Diagnosing Schistosomiasis by Detection of Cell-Free Parasite DNA in Human Plasma 英文参考文献.docVIP

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Diagnosing Schistosomiasis by Detection of Cell-Free Parasite DNA in Human Plasma 英文参考文献.doc

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Diagnosing Schistosomiasis by Detection of Cell-Free Parasite DNA in Human Plasma 英文参考文献

DiagnosingSchistosomiasisbyDetectionofCell-Free ParasiteDNAinHumanPlasma DominicWichmann1,MarcusPanning2,ThomasQuack3,StefanieKramme2,Gerd-DieterBurchard1, ChristophGrevelding3,ChristianDrosten2¤* 1SektionInfektiologieundTropenmedizin,I.MedizinischeKlinik,Universita¨tsklinikumEppendorf,Hamburg,Germany,2ClinicalVirologyGroup,BernhardNochtInstitute forTropicalMedicine,Hamburg,Germany,3InstituteofParasitology,FacultyofVeterinaryMedicine,JustusLiebigUniversity,Giessen,Germany Abstract Introduction: Schistosomiasis (bilharzia), one of the most relevant parasitoses of humans, is confirmed by microscopic detectionofeggsinstool,urine,ororganbiopsies.Thesensitivityoftheseproceduresisvariableduetofluctuationofegg shedding.Serologicaltestsontheotherhanddonotdistinguishbetweenactiveandpastdisease.Inpatientswithacute disease(Katayamasyndrome),bothserologyanddirectdetectionmayproducefalsenegativeresults.Toovercomethese obstacles,wedevelopedanoveldiagnosticstrategy,followingtherationalethatSchistosomaDNAmaybeliberatedasa resultofparasiteturnoverandreachtheblood.Cell-freeparasiteDNA(CFPD)wasdetectedinplasmabyPCR. Methodology/PrincipalFindings:Real-timePCRwithinternalcontrolwasdevelopedandoptimizedfordetectionofCFPD in human plasma. Distribution was studied in a mouse model for Schistosoma replication and elimination, as well as in humanpatientsseenbeforeandaftertreatment.CFPDwasdetectableinmouseplasma,anditsconcentrationcorrelated withthecourseofanti-Schistosomatreatment.Humanswithchronicdiseaseandeggsinstoolorurine(n=14)showeda 100%rateofCFPDdetection.CFPDwasalsodetectedinall(n=8)patientswithKatayamasyndrome.Patientsinwhomno viableeggscouldbedetectedandwhohadbeentreatedforschistomiasisinthepast(n=30)showedlowerdetectionrates (33.3%)andsignificantlylowerCFPDconcentrations.ThedurationfromtreatmenttototaleliminationofCFPDfromplasma wasprojectedtoexceedoneyear. Conclusions/Significance:PCRfordetectionofCFPDinhumanplasmamayprovideanewlaboratorytoolfordiagnosing schistosomiasisinallph