結(jié)核病的有效診斷治療和控制英文

1、Effective Diagnosis, Treatment, and Control of Tuberculosis2South-East Asia accounts for nearly40% of all tuberculosis casesWPR25%AFR18%EMR8%EUR6%AMR5%SEAR38%3TB is the leading single infectious cause of death in South-East Asia0100200300400500600700800TuberculosisHIVSTDMalariaTropicalDiseasesMeasle

2、sNumber of deaths (1000s)Deaths from infectiousagents in South-East Asia4TB is a Leading Killer of Women48,000101,000493,000538,000605,000TropicalDiseasesSTDMaternalMortalityMalariaTBDeaths among women5Tuberculosis A Global Emergency TB kills 5,000 people a day 2-3 million each year One third of the

3、 worlds population is infected with TB TB kills more young women than any other disease More than 100,000 children will die needlessly from TB this year Hundreds of thousands of children will become TB orphans this year6TB and AIDS10%60%0%10%20%30%40%50%60%70%PPD+/HIV-negativePPD+/HIV+Lifetime Risk

4、of TB7TB Control:The 5 components of DOTSTB RegisterlPolitical commitmentlDiagnosis by microscopylAdequate supply of SCC drugslDirectly observed treatmentlAccountability8Diagnosis of pulmonary tuberculosis lPatients with TB feel ill and seek care promptlylActive case finding is unnecessary and unpro

5、ductive lMicroscopy is appropriate technology, indicating infectiousness, risk of death, and priority for treatment lX-ray is non-specific for TB diagnosis lSerological and amplification technologies (PCR, etc.) currently of no proven value in TB control9Diagnosis of Pulmonary TuberculosisThree spec

6、imens optimall Spot specimen on first visit; sputum container given to patientl Early morning collection by patient on next dayl Spot specimen during second visit1081%93%100%0%50%100%FirstSecondThirdCumulative PositivityThree sputum smears are optimal11Reporting on AFB MicroscopyNumber of bacilli se

7、enResult reportedNone per 100 oil immersion fieldsNegative1-9 per 100 oil immersion fieldsScanty, reportexact number10-99 per 100 oil immersion fields1+1-10 per oil immersion field2+ 10 per oil immersion field3+12Diagnosis of Pulmonary TBCough 3 weeksAFB X 3Broad-spectrum antibiotic 10-14 daysIf sym

8、ptoms persist, repeat AFB smears, X-rayIf consistent with TBAnti-TB TreatmentIf 1 positive, X-ray and evaluation If 2/3 positive: Anti-TB RxIf negative:1398%70%020406080100AFB MicroscopyX-rayMicroscopy is more objective and reliable than X-rayInter-observeragreement1450%50%98%98%0 020204040606080801

9、00100AFB MicroscopyX-rayMicroscopy is a more specific test than X-ray for TB diagnosisSpecificity15020406080100Diagnosed by X-ray aloneActual casesX-ray-based evaluation causes over-diagnosis of TBNTI, Ind J Tuberc, 1974Over-diagnosis16Role of Chest X-ray No chest X-ray pattern is absolutely typical

10、 of TB 10-15% of culture-positive TB patients not diagnosed by X-ray 40% of patients diagnosed as having TB on the basis of x-ray alone do not have active TBToman K. Tuberculosis case finding and chemotherapy. WHO, 1979X-ray is unreliable for diagnosing and monitoring treatment of tuberculosis17Prop

11、ortion of patients with pulmonaryTB who have positive AFB smears 010203040506070HIV NegativeEarly HIVLate HIVAFB positivity in TB patients18X-ray findings in TB patients with HIV infectionEarly HIVLate HIV(severe immuno-compromise)19DOTS more than doubles accuracy of diagnosis of TB in SEAR70%27%010

12、20304050607080Non-DOTSDOTS% of cases with lab confirmationExpected range20Prompt treatment of infectious cases reduces spread of tuberculosis Smear-positive patients usually seek care Smear-positive patients are 4-20 times more infectious Untreated, a smear-positive patient may infect 10-15 persons/

13、year Smear-positive patients are much more likely to die if untreatedRouillon A. Tubercle 1976;57:275-9921Treatment CategoriesTB treatmentcategoryTB PatientsIlNew smear-positive pulmonary TBlNew smear-negative pulmonary TB with extensiveparenchymal involvementlNew cases of severe forms of extra-pulm

14、onary TBIIlSputum smear-positive relapseslSputum smear-positive t reatment failure caseslSputum smear-positive cases requiring treatmentafter interruptionIIIlNew smear-negative pulmonary TBlNew less severe forms of extra-pulmonary TB22Severe and less severe forms of extra-pulmonary TBSevereMeningiti

15、sLess SevereLymph nodesMiliaryPericarditisBone (excluding spine)Bilateral or extensivepleural effusionSpinalIntestinalTB/HIV, A Clinical Manual, World Health Organization 1996Pleural effusion (unilateral)Peripheral joint234 H RI2 HRZE(2 HRZS)2 H3R3Z3E3 (2 H3R3Z3S3)6 HE4 HR33Recommended treatment reg

16、imensDirect observation is recommended for all patients and is particularly essential when intermittent regimens are usedContinuation PhaseAlternative treatment regimens(if smear + at end of initial phase of Cat I or Cat II,one more month of initial phase is given)TBtreatmentcategoryInitial phaseIII

17、2 HRZ2 H3R3Z36 HE4 HRR4 H33333(2 S H R Z E /1 H R Z E5 H R EII2 SHRZE/1 HRZE333333333)5 HRE24Doses of first-line anti-TB drugsPyrazinamide (Z)25 (20-30)35 (30-40)Ethambutol (E)15 (15-20)30 (25-35)All these anti-TB drugs should be given as a single daily dose. Direct observation is recommended for al

18、l patients and is particularly essential when intermittent regimens are used.Thiacetazone is not effective when given intermittently and is not recommended for use in high HIV prevalence areas.Isoniazid (H)5(4-6)10 (8-12)Recommended Dose (mg/kg)Anti-TB Drug(Abbreviation)DailyIntermittent3x/wkRifampi

19、cin (R)10 (8-12)10 (8-12)Streptomycin (S)15 (12-18)15 (12-18)Thiacetazone (T)2.5Not applicable25Role of Isoniazid Mainstay of anti-TB treatment Life saving in TB meningitis Bactericidal for rapidly dividing organisms Prevents emergence of resistance to other drugs Intermittent treatment more effecti

20、ve than daily treatment in animal model and equally effective in clinical trials Safe and effective for preventive treatment26Role of Rifampicin Necessary for short-course treatment Essential for at least first 2 months of regimens of 6-9 month duration Bactericidal for rapidly dividing and slow-gro

21、wing organisms Prevents emergence of resistance to other drugs Intermittent treatment more effective than daily treatment in animal model and equally effective in clinical trials27Role of Pyrazinamide Essential for 6- and 8-month regimens No benefit if given for more than 2 months Relatively ineffec

22、tive at preventing emergence of resistance to other drugs283.4%10.3%020406080100PyrazinamideNo PyrazinamideRelapses (%)Pyrazinamide is essential for the first two months of 6/8-month treatmentAm Rev Respir Dis 1987;136:1339-42Relapses299690920204060801002 months PZA4 months PZA6 months PZAPyrazinami

23、de does not give any additional benefit if given beyond two months in short-course treatmentAm Rev Respir Dis 1991;143:700-6Cure Rate (%)30Role of Ethambutol/ Streptomycin Prevent emergence of resistance to other drugs given Hasten sputum conversion Bacteriostatic or weakly bactericidal against rapi

24、dly dividing organisms31Role of Thiacetazone Prevent emergence of resistance to other drugs given Bacteriostatic Should not be given to HIV+ patients because of risk of fatal skin reactions323%5%020406080100HIV-uninfectedHIV-infectedRelapse rates are low with directly observed intermittent treatment

25、 in both HIV-positive and HIV-negative patientsAm J Respir Crit Care Med 1996:154:1034-38Relapse ratesRelapse (%)33Adverse reactions to anti-TB drugsIsoniazidl Peripheral neuropathyl HepatitisDrugsAdverse reactionsPyrazinamidel Joint painsl HepatitisRifampicinl Gastroentestinal (anorexia, nausea,vom

26、iting, abdominal pain)l Hepatitisl Reduced effectiveness of oralcontraceptive pillEthambutoll Optic neuritisStreptomycinl Auditory & vestibular nerve damage(also to foetus)l Renal damage34Management of LogisticsManagementof StocksCHOICEUSEPURCHASEDISTRIBUTIONSTORAGEQuantificationFinancingTender

27、bidsOrderQuality ControlRe-packagingTransportationInformationfor user & for consumerAdequate buffer stocks must be maintained at national, state/regional, and local levels35Drug requirements are determined based on:l Number of cases in different treatment categories treated in previous yearl Sta

28、ndardized regimens usedl Existing stocksl Ensuring reserve (buffer) stocks at each level36Keys for effective distribution and storage of anti-TB drugs Storage conditions (temperature and humidity) Management inside the stores: appropriate space implementation of FEFO principle (First-Expired, First-

29、Out) reserve stocks Conditions of handling and transportation to the peripheral level Implementation of drug accounting system at all levels where drugs are stored or administered37Directly Observed Treatment Treatment observer must be accessible and acceptable to the patient and accountable to the

30、health system Observation is a service to patients and providers Many patients do not take medicines regularly, even if excellent health education is provided Impossible to predict which patient will take medicine38Directly Observed Treatment(DOT) vs DOTSlDirectly observed treatment (DOT) is one ele

31、ment of the DOTS strategylAn observer watches and helps the patient swallow the tabletslDirect observation ensures treatment for the entire course uwith the right drugsuin the right dosesuat the right intervals39DOT is necessary even whendrug supply ensured 88%61%0%20%40%60%80%100%Chaulk CP. JAMA 19

32、98;279:943-8Treatment SuccessDOTNo DOT40Directly Observed Treatment is the Standard of Care“DOT has emerged as the standard of care”(Bayer, Lancet, 1995)“Every patient with TB in this country should receive DOT” (Iseman, NEJM, 1993)“DOT seems imperative where the disease has become epidemic” (Chaulk

33、, JAMA, 1996)41Why is it necessary to directly observe treatment?lAt least one third of patients receiving self-administered treatment do not adhere to treatmentlImpossible to predict which patients will take medicineslDOT necessary at least in the initial phase of treatment to ensure adherence and

34、achieve sputum smear conversionlA TB patient missing one attendance can be traced immediately and counseled42Modes of Observation Health care workers Non-governmental organizations Community volunteers Religious leaders Child survival workers, lay midwives, etc.DOT is feasible in each community by i

35、dentifying and involving the strengths of the community.43DOT prolongs survival ofHIV-infected TB patients Survived 56.7%Died43.3%SCC with DOTSCC without DOTSurvived85.4%Died14.6%44Systematic Monitoringand AccountabilitylGood record-keeping is the cornerstone of successlThe DOTS recording system ena

36、blesuMonitoring of patient outcomesuEvaluation of programme performanceuAnalysis of epidemiologic datauOperational researchlEvery level of health system accountable for patient diagnosis and cure45Treatment outcomes in sputum smear-positive patientsCurePatient who is smear negative at (orone month p

37、rior to) completion oftreatment and on at least oneprevious occasionTreatmentcompletedCompleted treatment but follow-up smearresults are not availableTreatment failureRemains or becomes again smearpositive 5 months or more after startingtreatmentDiedPatient who dies for any reason duringtreatmentTra

38、nsferred outPatient who has been transferred toanother treatment centre and whosetreatment results are not knownDefaulted (treatment interrupted)Patient whose treatment has beeninterrupted for more than 2 consecutive months before the end of treatment46Supervision Effective supervision at all levels

39、 is key to success Supervision is the process of helping staff improve their performance Key areas: 4laboratory work 4patient categorization4direct observation4drug storage and stock4record keeping4reporting47DOTS can reduce the burden of TBChileUruguayS. KoreaCubaPeruNew YorkBeijingEdinburgh-25-20-

40、15-10-50Annual percentage decline in incidence/prevalence48DOTS can reduce drug resistanceTexasBeijingBurkina FasoNew York CityEdinburgh-100-80-60-40-200Decline (percent)4981%81%90%90%020406080100 Results of DOTS in 112,842 patients with smear-positive pulmonary TB in ChinaLancet 1996;347:358-62Cure

41、 rateCure rate (%) New Patients 2 H3R3Z3S3 / 4 H3R3 Previously treated patients2 H3R3Z3S3E3 / 6 H3R3E350Treatment outcomes, DOTS areas, South East Asia, New Smear+ Patients 19970%20%40%60%80%100%BAN BHU INDINOMAL MMR NEP SLA THATreated successfullyNot treated successfullyNot evaluated 25,871 308 7,7

42、08 19,492 94 9,014 2,303 3,506 1,87351DOTS triples treatment success in South East Asia23%77%020406080100Non-DOTSDOTS52DOTS is succeeding in South East Asia More than 500,000 TB patients treated with DOTS in South-East Asia More than 50,000 lives saved More than 2 million TB infections prevented Mor

43、e than 200,000 TB cases prevented More than US$150 million saved53DOTS in the context of HIVlDOTS can:uProlong life and improve its qualityuStop the spread of TBuPrevent emergence of MDRTBuReverse the trend of MDRTBFailure to use DOTS in the face of HIV can lead to explosive spread of TB, with cases

44、 tripling and drug resistance increasing rapidly54Economic benefits of DOTS: IndonesiaSawert, WHO, 19980123456789 10 11 12 13 14 15 16 17 18 19 20Years of implementation020406080Return on each dollar invested in DOTS$55 saved for every $1 invested55DOTS is Expandingin South East Asia 030050100150200

45、1994199519961997199819990100200400500600(Thousands)Cases treated Pop. Covered (million) Population covered Total Cases treated New SS+ 56The Sooner DOTS is Implemented, the FasterTB Will be Controlled in South-East Asia0199520002005201020150202YearGTB/WHO500100015002000250030003500400057020040060080

46、0100012001400160020002005201020152020DOTS by 2000No DOTS expansionDeaths from TB (thousands)Deaths from TB with and without rapidDOTS expansion, SE Asia, 2000-202058DOTS is accelerating in South-East Asia, but needs to become more extensive and intensive 010203040506070809010019941995199619971998Per

47、cent of Estimated TotalTarget Zone750,000 more new ss+ patients need to be treated yearly59Tuberculosis A Global Emergency TB kills 5,000 people a day 2-3 million each year One third of the worlds population is infected with TB TB kills more young women than any other disease More than 100,000 children will die needlessly from TB this year Hundreds of thousands of children will become TB orphans this year60X-ray findings in TB patients with HIV infectionEarly HIVLate HIV(severe immuno-compromise)61Role of Isoniazid Mainstay of anti-TB treatmen