結(jié)核病的有效診斷治療和控制英文

結(jié)核病的有效診斷，治療和控制英文South-EastAsiaaccountsfornearly

40%ofalltuberculosiscases2TBistheleadingsingleinfectiouscauseofdeathinSouth-EastAsiaNumberofdeaths(1000s)DeathsfrominfectiousagentsinSouth-EastAsia3TBisaLeadingKillerofWomenDeathsamongwomen4Tuberculosis

AGlobalEmergencyTBkills5,000peopleaday–2-3millioneachyearOnethirdoftheworld’spopulationisinfectedwithTBTBkillsmoreyoungwomenthananyotherdiseaseMorethan100,000childrenwilldieneedlesslyfromTBthisyearHundredsofthousandsofchildrenwillbecomeTBorphansthisyear5TBandAIDSLifetimeRiskofTB6TBControl:The5componentsofDOTSTBRegisterPoliticalcommitmentDiagnosisbymicroscopyAdequatesupplyofSCCdrugsDirectlyobservedtreatmentAccountability7Diagnosisofpulmonarytuberculosis

PatientswithTBfeelillandseekcarepromptlyActivecasefindingisunnecessaryandunproductiveMicroscopyisappropriatetechnology,indicatinginfectiousness,riskofdeath,andpriorityfortreatmentX-rayisnon-specificforTBdiagnosisSerologicalandamplificationtechnologies(PCR,etc.)currentlyofnoprovenvalueinTBcontrol8DiagnosisofPulmonaryTuberculosisThreespecimensoptimalSpotspecimenonfirstvisit;sputumcontainergiventopatientEarlymorningcollectionbypatientonnextdaySpotspecimenduringsecondvisit9Threesputumsmearsareoptimal10ReportingonAFBMicroscopyNumberofbacilliseenResultreportedNoneper100oilimmersionfieldsNegative1-9per100oilimmersionfieldsScanty,reportexactnumber10-99per100oilimmersionfields1+1-10peroilimmersionfield2+>10peroilimmersionfield3+11DiagnosisofPulmonaryTBCough3weeksAFBX3Broad-spectrumantibiotic10-14daysIfsymptomspersist,repeatAFBsmears,X-rayIfconsistentwithTBAnti-TBTreatmentIf1positive,X-rayandevaluationIf2/3positive:Anti-TBRxIf

negative:12MicroscopyismoreobjectiveandreliablethanX-rayInter-observeragreement13MicroscopyisamorespecifictestthanX-rayforTBdiagnosisSpecificity14X-ray-basedevaluationcausesover-diagnosisofTBNTI,IndJTuberc,1974Over-diagnosis15RoleofChestX-rayNochestX-raypatternisabsolutelytypicalofTB10-15%ofculture-positiveTBpatientsnotdiagnosedbyX-ray40%ofpatientsdiagnosedashavingTBonthebasisofx-rayalonedonothaveactiveTBTomanK.Tuberculosiscasefindingandchemotherapy.WHO,1979X-rayisunreliablefordiagnosingandmonitoringtreatmentoftuberculosis16ProportionofpatientswithpulmonaryTBwhohavepositiveAFBsmears010203040506070HIVNegativeEarlyHIVLateHIVAFBpositivityinTBpatients17X-rayfindingsinTBpatientswithHIVinfectionEarlyHIVLateHIV(severeimmuno-compromise)18DOTSmorethandoublesaccuracyofdiagnosisofTBinSEARExpectedrange19PrompttreatmentofinfectiouscasesreducesspreadoftuberculosisSmear-positivepatientsusuallyseekcareSmear-positivepatientsare4-20timesmoreinfectiousUntreated,asmear-positivepatientmayinfect10-15persons/yearSmear-positivepatientsaremuchmorelikelytodieifuntreatedRouillonA.Tubercle1976;57:275-9920TreatmentCategoriesTBtreatmentcategoryTBPatientsIlNewsmear-positivepulmonaryTBlNewsmear-negativepulmonaryTBwithextensiveparenchymalinvolvementlNewcasesofsevereformsofextra-pulmonaryTBIIlSputumsmear-positiverelapseslSputumsmear-positivetreatmentfailurecaseslSputumsmear-positivecasesrequiringtreatmentafterinterruptionIIIlNewsmear-negativepulmonaryTBlNewlesssevereformsofextra-pulmonaryTB21Severeandlesssevereformsofextra-pulmonaryTBSevereMeningitisLessSevereLymphnodesMiliaryPericarditisBone(excludingspine)BilateralorextensivepleuraleffusionSpinalIntestinalTB/HIV,AClinicalManual,WorldHealthOrganization1996Pleuraleffusion(unilateral)Peripheraljoint224HRI2HRZE(2HRZS)2H3R3Z3E3(2H3R3Z3S3)6HE4HR33RecommendedtreatmentregimensDirectobservationisrecommendedforallpatientsandisparticularlyessentialwhenintermittentregimensareusedContinuationPhaseAlternativetreatmentregimens(ifsmear+atendofinitialphaseofCatIorCatII,onemoremonthofinitialphaseisgiven)TBtreatmentcategoryInitialphaseIII2HRZ2H3R3Z36HE4HRR4H33333(2SHRZE/1HRZE5HREII2SHRZE/1HRZE333333333)5HRE23Dosesoffirst-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)2.5Notapplicable24RoleofIsoniazidMainstayofanti-TBtreatmentLifesavinginTBmeningitisBactericidalforrapidlydividingorganismsPreventsemergenceofresistancetootherdrugsIntermittenttreatmentmoreeffectivethandailytreatmentinanimalmodelandequallyeffectiveinclinicaltrialsSafeandeffectiveforpreventivetreatment25RoleofRifampicinNecessaryforshort-coursetreatmentEssentialforatleastfirst2monthsofregimensof6-9monthdurationBactericidalforrapidlydividingandslow-growingorganismsPreventsemergenceofresistancetootherdrugsIntermittenttreatmentmoreeffectivethandailytreatmentinanimalmodelandequallyeffectiveinclinicaltrials26RoleofPyrazinamideEssentialfor6-and8-monthregimensNobenefitifgivenformorethan2monthsRelativelyineffectiveatpreventingemergenceofresistancetootherdrugs27Pyrazinamideisessentialforthefirsttwomonthsof6/8-monthtreatmentAmRevRespirDis1987;136:1339-42Relapses28Pyrazinamidedoesnotgiveanyadditionalbenefitifgivenbeyondtwomonthsinshort-coursetreatmentAmRevRespirDis1991;143:700-6CureRate(%)29RoleofEthambutol/StreptomycinPreventemergenceofresistancetootherdrugsgivenHastensputumconversionBacteriostaticorweaklybactericidalagainstrapidlydividingorganisms30RoleofThiacetazonePreventemergenceofresistancetootherdrugsgivenBacteriostaticShouldnotbegiventoHIV+patientsbecauseofriskoffatalskinreactions31RelapseratesarelowwithdirectlyobservedintermittenttreatmentinbothHIV-positiveandHIV-negativepatientsAmJRespirCritCareMed1996:154:1034-38RelapseratesRelapse(%)32Adversereactionstoanti-TBdrugsIsoniazidl

Peripheralneuropathyl

HepatitisDrugsAdversereactionsPyrazinamidel

Jointpainsl

HepatitisRifampicinl

Gastroentestinal(anorexia,nausea,vomiting,abdominalpain)l

Hepatitisl

ReducedeffectivenessoforalcontraceptivepillEthambutoll

OpticneuritisStreptomycinl

Auditory&vestibularnervedamage(alsotofoetus)l

Renaldamage33ManagementofLogisticsManagementofStocksCHOICEUSEPURCHASEDISTRIBUTIONSTORAGEQuantificationFinancingTenderbidsOrderQualityControlRe-packagingTransportationInformationforuser&forconsumerAdequatebufferstocksmustbemaintainedatnational,state/regional,andlocallevels34Drugrequirementsaredeterminedbasedon:NumberofcasesindifferenttreatmentcategoriestreatedinpreviousyearStandardizedregimensusedExistingstocksEnsuringreserve(buffer)stocksateachlevel35Keysforeffectivedistributionandstorageofanti-TBdrugsStorageconditions(temperatureandhumidity)Managementinsidethestores:appropriatespaceimplementationofFEFOprinciple(First-Expired,First-Out)reservestocksConditionsofhandlingandtransportationtotheperipherallevelImplementationofdrugaccountingsystematalllevelswheredrugsarestoredoradministered36Directly

Observed

TreatmentTreatmentobservermustbeaccessibleandacceptabletothepatientandaccountabletothehealthsystemObservationisaservicetopatientsandprovidersManypatientsdonottakemedicinesregularly,evenifexcellenthealtheducationisprovidedImpossibletopredictwhichpatientwilltakemedicine37Directly

Observed

Treatment

(DOT)vsDOTSDirectlyobservedtreatment(DOT)isoneelementoftheDOTSstrategyAnobserverwatchesandhelpsthepatientswallowthetabletsDirectobservationensurestreatmentfortheentirecoursewiththerightdrugsintherightdosesattherightintervals38DOTisnecessaryevenwhendrugsupplyensuredChaulkCP.JAMA1998;279:943-8TreatmentSuccessDOTNoDOT39Directly

Observed

Treatment

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

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

(Chaulk,JAMA,1996)40Whyisitnecessarytodirectlyobservetreatment?Atleastonethirdofpatientsreceivingself-administeredtreatmentdonotadheretotreatmentImpossibletopredictwhichpatientswilltakemedicinesDOTnecessaryatleastintheinitialphaseoftreatmenttoensureadherenceandachievesputumsmearconversionATBpatientmissingoneattendancecanbetracedimmediatelyandcounseled41ModesofObservationHealthcareworkersNon-governmentalorganizationsCommunityvolunteersReligiousleadersChildsurvivalworkers,laymidwives,etc.DOTisfeasibleineachcommunitybyidentifyingandinvolvingthestrengthsofthecommunity.42DOTprolongssurvivalofHIV-infectedTBpatientsSCCwithDOTSCCwithoutDOT43SystematicMonitoring

andAccountabilityGoodrecord-keepingisthecornerstoneofsuccessTheDOTSrecordingsystemenablesMonitoringofpatientoutcomesEvaluationofprogrammeperformanceAnalysisofepidemiologicdataOperationalresearchEverylevelofhealthsystemaccountableforpatientdiagnosisandcure44Treatmentoutcomesinsputum

smear-positivepatientsCurePatientwhoissmearnegativeat(oronemonthpriorto)completionoftreatmentandonatleastonepreviousoccasionTreatmentcompletedCompletedtreatmentbutfollow-upsmearresultsarenotavailableTreatmentfailureRemainsorbecomesagainsmearpositive5monthsormoreafterstartingtreatmentDiedPatientwhodiesforanyreasonduringtreatmentTransferredoutPatientwhohasbeentransferredtoanothertreatmentcentreandwhosetreatmentresultsarenotknownDefaulted(treatmentinterrupted)Patientwhosetreatmenthasbeeninterruptedformorethan2consecutivemonthsbeforetheendoftreatment45SupervisionEffectivesupervisionatalllevelsiskeytosuccessSupervisionistheprocessofhelpingstaffimprovetheirperformanceKeyareas:laboratoryworkpatientcategorizationdirectobservationdrugstorageandstockrecordkeepingreporting46DOTScanreducetheburdenofTBAnnualpercentagedeclineinincidence/prevalence47DOTScanreducedrugresistanceDecline(percent)48ResultsofDOTSin112,842patientswithsmear-positivepulmonaryTBinChinaLancet1996;347:358-62CurerateCurerate(%)NewPatients2H3R3Z3S3/4H3R3

Previouslytreatedpatients2H3R3Z3S3E3/6H3R3E349Treatmentoutcomes,DOTSareas,SouthEastAsia,NewSmear+Patients199725,871 308 7,708 19,492 94 9,014 2,303 3,5061,87350DOTStriplestreatmentsuccessinSo