1,2 1,5 1,5 a b i c c d g, m

A B 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 Typhidot Widal 86.4 74.7 69.9 84.6 96.1 73.0 95.7 98.7 91.1 61.1 49.0 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

Outsideintestinaltract

peritonitis, bleeding, perforation

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 Ampicillin Amoxycillin Nalidixic acid Chloramphenicol Cefixime Azithromycine Cotrimoxazole Ciprofloxacin

Sensitive 34 28 64 46 80 78 64 84

Interme diate 10 6 12 40 14 22 0 1

Resistant 54 66 24 24 6 0 36 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