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Epidemiology,microbiology,clinicalmanifestations,anddiagnosisoftyphoidfever

OfficialreprintfromUpToDate
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Epidemiology,microbiology,clinicalmanifestations,anddiagnosisoftyphoidfever
Author
ElizabethLHohmann,MD

SectionEditor
StephenBCalderwood,
MD

DeputyEditor
AllysonBloom,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jul2015.|Thistopiclastupdated:Sep26,2013.
INTRODUCTIONTyphoidfeverischaracterizedbyseveresystemicillnesswithfeverandabdominalpain
[1].TheorganismclassicallyresponsiblefortheentericfeversyndromeisS.entericaserotypeTyphi(formerly
S.typhi).OtherSalmonellaserotypes,particularlyS.entericaserotypeparatyphiA,B,orC,cancausea
similarsyndromehowever,itisusuallynotclinicallyusefulorpossibletoreliablypredictthecausative
organismbasedonclinicalfindings[2].Theterm"entericfever"isacollectivetermthatreferstobothtyphoid
andparatyphoidfever.
Theepidemiology,microbiology,clinicalmanifestations,anddiagnosisoftyphoidfeverwillbereviewedhere.
Thepathogenesis,treatmentandpreventionoftyphoidfeverarediscussedseparately.(See"Pathogenesisof
typhoidfever"and"Treatmentandpreventionoftyphoidfever"and"Immunizationsfortravel".)
EPIDEMIOLOGYTyphoidfeverismorecommoninchildrenandyoungadultsthaninolderpatients[3].
Worldwide,typhoidfeverismostprevalentinimpoverishedareasthatareovercrowdedwithpooraccessto
sanitation.NonepidemicincidenceestimatessuggestthatsouthcentralAsia,SoutheastAsia,andsouthern
AfricaareregionswithhighincidenceofS.typhiinfection(morethan100casesper100,000personyears)[4].
OtherregionsofAsiaandAfrica,LatinAmerica,theCaribbean,andOceaniahaveamediumincidenceof10to
100casesper100,000personyears.Theseestimates,though,arelimitedbylackofconsistentreportingfrom
allareasoftheworldandarebasedonextrapolationofdataacrossregionsandagegroups.Asanexample,
theincidenceestimateswithinAfricaarebaseduponreportsfromEgyptandSouthAfricaonlyandthusmay
notbeaccuratelydefined.
BecausehumansaretheonlyreservoirforS.entericaserotypeTyphi,ahistoryoftraveltosettingsinwhich
sanitationispoororcontactwithaknowntyphoidcaseorcarrierisusefulforidentifyingpeopleatriskof
infectionoutsideofendemicareas,althoughaspecificsourceorcontactisidentifiedinaminorityofcases.
Approximately200to300casesofS.typhiarereportedintheUnitedStateseachyear[5].About80percentof
thesecasesoccuramongtravelerstocountrieswheretyphoidfeverisendemic,particularlycountriesinSouth
CentralAsia.Inastudyof428casesoftyphoidfeverreportedamongtravelersfromresourcerichcountries
throughthemultinationalGeoSentinelSurveillanceNetworkbetween2006and2011,67percentofcaseswere
acquiredinsouthcentralAsia(34,13,7,and6percentoftotalfromIndia,Nepal,Pakistan,andBangladesh,
respectively)(figure1)[6].Individualsvisitingrelativesinendemiccountriesaccountedfor28percentofthe
typhoidcases.
Manytravelerswhosubsequentlydeveloptyphoidfeverhavenotreceivedappropriatevaccinationdespite
guidelinerecommendations.Among580casesofvaccinepreventablediseasesamongreturnedinternational
travelersreportedtotheGeoSentinelSurveillanceNetworkbetween1997and2007,confirmedorprobable
entericfever(duemainlytoS.typhi,butalsoS.paratyphi)wasthemostcommon[7].Only38percentofthose
withentericfeverhadapretravelclinicalencounter.However,thepossibilityofS.typhiinfectioninreturning
travelerswithahistoryofvaccinereceiptshouldnotbediscounted,sincethevaccineisnotcompletely
effective.(See"Immunizationsfortravel",sectionon'Typhoidvaccine'.)
PatientswhoacquireinfectionabroadareusuallyolderthanthosewhoacquirediseaseinUSoutbreaksand
aremorelikelytohavedrugresistantinfection.S.typhioutbreaksintheUnitedStatesaremostoften
foodbornetheyaregenerallylimitedinsizebutcancausesubstantialmorbidity[8,9].
Theriskfactorsforthedevelopmentofentericfeverduetotyphoidorparatyphoidmaydiffer.InanIndonesian
study,transmissionofparatyphoidfeverwasmorefrequentlyobservedoutsidethehome(eg,viaconsumption
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offoodpurchasedfromstreetvendors)transmissionoftyphoidfeverwasmorefrequentlyobservedwithinthe
household(eg,viasharingutensils,presenceofapatientwithtyphoid,lackofsoaporadequatetoiletfacilities)
[10].S.paratyphialsoappearstobeanincreasingcauseofentericfeveramongvaccinatedtravelers,asthe
typhoidvaccineisineffectiveagainstmostS.paratyphiinfections[11,12].
Issuesrelatedtotheepidemiologyofdrugresistancearediscussedseparately.(See"Treatmentand
preventionoftyphoidfever",sectionon'Multidrugresistantstrains'.)
ChroniccarriageChronicSalmonellacarriageisdefinedasexcretionoftheorganisminstoolorurine>12
monthsafteracuteinfection.RatesofchroniccarriageafterS.typhiinfectionrangefrom1to6percent
[1,13,14].Chroniccarriageoccursmorefrequentlyinwomenandinpatientswithcholelithiasisorotherbiliary
tractabnormalities[15,16].Chroniccarriageintheurineisalmostalwaysassociatedwithadefectinthe
urinarytract(eg,urolithiasis,prostatichyperplasia)orconcurrentbladderinfectionwithSchistosoma[17].
Chroniccarriersrepresentaninfectiousrisktoothers,particularlyinthesettingoffoodpreparation.Thestory
of"TyphoidMary,"acookinearly20thcenturyNewYorkwhoinfectedapproximately50people(threefatally),
highlightstheroleofasymptomaticcarriersinmaintainingthecycleofpersontopersonspread[18].Forthis
reason,eradicationofcarriagewhenidentifiedshouldbeattempted.Thisisdiscussedfurtherseparately.(See
"Treatmentandpreventionoftyphoidfever",sectionon'Chroniccarriage'.)
TheS.typhicarrierstatemaybeanindependentriskfactorforcarcinomaofthegallbladderaswellasother
cancers[19,20].(See"Gallbladdercancer:Epidemiology,riskfactors,clinicalfeatures,anddiagnosis".)
MICROBIOLOGYTheorganismclassicallyresponsiblefortheentericfeversyndromeisS.enterica
serotypeTyphi(formerlyS.typhi).OtherSalmonellaethatcancauseasimilarclinicalsyndromeincludebutare
notlimitedto[21]:
SalmonellaparatyphiA
SalmonellaparatyphiB
SalmonellaparatyphiC
Salmonellacholeraesuis
Theseorganismsareingestedandsurviveexposuretogastricacidbeforegainingaccesstothesmallbowel,
wheretheypenetratetheepithelium,enterthelymphoidtissue,anddisseminateviathelymphaticor
hematogenousroute.(See"Pathogenesisoftyphoidfever".)
S.entericaserotypeTyphicausesdiseaseonlyinhumansithasnoknownanimalreservoir.Infection
thereforeimpliesdirectcontactwithaninfectedindividualorindirectcontactviacontaminatedfoodorwater.
InfectionduetoSalmonellaparatyphispecies(alsocalledS.enteritidisserotypeparatyphiinolderreports)is
lesscommonthaninfectionduetoS.entericaserotypeTyphi.RegionalvariationinprevalenceofS.paratyphi
specieshasbeendescribed:S.paratyphiBismorefrequentlyculturedthanS.paratyphiAS.paratyphiCis
rarelyisolated[22,23].S.paratyphispeciesaregenerallythoughttocausemilderillnessesthanS.typhi,
althoughitisnotpossibletopredictthecausativeorganismbaseduponclinicalfindings[2].Among609cases
ofbacteremicentericfeverinNepal(409withS.typhiand200withS.paratyphiA),theclinicalsyndromes
causedbythesetwoorganismswereindistinguishableandofequalseverity[24].
"Nontyphoidal"Salmonellaemayalsocausesevereillnessconsistentwithentericfever.Inastudyof809
patientssuspectedofhavingentericfeverinNigeria,forexample,nontyphoidalSalmonellae(mostcommonly
S.enteritidisandS.typhimurium)wereisolatedin7percentofcases[22].InAfrica,bacteremiawith
nontyphoidalSalmonellaeisoftenassociatedwithunderlyingHIVinfection,whichshouldbeconsideredin
suchpatients.(See"NontyphoidalSalmonellabacteremia",sectionon'Epidemiology'.)
CLINICALFEATURESTyphoidisafebrileillnesswithonsetofsymptoms5to21daysafteringestionof
thecausativemicroorganismincontaminatedfoodorwater.Ingeneral,lowerinoculaareassociatedwith
longerincubationtimes.However,boththeincubationperiodandinoculumneededtocausediseasevary
dependinguponhostfactorssuchasage,gastricacidity,andimmunologicstatus.(See"Pathogenesisof
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typhoidfever",sectionon'Infectiousdose'.)
Themajorityofpatientswithtyphoidfeverpresentwithabdominalpain,fever,andchills.
ClassicpresentationClassicreportsdescribedthecharacteristicstagesoftyphoidfeverinuntreated
individuals[25].Inthefirstweekofillness,rising("stepwise")feverandbacteremiadevelop[26].Whilechills
aretypical,frankrigorsarerare[11].Relativebradycardiaorpulsetemperaturedissociationmaybeobserved.
Inthesecondweekofillness,abdominalpaindevelopsand"rosespots"(faintsalmoncoloredmaculesonthe
trunkandabdomen)maybeseen.Duringthethirdweekofillness,hepatosplenomegaly,intestinalbleeding,
andperforationduetoileocecallymphatichyperplasiaofthePeyer'spatchesmayoccur,togetherwith
secondarybacteremiaandperitonitis.Septicshockoranalteredlevelofconsciousnessmaydevelopamong
300casesoftyphoidfeverinIndonesia,thesefindingswereobservedinapproximately15percentofpatients
[27].Intheabsenceofacutecomplicationsordeathfromoverwhelmingsepsis,symptomsgraduallyresolve
overweekstomonths.
EffectofantimicrobialtherapyTheclinicalfeaturesoftyphoidfeverintheUnitedStateshavechanged
dramaticallyintheantibioticera.Whencaseseriesfromthe1930swerecomparedwithseriesfromthe1970s
and1980s,theprevalenceofsplenomegalyfellfrom63to10percent,andtheprevalenceofrosespotsfell
from30to1.5percent[28].Intestinalbleedingwasalsolessfrequent.
Inthepreantibioticera,mortalityrateswere15percentorgreater[25,29]andsurvivorsexperienceda
prolongedillnesslastingweeks,withmonthsofsubsequentdebilitation.Approximately10percentofuntreated
patientsrelapsed,andupto4percentbecomechroniccarriersoftheorganism.
Inthepostantibioticera,theaveragemortalityratefromtyphoidfeverisestimatedtobelessthan1percent
[1],butthisvarieswidelybaseduponsiteandresources,andmaybe10to20foldhigherinthemost
resourcelimitedsettings.Anepidemiologicalsurveyofabout1100casesinSpain(19972005)demonstrateda
fatalityrateof0.9percent[30].ACentersforDiseaseControlandPrevention(CDC)compilationof10
hospitalbasedtyphoidfeverseriesreportedameancasefatalityrateof2percent(range0to14.8percent),but
notedthattheseseriescaptureonlythemostsevereandhospitalizedcasesinthosewithaccesstocare[31].

OtherclinicalmanifestationsThesymptoms,signs,andcomplicationsoftyphoidfevervarywidelyin
differentseriesandmayberelatedtoage,geographicarea,thecausativeorganism,orthetimeatwhich
patientsseekmedicalcare.
GastrointestinalmanifestationsReportsinthepreantibioticerasuggestedthatconstipationoccurred
morefrequentlythandiarrhea[25].Subsequentreportssuggestthatthesesymptomsoccurwithapproximately
equalfrequencyorthatdiarrheamaybemorecommon,particularlyinyoungchildrenandinadultswithHIV
infection[32,33].Specifically,theincidenceofdiarrheainchildrenwithcultureproventyphoidfeverwas78
percentinaseriesfromAustralia[34]and50percentinareportfromVietnam[35].Constipationoccursin
approximately30percentofindividuals[35,36],perhapsmorefrequentlyinadults.Among552patientswith
cultureconfirmedtyphoidfeverinBangladesh,abdominaltendernessordistension(57percent)andrectal
bleeding(9percent)wereequallydistributedacrossagegroups[37].(See"Pathogenesisoftyphoidfever",
sectionon'Gastrointestinalinfection'.)
Intestinalperforationgenerallyoccursmorefrequentlyamongadultsthanchildrenandisassociatedwithhigh
mortalityrates.Among105adultswithtyphoidfeverinIndia,thiscomplicationwasobservedin10percentof
patients[38].IntheBangladeshstudy,intestinalperforationwasobservedinthreepercentofpatientsoverall,
butin25percentofpatientsover31yearsold[37].AnoutbreakoftyphoidfeverinUgandawasdetected
specificallybecauseofahighincidenceofintestinalperforation,seeninpatientsofallages[39].Overan18
monthperiod,249caseswithamedianageof16yearswereidentifiedand18percentofthemdied.
NeurologicalmanifestationsAlthoughheadacheisafrequentsymptomreportedin44to94percentof
cases[35,36,39,40],otherneurologicalmanifestationsincludingdisorderedsleeppatterns,acutepsychosis,
myelitis,andrigidityhavebeenobservedbutareuncommon[41],asaremeningitisandfocalcentralnervous
infectionswithS.typhi[42].AnoutbreakoftyphoidfeverattheMalawiMozambiqueborderwasnotablefora
relativelyhighincidenceofassociatedneurologicalfindings,foundin40of303cases(13percent)[40].These
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includedsignsofuppermotorneurondisease(eg,hyperreflexia,spasticity,sustainedclonus),ataxia,and
Parkinsonism.
Patientswithseveretyphoidfevermaydevelop"typhoidencephalopathy,"withalteredconsciousness,
delirium,andconfusion.Thishasbeenobservedinupto17percentofpatients,withnoclearfrequency
differencebetweenchildrenandadults[37].Inonestudyof38patientsinIndonesiawithtyphoidfever,
delirium,obtundation,andstuporweregraveprognosticsigns,withamortalityrateashighas55percent[27].
Inthisstudy,intravenousdexamethasonewasadministeredinarandomizedplacebocontrolledfashionasan
adjunctivetoantibiotictherapyareductioninmortalityfrom55to10percentwasobserved.Inanotherseries
of23casesoftyphoidencephalopathyfromBangladesh,themortalityratewas13percentinaretrospective
analysisofthisseries,survivorsweremorelikelytohavereceivedIVdexamethasone[43].(See"Treatment
andpreventionoftyphoidfever".)
OtherextraintestinalmanifestationsOtherproteansymptomshavebeenreportedtovaryingdegrees.
Coughisnotrareandhasbeenobservedinapproximately20to45percentarthralgiasandmyalgiasoccurin
about20percent[35,36,39,40].Focalextraintestinalmanifestationsincludinginvolvementofthehepatobiliary,
cardiovascular,respiratory,genitourinary,musculoskeletal,andcentralnervoussystemshavebeendescribed
asaresultofbacteremicseeding,butareobservedinfrequently[44].
LaboratoryabnormalitiesPatientswithtyphoidfeverfrequentlyhaveanemiaandeitherleukopeniaor
leukocytosisleukopeniawithleftshiftistypicallyseeninadultswhileleukocytosisismorecommonin
children.Ifobservedinthethirdweekofillness,leukocytosisshouldpromptsuspicionforintestinalperforation.
Abnormalliverfunctiontestsarefrequentlyobserved[28,45].Inanoutbreakin34patients,abnormalliver
functiontestswereobservedinallbutonepatient[28].Insomepatients,theclinicalandlaboratorypicture
maybesuggestiveofacuteviralhepatitis[46].Inonestudycomparing27patientswithSalmonellahepatitisto
27casesofviralhepatitis,Salmonellahepatitiswasmorefrequentlyassociatedwithbradycardia(42versus4
percent)andfever>40C(44versus4percent)serumaminotransferasesalsotendedtobelower(peakserum
ALT296versus3234IU/L).Apotentialdiagnosticchallengeinpatientspresentingwithabnormalliverfunction
testsisthatthetwoinfectionsmaybepresentatonce.
Cerebrospinalfluidstudiesareusuallynormalorrevealamildpleocytosis(<35cells/mm3),eveninpatients
withneuropsychiatricsymptoms[42].
Specialpopulations
ChildrenCertainclinicalmanifestationsassociatedwithtyphoidfeveroccurwithdifferentfrequencyin
childrencomparedwithadultsagedifferenceswerespecificallyexaminedinareviewof552cultureconfirmed
casesinBangladesh[37].Pneumoniaandfebrileseizureswereoverallinfrequentbutoccurredmorecommonly
inchildren,whereasintestinalperforationwasnotseeninpatientsunderfiveyearsold.Youngerpatientsalso
tendedtohavehigherWBCcounts14ofthe15patientswithaWBCcount>20x103/mm3wereyoungerthan
fiveyearsold.
Evenamonginfants,thereisvariabilityintheseverityofthedisease.InaseriesfromChile,febrileinfantswith
typhoidfeverhadrelativelymildillnessesnotrequiringhospitalization[47],whileastudyfromBangladesh
notedafatalityrateof11percent[37].
HIVinfectedpatientsTheseverityofentericfeverdoesnotappeartobemarkedlyincreasedinthe
settingofHIVinfection,althoughnontyphoidalsalmonellosisisknowntobemorecomplicatedinHIVinfection.
However,thereissomeevidencethatimmunocompromisedpatientsfarepoorlywithtyphoidalinfections.One
studyoffourindividualswithAIDSinPerudescribedatypicallyseverediarrheaorcolitis[32].InaTanzanian
seriesof104casesofintestinalperforationsduetotyphoidfevertreatedsurgicallyatauniversityhospital,
mortalitywasassociatedwithHIVpositivityandlowCD4countatadmission,amongotherfactors[48].Other
casereportshavedocumentedunusualmanifestationsofS.typhiinfectionsuchasarteritis[49]or
chorioamnionitis[50]inHIVinfectedpatients.
ChroniccarriersIngeneral,chroniccarriersdonotdeveloprecurrentsymptomaticdisease.They
appeartoreachanimmunologicequilibriuminwhichtheyarechronicallycolonizedandmayexcretelarge
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numbersoforganisms,buthaveahighlevelofimmunityanddonotdevelopclinicaldisease[13,5153].
ChroniccarriersfrequentlyhavehighserumantibodytitersagainsttheViantigen,whichisaclinicallyuseful
testforrapididentificationofsuchpatients[14,54].(See"Pathogenesisoftyphoidfever",sectionon'Chronic
carriage'.)
DIAGNOSISThediagnosisoftyphoidfeverismadebycultureofthecausativemicroorganisminthe
settingofacompatibleclinicalillness.Typhoidfevershouldbeconsideredinapatientlivingin,travelingfrom,
orvisitingfromanendemicareawhopresentswithabdominalpain,fever,andchills.Inaddition,
autochthonouscasesoroutbreakscanoccurduetotransmissionviachroniccarriers[5557].Serologictests
areoflimitedclinicalutility.Inresourcelimitedsettings,thediagnosisoftyphoidfeverisoftenbasedupon
clinicalmanifestationsalone.
Thedifferentialdiagnosisisbroadandincludesmalaria,amebiasis,denguefever,leishmaniasis,andother
causesofbacterialgastroenteritis.(See"Evaluationoffeverinthereturningtraveler".)
CultureBloodculturesarepositivein40to80percentofpatients,dependingupontheseriesandculture
techniquesused.Bloodculturesmayrequireseveraldaysofincubation.Thediagnosiscanalsobemadeby
cultureofstool,urine,rosespots,orduodenalcontents(viastringcapsule)[58].Stoolcultureispositiveinup
to30to40percentofcases,butisoftennegativebythetimethatsystemicsymptomsbringpatientsto
medicalattention[47].
Bonemarrowcultureisthemostsensitiveroutinelyavailablediagnostictool[59].Thismaybeparticularly
importantincomplicatedcasesorwhenantimicrobialtherapyhasalreadybeeninitiatedandthediagnosis
remainsuncertain.Bonemarrowculturesmaybepositiveinasmanyas50percentofpatientsafterasmany
asfivedaysofantibiotics[33].Inoneseriesof44patientswithtyphoidfever,S.typhiwasisolatedfrom98
percentofbonemarrowculturescomparedwith70percentofbloodcultures[60].
S.typhiisolatesshouldbescreenedforresistancetonalidixicacid,orhaveformalsensitivitytestingforthe
clinicallyusedfluoroquinolones[61,62].Organismswithnalidixicacidresistanceshouldbeanticipatedtohave
reducedsusceptibilitytofluoroquinolones,eveniffluoroquinolonesensitivityisreportedbythelaboratory.(See
"Treatmentandpreventionoftyphoidfever",sectionon'Fluoroquinoloneresistantorganisms'.)
SerologySerologictestssuchastheWidaltestareoflimitedclinicalutilityinendemicareasbecause
positiveresultsmayrepresentpreviousinfection.TheWidaltestdetectsantiS.typhiantibodies,andthe
minimaltitersdefinedaspositivefortheO(surfacepolysaccharide)antigensandH(flagellar)antigensmustbe
determinedforindividualgeographicareastheyarehigherindevelopingregionsthanintheUnitedStates[63].
Whenpairedacuteandconvalescentsamplesarestudied,afourfoldorgreaterincreaseisconsideredpositive.
Positiveresultshavebeenreportedin46to94percentofcases[64].Inastudyofhealthyblooddonors
performedincentralIndia,seropositivityfortyphoidfeverusingtheS.typhiOantigenorS.typhiHantigen
wasobservedin8and14percent,respectively[64].
Newerserologicassaysusingenzymelinkedimmunosorbentassay(ELISA)anddipsticktechniquesperform
somewhatbetterthantheWidaltest,butsensitivityandspecificityarenotadequateforroutinediagnosticuse
[65].AnELISAforantibodiestothecapsularpolysaccharideViantigenisusefulfordetectionofcarriers,but
notforthediagnosisofacuteillness[14,54].
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"
and"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
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Basicstopics(see"Patientinformation:Typhoidfever(TheBasics)")
SUMMARY
Typhoidfeveristransmittedbycontaminatedfoodorwater.Theorganismclassicallyresponsibleforthe
entericfeversyndromeisS.entericaserotypeTyphi(formerlyS.typhi)otherSalmonellaemaycausea
similarclinicalsyndrome.(See'Introduction'above.)
Typhoidfeverismorecommoninchildrenandyoungadultsthaninolderpatients.Humansaretheonly
reservoirforS.entericaserotypeTyphi.Inresourcerichsettings,mostcasesoftyphoidfeveroccurin
patientswhohavetraveledtoendemicregions,particularlysouthcentralAsia.Ahistoryoftravelto
settingsinwhichsanitationispoororhistoryofcontactwithaknowntyphoidcaseorcarrierisusefulfor
identifyingpatientsatriskofinfection,althoughaspecificcontactisidentifiedinaminorityofcases.
(See'Epidemiology'above.)
ChronicSalmonellacarriageisdefinedasexcretionoftheorganisminstoolorurine>12monthsafter
acuteinfection.RatesofchroniccarriageafterS.typhiinfectionrangefrom1to6percent.Chronic
carriageoccursmorefrequentlyinwomenandinpatientswithcholelithiasisorotherbiliarytract
abnormalities.Chroniccarriersrepresentaninfectiousrisktoothers,particularlyinthesettingoffood
preparation.(See'Chroniccarriage'above.)
Typhoidfeverusuallypresentswithabdominalpain,fever,andchillsapproximately5to21daysafter
ingestionofthecausativemicroorganism.Classicmanifestationsincluderelativebradycardia,pulse
temperaturedissociation,and"rosespots"(faintsalmoncoloredmaculesonthetrunkandabdomen).
Hepatosplenomegaly,intestinalbleeding,andperforationmayoccur,leadingtosecondarybacteremiaand
peritonitis.Laboratoryfindingsmayincludeanemia,leukopenia,leukocytosis,andabnormalliverfunction
tests.(See'Clinicalfeatures'above.)
Thediagnosisoftyphoidfeverismadebycultureofthecausativemicroorganisminthesettingofa
compatibleclinicalillness.Theorganismcanbeculturedfromblood,stool,urine,rosespots,duodenal
contents,orbonemarrow.Serologictestsareoflimitedclinicalutilitygiveninsufficientsensitivityand
specificity.(See'Diagnosis'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Topic2708Version12.0

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GRAPHICS
Infectionsinreturningtravelersbyregionofexposure,1996to2011

Thismapindicatesthenumberofcasesofselectedacuteandpotentiallylifethreateningdiseasesreg
reportedamong82,825travelersfromresourcerichcountriestovarioustropicalregionsbetween1996
2011.DataarefromtheGeoSentinelsurveillancenetwork.

ReproducedwithpermissionofAmericanSocietyofTropicalMedicineandHygiene,JenseniusM,HanPV,Schlagen

al.AcuteandpotentiallylifethreateningtropicaldiseasesinwesterntravelersaGeoSentinelmulticenterstudy,1
2011.AmJTropMedHyg201388:397.Copyright2013permissionconveyedthroughCopyrightClearanceC
Inc.
Graphic90927Version2.0

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