Shiga Toxin-Mediated Hemolytic Uremic Syndrome Time to Change the Diagnostic Paradigm 英文参考文献.docVIP

ShigaToxin-MediatedHemolyticUremicSyndrome:Time toChangetheDiagnosticParadigm? MartinaBielaszewska1*,RobinKo¨ck1,AlexanderW.Friedrich1,ChristofvonEiff2,LotharB.Zimmerhackl3,HelgeKarch1,AlexanderMellmann1 1InstituteofHygieneandtheNationalConsultingLaboratoryonHemolyticUremicSyndrome,UniversityofMu¨nster,Mu¨nster,Germany,2Institute ofMedicalMicrobiology,UniversityofMu¨nster,Mu¨nster,Germany,3DepartmentofPediatrics,UniversityHospitalofInnsbruck,Innsbruck,Austria Background.Hemolyticuremicsyndrome(HUS)iscausedbyenterohemorrhagicEscherichiacoli(EHEC)whichpossessgenes encodingShigatoxin(stx),themajorvirulencefactor,andadhesinintimin(eae).However,thefrequencyofstx-negative/eae- positiveE. coliin stoolsofHUSpatients andtheclinical significanceofsuchstrainsareunknown. Methodology/Principal Findings. Between 1996 and 2006, we sought stx-negative/eae-positive E. coli in stools of HUS patients using colony blot hybridization with the eae probe and compared the isolates to EHEC causing HUS. stx-negative/eae-positive E. coli were isolatedastheonlypathogensfromstoolsof43(5.5%)of787HUSpatients;additional440(55.9%)patientsexcretedEHEC. Themajority(90.7%)ofthestx-negative/eae-positiveisolatesbelongedtoserotypesO26:H11/NM(nonmotile),O103:H2/NM, O145:H28/NM, and O157:H7/NM, which were also the most frequent serotypes identified among EHEC. The stx-negative isolatessharednon-stxvirulenceandfitnessgeneswithEHECofthecorrespondingserotypesandclusteredwiththemintothe same clonal complexes in multilocus sequence typing, demonstrating their close relatedness to EHEC. Conclusions/ Significance.Atthetimeofmicrobiologicalanalysis,,5%ofHUSpatientsshednolongerthecausativeEHEC,butdoexcrete stx-negative derivatives of EHEC that lost stx during infection. In such patients, the EHEC etiology of HUS is missed using currentmethodsdetectingsolelystxorShigatoxin;thiscanhamperepidemiologicalinvestigationsandleadtoinappropriate clinical management. While maintaining the paradigm that HUS is trigger