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首页 肺结核进展

肺结核进展.pdf

肺结核进展

xulei0427_x3htc
2011-12-02 0人阅读 举报 0 0 暂无简介

简介:本文档为《肺结核进展pdf》,可适用于自然科学领域

CopyrigNewandimprovedtuberculosisdiagnostics:evidence,policy,pracMadhgaIntroductionIn,poordiagnosisremainsamajorobstacletoglobaltuberculosis(TB)controlInmosthighburdencountries,TBisstilldiagnosedusingtoolssuchasdirectsputummicroscopyandchestradiographsFortunately,thepastfewyearshaveseenanunprecedentedlevelofinterest,fundingsupport,andactivityfocusedonthedevelopmentofnewtoolsforTBdiagnosis,andthenewdiagnosticspipelineforTBisrapidlyexpandingInparallel,therehavebeenseveralnewpolicyrecommendationsonTBdiagnosticsbytheWHOBecauserecentpublications�,,�,haveexhaustivelyreviewedthecurrentpipelineofnewdiagnosticsandtheexpandingevidencebasefortheiruse,wefocusourattentiononhowevidenceistranslatedintopolicy,limitationsoftheexistingevidencebase,deficienciesinthecurrentdiagnosticspipeline,andchallengesinvolvedintranslatingpoliciesintopracticeandimpactWhatistheevidencebasefortuberculosisdiagnoTheevderivedindividualstudiesareseldomsufficienttoinformpolicyandguidelinedevelopment,thetotalityofavailableevidencemustbesynthesizedThus,systematicreviewsandmetaanalysesareoftennecessarytosummarizetheevidenceonagivendiagnostictestInthepastdecade,therehavebeenoversystematicreviewspublishedonTBdiagnostics,ontopicsrangingfromsmearmicroscopytomoleculardiagnosticsandinvitroassaysforlatentTBinfection(LTBI)Allofthesesystematicreviewshavebeenmadeavailableonanewwebsite‘EvidencebasedTuberculosisDiagnosis’(wwwtbevidenceorg)compiledbytheStopTBPartnership’sNewDiagnosticsWorkingGroup,incollaborationwithseveralagencies�WhilethekeyfindingsofpublishedsystematicreviewsandmetaanalysesonTBdiagnosticshavebeenreviewedelsewhere�,TableprovidesabriefoverviewoftheevidencebaseforTBdiagnosis,essentiallysynthesizingtheevidencefromseveralsystematicreviews–WhatislackingincurrentevidencebaseaDepartmeOccupationCanada,bFCenter,UnCalifornia,UWHOSpecTropicalDiGeneva,SwCorrespondProfessor,andOccupAvenueWeTel:email:madCurrentO:–evostics,anddiscussissuessuchashowevidenceisonspabevelxpasHtesturadiagactnddegeepdiagnostics,evidence,impact,policy,tuberculosisCurrOpinPulmMed:–�WoltersKluwerHealth|LippincottWilliamsWilkinssticsidencebaseforTBdiagnosticsisultimatelyfromalargebodyoforiginalresearchBecauseAlthoughalargenumberofsystematicreviewshavebeenpublishedonTBdiagnostics,almostallfocusontestaccuracy(iesensitivityandspecificity)Thisisinpart�WoltersKluwerHealth|LippincottWilliamsWilkinsDOI:MCPbeftice,andimpactukarPaia,JessicaMiniona,KarenSteinntofEpidemiology,BiostatisticsandalHealth,McGillUniversity,Montreal,rancisJCurryNationalTuberculosisiversityofCalifornia,SanFrancisco,SAandcUNICEFUNDPWorldBankialProgrammeforResearchandTraininginseases(TDR),WorldHealthOrganization,itzerlandencetoMadhukarPai,MD,PhD,AssistantDepartmentofEpidemiology,BiostatisticsationalHealth,McGillUniversity,Pinest,Montreal,QCHAA,Canadafax:hukarpaimcgillcapinioninPulmonaryMedicine,PurposeofreviewTheaimistosummarizetherecentpoliciesonTBdiagntranslatedintopolicy,limitatiintranslatingpoliciesintoimRecentfindingsCasedetectioncontinuestoduetoanunprecedentedlepipelineforTBhasrapidlyeguidelinesonTBdiagnostic(eglackofapointofcareresearchstudiesoftestaccSummaryWiththeavailabilityofnewistranslationofpolicyintoprextentoftheirintroductionaitselfdependinpartonpolicyTBprogramsWiththeengaevidencebasedpoliciesintoKeywordsht©LippincottWilliamsWilkinsUnauthorizedoftheexistingevidencebase,andchallengesinvolvedctamajorobstacletoglobalTBcontrolFortunately,ofinterest,funding,andactivity,thenewdiagnosticsndedTherehavebeenseveralnewpoliciesandowever,therearemajorgapsintheexistingpipeline)andtheevidencebaseispredominantlymadeupofcynosticsandsupportingpolicies,thenextmajorstepiceTheimpactofnewtestswilldependlargelyontheacceptanceintotheglobalpublicsectorThiswillcisionsbyinternationaltechnicalagenciesandnationalmentofallkeystakeholders,wewillneedtotranslateidemiologicalandpublichealthimpactrtbandAndrewRamsaycidencebasefortuberculosis(TB)diagnostics,reviewreproductionofthisarticleisprohibitedCopyright©LippincottWilliamsWilkinsUnauthorizedreproductionofthisarticleisprohibitedInfectiousdiseasesTableSummaryoffindingsfromsystematicreviewsontuberculosisdiagnostictestsDiagnostictestDescriptionDiseasesiteMajorfindingsresultsofsystematicreviewsMajorreferencesDiagnosisofactiveTBSputumsmearmicroscopyMicroscopicobservationofstainedacidfastbacilliPulmonaryTBFluorescencemicroscopy(FM)isonaveragemoresensitivethanconventionalmicroscopySpecificityofbothfluorescenceandconventionalmicroscopyissimilarFluorescentmicroscopyisassociatedwithimprovedtimeefficiency–LEDFMperformsequivalentlytoconventionalFM,withaddedbenefitsoflowcost,durability,andabilitytousewithoutadarkroomCentrifugationandovernightsedimentation,precededwithanyofseveralchemicalmethods(includingbleach)isslightlymoresensitive(–)thandirectmicroscopyspecificitymaybeslightlydecreased(–)bysputumprocessingmethodsWhenserialsputumspecimensareexamined,themeanincrementalyieldandorincreaseinsensitivityfromexaminationofthirdsputumspecimenrangesbetweenandNucleicacidamplificationtests(NAATs)Isolation,replication,anddetectionofnucleicacidsequencesspecificforMycobacteriumtuberculosisPulmonaryandextrapulmonaryTBNAATshavehighspecificityandpositivepredictivevalueNAATs,however,haverelativelylower(andhighlyvariable)sensitivityandnegativepredictivevalueforallformsofTB,especiallyinsmearnegativeandextrapulmonarydiseaseInhouse(‘homebrew’)NAATsproducehighlyinconsistentresultsascomparedwithcommercial,standardizedNAATs–CommercialserologicalantibodydetectiontestsDetectionofhostantibodyresponsetoMycobacteriumtuberculosisantigensPulmonaryandextrapulmonaryTBSerologicaltestsforbothpulmonaryandextrapulmonaryTBproducehighlyinconsistentestimatesofsensitivityandspecificitynoneofthecurrentassaysperformwellenoughtoreplacemicroscopy,,Noncommercial(inhouse)serologicalantibodydetectiontestsDetectionofhostantibodyresponsetoMycobacteriumtuberculosisantigensPulmonaryTBSeveralpotentialcandidateantigensforinclusioninanantibodydetectionbaseddiagnostictestforpulmonaryTBinHIVinfectedanduninfectedindividualswereidentifiedCombinationsofselectantigensprovidehighersensitivitiesthansingleantigensAdenosinedeaminase(ADA)DetectionofhostcellularenzymereleasedbylymphocytesinresponsetoliveintracellularpathogensTBpleuritis,pericarditis,peritonitisMeasurementofADAlevelsinpleural,pericardial,andasciticfluidisausefuladjuncttestforTBpleuritis,pericarditis,andperitonitisSystematicreviewshavereportedpooledsensitivityestimatesbetweenand,andspecificityestimatesbetweenand,Interferongamma(IFNg)MeasurementofIFNgTBpleuritisPleuralfluidIFNgdeterminationappearstobeausefuldiagnosticforTBpleuritis,withsystematicreviewsreportingpooledsensitivityestimatesbetweenand,andspecificityestimatesbetweenand,PhageamplificationassaysDetectionofMycobacteriumtuberculosisspecificphageviruses,aftertheirinfectionandamplificationofliveMTBPulmonaryTBDespitehighaccuracyestimates,currentphagebasedassaysarelimitedbyhighratesofindeterminateresults(upto)AutomatedliquidculturesAutomateddetectionofchangesinoxygen,carbondioxide,orpressureresultingfrombacterialgrowthPulmonaryTBAutomatedliquidculturesaremoresensitivethansolidculturestimetodetectionismorerapidthansolidcultures,DiagnosisoflatentTBTuberculinskintest(TST)MeasurementofindurationasaresultofexposuretointradermaltuberculinLatentTBinfectionIndividualswhohavereceivedBCGvaccinationaremorelikelytohaveapositiveTSTtheeffectofBCGonTSTresultsislessafteryearspositiveTSTwithindurationsof>mmaremorelikelytobetheresultofTBinfectionthanofBCGvaccination,TheeffectonTSTofBCGreceivedininfancyisminimal,especiallyyearsaftervaccinationBCGreceivedafterinfancyproducesmorefrequent,morepersistent,andlargerTSTreactionsNontuberculousmycobacterial(NTM)infectionisnotaclinicallyimportantcauseoffalsepositiveTST,exceptinpopulationswithahighprevalenceofNTMsensitizationandaverylowprevalenceofTBinfectionTcellbasedinterferongreleaseassays(IGRAs)MeasurementofIFNgreleasedfromlymphocyteswhenstimulatedbyMycobacteriumtuberculosisspecificantigensLatentTBinfectionIGRAshaveexcellentspecificity(higherthanthetuberculinskintest)andareunaffectedbypriorBCGvaccination,–IGRAscannotdistinguishbetweenLTBIandactiveTBandhavenoroleforactiveTBdiagnosisinadultsUsedasanadjunctivediagnostic,IGRAsmayaidintheinvestigationofpediatricTBIGRAscorrelatewellwithmarkersofTBexposureinlowincidencecountriesIGRAperformanceappearstodifferinhighendemicvslowendemiccountriesIGRAsensitivityvariesacrosspopulationsandtendstobelowerinhighendemiccountriesandinHIVinfectedindividualsCopyright©LippincottWilliamsWilkinsUnauthorizedreproductionofthisarticleisprohibitedNewandimprovedtuberculosisdiagnosticsPaietalDiagnosisofdrugresistancePhageamplificationassaysDetectionofMycobacteriumtuberculosisspecificphageviruses,aftertheirinfectionandamplificationofliveMTBþinhibitionofgrowthinpresenceofantituberculousdrugsRapiddetectionofrifampicinresistanceWhenusedoncultureisolates,phageassayshavehighsensitivity,butvariableandlowerspecificityIncontrast,evidenceislackingontheaccuracyoftheseassayswhentheyaredirectlyappliedtosputumspecimensRecentstudieshaveraisedconcernsaboutcontamination,falsepositiveresults,andtechnicalassayfailures,Lineprobeassays:INNOLiPARifTBLiPAandGenoTypeMTBDRassayDetectionofgeneticsequencesassociatedwithresistance(afterextractionandamplification)usingimmobilizedprobesandcolorimetricdevelopmentRapiddetectionofrifampicinresistanceLiPAisahighlysensitiveandspecifictestforthedetectionofrifampicinresistanceincultureisolatesThetesthasrelativelylowersensitivitywhenuseddirectlyonclinicalspecimensTheGenoTypeMTBDRassayshaveexcellentsensitivityandspecificityforrifampicinresistanceevenwhendirectlyusedonclinicalspecimens–Colorimetricredoxindicators(CRIs)DeterminationofMICusingmicrodilution,followedbyadditionofreagentwhichwillbecomereducedinthepresenceofactivelygrowingMTBresultinginacolorchangeRapiddetectionofrifampicinandisoniazidresistanceColorimetricmethodsaresensitiveandspecificforthedetectionofrifampicinandisoniazidresistanceincultureisolatesCRIsuseinexpensivenoncommercialsuppliesandequipmentandhavearapidturnaroundtime(days)Nitratereductaseassays(NRAs)DirectorindirectinoculationofdrugfreeanddrugcontainingmediacontainingKNOAdditionofGreissreagentdetectsearlygrowthbyreactingwithenzymaticbyproductandresultinginacolorchangeRapiddetectionofrifampicinandisoniazidresistanceNRAhashighaccuracywhenusedtodetectrifampicinandisoniazidresistanceincultureisolatesLimiteddataareavailableonitsusewhendirectlyappliedtoclinicalspecimens,butresultsarepromisingTheNRAissimple,usesinexpensivenoncommercialsuppliesandequipment,andhasarapidturnaroundtime(–days)comparedtoconventionalmethodsMicroscopicobservationdrugsusceptibility(MODS)Directorindirectinoculationofdrugfreeanddrugcontainingliquidmedia,followedbyexaminationusinganinvertedmicroscopetodetectearlygrowthRapiddetectionofrifampicinandisoniazidresistanceMODShashighaccuracywhentestingforrifampicinresistance,butshowsslightlylowersensitivitywhendetectingisoniazidresistanceMODSappearstoperformequallywellusingdirectpatientspecimensandcultureisolatesMODSusesnoncommercialsuppliesandequipment,andhasarapidturnaroundtime(days)comparedwithconventionalmethodsThinlayeragar(TLA)Directorindirectinoculationofdrugfreeanddrugcontainingsolidmedia,followedbyexaminationusingamicroscopetodetectearlygrowthRapiddetectionofrifampicinandisoniazidresistanceThereisapaucityofdataevaluatingTLAforthedetectionofdrugsusceptibilityhowever,allstudiestodatehavefoundconcordancewiththeirreferencestandardsTLAusesinexpensivenoncommercialsuppliesandequipment,andhasarapidturnaroundtime(days)comparedwithconventionalmethodsBCG,bacillusCalmetteGue´rinLED,lightemittingdiodeLTBI,latentTBinfectionMIC,minimalinhibitoryconcentrationMTB,MycobacteriumtuberculosisTB,tuberculosisAdaptedfrom�(OpenAccessunderCreativeCommonsAttributionLicense)CopyrighbecausealargeproportionofTBdiagnosticresearchstudiesarefocusedonmeasuringtestaccuracyFindingsfromsystematicreviewssuggestthatevenrelativelystraightforwardstudiesoftestaccuracyareoftenpoorlydesignedandreported,BothresearchersofprimaryTBdiagnosticstudiesandauthorsofsystematicreviewsandmetaanalysesneedtomakeeffortstofollowpublishedguidelinesforconductingandreportingtheirwork,,tomakethemostoftheircontributiontoausefulandunbiasedliteraturebaseAlthoughthequalityofdiagnosticstudiesmeasuringtestaccuracyisimportant,evidenceabouttestaccuracyisonlyonelinkinalongchainofactivitiesthatmakeupthepathwaytodevelopingandimplementinganewTBdiagnosticIn,theStopTBPartnership’sNewDiagnosticsWorkingGrouppublishedascientificblueprintfordevelopmentofnewTBdiagnostics��Thispublicationprovidesacomprehensive,wellreferencedplantoguideresearchers,clinicians,industrypartners,academics,andTBcontrollersinallsectorsinallaspectsofTB��needs’atotestdscaleupimpactAsshowbutpolitestacctoconsioutcomsophisti,,diagnosrelevantoutcomincreasednumberofpatientsdetectedandreceivingappropriatetreatment,fewerpatientsdefaultingfromthedia

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