Typhoid FeverTyphoid Fever

EpidemiologyEpidemiology IncidenceIncidence

– US, Western Europe, Japan: 0.2 – 0.7 / US, Western Europe, Japan: 0.2 – 0.7 / 100.000100.000

– Southern Europe: 4.3 – 14.5 / 100.000Southern Europe: 4.3 – 14.5 / 100.000– Developing country: 10 – 540 / 100.000Developing country: 10 – 540 / 100.000– Indonesia: 350 – 810 / 100.000 = Indonesia: 350 – 810 / 100.000 =

600.000 – 1.5 million cases/yr600.000 – 1.5 million cases/yr

EpidemiologyEpidemiology TransmissionTransmission

– Contaminated drinking water or food. Contaminated drinking water or food. – Large epidemicsLarge epidemics: : most often related to most often related to

fecal contamination of water supplies or fecal contamination of water supplies or street vended foods. street vended foods.

– A chronic carrier state--excretion of the A chronic carrier state--excretion of the organism for more than 1 year--occurs in organism for more than 1 year--occurs in approximately 5% of infected persons.approximately 5% of infected persons.

EtiologyEtiology Acute systemic infection, caused by:Acute systemic infection, caused by:

– Salmonella typhi (96%)Salmonella typhi (96%)– Others: S.paratyphiOthers: S.paratyphi

SalmonellaeSalmonellae: : – grgram-negative am-negative bacillibacilli, ,

EnEnterobacteriaceae familyterobacteriaceae family, , non-spore-non-spore-forming, nonencapsulated, flagella. forming, nonencapsulated, flagella.

A photomicrograph of Salmonella typhosus bacteria using a Flagellar stain technique (1979)

EtiologEtiologyy– KKilled by heating to 130°F (54.4°C) for illed by heating to 130°F (54.4°C) for

1 hr or 140°F (60°C) for 15 min. 1 hr or 140°F (60°C) for 15 min. – RRemain viable at ambient or reduced emain viable at ambient or reduced

temperatures for daystemperatures for days, , survive for survive for weeks in sewage, dried foodstuffs, weeks in sewage, dried foodstuffs, pharmaceutical agents, and fecal pharmaceutical agents, and fecal material.material.

PathogenesisPathogenesis

Clinical ManifestationClinical Manifestation

VarVaryy: mild – severe : mild – severe Incubation: 3Incubation: 3––3030 ( (range 7range 7–14–14)) daysdays

Clinical ManifestationClinical Manifestation

11stst week week::– Fever Fever ““step ladder temperature chartstep ladder temperature chart””, ,

Insidious increase, unremitting, highest: Insidious increase, unremitting, highest: end of 1end of 1stst week week

– Systemic symptoms: headache, Systemic symptoms: headache, lethargy, malaise, myalgia, nausea, lethargy, malaise, myalgia, nausea, vomiting, abdominal painvomiting, abdominal pain

Clinical ManifestationClinical Manifestation 22ndnd week week::

– HepatosplenomegalHepatosplenomegalyy, , rose rose spotspot, , headache headache stupor stupor

– Relative bRelative bradiradiccardardia: rare in ia: rare in childrenchildren

Clinical ManifestationClinical Manifestation 33rdrd – 4 – 4thth week week::

– Intestinal haemorrhage and Intestinal haemorrhage and perforation are commonperforation are common

– End of 4End of 4thth week: fever week: fever gradually declinegradually decline

Clinical ManifestationClinical Manifestation GIT symptoms: varyGIT symptoms: vary

– DiaDiarrhearrhea– ObstipaObstipationtion– ObstipaObstipation tion diarrhea diarrhea

Coated tongueCoated tongue

DiagnosisDiagnosis Clinical FeaturesClinical Features

– Clinically mild, can be asymptomatic Clinically mild, can be asymptomatic

– ObviouslyObviously: : FeverFever GIT distubanceGIT distubance

– Change of level of consciousnessChange of level of consciousness

DiagnosisDiagnosis

– Constitutional symptoms: headache, Constitutional symptoms: headache, malaise, abdominal pain, hepato/malaise, abdominal pain, hepato/ splenomegaly, altered mental statussplenomegaly, altered mental status

Fever > 7 days + GI symptoms, in Fever > 7 days + GI symptoms, in children > 5 yr, children > 5 yr, no no additional additional symptoms symptoms suspect typhoid fever suspect typhoid fever

Diagnosis:Diagnosis: Maculopapular Maculopapular rashrash in chest and abdomen in chest and abdomen

(rose spot): in 40-80% cases for 2-3 days (rose spot): in 40-80% cases for 2-3 days Diarrhea (39%) > constipation (15%) in Diarrhea (39%) > constipation (15%) in

child Vomiting (26%) and nausea child Vomiting (26%) and nausea (42%) (42%) Headache (76%), abdominal pain (60%), Headache (76%), abdominal pain (60%),

altered mental status altered mental status (34%), (34%), also also apatis apatis (31%) (31%) and and delirium (3%) delirium (3%)

(Rivai AT, Mulyadi T, Kustedi P, Pulungsih SP, Janas. Balai (Rivai AT, Mulyadi T, Kustedi P, Pulungsih SP, Janas. Balai Penerbit FKUI, 1992; 85-93. )Penerbit FKUI, 1992; 85-93. )

Diagnosis:Diagnosis: LaboratorLaboratoryy

– Culturing Salmonella Culturing Salmonella Blood (40 – 54%), Blood (40 – 54%), bone marrow (80 – 90%), bone marrow (80 – 90%), urine (7%), urine (7%), stool (35 – 37%), stool (35 – 37%), duodenal fluid (58%), rose spot (63%)duodenal fluid (58%), rose spot (63%)

LaboratoryLaboratory

Diagnosis:Diagnosis: LaboratorLaboratoryy

– SerologySerology Widal: four fold rise in O agglutinin or a titer Widal: four fold rise in O agglutinin or a titer

of ≥ 1/160 of ≥ 1/160 not recommended by WHO not recommended by WHO IgM and IgG for Salmonella, Tubex, Typhi IgM and IgG for Salmonella, Tubex, Typhi

dotdot– DNA probeDNA probe– PCRPCR

Diagnosis:Diagnosis: LaboratoryLaboratory

– Peripheral blood exam:Peripheral blood exam: Lekopenia, relative lymphocytosis, Lekopenia, relative lymphocytosis,

aneosinophiliaaneosinophilia Not spesificNot spesific

ComplicationComplication Intestinal haemorrhage Intestinal haemorrhage (1 – 10%) (1 – 10%)

and perforation and perforation (0.5 – 3%) (0.5 – 3%) – Decrease temperature and blood Decrease temperature and blood

pressure pressure acute abdomen signs acute abdomen signs and peritonitisand peritonitis

ComplicationComplication Others:Others:

– Typhoid hepatitis, typhoid Typhoid hepatitis, typhoid encephalopathy, cholecystitis, encephalopathy, cholecystitis, pneumonia, septic shock, pneumonia, septic shock, pyelonephritis, endocarditis, pyelonephritis, endocarditis, osteomyelitis, meningitis, cerebral osteomyelitis, meningitis, cerebral thrombosis, ataxia, aphasia, etcthrombosis, ataxia, aphasia, etc

TherapyTherapy Causal: appropriate antibioticCausal: appropriate antibiotic Severe typhoid fever: hospitalizedSevere typhoid fever: hospitalized Supportive therapySupportive therapy

– MonitoringMonitoring– Fluid managementFluid management

TherapyTherapy– Detection and manage complicationDetection and manage complication

Surgery for intestinal perforationSurgery for intestinal perforation– DieteticDietetic

Non fibre and digestableNon fibre and digestable Fever (-): solid food with adequate Fever (-): solid food with adequate

calorycalory– Blood transfusionBlood transfusion

Intestinal haemorrhage and perforationIntestinal haemorrhage and perforation

TherapyTherapy

ANTIBIOTICANTIBIOTIC Empiric therapyEmpiric therapy

– Narrow spectrum AB, good penetration, Narrow spectrum AB, good penetration, easy to give, resistency <, minimal side easy to give, resistency <, minimal side effect, clinical effication evidenceeffect, clinical effication evidence

Treatment successfull parameter: Treatment successfull parameter: time of defervescencetime of defervescence– Min. 36 hours of therapy for Min. 36 hours of therapy for fever fever

TherapyTherapy

ANTIBIOTICANTIBIOTIC 1st Line1st Line

– Chloramphenicol (1st Chloramphenicol (1st drug of choicedrug of choice))– Ampicillin / amoxicillinAmpicillin / amoxicillin– CotrimoxazoleCotrimoxazole

TherapyTherapy

ANTIBIOTICANTIBIOTIC 2nd Line2nd Line

– CeftriaxonCeftriaxon– CefiximCefixim– Fluoroquinolon Fluoroquinolon not recommended for not recommended for

childrenchildren– AzythromycineAzythromycine– AAzztreonamtreonam

TherapyTherapy

ANTIBIOTICANTIBIOTIC 1st Line1st Line

– ChloramphenicolChloramphenicol 7575 – 100 mg/kgBW/day IV or PO in 2 divided – 100 mg/kgBW/day IV or PO in 2 divided

dose for 10 – 14 daysdose for 10 – 14 days Max. dose 2 gr/dayMax. dose 2 gr/day CI: leukopenia (< 2000/ul)CI: leukopenia (< 2000/ul)

TerapiTerapi

ANTIBIOTICANTIBIOTIC 1st Line1st Line

– AmpicillinAmpicillin 200 mg/kgBW/day PO or IV in 4 divided 200 mg/kgBW/day PO or IV in 4 divided

dose for 10 – 14 days or,dose for 10 – 14 days or,– CotrimoxazoleCotrimoxazole

10 mg/kgBW/day (TMP) in 2 divided 10 mg/kgBW/day (TMP) in 2 divided dose for 14 days dose for 14 days

TerapiTerapi

ANTIBIOTICANTIBIOTIC 2nd Line2nd Line

– CeftriaxonCeftriaxon 50 – 80 mg/kgBW/day, single dose for 50 – 80 mg/kgBW/day, single dose for

10 days10 days Cure rate up to 90% in 3 – 5 days Cure rate up to 90% in 3 – 5 days

duration of therapy duration of therapy

TherapyTherapy

ANTIBIOTICANTIBIOTIC 2nd Line2nd Line

– CefiximCefixim 10 – 15 mg/kg10 – 15 mg/kgBWBW//day PO in 2 divided day PO in 2 divided

dose for dose for 10 - 14 10 - 14 daysdays Cure rate in Cure rate in IKA RSCM 1999 – 2000IKA RSCM 1999 – 2000::

84%84%

TherapyTherapy

ANTIBIOTICANTIBIOTIC 2nd line2nd line

– FluoroFluoroquinolonequinolone Superior than cephalosporinSuperior than cephalosporin, c, cure rate ≈ ure rate ≈

100%100%, c, child hild controversion controversion – Ciprofloxacine, Ciprofloxacine, 10 mg/kg10 mg/kgBWBW//day in 2 divided day in 2 divided

dose,dose,– Ofloxacine 10 -15 mg/kgBW/day in 2 divided Ofloxacine 10 -15 mg/kgBW/day in 2 divided

dosedose– Duration: 2 – 5 dayDuration: 2 – 5 day– MDR typhoidMDR typhoid

TherapyTherapy

DexamethasoneDexamethasone Severe case with altered mental status Severe case with altered mental status Initial dose 3 mg/kgBW Initial dose 3 mg/kgBW 1 mg/kgBW 1 mg/kgBW

every 6 hr for 48 hr every 6 hr for 48 hr mortality mortality from from 35-55% to 10%35-55% to 10%

PrognosisPrognosis Mortality: developed country < 1%, Mortality: developed country < 1%,

developing country > 10% developing country > 10% ComplicationComplication high mortality and high mortality and

morbiditymorbidity AB (-) AB (-) relapse 4-8%. relapse 4-8%. Adequate AB, clinical manifestation Adequate AB, clinical manifestation

occur occur ±± 2 weeks after th/ (-), ≈ acute 2 weeks after th/ (-), ≈ acute disease, milder & shorter.disease, milder & shorter.

PrognosisPrognosis Chronic carrier 1-5% Chronic carrier 1-5%

– Billiary tr disease incidence in chronic Billiary tr disease incidence in chronic carrier > general populationcarrier > general population

– TreatmentTreatment AmpiAmpicillin or cillin or amoamoxicillin xicillin + probenecid + probenecid high dose high dose

or or TMP-SMZ TMP-SMZ for for 4 – 6 4 – 6 weeksweeks If cholecystitis or cholelithiasis (+) If cholecystitis or cholelithiasis (+)

cholecystectomy after 14 days antibiotics cholecystectomy after 14 days antibiotics

PreventionPrevention Good sanitation and personal Good sanitation and personal

hygienehygiene Typhoid vaccination Typhoid vaccination for for

traveler to endemic areatraveler to endemic area