Ann Intern Med Liu XQ.pdf

该【Ann Intern Med Liu XQ 】是由【鼠标】上传分享，文档一共【22】页，该文档可以免费在线阅读，需要了解更多关于【Ann Intern Med Liu XQ 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。:..;:;148(5):325–,DPhil*,?,,MRCP*,?,,MDFRCP?,,PhD§,GeoffreyPasvol,FRCP,DPhil∥,SarahHackforth,RGN?,HansaVaria,RGN∥,Xiao-QingLiu,MD*,,DPhil*,RubamalarGunatheesan,BSc*,ValerieGuyot-Revol,PhD*,andAjitLalvani,FRCP,DM**TuberculosisImmunologyGroup,DepartmentofRespiratoryMedicine,NationalHeartandLungInstitute,ImperialCollegeLondon,StMary’sCampus,NorfolkPlace,London,W21PG,UnitedKingdom?DepartmentofInfection&TropicalMedicine,BirminghamHeartlandsHospital,Birmingham,UnitedKingdom§DepartmentofPublicHealthandEpidemiology,UniversityofBirmingham,Edgbaston,Birmingham,UnitedKingdom∥DepartmentofInfectionandTropicalMedicine,NorthwickParkHospital,Harrow,UnitedKingdomAbstractBackground—TheroleofnewT-cell–—pManuscriptsaretheperformanceof2intγerassaysferon-———389adults,predominantlyofSouthAsianandblackethnicity,—Tuberculinskintesting,theenzyme-linkedimmunospotassay(ELISpot)incorporatingearlysecretoryantigenictarget-6andculturefiltrateprotein-10(standardELISpot),Correspondingauthor:,DepartmentofRespiratoryMedicine,NationalHeartandLungInstitute,ImperialCollegeLondon,StMary’sCampus,NorfolkPlace,London,W21PG,UnitedKingdoma.******@:+442075940883.?DPSDandTSCHcontributedequallytothisstudyPotentialFinancialConflictsofIntPreroestfessorLalvaniisanamedinventorforseveralpatentsunderpinningTcell-(T-)hasbeenundertakenbyaspin-panyoftheUniversityofOxford(OxfordImmunotecLtd,Oxford,UK),inwhichProfessorLalvanihasashareofequityandtowhichheactsasadvisorinanon-'sDisclaimerThis:istheprepublication,author--,thepublisherofAnnalsofInternalMedicine,isnotresponsibleforthecontentorpresentationoftheauthor-(.,correspondence,corrections,editorials,linkedarticles),,Rv3879cPLUS(ELISpot)—Sensitivity,specificity,predictivevalues,andlikelihoodratios.:..Results—194patientshadafinaldiagnosisofactivetuberculosis,ofwhich79%wereculture--confirmedandhighlyprobabletuberculosiswas89%(95%CI,84%to93%)withELISpotPLUS,85%(CI,79%to90%)withstandardELISpot,79%(CI,72%toEuropePMCFundersAuthorManuscripts85%)with15-mmthresholdtuberculinskintesting,and83%(CI,77%to89%)withthresholdsofinatedpatients,-mmPcut=)ffpointsbut(notwithstratified10-mmcutoffpointsP=).(TheELISpotPLUSassayhad4%higherdiagnosticsensitivitythanstandardELISpotP=).(CombinedsensitivityofPLELISpotUSandtuberculinskintestingwas99%(CI,95%to100%),(CI,)——TheELISpotPLUSisamoresensitiveassaythanstandardELISpotand,whenbinationwithtuberculinskintesting,;specificity;diagnosis;tuberculosis;ESAT-6;CFP10;ELISpot;interferon-gamma;Rv3873;Rv3878;Rv3879cIntroductionImproveddiagnosisoftuberculosisisnecessarytocontainandreversetherisingglobalburdenofthisdisease(1).Thepoorspeedandsensitivityofexistingdiagnostictools(2–4)causesdelaysindiagnosisandtreatmentofactivetuberculosis,,-cell–basedγintreleaseerferon-assaysforesomeofthelimitationsofthetuberculinskintest(5–10).Theseimmunoassaysdetectinterγfersecron-,isagenomicsegmentabsentfrombacilleCalmette–Guérinandmostenvironmentalmycobacteria(11).TestresultsarethereforenotconfoundedbypreviousbacilleCalmette–ination,conferringhigherspecificitythanthetuberculinskintest(7–10).Moreover,resultsareavailablethenextdayandareunaffectedbytheboostingphenomenon(12).The2typesofT-cell–basedinterγferreleaseon-assayarewhole-bloodenzyme-linkedimmunosorbentassay(ELISA)andenzyme-linkedimmunospotassay(ELISpot).Thewhole-merciallyasQuantiFERON-TBGoldandan“in-tube”variant,QuantiFERON-TBGoldIn-tube(Cellestis,Carnegie,Australia)(13,14).TheELISpot,developedbyLalvani,merciallyasT-(OxfordImmunotec,Oxford,UnitedKingdom)(15–18).(19,20)mendT-cell–basedintγrereleaseferon-assaysfordiagnosisoflatenttuberculosis,;--6andculturefiltrateprotein-10,thesamepeptidesasthe2regionofdifference1–encodedantigensincludedinT-–encodedantigen,Rv3879c,alongsideearlysecretoryantigenictarget-6andculturefiltrateEuropePMCFundersprAuthorotein-10Manuscripts(21).MethodsParticipantsOnedayeachweekfrom12July2002to29June2005,weprospectivelyenrolledadultswhopresentedtoHeartlandsHospital,Birmingham,andNorthwickParkHospital,London,:..pp,g,p,,UnitedKingdom,,Harrow,(22),wetestedpatientsforHIVantibodiesduringdiagnosticwork-–,(10tuberculinunits)ofpurifiedproteinderivative(PPD)–Siebert(ines,Liverpool,UnitedKingdom).Intradermalinoculationwasconfirmedbythecutaneousappearanceofpeaud’,104patientsweretestedbyusingtheHeafmethod,withthestandardmultiplepuncture6-needleEuropePMCFundersdisposable-headAuthorManuscriptsHeafgun(BignallSurgicalInstruments,Littlehampton,UnitedKingdom)andconcentratedPPD(100000tuberculinunits/mL,ines).Heaftestswereread1weeklater,mended,(whichisconsideredequivalenttothe15-mmthreshold[23,24])–Guérininationstatusbyhistoryand,wherepresent,(grade2to4ontheHeaftest)inatedpatients,respectively(“stratified10mmthreshold”)(23,24).TheELISpotAssayBeforeorwithin1weekofinitiatingtherapy,×-ELISpotplates(MabtechAB,Stockholm,Sweden)×10peripheralbloodmononuclearcellsperwell(17).Duplicatewellscontainednoantigen(negativecontrol)orphytohemagglutinin(positivecontrol)(ICNBiomedical,Aurora,Ohio)at5μg/,whichincorporated5to7overlapping15--,prises35suchpeptidesassembledinto6poolsandspanningthelengthofearlysecretoryantigenictarget-6andculturefiltrateprotein--fivepeptidesfromselectedregionsofRv3873,Rv3878,;(ics,Huntsville,Alabama)wereassembledinto7pools(21).TheELISpotPLUSassaywasdefinedasthe35earlysecretoryantigenictarget-6andculturefiltrateprotein-10peptides,with17peptidesfromRv3879c,°Cin5%carbondioxide,theplatesweredevelopedwithpreconjugateddetectorantibody(MabtechAB)followedbychromogenicsubstrate(Moss,Pasadena,Maryland)(17).Spot-EuropePMCFundersforAuthormingcellsManuscriptswerecountedbyusinganautomatedELISpotreader(AID-GmbH,Strassberg,Germany).,ELISTAT(AID-GmbH).Wescoredresponsesaspositiveiftestwellscontainedameanofatleast5spot-(15–17,25–30).-upaspartofroutineclinicalpractice,whichwasdirectedonacase-by-casebasisbythepatient’,radiologic,andmicrobiologicaldataonstandardized:..,g,gformsatrecruitment,duringfollow-up,(Table1),whicharesimilartothoseusedinotherstudies(25).,wefurtherclassifiedpatientsinthiscategoryinto4predefinedsubgroups,analogoustoAmericanThoracicSocietyclasses4,2,1,and0(31),indecreasinglikelihoodoflatenttuberculosis(Table1).Westratifiedbyradiologicevidenceorhistoryofprevioustuberculosis,riskfactorsforlatentinfection,,specificity,likelihoodratios,-basedtestingistoruleouttuberculosis,ourpredefinedanalyticalplanfocusedprimarilyonsensitivities,negativelikelihoodratios,-squareandFisherexacttestswheresamplesizesdifferedsubstantially(becauseofmissingresultsfor1ofthetests).paredthedataemarchi-squaretest,treatingthedataaspairedanddroppingthe6individualswhodidnotPLhavUSeresul