阿米巴病和贾第鞭毛虫病
Vo1.6,No.2Feb,2006
Amoebiasmandgmrcliasmii???0??-
StephenWright
Amoebiasis
AetioIogy
Entamoebahistol}ticaisamicro.aerophilicprotozoanparasite. Themotiletrophozoiteisfoundinthelargeintestineinhumans. Trophozoitesencystandthesecysts,excretedinfaeces,arethe meansoftransmissionbythefaeco.oralroute.Itwasrecognized thatmanyindividualsappearedtoexcretetheauadrinucleate, 7.5—15HmdiametercystsofEhistolyticabutexhibitednofea—
turesoftissueinvasion,andthatmanyfewerindividualshave. invasiveamoebicdisease,dysenteryorliverabscess.In1937, EmileBrumptsuggestedthatthereweretwodistinctspeciespro ducingidenticalc,rsts—E.histolytica,associatedwithinvasion, andE.dispar,aharmlesscommensa1.Thisnotionwasrejected.In the1970s.PeterSargeauntexaminedamoebaefromasymptomatic cyst—excreterswithnegativeamoebicserologyandamoebaefrom patientswithinvasivedisease.andshowedthatinvasivestrains wereassociatedwithonegroupofisoenzymepatternsandnon—
invasivestrainshadaconsistentlydifferentpattern.Otherdiffer—
enceswereshown.
?Invasiveamoebaecouldbeculturedaloneinvitro.whereasnon—
invasivestrainsalwaysrequiredco.cultivationwithbacteria. ?Invasivestrainswereresistanttocomplement—inducedlysis.
?Asurfacelectinwithgalactosen—acetylgalactosaminecarbo—
hydratedeterminantsmediatedadhesionininvasiveamoebae. TannichwasabletodistinguishinvasivestrainsbvDNAhybridi—
zation,and,later,ribosomalRNAsequencedatashowedsufficient differencestomeritseparatespeciesstatusforEhistolyrticaand E.dispar,asBrumpthadsuggested.
EpidemioIogYandtransmission
Amoebiasisismainlyadiseaseofthetropicsandsubtropics,where sanitationiscommonlyinadequate.thoughcaseshaveoccurredin individualswhohaveneverbeenoutsidetheUK.Itaffectsadults moreoftenthanchildren,andmalesmorethanfemalesinthecase ofamoebicliverabscess.TrueEhistolyticacystsareexcretedby 2—4%ofasymptomaticindividualsandarethesourceofinfection inothersbycontaminationoftheenvironment.foodandwater. Cystsinwateraredestroyedbyboilingandremovedbyfiltration, butarenotkilledbyordinarylevelsofchlorination;cystsinfood arekiliedbythoroughcooking.ItisunknownwhetherEhistob,tica istransmittedbylong—termasymptomaticcyst—excretersorbythose
whoexcretecystsforashortperiodoftime.Theinfectiousdose ofcystsisalsounknown.
StephenWrightisConsultantPhysicianattheHospitalforTropical Diseases,London.UK.Conflictsofinterest:nonedeclared. MEDlClNElNTERNATlONAL
Pathogenesisandpathology
Bowel:excystationoccursintheintestineandtrophozoitesinvade thelargebowe1.Lectin—mediatedcelladhesionisthefirststepinthe pathogenesis.Mucinfromthegutmayprotectagainstthisprocess bybindingtothelectin,butamoebaeingestmucus,reducingits protectiveefficacy.Colonicbacteriahaveglucosidases,whichmay altermucustoincreasesusceptibility.Amoebaemovebetween cellsandkillthembyinsertingalarge.permanentionchannel
famoebapore)intothehostcellmembrane.Individualamoeba—
poreunitspolymerizetoformthechanne1.Thethreeamoebapores exhibit25—30%sequencehomologywiththeperforinmolecule ofnaturalkillercellsandcytotoxicTcells.Withinamoebae, theseproteinskillbacteriaphagocytosedasnutrientsources.It isunknownhowtheamoebaeavoiddestroyingthemselveswith amoebapore.Parasitecysteineproteinasesdisrupthostcelladhe? sion,aidinginvasionandmovementthroughtissue. Humoralandcellularresponsesaredemonstrableininvasive diseaseandfnvitro,buttheextenttowhicht|levsignifyprotection iSquestionable.Effectivehostresponsesmightbeprotectiveinthe smallproportionofindividualswhoareasymptomaticexcreters 0fEhistolytica.Itiscurrentlyunknownwhatwouldbeseenat colonoscopyinthesecyst—excreters.Necrosisisthehallmarkof
invasiveamoebiasis,producingflask—shaped,underminedulcers
withamoebaeinthebaseandadvancingmargins.
Amoebicliverabscess:amoebaeenterbloodvesselsandspread haematogenouslyviatheportalvein,reachingtheliverand producinganabscessbythecytotoxiceffectdescribedabove; thisbeginsfocallywhenasingleorperhapsagroupofamoebae gainaccesstotheliverandreproduceasexually.Asthenumber ofamoebaeincreases,thenecroticfoCUSexpandsirregularlyout—
wards.Lysedlivercells,RBCsandserumproduceamoebicpus, butneutrophilsareabsentdespiteperipheralbloodneutrophil leucocytosis.Theseneutrophilsmayundergocontact—mediated
lysiswithamoebaeintheadvancingedgeoftheabscess.Emboli—
zationofamoebaetoseveralfociproducesmultipleabscesses. Metastasisfromthelivertocausebrainabscesscanoccur. ClinicaIfeatures
Dysentery:Figure1describesthetypicalhistoryinintestinal
amoebiasis,whichdoesnotbeginwithafebrileillnessandacute waterydiarrhoea.Theextentofcolonicinvolvementcanvary; thegreatertheextent,themoreseveretheclinicalmanifestations. Patientswithgreatermucosalulcerationsuffermoresignificant bleedingandproteinlOSSintothegutlumen.andbacteraemia maycontributetosystemicupset.
Thetypicalappearanceisofdiscreteulcerswithsloughin thebaseandsurroundingerythemascatteredoveranotherwise normalmucosa,butthereisarangeofappearances,anddiffusely inflamed,bleedingmucosamaybeseen.Symptomsandsignsare listedinFigure2.Toxicdilatation,perforationandhaemorrhage arecomplicationsofsevereamoebiasis;occasionally,alengthof mucosamaybesloughedoffandpassedperrectum—anillus—
trationoftheextenttowhichamoebaeunderminethesu~ce mucosa.Stricturescanoccurduringthecourseofamoebicdys—
entery.andcutaneousamoebiasiscandevelopintheperianalahd perinealareasandonthegenitalia.
Examinationoffaecalsmearsshowsmotiletrophozoites.These arealsoseeninmaterialscrapedfrominflamedorulcerated @20O6TheMedicinePublishingcompanyud
MrKhadbeent……ng1nSouIhEaslAsiaf0r3monthsAbouI
6weeksIntohislOurHev.hen0Ledachangeinbowelhabit. withstooisofvariablecGnsistencyandobservedflecksO『
~Lood5tajnedmuE~5ontheou~ide0fIheMooLsTherewasno paln0rsyslemlcupse[PhysicalexamlnallOn0fthEabdomenand re?Ix…inatEoner…m1alOn5Jgmo[doscopy,s~ttered
haemorrhagicarea5WereseenOHthelops0f…OsaI【ds
Ascrap1noftheseaTeasmounted…slidecoveredwithsalTne
andaco~ersEi口showedmotFletrophozoileswilhlngestedBCS AnamoebicIndIrecIflu0res【e"tantibodytwasnegatlve
iii")sj…n1nl?c?I1v.}l1Iiiioll?le(1iis,1Il'hlrd1r『IIIr【l
sCOpyBItl【{Figure3Jsh,'wr%mf~ehaeiT]S~'clillnSslalnedwilh II^c1'I(_rilerilldicjIlIScIiIIW1tl1j】(rsi】xteiiInfcc)1'J…c
…vvnIPrIaibum】I1】vbdec】l…nll(rcacliveprmeln{CRP】
】iicross~sAmoebicSelolog~rlsposltl…n1wotlliJdsofc~sos
t…r0.egi~li,semi】【'Hvth'c1xd?{i…ilIDI…iihls
I{dll~111]udiesshow/il…tl_~lucosa
AmoebomadI"colontom!,|1[Il…fDreviou~a.1oeblc
Llvse=ltelvTilei…ca】fii1d1ngaf1t1linsssI…11Il'aIisusll
allysinglenhenlI_theca~curllbul{Jcc.~sioualiy.1ultlilleTI d…10I1tIdiagnoses.…l1f『,llixdl,s一…')fn.1I】I)
L】】0sj…ltJl】rlcIdl_s*^f11tl_.1Tn,lydlfficuIttoIind 】iiIheIesilm0ncolonoscopvHistologystrawsgranuladoll[[sslle Amoebicselologyialwaysposi~iv
Amoebicliverabscess:sv~lpronisandsignsrelate【othesiteand
z0fIheabscessPade.1sw1thdsn/idlabscessll1dvexhillilonly f~veran~rexil1.…【1nighlswe,1Iw…IJillteasing~hscesssizepain
C~)ll~hIIIIfPI1…r【1rlt…?vmultipleabsc~sesa…0n
L?s…Sfever,chills.t11~1riggersw1II1Ilep,t4painSometimes.fever Clinicalfeaturesofamoebicdysentew
sourAdam【BMcEleod1~ledicine蛳?…J1977;5
,1523
3Amoebia$i$Thi5Eolonicbiopsy5how5uIEera[ion.withtrophozoltesof Entom~loahistolvtic~0nthesurfaceandinvadingthemucosa 燕垂
一
黧一_宝吣,sckO?曲,ev,.,咕?mm郫ngl二l二?aP?nel三m.毫叫m一
一一一
,
,
%
w
%
鬟
Vo1.6,No.2Feb,2006
4
5
Differentialdiagnosisofamoebicliverabscess ?Pvogenicliverabscess
?Subphrenicabscess
?Infectedhydatidcyst
?HepatoceUularcarcinoma
Drugtreatmentofamoebiasisandgiardiasis Amoeblasls—cyst-excreter
(Entomoebohistolytico,untypableorunknown) ?Diloxanidefuroate,500mgt.d.s.(25mg/kginthreedivided doses)for10days
Amoebicdysenteryoramoeboma
?Tinidazole,2g(50-75mg/k曲singledailydosefor3days, plusdiloxanidefuroate(asabove)ormetronidazole,800mg t.d.s.for5days,plusdiloxanidefuroate(asabove) Amoebicliverabscess
?Tinidazole,2g/day(50-75mg/k曲singledosefor3days
initially,occasionallyupto6days,plusdiloxanidefuroate
(asabove)
?MetrOnidazole,400mgt.d.s.for5days,plusdiloxanide
furoate(asabov~
GIardlasls
?Tinidazole,2g(50-75mg/kg)singledose,occasionally repeated7daysIater
?Metronidazole,2gsingledailydosefor3days.canbe repeated7daysIater
^ftemotives
?Mepacrine,100mgt.d.s.for5-7days
?Albendazole.400mgo.d.orb.d.for3-5days
'Physiciansinthetropicsmayconsiderthisexcessive,becausemany patientsareexcretingEntomoebadispor
DosereductionsforchildrenasjnmanufactureYsIiterature side—effect.Tinidazoleandmetronidazoleexhibitdisulfiram—like
interactionswithalcoholjnabout25%ofindividuals.soalcohol shouldbeavoidedduringtreatment.Amoebiccolitissettlesrapidly ontreatment.
Moreseriouslyaffectedpatientsshouldbeadmittedtohospital; theyrequirecarefulmonitoringwithfluidreplacement,transfusion asnecessary,andcombinedmedicalandsurgicalmanagementif dilatationorperforationoccurs.
Amoebomaregresseswithtreatment.butcarefulclinicalreview isneededtoensuresatisfactoryresolution.Amoebicliverabscess usuallyresolveswithanti—amoebictreatmentalone;improvement
infeverandpainisseenwithin24—48hoursofinitiationoftherapy.
Howeve~theneedforaspirationmustbeconsideredinallpatients withabscess;promptaspirationisneededwhen:
MEDICINEINTERNATIoNAL
?theabscessispointing
?theliverisve13itender
?theabscessisverylarge
?thereisconcernaboutimminentrupture.
MortalityisgreatestwhentheabscessextendsoutsidetheliveL Ruptureintothepericardiumcausesthegreatestmortality,asa resultoftamponade.
Giardiasis
Aetiology
Giardialambliaisamicro—aerophilic,flagellateprotozoanpara? siteoftheproximalsmallbowelinhumans,wherethemotile, free—livingtrophozoitesreplicateasexuallyandcystformationis initiated.Manyofthoseinfectedareasymptomaticcyst—excreters.
Giardiasiscausesdiarrhoeaofvaryingseverity,andmalabsorption insomepatients.
Tl_ansmissionandepidemiololp/
G{nrdiaisfoundworldwide,butismorecommoninareaswhere personalandpublicsanitationareinadequate.Intheseareas.itis mainlyaninfectionofchildren.nansmissionOCCUrsbyingestion ofcystsincontaminatedfoodorwate~orthroughperson—to—
personcontactduringsexualactivityoramongchildren;asfew astencystscancauseinfection.Contaminatedswimmingpools canbesourcesofinfection;relativelyhighlevelsofchlorination areinsufficienttoinactivatecysts.Cystscansurviveinwaterat 8.Cf0rseveralweeks.butarekiliedbyboilingandfiltrationof waterandthoroughcookingoffood.Hypogammaglobulinaemia predisposestopersistentsevereorrelapsinggiardiasis.Giardiais notacommoncauseofdiarrhoeainAIDS.
Thereisevidencethatgiardiasisisazoonoticinfection.Beavers trappedatasurfacewatersourceinCamas,USAwerefoundtobe excretingGiardiacysts,andmoleculargeneticsofisolatesfroma rangeofmammalshaveshownisolatesfromassemblagesAand Bthatincludeisolatescausinghumaninfection.
Pathogenesisandpathology
Gfnrdisnotcytotoxictohostcells.Carbohydrate.bearinglectins areinvolvedinadhesionoftrophozoitestotheenterocvtebrush bordeLTheorganismprobablydamagesthefuzzycoatfasiteof extracellulardigestion)andtheenterocytesurfacemembrane, impairingdigestivefunctions.Intraluminaldigestionisalsodis—
turbed(e.g.alteredlipaseactivity).Theabnormaliejunalmicro—
floraseeningiardiasisissimilartothatfoundintropicalsprue. butlackstheobligateanaerobesfoundinblind—loopsyndrome.
Invivoevidenceofalteredsmallbowelmucosalpermeabilityin micewasfoundinbothathymicandimmunocompetentmice. suggestingthatthiswasnotTcellmediated.
GfnrdfdaffectsvitaminB,,absorptionbyalteringintraluminal eventsratherthandamagingilealmucosa,whichisnormalon biopsy.Jejunalbiopsiesshowarangeofabnormalities,including reducedvillousheight,increasedcryptdepthandincreasedlamina propriainfiltrateofplasmacellsandlymphocytesinpatientswith moreseveresymptomsandmalabsorption.
Clinicalfeatures
Theseverityanddurationofsymptomsvary.Severelyaffected patientsexhibit:
?2oo6TheMedicinePublishingCompanyLtd
TropicalinfectinosVo1.6,No.2Feb,20O6
6
Differentialdiagnosisofgiardiasis
Acutepstrointestinaljnfections
?Salmonella.Shigella,Campylobacter(usuallyassociatedwith febrilesymptoms,colickyabdominalpainandoftendysentery alsopuscellsinstools)
?E5cerichiacoliandrotavirus
?Cryptosporidium(self-limitinginimmunocompetentpatients) ?Cyclosporacayatenesis
Persistentdiarrhoeaandmalabsorption
?Coeliacdisease(Giardiamayrenderovertpreviouslycovert coeliacdisease)
?Jejunaldiverticulosis
?IntestinaIstricture
?Pancreaticdisease
.pale,foul?smellingdiarrhoea(onsetcanbeacute) .abdominaldistension.discomfortandflatulence
.markedlethargy
.weightloss.
Manyinfectedindividualsareasymptomaticcyst—excreters.Symp—
tomsmayregressspontaneouslyafterseveralweeksor,rarely,per—
sistformonths.Prospectivestudieshaveshownthatgutinfections, includinggiardiasis,inthefirst2yearsoflifecanhaveadverse effectsoncognitivefunctionassessedseveralyearslater. Investigations
Stoolmicroscopyafterformolethylacetateconcentrationreveals cysts,butexaminationofmultiplespecimensmaybenecessary. Smearsoffluidstoolsfromacute?onsetcasesmayshowtropho? zoites.Thereisnofaecalcellularexudate.CommercialGiardia antigentestsarenowavailable.Trophozoitesareseeniniejunal fluidandinHandE—stainedduodenalbiopsysections.Folate
depletionoccursoccasionally.Bariumstudiesshownonspecific changeswiththickeningofmucosalfoldsanddilatedloopsofsmall bowe1.SerumantibodiestoGiardiacanbefoundinpatientswith malabsOrDtiOn.DifferentialdiagnosesareshowninFigure6. Management
TreatmentofgiardiasisisshowninFigure5.Patientsinwhom treatmentwithtinidazoleormetrOnidazOlefailsinitiallymay requireasecondcourseoftreatmentwiththesamedrugand,if thisremainsunsuccessful,alternativetreatmentwithmepacrine (quinacrine),100mgt.d.s.for7days,thoughthelatterdrugmay bedifficulttoobtain.Albendazoleisanotherpossiblechoice.The symptomsofgiardiasissettlewithin1weekandabnormalities relatedtointestinalabsorptionregressover2months. Persistingmildergutsymptomsmayberelatedtoafter—effects
suchashypolactasiaandfoodsensitivities,andappropriatedietary changesmayhelp.Relapseofinfectionandre—infectionfroma
regularcontact(e.g.ayoungchildwhoisexcretingcysts)must alsobeconsidered.
Iftreatmentduringpregnancyisnecessary,metronidazole, 200mgt.d.s.for7days.isrecommended.Metronidazoleand similardrugsshouldbeavoidedinthefirsttrimester.?
MEDICINEINTERNATIONAL
Trypanosomiasis:
AfricanandAmerican
SanjeevKrishna
AugustStich
DifferentspeciesoftheprotozoanT~ypanosomaareofsimilar appearance(Figure1),andallaretermed'kinetoplastids'because theymoveusingaflagellumthatobtainsenergyfromamitochon' drioncalledaplastid.However,trypanosomesalsodifferinmany ways,includingaspectsoftheirmolecularandcellularbiology, theirtransmission,andthediseasesthattheycause. ?InfectionwithTbruceicausestwoformsofsleepingsickness inhumansfFigure2)一acuteinfectionoftheEastAfricantype,
causedbyTb.rhodesiense,andamorechronicinfectioncausedby
b.gambiense(WestAfricantype).Botharefatalifuntreated. ?CrUZfinfectionacquiredinCentralorSouthAmerica progressesovermanyyearstoChagasdiseaseinupto30%of patients.
SleepingsicknessandChagasdiseaseareneglected,particularly becausetheyareonlyrarelyimportedintoEurope.Twobrothers returningfromanEastAfricansafariwererecentlydiagnosed withAfricant?