阿米巴病和贾第鞭毛虫病

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?