Transmission of Extensively Drug-Resistant Tuberculosis in South Africa.
Transmission of Extensively Drug-Resistant Tuberculosis in South Africa.
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南非广泛耐药结核病的传播。
DOI：
10.1056/nejmoa1604544
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发表时间：
2017-01-19
期刊：
影响因子：
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通讯作者：
Gandhi NR
中科院分区：
文献类型：
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作者：
Shah NS;Auld SC;Brust JC;Mathema B;Ismail N;Moodley P;Mlisana K;Allana S;Campbell A;Mthiyane T;Morris N;Mpangase P;van der Meulen H;Omar SV;Brown TS;Narechania A;Shaskina E;Kapwata T;Kreiswirth B;Gandhi NR
抗药性结核病威胁着全世界最近在治疗结核病和人体免疫缺陷病毒（艾滋病毒）感染方面取得的进展。广泛耐药结核病（XDR）正在南非广泛流行，自2002年以来病例大幅增加。推动这一快速增长的因素尚未完全阐明，但需要这些知识来指导公共卫生干预措施。我们进行了一项前瞻性研究，涉及南非夸祖鲁-纳塔尔省的404名参与者，他们在2011年至2014年期间被诊断为XDR结核病。访谈和医疗记录审查被用来获取参与者的结核病和艾滋病感染史，住院和社交网络的信息。结核分枝杆菌分离株进行插入序列（IS）6110限制性片段长度多态性分析，靶向基因测序和全基因组测序。我们使用临床和基因型病例定义来计算由于多药耐药（MDR）结核病治疗不足而导致的XDR结核病病例比例（即，获得性抗性）与由于传播引起的那些（即，传输电阻）。我们使用社交网络分析来确定社区和医院的传播位置。在404名参与者中，311名（77%）患有HIV感染;中位CD 4+计数为每立方毫米340个细胞（四分位数范围，117至431）。共有280名参与者（69%）从未接受过MDR结核病治疗。对386名参与者的基因型分析显示，323名（84%）属于31个聚类中的1个。集群范围从2到14名参与者，除了一个大集群的212名参与者（55%）与LAM 4/KZN菌株。404名参与者中有123名（30%）确定了人与人或医院的流行病学联系。南非夸祖鲁-纳塔尔是一个结核病负担高的地区，大多数XDR结核病病例可能是由于传播而不是MDR结核病治疗不足。这些数据表明，控制耐药结核病的流行需要更加注重阻断传播。（由国家过敏和传染病研究所和其他机构资助。
Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants’ history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment– length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrug-resistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission. Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%). The majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug-resistant tuberculosis requires an increased focus on interrupting transmission. (Funded by the National Institute of Allergy and Infectious Diseases and others.)