预防性异烟肼治疗不能改善肺结核总发病率

1、nejm：预防性异烟脐治疗不能改善肺结核总发病率研究要点： 本研究对所有受试者提供肺结核筛査。诊断为活动性肺结核者转诊接受常规治疗；未诊断为 活动性肺结核者则提供9个月的异烟册预防性治疗。 使用界烟册可在治疗期间降低肺结核发病率，但人规模筛査和潜伏性肺结核治疗对肺结核总 体发病率的控制无显著效果。南非洲黄金矿工hiv和矽肺的发病率很高，二者都是肺结核的高危因素。有研究表明，异烟脏预防性 治疗可使肺结核发病率下降55%。为探讨异烟脏对矿工的预防性治疗是否也有同样作用，來口南非约翰内斯堡aurum研究所和 witwatersrand大学公共卫生学院的churchyard等人开展了一-项研究，结果发

2、现：异烟册预防性治 疗対肺结核总体发病率的控制无明显效果。该结果在线发表于2014年1月23 的nejm上。 研究主要通过大规模筛查联合对活动性或潜伏性肺结核感染者的干预治疗，以评估异烟腓预防性治疗 对阻止肺结核传播的作用。78744名矿工随机分为8个干预组（40981人）和7个对照组（37763人）。对干预组矿工提供结核 病筛查，诊断为活动性肺结核者转诊接受治疗，其余则提供9个月的异朋册预防性治疗。主要研究终点为干预治疗结束后12个月内各组的肺结核发病率。次要研究终点为研究结束时的肺结 核患病率。表1研究的总体和主要与次要研究终点分析干预组中共27126名矿工（66.2%）接受筛查，2365

3、9（87.2%）名矿工开始服用异烟册，其中35%-79% 给药6个月或以上。研究结果显示，干预治疗并没有降低肺结核的发病率。干预组发病率为3.02/100人年，对照组发病 率为2.95/100人年（干预组率比1.00；调整率比0.96）。两组肺结核患病率比为2.35%vs2.14%, 调整率比0.98o表2.全社区异烟腓预防性治疗总疗效：肺结核的发病率与患病率t able 2. overall effect of comm unity-wide isoniazid preventive therapy: tuberculosis incidence and prevalence.qsesrat

4、ecasesrateunadjustedp valueadjusted!p valueno./no. of penon-yrper 100 penon-yrfw./no. of penon-yrper 100 penon-yrfprimary outcome: tuberculosis incidenceany856/29.01429s887/29.3523.021.00(0.75-134)0.980.96 (0.76-l21)071definite or probable656/29.0142.26703/29.3522.40107 (0.70-1.64)072l04 (0.73-l48)0

5、.80prevalence ratio (95% cl)。no. of cases/ total no.no. cf akn/ total no.secondary outcome: tuberculosis prevalenceall employees119/5557114166/7049235l.os(0.60-1.82)0.860-98 (0.6s-148)0.90employees in work force at the time of duster enrollment97/44572 18128/s4232.361.05(0 62-1.78)08sl01j-(0.6 iss)/

6、 j ul0.94-control clustersintervention clustersrate ratio (95% cl)。outcome分析10909名矿工界烟脏预防性治疗的直接效应发现，治疗使肺结核发病率降低（接受界烟脏治疗 的矿工发病率为1.10例/100人年,对照组发病率为2.91例/100人-年：调整率比0.42,但异烟腓的 保护作用很短暂，随后迅速消失。研究结果认为，尽管使用异烟腓可在治疗期间成功预防肺结核，但大规模筛查及异烟腓预防性治疗, 对南非矿工潜伏性肺结核总体发病率的控制并无显著效果。总之,9个月异烟脏预防性治疗,并未改善南非矿工的肺结核总体发病率。即使有些亚组疗

7、效较好, 但干预措施温和，效果短暂，没能改变总体结果。对丁-肺结核离危人群（hiv感染者或矽肺者），应考虑连续的异烟腓预防性治疗和能够最大化疗效持 久性的方案。数学模型或可帮助确定能够有效控制肺结核总体发病率的用药方案。研究发现： 本研究的t预并没有减少肺结核的发病率、患病率或任何原因引起的死亡率，其结果不同于阿拉斯 加临床试验的成功干预。 接受异烟脏预防性治疗的矿工，其肺结核发病率在9个月的治疗期间减少了 58%,但对结核控制 的持久性疗效在治疗停止后立刻消失。 使用更敏感例行筛査方法，如自动xpert mtb/rif检测（检测结核分枝杆菌和利福平耐药的存在）， 可减少从诊断肺结核到开始治疗

8、的吋间，从而减少传染的持续时间以及传播风险。 预防性治疗对个体保护作用迅速减弱，对能是由于潜伏性肺结核感染治疗不当、再次激活或结核的 高传播率所导致的。 抗逆转录病毒疗法町减少肺结核个体的发病风险，但对总体水平的疗效取决于治疗覆盖的范围， 主要山研究入选的标准、药物吸收、疗效持久性和患者依从性等决定。早期开始抗逆转录病毒治疗和最大化治疗范围，可进一步减少hiv相关肺结核的易感性。同时，加强 粉尘控制以减少矽肺也是至关重要的，但短期内不太可能对肺结核病例通报率产僅影响。研究背景：结核病是全球成年人死亡的首要原因，2011年有约140万人死于肺结核。hiv感染、接触超深矿井 下的矽尘、封闭的工作环

9、境和生活条件使南非金矿矿工易患肺结核。不断上升的hiv患病率(2001 年为29%)更加剧了肺结核的流行趋势。1999年，南非黄金矿工的肺结核病例通报率超过4%。尽管hiv检测率的提高、免费抗逆转录病毒 治疗，以及有针对性的对hiv感染矿工进行异烟耕预防性治疗，人大降低了肺结核的发病率，但到 2008年，肺结核发病率仍保持在较高水平(3%) o20 lit纪60年代，结核病在阿拉斯加呈现流行趋势，在一个随机临床试验中，异烟聊预防性治疗使结核病发病率下降55%o因此促使研究者为南非黄金矿工考虑一个新的干预方案。原文见 pdf： a trial of mass isoniazid preventi

10、ve therapy for tuberculosis control新闻链接：http:/www.medpagetodav.eom/lnfectiousdisease/tuberculosis/43936tb prevention trial failspreventive tuberculosis therapy had no lasting effect on tb incidcnee among south african gold miners agroup hard-hit by the disease, researchers reported.in a cluster-rand

11、omized trial, the therapy 一 9 months of isoniazid (nydrazid) 一 also did not cut prevalenceof tb among the miners, according to gavin churchyakl, mbbch, phd, of the aurum institute injohannesburg, south africa, and colleagues.on the other hand, while miners were actually taking the drug, they were le

12、ss likely to develop tb,churchyard and colleagues reported in the jan. 23 issue of the new england joumal of medicine. bui thatso-called direct effect vanished when the treatment period ended, they reported.an i inporta nt implication of the finding might be that preventive therapy with isoniazid is

13、 even less likely towork in places like the u.s. where tb prevalence is low, commented eic rubin, md, phd, of harvardschool of public health."even in this high-risk, counseled population, the uptake of isoniazid preventive therapy was unimpressive/ rubin noted in an accompanying editorial."

14、;such an outcome is probably even more common in low-burden situations/1 rubin argued, noting that it'smnot uncommon" in the u.s. for patients to start isoniazid but fail to complete the 9-month regimen.the findings are disappointing, the researchers said, because previous smaller studies h

15、ad shownthat prevenlive 山erapy could interrupl the transmission of【he disease in a lasting fashion.gold miners in south africa, they noted, are in desperate need of interventions to reduce the burden of tb: they live and work in close quarters, they are exposed to silica dust, and there is a high pr

16、evalence of hiv among them.in 2008, churchyard and colleagues wrote, tb case notifications reached 3,000 per 100,000 miners, despite hiv testing linked to free antiretroviral therapy and preventive isoniazid for those with hiv.to test the effect of wider preventive treatment, they designated 15 clus

17、ters of miners 一 40,981 miners in eight intervention clusters and 37,763 miners in seven control clusters.miners in the intervention clusters were offered tb screening and, if they had active disease, were referred for treatment. those without active disease were offered 9 months of isoniazid preven

18、tive thcrapy.the main outcome of the study was cluster-level tb incidence during the year after the end of the 9-month intervention. a sccondary outcome was tb prevalence at the end of the study.in the intervention clusters, 27,126 miners, or 66.2%, agreed to be screened and some 23,659 of those (87

19、.2%) started taking isoniazid. the drug was dispensed for at least 6 months to 35% to 79% of miners, depending on the cluster, the investigators reportedbut the intervention had little effect. specifically:the post-intervention incidenee of tb was 3.02 cases per 100 person-years in the intervention

20、clusters and 2.95 per 100 person-years in the control clusters (adjusted rate ratio rr 0.96, 95% cl 0.76-1.21).the prevale nee of tb was 2.35% in the intervention clusters and 2.14% in the control clusters (adjusted prevalence ratio 0.98, 95% cl 0.65-1.48).during the intervention, the incidence of tb was significantly reduced 1.10 cases per 100