NEJM:预防性异烟肼治疗不能改善肺结核总发病率

2014-02-14 daerwen2008 dxy

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,异烟肼预防性治疗可使肺结核发病率下降55%。 为探讨异烟肼对矿工的预防性治疗是否也有同样作用,来自南非约翰内斯堡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,结果发现:异烟肼预防性治疗对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2

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,异烟肼预防性治疗可使肺结核发病率下降55%。

为探讨异烟肼对矿工的预防性治疗是否也有同样作用,来自南非约翰内斯堡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,结果发现:异烟肼预防性治疗对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日的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,以评估异烟肼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个月的异烟肼预防性治疗。

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,23659(87.2%)名矿工开始服用异烟肼,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0.98。

表2. 全社区异烟肼预防性治疗总疗效:肺结核的发病率与患病率


分析10909名矿工异烟肼预防性治疗的直接效应发现,治疗使肺结核发病率降低(接受异烟肼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,但异烟肼的保护作用很短暂,随后迅速消失。

研究结果认为,尽管使用异烟肼可在治疗期间成功预防肺结核,但大规模筛查及异烟肼预防性治疗,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个月异烟肼预防性治疗,并未改善南非矿工的肺结核总体发病率。即使有些亚组疗效较好,但干预措施温和,效果短暂,没能改变总体结果。

对于肺结核高危人群(HIV感染者或矽肺者),应考虑连续的异烟肼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:

①本研究的干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。
② 接受异烟肼预防性治疗的矿工,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。
③使用更敏感例行筛查方法,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的时间,从而减少传染的持续时间以及传播风险。
④预防性治疗对个体保护作用迅速减弱,可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。
⑤ 抗逆转录病毒疗法可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,主要由研究入选的标准、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生影响。

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