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PathogenicEscherichiacoli

OfficialreprintfromUpToDate
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PathogenicEscherichiacoli
Author
Christine
A
Wanke,
MD

Section
Editor
Stephen
B
Calderwo
od,MD

Deputy
Editor
Allyson
Bloom,
MD

Disclosures:ChristineAWanke,MDConsultant/AdvisoryBoards:Cubist[DSMB].OtherFinancialInterest:ParrPharmaceuticals
[Expertwitnessinpatentcase(Megestrolacetate)].StephenBCalderwood,MDPatentHolder:VaccineTechnologiesInc.
[Vaccines(Choleravaccines)].EquityOwnership/StockOptions:Pulmatrix[Inhaledantimicrobials]PharmAthene[Anthrax(Anti
protectiveantigenmonoclonalantibody)].AllysonBloom,MDNothingtodisclose.

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jun2015.|Thistopiclastupdated:Oct15,2013.
INTRODUCTIONEscherichiacoliarenormalinhabitantsofthehumangastrointestinaltractandareamongthe
bacterialspeciesmostfrequentlyisolatedfromstoolcultures.WhenE.colistrainsacquirecertaingenetic
material,theycanbecomepathogenic.E.coliareamongthemostfrequentbacterialcausesofdiarrheaandare
classifiedbyclinicalsyndrometheyproduce(table1)[1].
ThecharacteristicsofdiarrhealillnesscausedbyenterotoxigenicE.coli(ETEC),enteropathogenicE.coli(EPEC),
enterohemorrhagicE.coli(EHEC,alsocalledShigatoxinproducingE.coliorSTEC),enteroinvasiveE.coli
(EIEC),andenteroaggregativeE.coli(EAECorEAggEc)willbereviewedhere.EHECisalsodiscussedin
greaterdetailseparately.(See"Microbiology,pathogenesis,epidemiology,andpreventionofenterohemorrhagic
Escherichiacoli(EHEC)"and"Clinicalmanifestations,diagnosisandtreatmentofenterohemorrhagicEscherichia
coli(EHEC)infection".)
MICROBIOLOGYE.colicanbeculturedreadilyfromthestoolunderaerobicconditions.Onselectivemedia,
suchasMacConkeyagar,E.coliusuallyappearaspinkcolonies,indicatingthattheorganismfermentslactose
(picture1).Additionalbiochemicalidentificationshouldalsobeperformed,sinceupto10percentofE.colidonot
fermentlactoseorfermentlactoserelativelyslowly.ThemostusefulbiochemicalidentificationtestforE.coliis
theindoletest,whichispositiveinupto99percentofE.colistrains.
PathogenicE.coliarenotdistinguishablefromotherstrainsorfromeachotherbytheappearanceonculture
platesorbytheresultsoftheusualbiochemicaltests.Todeterminewhethertheisolatedstrainisoneofthe
pathogenicstrainsormerelyaconstituentofthenormalflora,additionalidentificationtechniquesmustbe
employed,whicharegenerallylimitedtoresearchlaboratorysettings.
EHECO157istheonlypathogenicstrainthatcanbeidentifiedreadilyintheclinicallaboratory[2].Furthertesting
onpathogenicE.coliisolatesmustbeperformedinaresearchorreferencelaboratory.Thistestingcaninclude
determiningtheserotypeofthestrain,performingbiologicalassays(bioassays)thatdemonstratestrainvirulence,
andusinggenetictools,suchasDNAprobingorpolymerasechainreaction(PCR)amplification,toidentify
geneticmaterialthatencodesforspecificvirulencefactors.
ThevirulencetraitsaredistinctforeachcategoryofpathogenicE.coli[3].Thesevirulencetraitsinclude
adherencefactorsthatallowE.colitoattachtotheintestinalmucosa,andtoxinsthatinterruptnormalintestinal
cellsecretionandabsorption(secretorytoxins)orthatdamagetheintestinalcell(cytotoxins).Theseadherence
factorsandtoxinsareencodedonaccessorygeneticelementsinE.coli,suchasplasmids,transposons,and
bacteriophages.
ENTEROTOXIGENICESCHERICHIACOLI(ETEC)EnterotoxigenicE.coli(ETEC)causeswaterydiarrheain
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younghumansandothermammals,aswellasinolderindividualswhohavenotbeenexposedtotheorganism[4].
ETECsurvivereadilyinwaterandfoodsuppliesinthedevelopingworldandisoneofthemostcommonbacterial
causesofdehydratingdiarrhealillnessinchildrenundertwoyearsofageintheseregions[5].Thesestrainscan
alsocausediarrheaintravelerstotropicalregionswhoareexposedtocontaminatedfoodandwater.Inaddition,
ETECisemergingasasignificantdiarrhealpathogenindevelopedregions[68].(See"Travelers'diarrhea:
Microbiology,epidemiology,andprevention".)
PathogenesisThepathogenesisofdiseaseduetoETECconsistsoftransmissionofbacteria,intestinal
colonization,andelaborationofvirulencefactor(s).ETECmustcontaincolonizingfimbriaetopermitthe
attachmentofthebacteriatotheintestine.Antibodiestofimbrialadhesins,specificallycolonizationfactorantigen
I,havebeenshowntobeprotectiveinamousemodel[9].
E.colicapableofattachingtotheintestinemustalsobecapableofelaboratingvirulencefactorsinordertocause
disease.TherearetwomajorclassesofsecretorytoxinsencodedonplasmidsinETECstrains:heatlabiletoxins
(LT)andheatstabletoxins(ST)[10].E.colithatcontainoneorbothofthesetoxinclassesareclassifiedas
ETEC[11].
LTisacomplexfamilyoftoxinsrelatedtocholeratoxinproducedbyVibriocholeraewithrespecttostructure,
functionandmechanism.LTactsbystimulatingadenylatecyclaseandincreasingintracellularcyclicAMP,which
resultsinsecretionofchloridefromintestinalcryptcellsandinhibitionofabsorptionofsodiumchlorideatthevillus
tips.Secretionoffreewaterintotheintestinallumenfollows,manifestingclinicallyaswaterydiarrhea[12].Studies
suggestthatLTanditssecretionapparatuscanclusteratoneendofthebacterialorganism,whichmaypermit
ETECtofocustoxindeliverytothehostintestinalcell[13].(See"PathogenesisofVibriocholeraeinfection".)
TherearetwomajorSTsthatmaybepresentinETEConlyoneofthese,STa,isassociatedwithhuman
disease.STactivatesenterocytecyclicGMPandalsoleadstothestimulationofchloridesecretionandinhibition
ofsodiumchlorideabsorption.Theendresultissecretionoffreewaterintotheintestinallumen,whichmanifests
clinicallyaswaterydiarrhea[12].
Approximately10(8)to10(10)ETECmustbeingestedtoinducediarrheainanotherwisehealthyindividual[1].
Exposuretothislargeinoculumoccursreadilysincethepathogenthrivesintheenvironment.Theillnesshasa
shortincubationperiod,andtheonsetofsymptomsandsignsisrapid.Patientsmayreportnausea,butvomitingis
uncommon.Diarrheaiswateryandmaybemildorsevere.Theillnessmaylastforonetofivedays.
DiagnosisandtreatmentThediagnosisofETECiscurrentlyperformedintheresearchorreferencelaboratory
usingDNAprobesthatidentifythegenesforLTorST[14,15].Classicallytheseorganismswereidentifiedby
bioassaysforthesecretorytoxins:therabbitilealloopforLTandthesucklingmouseassayforST.
TreatmentofdiarrhealillnessduetoETECisdiscussedindetailseparately.(See"Travelers'diarrhea:Clinical
manifestations,diagnosis,andtreatment".)
ENTEROPATHOGENICESCHERICHIACOLI(EPEC)EnteropathogenicE.coli(EPEC)strainsaredefined
bythecharacteristic"attachingandeffacing"effecttheyelicituponinteractionwithepithelialcellsandbythefact
thattheydonotproduceShigatoxin(figure1).EPEChavebeenassociatedwithsporadicdiarrhealillnessand
diarrheaoutbreaks,mostcommonlyamongchildrenlessthansixmonthsofageindevelopingcountries[16].
DiseaseduetoEPECstrainshasbeendescribedamongadults,althoughovertillnessismuchlesscommon.
ThisistrueevenamongadultsinthedevelopingworldwhofrequentlydevelopdiarrheaduetoETEC[17].
PathogenesisEPECproteinsdonotbehavelikeclassictoxinsthefollowingobservationshavefurtheredour
understandingofhowbacterialorganismscanaffectcellphysiologythroughadherence,evenintheabsenceof
toxinproduction.ThestepsinpathogenesisofEPECforinitiationofdiarrhealillnessinclude[1821]:
Initiallocalizedadherenceoftheorganismstotheenterocyte
InductionofsignaltransductionintheenterocytebyEPECproteinsecretion
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Developmentofintimateadherencewiththeenterocyte
Signaltransductionisinitiatedbybacterialsecretionofproteinsdirectlyintotheenterocyte[22].Thiscauses
mobilizationofintracellularcalcium,activationofproteinkinaseCandthemyosinlightchainkinase,andinduction
oftyrosinephosphorylationofproteins[23].Activationofthesesignaltransductionpathwaysproduceschangesin
theenterocyte(resultingintheclassic"attachingandeffacing"lesion),alterationsinwaterandelectrolyte
secretion,andincreasedpermeabilityofintestinaltightjunctions.Thegenesthatencodethesevirulencetraitsare
locatedonaplasmid(bundleformingpili)orwithinachromosomalpathogenicityislandoftheorganism.Atypical
EPECdonotproducebundleformingpili.
EspFisasecretedproteinthatisnotinvolvedwithattachingandeffacingitappearstodisruptintestinalbarrier
functionbyincreasingmonolayerpermeabilityviaalterationofelectricalresistance[24].EspFhasseveralprotein
proteininteractiondomainsthatmayfunctionbyinteractingwithendocyticregulation[25].Twoothersecreted
proteins,EspGandEspG2,inhibitluminalmembranechlorideabsorptionbydecreasingsurfaceexpressionofthe
Cl/OHexchangerviadisruptionofmicrotubules[26].
ThediarrheaassociatedwithEPECinchildrencanbesevere,withconcomitantvomitinganddehydration.If
diarrheapersists,malnutritioncanbeadevastatingcomplication,particularlyinthedevelopingworldwhere
resourcesforsupportivetherapymaybelimited.CellculturedatasuggestthatEPECinfectioninhibitsabsorption
ofthiaminethismaybeonemechanismbywhichEPECinfectioncontributestomalnutritionofsome
micronutrients[27].
DiagnosisandtreatmentThegoldstandardforidentificationofEPECisthedetectionbyDNAprobeor
polymerasechainreaction(PCR)oftheEPECadherencefactor(EAF).Thesediagnosticassaysareavailable
onlyinresearchorreferencelaboratories.
EPECwasoriginallycategorizedandrecognizedbyserotypeandlater,byitsabilitytoadhereinalocalized
fashiontoepithelialcellsinatissuecultureadherenceassay[28,29].Subsequently,itwasidentifiedbyitsability
tomobilizecellularactininafluorescentactinstaining(FAS)assay[30].Usingtheseoldertechniques,the
absenceofEHECtoxinsalsohadtobedemonstratedinaputativeEPECorganismbecausesomestrainsof
EHECalsodevelopattachingandeffacinglesions.
TreatmentofdiarrhealillnessduetoEPECisdiscussedindetailseparately(See"Approachtothechildwithacute
diarrheainresourcelimitedcountries",sectionon'Treatment'.)
ENTEROHEMORRHAGICESCHERICHIACOLI(EHEC)EnterohemorrhagicE.coli(EHEC)strainsare
capableofproducingShigatoxinandlikeEPECstrains,demonstratean"attachingandeffacing"lesion(figure1).
AsubsetofEHECorganismsareserotypeO157:H7[2,31].InMay2011,anewShigatoxinproducingEHEC
similartoEAEC55989wasidentifiedasthecauseofanoutbreakinGermanyandinothercountriesinEurope
[32,33].Thisstrain,O104:H4,hasthetypicalplasmidadherencegenesofEAECbacteriaaswellasShigatoxin
genesseeninEHEC,andhasdemonstratedaggressivevirulence[34,35].(See"Clinicalmanifestations,diagnosis
andtreatmentofenterohemorrhagicEscherichiacoli(EHEC)infection".)
TherearealsoShigatoxinnegativeO157strainsinareviewofO157isolatesfromstoolspecimensrelatedto
sporadiccasesofdiarrhea,4percentwereShigatoxinnegative[36].ThesestrainswereeitherinherentlyShiga
toxinnegativeanddidnotcausebloodydiarrheaorHUSorweredescendedfromEHECstrainsbythelossof
Shigatoxingenes.ThesestrainsmaystillcauseHUS[36,37].
EHECstrains,especiallythosebelongingtoserotypeO157:H7,havebeenresponsibleforlargeoutbreaksof
bloodydiarrhea,someassociatedwithhemolyticuremicsyndrome(HUS),atriadofmicroangiopathicanemia,
renalfailure,andthrombocytopenia[38,39].
EHECinfectionisdiscussedfurtherseparately.(See"Microbiology,pathogenesis,epidemiology,andprevention
ofenterohemorrhagicEscherichiacoli(EHEC)"and"Clinicalmanifestations,diagnosisandtreatmentof
enterohemorrhagicEscherichiacoli(EHEC)infection".)
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Shigatoxinassociatedhemolyticuremicsyndromeisdiscussedfurtherseparately.(See"Clinicalmanifestations
anddiagnosisofShigatoxinproducingEscherichiacoli(STEC)hemolyticuremicsyndrome(HUS)inchildren"and
"TreatmentandprognosisofShigatoxinproducingEscherichiacoli(STEC)hemolyticuremicsyndrome(HUS)in
children".)
ENTEROINVASIVEESCHERICHIACOLI(EIEC)EnteroinvasiveE.coli(EIEC)iscloselyrelatedtoShigella
andcausesdiseasethatissimilartoshigellosis.EIECinvadestheintestinalcell,multipliesintracellularly,and
extendsintotheadjacentintestinalcells.ThesamegenesfacilitatepathogenesisofbothEIECandShigella[40].
EIECmaybedifferentiatedfromShigellaprincipallybythefactthatEIECstrainsfermentglucoseandxylose.
(See"Shigellainfection:Epidemiology,microbiology,andpathogenesis".)
ClinicalEIECinfectionappearstobeuncommon,althoughitmaybeunderdiagnosed.ClinicaldiseasewithEIEC
beginsaswaterydiarrheaandmayormaynotproceedtobloodydiarrhea.Theorganismscanbedetectedby
DNAprobe,althoughthistoolisnotroutinelyavailableinclinicallaboratories.
TheclinicalapproachisasoutlinedseparatelyforShigellainfection.(See"Shigellainfection:Treatmentand
preventioninadults".)
ENTEROAGGREGATIVEESCHERICHIACOLI(EAEC)EnteroaggregativeE.coli(EAECorEAggEc)was
firstdescribedinthe1980s,whencollectionsofE.colifromstudiesofdiarrheainthedevelopingworldwere
examinedintissuecultureadherenceassays[41].E.colithathadadistinctivecascadingadherenceonHep2
cellswereobservedmorefrequentlyinthestoolsofchildrenwithdiarrheathanchildrenwithoutdiarrhea[42].
TherehasbeenaconsistentassociationbetweenpersistentdiarrheaamongchildrenandthepresenceofEAECin
thestoolinstudiesfromChile,Brazil,Mexico,India,andBangladesh[4349].
EAECappearstobeacauseofacutediarrhealillnessamongmanydifferentsubpopulationsinbothdeveloping
andindustrializedregions.SurveysofE.colifromdiarrheaoutbreaksinEuropehavedemonstratedthepresence
ofEAECinbothoutbreaksandsporadiccasesofdiarrhea[50,51].EAEChavealsobeenassociatedwith
persistentdiarrheainadultswithHIVinfectionintheUnitedStatesandSwitzerland[52,53].Inthesestudies,
EAECdiarrheawasmorecommoninpatientswithadvancedimmunecompromise.
InaUSprospectivestudyofdiarrhealillnessamongpatientsandcontrols,EAECwasobservedin4.5percentof
casesandoccurredsignificantlymorefrequentlyamongcasesthancontrolstherewasnoassociationwithtravel
orimmunodeficiency[54].AmetaanalysisnotedapositivecorrelationbetweenacutediarrhealillnessandEAEC
excretioninthefollowinggroups[55]:
Childrenresidinginbothdevelopingandindustrializedregions
AdultswithHIVinfectionresidingindevelopingregions
Adultsresidingindevelopingregions
Internationaltravelerstodevelopingregions
PathogenesisThepathogenesisofdiarrheacausedbyEAECisnotwellunderstood[42].EAECarecapableof
inducingthereleaseofinterleukin(IL)8fromCaco2humancolonicepithelialcells[56].Investigatorshavecloned
andsequencedasolublefactorfromEAECresponsibleforIL8releaseandidentifiedittobeanovelflagellin[57].
StrainsofEAECthatlackthisflagellindonotpromoteIL8release,whichmaybeimplicatedintheinductionof
chronicintestinalinflammation.
Avarietyofotherpathogeneticmechanismshavebeenpostulated:
Adherencefimbriae(AAF/1AAF/III)havebeenidentified,butthemajorityofEAECstrainsdonotexpress
theseadherencefactors[58].Thegenesforthesefimbriaeareencodedinavirulenceplasmidthatappears
tobepresentinmostEAECstrainsregardlessofwhetherornotAAF/IorAAF/IIisexpressed.TheaggR
geneencodesaproteinlabeleddispersin,whichactstodispersethebacteriaonthecolonicmucosa[59].
Mucosaldestructionhasbeendemonstratedinclinicalspecimensandintissuecultureassays,anda
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cytotoxinhasbeenidentifiedinEAECstrains.
OthergroupshaveidentifiedEAECstrainsthatinvadetissueculturecellsandinduceIL8productionvia
mitogenactivatedproteinkinase[60,61].
A"package"ofplasmidborneandchromosomallymediatedvirulencefactorsisthoughttobepredictiveof
pathogenesis.Itispostulatedthatthis"package"isunderthecontrolofatranscriptionalactivatorcalledAggR
[62].ThesevirulencefactorsappeartobeassociatedwiththepresenceofdiarrheainindividualswithEAEC
strainsinthestool[63].AnewlyidentifiedHdaAgeneclusteralsoappearstoconferaggregativeadherenceand
mayexplaintheaggregativeadherencethathasnotbeenassociatedwiththeotherrecognizedadhesins[64].
DiagnosisandtreatmentThegoldstandardforthediagnosisofEAECisthetissuecultureadherenceassay.
ThereisnoDNAprobethatreliablyidentifiesEAECstrainsthus,EAECcanonlybediagnosedinresearchor
referencelaboratories[1].
SeveralstudieshavedemonstratedthatdiarrhearesolvedwhenEAECwasclearedfromthestoolwithantibiotic
treatment[65,66].Inaplacebocontrolledtrialincluding29patientswithEAEC,treatmentwithciprofloxacin
reducedthedurationofdiarrheacomparedtoplacebo(35versus56hours)[65].Inacrossovertrialof24HIV
infectedpatientswithEAEC,treatmentwithciprofloxacineradicatedtheorganismfromstoolandreduceddaily
stooloutputby50percent[66].
SinceidentificationofEAECrequiresreferencelaboratorytools,patientswithsuspectedEAECinfectioninthe
absenceofdiagnosticconfirmationshouldbemanagedsyndromicallyasdiscussedindetailseparately.(See
"Approachtotheadultwithacutediarrheainresourcerichcountries"and"Approachtotheadultwithacute
diarrheainresourcelimitedcountries"and"Approachtothechildwithacutediarrheainresourcelimitedcountries"
and"Evaluationofdiarrheainchildren".)
OTHERESCHERICHIACOLISTRAINSTherearenogooddatasupportingtheassociationofothertypesof
E.coli(eg,diffuselyadherentE.coli,detachingE.coli)withdiarrhea.However,sinceE.coliareubiquitousand
haveademonstratedcapacityforacquiringtheDNAforvirulencetraitsfromotherorganisms,additionalgroupsof
E.coliwillprobablybeassociatedwithdiarrhealdiseaseinthefuture.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Travelersdiarrhea(TheBasics)"and"Patientinformation:E.coli
(TheBasics)")
SUMMARY
Escherichiacoliarenormalinhabitantsofthehumangastrointestinaltractandareamongthebacterial
speciesmostfrequentlyisolatedfromstoolcultures.WhenE.colistrainsacquirecertaingeneticmaterial,
theycanbecomepathogenic.E.coliareamongthemostfrequentbacterialcausesofdiarrheaandare
classifiedbyclinicalsyndrometheyproduce(table1).(See'Introduction'above.)
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E.colicanbeculturedreadilyfromthestoolunderaerobicconditions.PathogenicE.coliarenot
distinguishablefromotherstrainsorfromeachotherbytheirappearanceoncultureplatesorbytheresults
oftheusualbiochemicaltests.Todistinguishpathogenicstrainsfromnormalflora,additionalidentification
techniquesmustbeemployedinaresearchorreferencelaboratory.EHECO157istheonlypathogenic
strainthatcanbeidentifiedreadilyintheclinicallaboratory.(See'Microbiology'above.)
EnterotoxigenicE.coli(ETEC)causeswaterydiarrhea.ETECsurvivesreadilyinwaterandfoodandisone
ofthemostcommonbacterialcausesofdehydratingdiarrhealillnessinchildrenundertwoyearsofagein
developingregions.ETECcanalsocausediarrheaamongtravelerstotropicalregionswhoareexposedto
contaminatedfoodandwaterand,inaddition,isemergingasapathogenindevelopedregions.Thereare
twomajorclassesofsecretorytoxinsencodedonplasmidsinETECstrains:heatlabiletoxins(LT)and
heatstabletoxins(ST).ThesetoxinsactivatecyclicAMPorGMPrespectively,leadingtostimulationof
chloridesecretion,inhibitionofsodiumchlorideabsorption,andsecretionoffreewaterintotheintestinal
lumen,manifestingaswaterydiarrhea.(See'EnterotoxigenicEscherichiacoli(ETEC)'above.)
EnteropathogenicE.coli(EPEC)strainsaredefinedbythecharacteristic"attachingandeffacing"effect
theyelicituponinteractionwithepithelialcellsandbythefactthattheydonotproduceShigatoxin.EPEC
havebeenassociatedwithsporadicdiarrhealillnessanddiarrheaoutbreaks,mostcommonlyamong
childrenlessthansixmonthsofageindevelopingcountries.EPECproteinsdonotbehavelikeclassic
toxinsrather,theyaffectcellphysiologythroughadherenceandinductionofsignaltransduction.(See
'EnteropathogenicEscherichiacoli(EPEC)'above.)
EnterohemorrhagicE.coli(EHEC)strainsarecapableofproducingShigatoxinandlikeEPECstrains,
demonstratean"attachingandeffacing"lesion.AsubsetofEHECorganismsareserotypeO157:H7.
EHECstrains,especiallythosebelongingtoserotypesO157:H7(andsubsequently,O104:H4)havebeen
responsibleforlargeoutbreaksofbloodydiarrhea,someassociatedwithhemolyticuremicsyndrome.(See
'EnterohemorrhagicEscherichiacoli(EHEC)'aboveand"Clinicalmanifestations,diagnosisandtreatment
ofenterohemorrhagicEscherichiacoli(EHEC)infection".)
EnteroinvasiveE.coli(EIEC)iscloselyrelatedtoShigellaandcausesdiseasethatissimilartoshigellosis.
EIECinvadestheintestinalcell,multipliesintracellularly,andextendsintotheadjacentintestinalcells.The
samegenesfacilitatepathogenesisofbothEIECandShigella.ClinicaldiseasewithEIECbeginsas
waterydiarrheaandmayormaynotprogresstobloodydiarrhea.(See'EnteroinvasiveEscherichiacoli
(EIEC)'above.)
EnteroaggregativeE.coli(EAEC)wasfirstdescribedinthe1980s,whencollectionsofE.colifromstudies
ofdiarrheaindevelopingworldsettingswereexaminedintissuecultureadherenceassays.E.colithathad
adistinctivecascadingadherenceonHep2cellswereobservedmorefrequentlyinthestoolsofchildren
withdiarrheathanchildrenwithoutdiarrhea.EAECappearstobeacauseofpersistentandacutediarrheal
illnessamongmanydemographicgroupsinbothdevelopinganddevelopedregions.(See
'EnteroaggregativeEscherichiacoli(EAEC)'above.)

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