结核病的有效诊断治疗和控制英文

结核病的有效诊断治疗和控制英文第1页/共59页EffectiveDiagnosis,Treatment,andControlofTuberculosis第2页/共59页3South-EastAsiaaccountsfornearly

40%ofalltuberculosiscases第3页/共59页4TBistheleadingsingleinfectiouscauseofdeathinSouth-EastAsiaNumberofdeaths(1000s)DeathsfrominfectiousagentsinSouth-EastAsia第4页/共59页5TBisaLeadingKillerofWomenDeathsamongwomen第5页/共59页6Tuberculosis

AGlobalEmergencyTBkills5,000peopleaday–2-3millioneachyearOnethirdoftheworld’spopulationisinfectedwithTBTBkillsmoreyoungwomenthananyotherdiseaseMorethan100,000childrenwilldieneedlesslyfromTBthisyearHundredsofthousandsofchildrenwillbecomeTBorphansthisyear第6页/共59页7TBandAIDSLifetimeRiskofTB第7页/共59页8TBControl:The5componentsofDOTSTBRegisterPoliticalcommitmentDiagnosisbymicroscopyAdequatesupplyofSCCdrugsDirectlyobservedtreatmentAccountability第8页/共59页9Diagnosisofpulmonarytuberculosis

PatientswithTBfeelillandseekcarepromptlyActivecasefindingisunnecessaryandunproductiveMicroscopyisappropriatetechnology,indicatinginfectiousness,riskofdeath,andpriorityfortreatmentX-rayisnon-specificforTBdiagnosisSerologicalandamplificationtechnologies(PCR,etc.)currentlyofnoprovenvalueinTBcontrol第9页/共59页10DiagnosisofPulmonaryTuberculosisThreespecimensoptimalSpotspecimenonfirstvisit;sputumcontainergiventopatientEarlymorningcollectionbypatientonnextdaySpotspecimenduringsecondvisit第10页/共59页11Threesputumsmearsareoptimal第11页/共59页12ReportingonAFBMicroscopyNumberofbacilliseenResultreportedNoneper100oilimmersionfieldsNegative1-9per100oilimmersionfieldsScanty,reportexactnumber10-99per100oilimmersionfields1+1-10peroilimmersionfield2+>10peroilimmersionfield3+第12页/共59页13DiagnosisofPulmonaryTBCough3weeksAFBX3Broad-spectrumantibiotic10-14daysIfsymptomspersist,repeatAFBsmears,X-rayIfconsistentwithTBAnti-TBTreatmentIf1positive,X-rayandevaluationIf2/3positive:Anti-TBRxIf

negative:第13页/共59页14MicroscopyismoreobjectiveandreliablethanX-rayInter-observeragreement第14页/共59页15MicroscopyisamorespecifictestthanX-rayforTBdiagnosisSpecificity第15页/共59页16X-ray-basedevaluationcausesover-diagnosisofTBNTI,IndJTuberc,1974Over-diagnosis第16页/共59页17RoleofChestX-rayNochestX-raypatternisabsolutelytypicalofTB10-15%ofculture-positiveTBpatientsnotdiagnosedbyX-ray40%ofpatientsdiagnosedashavingTBonthebasisofx-rayalonedonothaveactiveTBTomanK.Tuberculosiscasefindingandchemotherapy.WHO,1979X-rayisunreliablefordiagnosingandmonitoringtreatmentoftuberculosis第17页/共59页18ProportionofpatientswithpulmonaryTBwhohavepositiveAFBsmears010203040506070HIVNegativeEarlyHIVLateHIVAFBpositivityinTBpatients第18页/共59页19X-rayfindingsinTBpatientswithHIVinfectionEarlyHIVLateHIV(severeimmuno-compromise)第19页/共59页20DOTSmorethandoublesaccuracyofdiagnosisofTBinSEARExpectedrange第20页/共59页21PrompttreatmentofinfectiouscasesreducesspreadoftuberculosisSmear-positivepatientsusuallyseekcareSmear-positivepatientsare4-20timesmoreinfectiousUntreated,asmear-positivepatientmayinfect10-15persons/yearSmear-positivepatientsaremuchmorelikelytodieifuntreatedRouillonA.Tubercle1976;57:275-99第21页/共59页22TreatmentCategoriesTBtreatmentcategoryTBPatientsIlNewsmear-positivepulmonaryTBlNewsmear-negativepulmonaryTBwithextensiveparenchymalinvolvementlNewcasesofsevereformsofextra-pulmonaryTBIIlSputumsmear-positiverelapseslSputumsmear-positivetreatmentfailurecaseslSputumsmear-positivecasesrequiringtreatmentafterinterruptionIIIlNewsmear-negativepulmonaryTBlNewlesssevereformsofextra-pulmonaryTB第22页/共59页23Severeandlesssevereformsofextra-pulmonaryTBSevereMeningitisLessSevereLymphnodesMiliaryPericarditisBone(excludingspine)BilateralorextensivepleuraleffusionSpinalIntestinalTB/HIV,AClinicalManual,WorldHealthOrganization1996Pleuraleffusion(unilateral)Peripheraljoint第23页/共59页244HRI2HRZE(2HRZS)2H3R3Z3E3(2H3R3Z3S3)6HE4HR33RecommendedtreatmentregimensDirectobservationisrecommendedforallpatientsandisparticularlyessentialwhenintermittentregimensareusedContinuationPhaseAlternativetreatmentregimens(ifsmear+atendofinitialphaseofCatIorCatII,onemoremonthofinitialphaseisgiven)TBtreatmentcategoryInitialphaseIII2HRZ2H3R3Z36HE4HRR4H33333(2SHRZE/1HRZE5HREII2SHRZE/1HRZE333333333)5HRE第24页/共59页25Dosesoffirst-lineanti-TBdrugsPyrazinamide(Z)25(20-30)35(30-40)Ethambutol(E)15(15-20)30(25-35)Alltheseanti-TBdrugsshouldbegivenasasingledailydose.Directobservationisrecommendedforallpatientsandisparticularlyessentialwhenintermittentregimensareused.ThiacetazoneisnoteffectivewhengivenintermittentlyandisnotrecommendedforuseinhighHIVprevalenceareas.Isoniazid(H)5(4-6)10(8-12)RecommendedDose(mg/kg)Anti-TBDrug(Abbreviation)DailyIntermittent3x/wkRifampicin(R)10(8-12)10(8-12)Streptomycin(S)15(12-18)15(12-18)Thiacetazone(T)2.5Notapplicable第25页/共59页26RoleofIsoniazidMainstayofanti-TBtreatmentLifesavinginTBmeningitisBactericidalforrapidlydividingorganismsPreventsemergenceofresistancetootherdrugsIntermittenttreatmentmoreeffectivethandailytreatmentinanimalmodelandequallyeffectiveinclinicaltrialsSafeandeffectiveforpreventivetreatment第26页/共59页27RoleofRifampicinNecessaryforshort-coursetreatmentEssentialforatleastfirst2monthsofregimensof6-9monthdurationBactericidalforrapidlydividingandslow-growingorganismsPreventsemergenceofresistancetootherdrugsIntermittenttreatmentmoreeffectivethandailytreatmentinanimalmodelandequallyeffectiveinclinicaltrials第27页/共59页28RoleofPyrazinamideEssentialfor6-and8-monthregimensNobenefitifgivenformorethan2monthsRelativelyineffectiveatpreventingemergenceofresistancetootherdrugs第28页/共59页29Pyrazinamideisessentialforthefirsttwomonthsof6/8-monthtreatmentAmRevRespirDis1987;136:1339-42Relapses第29页/共59页30Pyrazinamidedoesnotgiveanyadditionalbenefitifgivenbeyondtwomonthsinshort-coursetreatmentAmRevRespirDis1991;143:700-6CureRate(%)第30页/共59页31RoleofEthambutol/StreptomycinPreventemergenceofresistancetootherdrugsgivenHastensputumconversionBacteriostaticorweaklybactericidalagainstrapidlydividingorganisms第31页/共59页32RoleofThiacetazonePreventemergenceofresistancetootherdrugsgivenBacteriostaticShouldnotbegiventoHIV+patientsbecauseofriskoffatalskinreactions第32页/共59页33RelapseratesarelowwithdirectlyobservedintermittenttreatmentinbothHIV-positiveandHIV-negativepatientsAmJRespirCritCareMed1996:154:1034-38RelapseratesRelapse(%)第33页/共59页34Adversereactionstoanti-TBdrugsIsoniazidl

Peripheralneuropathyl

HepatitisDrugsAdversereactionsPyrazinamidel

Jointpainsl

HepatitisRifampicinl

Gastroentestinal(anorexia,nausea,vomiting,abdominalpain)l

Hepatitisl

ReducedeffectivenessoforalcontraceptivepillEthambutoll

OpticneuritisStreptomycinl

Auditory&vestibularnervedamage(alsotofoetus)l

Renaldamage第34页/共59页35ManagementofLogisticsManagementofStocksCHOICEUSEPURCHASEDISTRIBUTIONSTORAGEQuantificationFinancingTenderbidsOrderQualityControlRe-packagingTransportationInformationforuser&forconsumerAdequatebufferstocksmustbemaintainedatnational,state/regional,andlocallevels第35页/共59页36Drugrequirementsaredeterminedbasedon:NumberofcasesindifferenttreatmentcategoriestreatedinpreviousyearStandardizedregimensusedExistingstocksEnsuringreserve(buffer)stocksateachlevel第36页/共59页37Keysforeffectivedistributionandstorageofanti-TBdrugsStorageconditions(temperatureandhumidity)Managementinsidethestores:appropriatespaceimplementationofFEFOprinciple(First-Expired,First-Out)reservestocksConditionsofhandlingandtransportationtotheperipherallevelImplementationofdrugaccountingsystematalllevelswheredrugsarestoredoradministered第37页/共59页38Directly

Observed

TreatmentTreatmentobservermustbeaccessibleandacceptabletothepatientandaccountabletothehealthsystemObservationisaservicetopatientsandprovidersManypatientsdonottakemedicinesregularly,evenifexcellenthealtheducationisprovidedImpossibletopredictwhichpatientwilltakemedicine第38页/共59页39Directly

Observed

Treatment

(DOT)vsDOTSDirectlyobservedtreatment(DOT)isoneelementoftheDOTSstrategyAnobserverwatchesandhelpsthepatientswallowthetabletsDirectobservationensurestreatmentfortheentirecoursewiththerightdrugsintherightdosesattherightintervals第39页/共59页40DOTisnecessaryevenwhendrugsupplyensuredChaulkCP.JAMA1998;279:943-8TreatmentSuccessDOTNoDOT第40页/共59页41Directly

Observed

Treatment

istheStandardofCare“DOThasemergedasthestandardofcare”(Bayer,Lancet,1995)“EverypatientwithTBinthiscountryshouldreceive

DOT”(Iseman,NEJM,1993)“DOTseemsimperative…wherethediseasehasbecomeepidemic”

(Chaulk,JAMA,1996)第41页/共59页42Whyisitnecessarytodirectlyobservetreatment?Atleastonethirdofpatientsreceivingself-administeredtreatmentdonotadheretotreatmentImpossibletopredictwhichpatientswilltakemedicinesDOTnecessaryatleastintheinitialphaseoftreatmenttoensureadherenceandachievesputumsmearconversionATBpatientmissingoneattendancecanbetracedimmediatelyandcounseled第42页/共59页43ModesofObservationHealthcareworkersNon-governmentalorganizationsCommunityvolunteersReligiousleadersChildsurvivalworkers,laymidwives,etc.DOTisfeasibleineachcommunitybyidentifyingandinvolvingthestrengthsofthecommunity.第43页/共59页44DOTprolongssurvivalofHIV-infectedTBpatientsSCCwithDOTSCCwithoutDOT第44页/共59页45SystematicMonitoring

andAccountabilityGoodrecord-keepingisthecornerstoneofsuccessTheDOTSrecordingsystemenablesMonitoringofpatientoutcomesEvaluationofprogrammeperformanceAnalysisofepidemiologicdataOperationalresearchEverylevelofhealthsystemaccountableforpatientdiagnosisandcure第45页/共59页46Treatmentoutcomesinsputum

smear-positivepatientsCurePatientwhoissmearnegativeat(oronemonthpriorto)completionoftreatmentandonatleastonepreviousoccasionTreatmentcompletedCompletedtreatmentbutfollow-upsmearresultsarenotavailableTreatmentfailureRemainsorbecomesagainsmearpositive5monthsormoreafterstartingtreatmentDiedPatientwhodiesforanyreasonduringtreatmentTransferredoutPatientwhohasbeentransferredtoanothertreatmentcentreandwhosetreatmentresultsarenotknownDefaulted(treatmentinterrupted)Patientwhosetreatmenthasbeeninterruptedformorethan2consecutivemonthsbeforetheendoftreatment第46页/共59页47SupervisionEffectivesupervisionatalllevelsiskeytosuccessSupervisionistheprocessofhelpingstaffimprovetheirperformanceKeyareas:laboratoryworkpatientcategorizationdirectobservationdrugstorageandstockrecordkeepingreporting第47页/共59页48DOTScanreducetheburdenofTBAnnualpercentagedeclineinincidence/prevalence第48页/共59页49DOTScanreducedrugresistanceDecline(percent)第49页/共59页50ResultsofDOTSin112,842patientswithsmear-positivepulmonaryTBinChinaLancet1996;347:358-62CurerateCurerate(%)NewPatients2H3R3Z3S3/4H3R3

Previouslytreatedpatients2H3R3Z3S3E3/6H3R3E3第50页/共59页51Treatmentoutcomes,DOTSareas,SouthEastAsia,NewSmear+Patients199725,871 308 7,708 19,492 94 9,014 2,303 3,5061,873第51页/共59页52DOTStriplestreatmentsuccessinSouthEastAsia第52页/共59页53