中国结核感染现状英文版.pptx

LatentInfectionofTuberculosisinChinaHUASHANHOSPITAL,FUDANUNIVERSITY,Shanghai,ChinaWenhongZhang,M.D&PhD.TB:A leading infectious killer-top 3 infectious killerTB kills about 2 million people each year 8 million people become sick with TB each yearTB is the leading killer of HIV/AIDS patients50 million people infected with drug-resistant TB TheNewTuberculosisHIVandDrug-resistantTBAlethalcombinationandamajorthreattoTBcontrolWHOdeclaredTBaglobalemergencyin1993TBChemotherapy:THEEffectiveTBControlPre-antibioticera:before 1940s(e.g.,cod liver oils,bed rest,fresh air)DrugsusedtotreatTB:Streptomycin first TB drug(1944),followed by PAS(1946),isoniazid(1952),pyrazinamide(1952),rifampin(1963)(a)Front-line Drugs:isoniazid(INH)rifampicin(RMP),pyrazinamide(PZA),streptomycin,ethambutol.(b)Second-line Drugs:PAS,kanamycin,cycloserine,ethionamide,thiacetazone,ciprofloxacin/ofloxacin,rifapentine,amikacin,viomycin,capreomycin.DOTS-The Best TB Therapysince 1991DOTS:6 month therapy-The best therapy against TB(78%-96%cure rate).Initial phase(daily,2 months)with 4 drugs:INH,RMP,PZA,Ethambutol.Continuation phase(3 times a week,4 months)with 2 drugs:INH and RMP.DOTS-PlusDOTS+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,2000dataPrevalence of active pulmonary diseases is 367100,000Prevalence of Sear positive pulmonary diseases is 122100,000130,000 patients die from tuberculosis every yearNo data of latent tuberculosis in China up to No data of latent tuberculosis in China up to nownowChinaCDC2006PrevalenceofSmearPositiveTuberculosisinChinaIncidenceoftuberculosisaccordingtothereportfromChinaCDCButincidencedonotdecrease!020000040000060000080000010000001200000140000016000002003200420052006ChinaCDC2006FactorscontributetotuberculosisreemerginginChinaMDRTB?HIVincreasing?Latentinfection?Diagnosistoolsaremoreaccuratetofindmorenewcases?HIV infected Tuberculosis Cases No bacilli found in infected organs(spleens/lungs)by plating-stop treatment-3 months later,1/3 mice relapse with TB(drug susceptible)and all mice relapse with TB if treated with immonosuppressing steroids-suggest existence of dormant bacilli or persisters(phenotypic resistance).NewTBcasesaredrivenbythereservoiroflatentlyinfectedpeople.IfwewanttostopactiveTBcases,weneedtoeliminatethisreservoirofinfection.This“hiddenepidemic”ofpeopleinfectedwithlatentTBisenormous.ThegrowthinlatentTBisbecomingaclinicaltimebomb.Weneedtodefusethisbombbyincreasingoureffortstoidentifyandtreatlatentlyinfectedpeople.LatenttuberculosisisthereservoirofactivetuberculosisActiveTB 8 million new cases a year-Unfortunately just the tip of the icebergLatentTB-the“hidden epidemic”-2 billion people infectedEpidemiologyoflatentinfectionintheworldFrothinghamR,etal.InternationalJournalofInfectiousDiseases(2005)9,29731145%45%55%55%Infected No infectionTST positive in China,2000TST positive in China,2000ShortageofTSTPoorspecificity:antigeniccross-reactivityofPPDwithBCGandenvironmentalmycobacteriaPoorsensitivity:75-90%inactivedisease(lowerindisseminatedTBandHIVinfection;unknownforlatentinfection)FactorsleadingtoFalse-PositiveTSTReactionsNontuberculousmycobacteriaReactionscausedbynontuberculousmycobacteriaareusually10mmofindurationBCGvaccinationReactivityinBCGvaccinerecipientsgenerallywanesovertime;positiveTSTresultislikelyduetoTBinfectionifriskfactorsarepresentTSPOTTMdetectINF-rreleasedbyspecificTcellsCollect white cells using BD CPT tube or Ficoll extraction.Add white cells and TB antigens to wells.T cells release interferon gamma.Interferon gamma captured by antibodies.Incubate,wash and add conjugated second antibody to interferon gamma.Add substrate and count spots by eye or use reader.Each spot is an individual T cell that has released interferon gamma.How does T-spot Technology WorkPatientWholebloodSamplePBMCESAT-6CFP10TcellsecretingINFAbcaptureINFBluespot2commercialKitavailablefordetectinglatentoractivetuberculosisT cell-based assay for interferon gamma,the enzyme-linked immunosorbent spot test(ELISPOT),has promise in the diagnosis of Mycobacterium tuberculosis infection after exposure to a known tuberculosis(TB)patient.Commercialisation of two T cellbased tests for the diagnosis of M.tuberculosis infection(T Spot TB by Oxford Immunotec and Quantiferon-TB Gold by Cellestis)T-cellbasedassayisrecommendedfordetectinginfectionofM.TbmeasuresindividualreactingTcells:Evenindividualcellscanbedetectedinasample.Thereforeeventhosewhoareseverelyimmunocompromised,ifasinglecellreactsthenitcanbedetected.measuresalltypesofTcells:BothCD4andCD8typeTcellsaredetected.ThereforeifonetypeofTcellsisdepletedinapatient(e.g.CD4TcellsinHIVinfectedpatients)aresponsecanstillbedetectedfromtheCD8Tcells.This sensitivity is key to the tests excellent performance in immunosuppressed populationsThestrategicfortreatinglatentinfectionoftuberculosisinChina?Lifetime Risk of Reactivation TuberculosisLifetime Risk of Reactivation TuberculosisC.Robert Horsburgh.n engl j med 2004;350;20:2060-7LatentinfectionoftuberculosisinChina:TreatornotTreat?BCGstrategicor“findandtreat”strategic?Conditionallytreatmentfocusinghigh-riskgroups:closehousecontactsandimmunocompromisedcasesChemotherapyorImmunotherapy?