Whole Genome Sequencing Shows a Low Proportion of Tuberculosis Disease Is Attributable to Known Close Contacts in Rural Malawi

Whole Genome Sequencing Shows a Low Proportion of Tuberculosis Disease Is Attributable to Known Close Contacts in Rural Malawi
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DOI:
10.1371/journal.pone.0132840
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发表时间:
2015-07-16
期刊:
影响因子:
3.7
通讯作者:
Clark, Taane G.
Clark, Taane G.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Glynn, Judith R.;Guerra-Assuncao, Jose Afonso;Clark, Taane G.

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背景 结核病由密切接触者传播的比例尚不清楚。对指示患者和既往接触者的菌株基因组进行比较,可以确认或排除传播。方法在马拉维卡龙加区,所有结核病患者都被询问以前与其他结核病患者的接触情况。对来自培养阳性患者的所有可用菌株进行了测序。指示患者与其先前接触者之间最多允许确认 10 个单核苷酸多态性,并且 >= 100 个用于排除。根据确诊传播比例和接触患者比例估算人群归因分数。 结果 1997-2010 年,新增培养确诊结核病患者 1907 名,其中 32% 报告至少有 1 名家庭接触者,另有 11% 至少有 1 名其他接触者; 60%的接触者患有涂片阳性疾病。在具有可用序列的病例接触对中,38% (62/163) 的涂片阳性先前接触者和 0/17 的涂片阴性先前接触者证实了传播。确诊的传播在与先前接触有关的人中(42.4%,56/132)比非亲属(19.4%,6/31,p = 0.02)更常见,并且在接触更频繁、年轻的指示病例和最近几年的人中更常见。据估计,由已知接触者感染的结核病比例总体为 9.4%。 结论 在该人群中,已知接触者只能解释一小部分结核病病例。即使那些以前有家庭接触过涂片阳性结核病的人也更有可能在其他地方感染。
BackgroundThe proportion of tuberculosis attributable to transmission from close contacts is not well known. Comparison of the genome of strains from index patients and prior contacts allows transmission to be confirmed or excluded.MethodsIn Karonga District, Malawi, all tuberculosis patients are asked about prior contact with others with tuberculosis. All available strains from culture-positive patients were sequenced. Up to 10 single nucleotide polymorphisms between index patients and their prior contacts were allowed for confirmation, and >= 100 for exclusion. The population attributable fraction was estimated from the proportion of confirmed transmissions and the proportion of patients with contacts.ResultsFrom 1997-2010 there were 1907 new culture-confirmed tuberculosis patients, of whom 32% reported at least one family contact and an additional 11% had at least one other contact; 60% of contacts had smear-positive disease. Among case-contact pairs with sequences available, transmission was confirmed from 38% (62/163) smear-positive prior contacts and 0/17 smear-negative prior contacts. Confirmed transmission was more common in those related to the prior contact (42.4%, 56/132) than in non-relatives (19.4%, 6/31, p = 0.02), and in those with more intense contact, to younger index cases, and in more recent years. The proportion of tuberculosis attributable to known contacts was estimated to be 9.4% overall.ConclusionsIn this population known contacts only explained a small proportion of tuberculosis cases. Even those with a prior family contact with smear positive tuberculosis were more likely to have acquired their infection elsewhere.