流行病1实验流病汇报汇总

1、A Trial of Mass Isoniazid Preventive Therapy for Tuberculosis Control vs. Protocol version 8第三组 汇报人：曹亚英 袁园 Why gold miners in South Africa?TB case rates in this workforce have risen progressively during the 1990s to over 2,000 per 100,000 employees per yearMathematical modelling suggest: a rapid imp

2、act on TB incidenceNo data to justify this approach and currently no support Other factors: HIV infection, exposure to silica dust and close working and living conditionsAim compare the efficacy of isoniazid preventive therapy (IPT) given on a community-wide basis vs current 、 standard of care on TB

3、 among gold miners in South Africa. current、standard of care expanded DOTS: radiological screening and isoniazid preventive therapy for individuals at highest risk (HIV/silicosis) objectivePrimary : =60% reduction in TB incidence in the final 12 months of the follow-up periodSecondary: =40% reductio

4、n in TB case notification rates during the follow-up period describe trends in TB case notification following the intervention, the prevalence of TB at the end of the follow-up period, safety of community-wide IPT, all-cause mortality and the incidence of isoniazid-resistant TB (limited to first TB

5、episodes) Study type open cluster-randomised studyMethodcluster selection (Population) geographically discrete mines in South Africa. a. at least 10 years b. a workforce of at least 1000 miners three gold-mining companies, 15 clusters.Gold miners ： all miners（including employees and contractors） at

6、participating mines and associated hostelsMethodRandomization of clusterStratify: two groups according to rates of tuberculosis case notification (low or high) in 2005 Randomize: restrict balance (mining company, province, and workforce size)1 out of 312 realizations A & BRandom number A is interven

7、tion or controlProcedure 15 clustersIntervention(40,981 in 8 clusters)Control(37,763 in 7 clusters)Methodbaseline survey for clustersMethods: a. interviews (demographic characteristics; tuberculosis history; risk factors) b. standardized reading of a previous occupational health chest radiograph. (b

8、lind)Respondents: a simple random sample of approximately 1000 miners per cluster Procedure 15 clustersInterventionBaseline (7561 Completed )ControlBaseline(6397 Completed)Methodinclusion criteria for both groupsall employees and contractors working within the specified clusters.Methodcriteria for I

9、PTIPTisoniazid preventive therapyInclusion criteria: all employees and contractors in the intervention groupScreening:symptoms (cough with duration 2 weeks, unintentional weight loss, or night sweats) chest radiographyMethodexclusion criteria for IPTExclusion criteria: Active TB (confirmed or suspec

10、ted) Weight less than 40kgKnown or suspected hypersensitivity to INH Self reported chronic liver disease or symptoms suggesting active hepatitisMethodIntervention measurea 9-month course of isoniazid (300 mg daily) with pyridoxine (25 mg daily)isoniazid preventive therapy(IPT).Monthly visits: dispen

11、se drugs and find active casesMethodstandard of care（Control）In all clusters, mine health services provided comprehensive free medical caretuberculosis diagnostictreatment servicesHIV testingantiretroviral therapy Timelinesintervention period Intervention clusters intervention enrollment period (3-1

12、6 mon) : recruit miners intervention follow-up period (9 mon) :allowed all participants to complete 9 months of isoniazid therapy control clusters: corresponding periodsprimary e period(12 mon):measured the incidence of tuberculosis in all clusters Final prevalence survey: measured the prevalence of

13、 tuberculosis among a consecutive sample of employees undergoing their annual medical examinationStudy esThe primary e： incidence of tuberculosisSecondary es： the prevalence of sputum culturepositive tuberculosis death from any cause rates of tuberculosis case notificationEffects of interventionIson

14、iazid cohort, excluding those who were receiving tuberculosis treatment or isoniazid preventive therapy at the time of the baseline surveyOverall effectsDirect effectsAnalysis levelcluster-level post hoc (based on cohort)Person-time at risk (start date)measurementDrugs dispensed; baseline survey for

15、 control cohortSpecial eThe rate of death from any cause was measured from the time of cluster enrollment to the end of the measurement period compared the incidence of tuberculosis between the isoniazid cohort and the control cohortEndpoint symptoms suggestive of hepatotoxicity (further assessment

16、)tuberculosis treatment was initiatedthe miner diedthe miner left the workforcethe end of the measurement period for the primary e whichever came first. Adherence enhancementattendance at monitoring visits；self-report；pill count；urine testing for isoniazid；Analysis instructionsincidence and prevalen

17、ce of tuberculosis and mortality permanent employees onlysince the ascertainment of es among contract workers, who accessed health care outside the mine, was pleteMain ResultsMass screening and treatment for latent tuberculosis had no significant effect on tuberculosis control in South African gold

18、mines, despite the successful use of isoniazid in preventing tuberculosis during treatment.Main ResultsOverall effect of Community-wide Isoniazid Preventive TherapyOut comeIntervention clusters Cohort(N=4646)Control clusters(N=6263)RRUnadjustedPAdjustedPPrimary: Any3.022.951.00(0.75-1.34)0.980.96(0.

19、76-1.21)0.71Definite of probable2.402.261.07(0.70-1.64)0.721.04(0.73-1.48)0.80Secondary: ALL2.352.141.05(0.60-1.82)0.860.98(0.65-1.48)0.90Secondary: part2.362.181.05(0.62-1.78)0.851.01(0.66-1.55)0.94Main ResultsDirect Effect of Isoniazid Preventive TherapyTime intervalIsoniazid Cohort(N=4646)Control

20、 Cohort(N=6263)RRUnadjustedPAdjustedPoverall1.912.770.77(0.52-1.15)0.180.82(0.58-1.15)0.230-9M1.102.910.38(0.19-0.75)0.010.42(0.20-0.88)0.039-18M2.342.710.97(0.57-1.65)0.890.93(0.53-1.61)0.9318M2.422.700.83(0.54-1.27)0.350.95(0.62-1.46)0.95DiscussionLack of effect：Our intervention did not reduce eit

21、her the incidence or prevalence of tuberculosis or the rate of death from any cause. The incidence of tuberculosis among employees was reduced by 58% during the 9-month treatment period, but the effect was lost immediately after treatment was discontinued.Possible reasons1 Participation were variable 2 The effectiveness may have been compromised 3 The rapid waning of individual protection4 High prevalence of HIV and silicosis in South Africa 5 The population-level effect of antiretroviral therapy Limitation1 The prevalence of HIV2 The relatively small numbers of cluste