中国结核感染现状.ppt

LatentInfectionofTuberculosisinChinaHUASHANHOSPITAL FUDANUNIVERSITY Shanghai ChinaWenhongZhang M D PhD TB Aleadinginfectiouskiller top3infectiouskiller TBkillsabout2millionpeopleeachyear8millionpeoplebecomesickwithTBeachyearTBistheleadingkillerofHIV AIDSpatients50millionpeopleinfectedwithdrug resistantTB TheNewTuberculosis HIVandDrug resistantTB AlethalcombinationandamajorthreattoTBcontrolWHOdeclaredTBaglobalemergencyin1993 TBChemotherapy THEEffectiveTBControl Pre antibioticera before1940s e g codliveroils bedrest freshair DrugsusedtotreatTB StreptomycinfirstTBdrug 1944 followedbyPAS 1946 isoniazid 1952 pyrazinamide 1952 rifampin 1963 a Front lineDrugs isoniazid INH rifampicin RMP pyrazinamide PZA streptomycin ethambutol b Second lineDrugs PAS kanamycin cycloserine ethionamide thiacetazone ciprofloxacin ofloxacin rifapentine amikacin viomycin capreomycin DOTS TheBestTBTherapysince1991 DOTS 6monththerapy ThebesttherapyagainstTB 78 96 curerate Initialphase daily 2months with4drugs INH RMP PZA Ethambutol Continuationphase 3timesaweek 4months with2drugs INHandRMP DOTS Plus DOTS second lineTBdrugs PAS ethionamide cycloserine kanamycin amikacinetc Tooexpensive TBcase 11to 100 costoftreatinganMDR TBcase 150 000 MDR TBrequiresextensivechemotherapy alsomoretoxictopatients sideeffects foruptotwoyearsDOTS PlusworksasasupplementtotheDOTS toaddressbothdrug susceptibleandMDR TBinareaswithsignificantMDR TB DiseaseBurdenofTuberculosisinChina 2000data Prevalenceofactivepulmonarydiseasesis367 100 000PrevalenceofSearpositivepulmonarydiseasesis122 100 000130 000patientsdiefromtuberculosiseveryyearNodataoflatenttuberculosisinChinauptonow ChinaCDC2019 PrevalenceofSmearPositiveTuberculosisinChina IncidenceoftuberculosisaccordingtothereportfromChinaCDC Butincidencedonotdecrease ChinaCDC2019 FactorscontributetotuberculosisreemerginginChina MDRTB HIVincreasing Latentinfection Diagnosistoolsaremoreaccuratetofindmorenewcases HIVinfectedTuberculosisCases 1 100 000populationinChina Latency TBbacillicanpersistforlongperiodsoftime decades inthehostbeforereactivatingandcausingactivediseaseHostfactors immunocompromisedconditions viralinfections e g HIVandmeasles steroids anti TNFantibody REMICADE infliximab aspartofthetreatmentofrheumatoidarthritisBacterialfactors e g isocitratelyase alpha crystallin 48 genedormancyregulon etc DormantorPersistentBacilli Cornellmodel MiceinfectedwithTBbacilliaretreatedfor3monthswithINHandPZA Nobacillifoundininfectedorgans spleens lungs byplating stoptreatment 3monthslater 1 3micerelapsewithTB drugsusceptible andallmicerelapsewithTBiftreatedwithimmonosuppressingsteroids suggestexistenceofdormantbacilliorpersisters phenotypicresistance NewTBcasesaredrivenbythereservoiroflatentlyinfectedpeople IfwewanttostopactiveTBcases weneedtoeliminatethisreservoirofinfection This hiddenepidemic ofpeopleinfectedwithlatentTBisenormous ThegrowthinlatentTBisbecomingaclinicaltimebomb Weneedtodefusethisbombbyincreasingoureffortstoidentifyandtreatlatentlyinfectedpeople Latenttuberculosisisthereservoirofactivetuberculosis ActiveTB 8millionnewcasesayear Unfortunatelyjustthetipoftheiceberg LatentTB the hiddenepidemic 2billionpeopleinfected Epidemiologyoflatentinfectionintheworld FrothinghamR etal InternationalJournalofInfectiousDiseases 2019 9 297 311 TSTpositiveinChina 2000 ShortageofTST Poorspecificity antigeniccross reactivityofPPDwithBCGandenvironmentalmycobacteriaPoorsensitivity 75 90 inactivedisease lowerindisseminatedTBandHIVinfection unknownforlatentinfection FactorsleadingtoFalse PositiveTSTReactions NontuberculousmycobacteriaReactionscausedbynontuberculousmycobacteriaareusually 10mmofindurationBCGvaccinationReactivityinBCGvaccinerecipientsgenerallywanesovertime positiveTSTresultislikelyduetoTBinfectionifriskfactorsarepresent TSPOTTMdetectINF rreleasedbyspecificTcells CollectwhitecellsusingBDCPTtubeorFicollextraction AddwhitecellsandTBantigenstowells Tcellsreleaseinterferongamma Interferongammacapturedbyantibodies Incubate washandaddconjugatedsecondantibodytointerferongamma Addsubstrateandcountspotsbyeyeorusereader EachspotisanindividualTcellthathasreleasedinterferongamma HowdoesT spotTechnologyWork PatientWholebloodSamplePBMCESAT 6CFP10TcellsecretingINFAbcaptureINFBluespot 2commercialKitavailablefordetectinglatentoractivetuberculosis Tcell basedassayforinterferongamma theenzyme linkedimmunosorbentspottest ELISPOT haspromiseinthediagnosisofMycobacteriumtuberculosisinfectionafterexposuretoaknowntuberculosis TB patient CommercialisationoftwoTcellbasedtestsforthediagnosisofM tuberculosisinfection TSpotTBbyOxfordImmunotecandQuantiferon TBGoldbyCellestis T cellbasedassayisrecommendedfordetectinginfectionofM Tb measuresindividualreactingTcells Evenindividualcellscanbedetectedinasample Thereforeeventhosewhoareseverelyimmunocompromised ifasinglecellreactsthenitcanbedetected measuresalltypesofTcells BothCD4andCD8typeTcellsaredetected ThereforeifonetypeofTcellsisdepletedinapatient e g CD4TcellsinHIVinfectedpatients aresponsecanstillbedetectedfromtheCD8Tcells Thissensitivityiskeytothetest sexcellentperformanceinimmunosuppressedpopulations ThestrategicfortreatinglatentinfectionoftuberculosisinChina LifetimeRiskofReactiva