Determinants of cluster distribution in the molecular epidemiology of tuberculosis

Recently developed molecular techniques have revolutionized the epidemiology of tuberculosis. Multiple studies have used these tools to examine the population structure of Mycobacterium tuberculosis isolates in different communities. The distributions of clusters of M. tuberculosis isolates in these settings may variously reflect social mixing patterns or the differential fitness of specific clones of the organism. We developed an individual-based microsimulation of tuberculosis transmission to explore social and demographic determinants of cluster distribution and to observe the effect of transmission dynamics on the empiric data from molecular epidemiologic studies. Our results demonstrate that multiple host-related factors contribute to wide variation in cluster distributions even when all strains of the organism are assumed to be equally transmissible. These host characteristics include interventions such as chemotherapy, vaccination and chemoprophylaxis, HIV prevalence, the age structure of the population, and the prevalence of latent tuberculosis infection. We consider the implications of these results for the interpretation of cluster studies of M. tuberculosis as well as the more general application of microsimulation models to infectious disease epidemiology.

近年来发展起来的分子生物技术彻底革新了结核病流行病学研究。多项研究已借助此类技术，针对不同社区分离得到的结核分枝杆菌（Mycobacterium tuberculosis）菌株的群体结构展开分析。在此类研究场景中，结核分枝杆菌分离株的聚类分布可从不同维度反映人群社交接触模式，或是该病原体特定克隆株的适应性差异。本研究构建了一套针对结核病传播的基于个体的微观模拟（individual-based microsimulation）模型，旨在探究聚类分布的社会与人口学决定因素，并观察传播动态对分子流行病学研究实证数据的影响。研究结果显示，即便假设该病原体所有菌株的传播能力完全一致，多种宿主相关因素仍会导致聚类分布出现显著差异。这些宿主相关特征包括化疗、疫苗接种与化学预防等干预措施、人类免疫缺陷病毒（HIV）感染率、人群年龄结构，以及潜伏性结核感染（latent tuberculosis infection）患病率。本研究还探讨了上述结果对解读结核分枝杆菌聚类研究的启示，以及微观模拟模型在传染病流行病学领域的更普适性应用。