Epidemic Spread of Multidrug-Resistant Tuberculosis in Johannesburg, South Africa

Epidemic Spread of Multidrug-Resistant Tuberculosis in Johannesburg, South Africa
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DOI:
10.1128/jcm.00200-13
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发表时间:
2013-06-01
影响因子:
9.4
通讯作者:
Warrend, Robin M.
Warrend, Robin M.
中科院分区:
医学2区
文献类型:
--
作者:
Marais, Ben J.;Mlambo, Charmaine K.;Warrend, Robin M.

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许多报告已经记录了多药耐药结核分枝杆菌菌株的孤立传播事件或克隆爆发,但对其流行传播的了解仍然有限。在这项研究中,我们评估了2004年3月至2007年12月在南非约翰内斯堡国家卫生实验室服务中心结核病实验室诊断为耐多药(MDR)结核病(TB)的患者的耐药性、菌株多样性和聚集率。表型药敏试验采用间接比例法进行,而每个分离株的基因分型采用spoligotyping和12-MIRU分型(12-位点多重散布重复单位分型)的组合。对434例耐多药结核病患者的分离株进行了评价,其中238例(54.8%)对4种一线药物(异烟肼、利福平、乙胺丁醇和链霉素)耐药。Spoligotyping鉴定出56种不同的菌株和28个大小不等的簇(每个簇2至71例病例),聚集率为87.1%。10个集群包括337例(77.6%)病例,其中北京基因型菌株最流行(16.4%)。Spoligotyping和12-MIRU分型的联合分析增加了区分能力(Hunter Gaston区分指数[HGDI] = 0.962),并将聚类率降低至66.8%。24-MIRU-VNTR(variable-number tandem repeat)分型方法进一步提高了北京基因型菌株的分辨率,从12个12-MIRU簇中鉴定出15个亚簇和19个独特菌株。各种菌株之间的高聚集性表明,在研究环境中,耐多药结核病确实存在流行性传播,强调了早期诊断和有效治疗以减少该社区内传播的紧迫性。
Numerous reports have documented isolated transmission events or clonal outbreaks of multidrug-resistant Mycobacterium tuberculosis strains, but knowledge of their epidemic spread remains limited. In this study, we evaluated drug resistance, strain diversity, and clustering rates in patients diagnosed with multidrug-resistant (MDR) tuberculosis (TB) at the National Health Laboratory Service (NHLS) Central TB Laboratory in Johannesburg, South Africa, between March 2004 and December 2007. Phenotypic drug susceptibility testing was done using the indirect proportion method, while each isolate was genotyped using a combination of spoligotyping and 12-MIRU typing (12-locus multiple interspersed repetitive unit typing). Isolates from 434 MDR-TB patients were evaluated, of which 238 (54.8%) were resistant to four first-line drugs (isoniazid, rifampin, ethambutol, and streptomycin). Spoligotyping identified 56 different strains and 28 clusters of variable size (2 to 71 cases per cluster) with a clustering rate of 87.1%. Ten clusters included 337 (77.6%) of all cases, with strains of the Beijing genotype being most prevalent (16.4%). Combined analysis of spoligotyping and 12-MIRU typing increased the discriminatory power (Hunter Gaston discriminatory index [HGDI] = 0.962) and reduced the clustering rate to 66.8%. Resolution of Beijing genotype strains was further enhanced with the 24-MIRU-VNTR (variable-number tandem repeat) typing method by identifying 15 subclusters and 19 unique strains from twelve 12-MIRU clusters. High levels of clustering among a variety of strains suggest a true epidemic spread of MDR-TB in the study setting, emphasizing the urgency of early diagnosis and effective treatment to reduce transmission within this community.