Importance of Study Design and Phenotype Definition in Ongoing Studies of Resistance to Latent Mycobacterium tuberculosis Infection.
Importance of Study Design and Phenotype Definition in Ongoing Studies of Resistance to Latent Mycobacterium tuberculosis Infection.
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研究设计和表型定义在正在进行的潜伏结核分枝杆菌感染耐药性研究中的重要性。
DOI：
10.1093/infdis/jiz539
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Boom,WHenry
中科院分区：
文献类型：
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作者：
Stein,CatherineM;Mayanja-Kizza,Harriet;Hawn,ThomasR;Boom,WHenry
致编辑-我们怀着极大的兴趣阅读了最近一项关于印度尼西亚队列的研究，该队列显示，尽管与结核病(TB)指标性病例密切接触，但干扰素-伽马释放试验(IGRA)仍呈阴性[1]。作者将这种现象称为“早期清除”，但在流行病学上，这与我们在乌干达的家庭接触研究[2-4]中描述的现象相同，我们称之为“对潜伏的结核分枝杆菌(Mtb)感染的抵抗力”(抵抗者[RSTR])。印度[5]和冈比亚[6]也进行了类似的研究设计。随着这种表型与结核病研究的相关性增加[7]，集中检查这些研究，以确定共同点和未来方向是有指导意义的。我们的乌干达研究和印度尼西亚的研究有两个重要的区别。首先，乌干达的研究在诊断出指示结核病病例后至少有12个月的随访，而印度尼西亚的研究只有14周(~3个月)的随访。虽然扩展观察在逻辑上具有挑战性，并有丢失后续工作的风险，但它对于避免受试者错误分类至关重要。在我们的乌干达研究[4]中，在接触活动性结核病患者的患者中，在基线为结核菌素皮肤试验(TST)阴性并转换为TST的患者中，我们发现25%的转换事件发生在登记后3至24个月之间，其中16%发生在3至6个月之间。印度尼西亚的全国结核病发病率为每10万人中有395人，相比之下，乌干达的全国结核病发病率为每10万人中有253人，尽管估计
To the Editor—We read with great interest the recent study of an Indonesian cohort who demonstrated persistently negative interferon-gamma release assay (IGRA) despite close exposure to an index tuberculosis (TB) case [1]. The authors termed this phenomenon “early clearance”, but epidemiologically it is the same phenomenon we have characterized in our household contact study in Uganda [2–4], which we have called “resistance to latent M. tuberculosis (Mtb) infection”(resister [RSTR]). Additional studies have been conducted in India [5], and The Gambia [6], with similar study designs. With the increased relevance of this phenotype for TB research [7], it is instructive to examine these studies collectively, to identify commonalities and future directions.There are 2 important differences between our Uganda study and the Indonesia study. First, the Uganda study had a minimum of 12 months follow-up after diagnosis of the index TB case, whereas the Indonesia study only had 14 weeks (~ 3 months) follow-up. Although extended observation is logistically challenging and risks loss to follow-up, it is critical for avoiding subject misclassification. In our Uganda study [4], among contacts of active TB patients who were tuberculin skin test (TST)-negative at baseline and converted their TST, we found that> 25% of conversion events occurred between 3 and 24 months post enrollment, including 16% between 3 and 6 months. The national TB incidence rate in Indonesia is 395 per 100 000, compared to 253 per 100 000 in Uganda at the national level, although the estimated