Community-wide isoniazid preventive therapy drives drug-resistant tuberculosis: a model-based analysis.
Community-wide isoniazid preventive therapy drives drug-resistant tuberculosis: a model-based analysis.
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DOI：
10.1126/scitranslmed.3005260
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发表时间：
2013-04-10
影响因子：
17.1
通讯作者：
Colijn C
中科院分区：
文献类型：
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作者：
Mills HL;Cohen T;Colijn C
事实证明，在艾滋病毒高流行的环境中，结核病控制尤其困难，因为艾滋病毒合并感染会侵蚀宿主免疫力，并导致发展为活动性结核病的高风险。研究表明，6个月（或更长时间）的异烟肼单药治疗（异烟肼预防治疗（IPT））可以降低这种进展的风险。世界卫生组织赞同对无症状的艾滋病毒/结核病合并感染患者使用IPT，并作出了相当大的努力，将IPT扩大到整个社区（全社区IPT）。虽然以前的综述没有发现在以前接受过IPT治疗的患者中异烟肼耐药结核病的风险显著升高，但社区范围内的IPT计划仍然可能产生实质性的选择性压力并增加耐药结核病（DRTB）的负担。我们开发了数学模型，以确定在何种情况下，社区范围内的IPT干预会增加耐异烟肼结核分枝杆菌的负担，即使IPT不选择接受IPT治疗的患者的耐药性。在任何明确或隐含包括菌株间竞争形式的模型中（如先前结核分枝杆菌感染所带来的部分免疫），社区范围内的IPT干预通过选择性抑制药物敏感感染，为耐药菌株带来间接益处。我们证明，积极的社区范围内的IPT可以对减少药物敏感疾病产生令人印象深刻的影响，但代价是增加耐药性的选择压力。改进耐药结核病的发现和治疗可以减轻这种风险。在有限时间的小规模研究中，接受IPT的患者中没有观察到DRTB风险的升高，这并不意味着社区范围内IPT施加的选择性压力不会很大。社区范围内的IPT规划可能在高发病率环境下的疾病控制中发挥重要作用，其推广应伴随着检测和治疗耐药疾病的干预措施。
Tuberculosis control has proven especially difficult in settings of high HIV prevalence as HIV co-infection erodes host immunity and leads to a high risk of progression to active tuberculosis. Studies have demonstrated that a 6-month (or longer) course of monotherapy with isoniazid (isoniazid preventative therapy (IPT)) can reduce this risk of progression. The World Health Organization endorses the use of IPT for symptom-free individuals with HIV/tuberculosis co-infection and has placed considerable effort in expanding IPT to entire communities (community-wide IPT). Though previous reviews have not found a statistically significant elevated risk of isoniazid-resistant tuberculosis among those previously treated with IPT, community-wide IPT programs may nonetheless generate substantial selective pressure and increase the burden of drug-resistant TB (DRTB). We develop mathematical models to identify the conditions under which community-wide IPT interventions can increase the burden of isoniazid-resistant M. tuberculosis, even when IPT does not select for resistance among those treated with IPT. In any model that explicitly or implicitly includes forms of inter-strain competition (such as partial immunity conferred by a previous M. tuberculosis infection), community-wide IPT interventions confer an indirect benefit to drug-resistant strains through selective suppression of drug-sensitive infections. We demonstrate that aggressive community-wide IPT can have an impressive impact on reductions of drug-sensitive disease, but at the cost of increasing the selective pressure for resistance. Improving the detection and treatment of DRTB can mitigate this risk. The lack of an observed elevation in the risk of DRTB among those receiving IPT in small-scale studies of limited duration does not imply that the selective pressure imposed by community-wide IPT will not be substantial. Community-wide IPT programs will likely play an important role in disease control in high incidence settings and their roll-out should be accompanied by interventions for the detection and treatment of drug-resistant disease.
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DOI：
10.1073/pnas.0901415106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Harrington, W. E.;Mutabingwa, T. K.;Duffy, P. E.
通讯作者：
Duffy, P. E.
影响因子：
6.4
作者：
Brooks-Pollock, Ellen;Becerra, Mercedes C.;Murray, Megan B.
通讯作者：
Murray, Megan B.
影响因子：
3.8
作者：
Churchyard, Gavin J.;Fielding, Katherine L.;Grant, Alison D.
通讯作者：
Grant, Alison D.
DOI：
10.1073/pnas.0600349103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Cohen, T;Lipsitch, M;Murray, M
通讯作者：
Murray, M
影响因子：
30.8
作者：
通讯作者：
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