Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia, United States of America.
Department of Epidemiology and Biostatistics, School of Public Health, College of Health Sciences, Makerere University, Kampala, Uganda.
PLoS One. 2021 Jan 22;16(1):e0245328. doi: 10.1371/journal.pone.0245328. eCollection 2021.
One principle of tuberculosis control is to prevent the development of tuberculosis disease by treating individuals with latent tuberculosis infection. The diagnosis of latent infection using the tuberculin skin test is not straightforward because of concerns about immunologic cross reactivity with the Bacille Calmette-Guerin (BCG) vaccine and environmental mycobacteria. To parse the effects of BCG vaccine and environmental mycobacteria on the tuberculin skin test, we estimated the frequency distribution of skin test results in two divisions of Kampala, Uganda, ten years apart. We then used mixture models to estimate parameters for underlying distributions and defined clinically meaningful criteria for latent infection, including an indeterminate category. Using percentiles of two underlying normal distributions, we defined two skin test readings to demarcate three ranges. Values of 10 mm or greater contained 90% of individuals with latent infection; values less than 7.2 mm contained 80% of individuals without infection. Contacts with values between 7.2 and 10 mm fell into an indeterminate zone where it was not possible to assign infection. We conclude that systematic tuberculin skin test surveys within populations at risk, combined with mixture model analysis, may be a reproducible, evidence-based approach to define meaningful criteria for latent tuberculosis infection.
结核病控制的一个原则是通过治疗潜伏性结核感染个体来预防结核病的发生。由于对卡介苗（BCG）疫苗和环境分枝杆菌的免疫交叉反应的担忧，使用结核菌素皮肤试验来诊断潜伏性感染并不简单。为了分析 BCG 疫苗和环境分枝杆菌对结核菌素皮肤试验的影响，我们估计了乌干达坎帕拉两个分区的皮肤试验结果的频率分布，这两个分区相隔十年。然后，我们使用混合模型来估计潜在分布的参数，并定义了具有临床意义的潜伏性感染标准，包括不确定类别。使用两个潜在正态分布的百分位数，我们定义了两个皮肤试验读数来划分三个范围。值为 10 毫米或更大包含 90%的潜伏性感染个体；值小于 7.2 毫米包含 80%的无感染个体。介于 7.2 和 10 毫米之间的值则落在不确定区域，无法确定感染情况。我们得出结论，在风险人群中进行系统的结核菌素皮肤试验调查，并结合混合模型分析，可能是一种可重复的、基于证据的方法，可以定义有意义的潜伏性结核感染标准。
