Recurrence due to relapse or reinfection with Mycobacterium tuberculosis: a whole-genome sequencing approach in a large, population-based cohort with a high HIV infection prevalence and active follow-up.

Recurrence due to relapse or reinfection with Mycobacterium tuberculosis: a whole-genome sequencing approach in a large, population-based cohort with a high HIV infection prevalence and active follow-up.
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由于结核分枝杆菌的复发或再感染引起的复发:在大型,基于人群的队列中,全基因组测序方法具有较高的HIV感染患病率和主动随访。

DOI:
10.1093/infdis/jiu574
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发表时间:
2015-04-01
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Glynn JR
Glynn JR
中科院分区:
其他
文献类型:
--
作者:
Guerra-Assunção JA;Houben RM;Crampin AC;Mzembe T;Mallard K;Coll F;Khan P;Banda L;Chiwaya A;Pereira RP;McNerney R;Harris D;Parkhill J;Clark TG;Glynn JR

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背景。复发性结核病是一种主要的健康负担,可能是由于原菌株复发或再感染新菌株所致。方法。在马拉维北部的一项基于人群的研究中,1996年至2010年诊断为结核病的患者在治疗结束后积极随访。对所有可用培养物进行全基因组测序,覆盖范围约为100倍。IS6110限制性片段长度多态性分析结果可用于截至2008年的培养。结果。根据我们的数据,用≤10个单核苷酸多态性(snp)的差异来定义复发,用bbb100个snp的差异来定义再感染。在被归类为再感染的患者中没有混合感染的证据。1471例患者中,139例实验室确诊复发:55例复发,20例再感染;有64种复发类型未分类。几乎所有的复发都发生在前2年。人类免疫缺陷病毒感染与再感染相关,但与复发无关。复发与异烟肼耐药、2007年以前的治疗和谱系-3菌株有关。我们发现了几个与复发相关的基因变异。在再感染株中,世系2(北京)的代表性过高,世系1的代表性不足(P = 0.004)。结论。虽然决定复发的一些因素取决于患者及其治疗,但结核分枝杆菌基因组的差异似乎在复发和再感染中都起作用。
Background. Recurrent tuberculosis is a major health burden and may be due to relapse with the original strain or reinfection with a new strain. Methods. In a population-based study in northern Malawi, patients with tuberculosis diagnosed from 1996 to 2010 were actively followed after the end of treatment. Whole-genome sequencing with approximately 100-fold coverage was performed on all available cultures. Results of IS6110 restriction fragment-length polymorphism analyses were available for cultures performed up to 2008. Results. Based on our data, a difference of ≤10 single-nucleotide polymorphisms (SNPs) was used to define relapse, and a difference of >100 SNPs was used to define reinfection. There was no evidence of mixed infections among those classified as reinfections. Of 1471 patients, 139 had laboratory-confirmed recurrences: 55 had relapse, and 20 had reinfection; for 64 type of recurrence was unclassified. Almost all relapses occurred in the first 2 years. Human immunodeficiency virus infection was associated with reinfection but not relapse. Relapses were associated with isoniazid resistance, treatment before 2007, and lineage-3 strains. We identified several gene variants associated with relapse. Lineage-2 (Beijing) was overrepresented and lineage-1 underrepresented among the reinfecting strains (P = .004). Conclusions. While some of the factors determining recurrence depend on the patient and their treatment, differences in the Mycobacterium tuberculosis genome appear to have a role in both relapse and reinfection.
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