TRANSMISSION OF PAUCIBACILLARY AND DRUG RESISTANT TB

正在作出相当大的努力，在全球范围内实施“短期直接观察治疗”。 然而，这一战略所依据的关于结核病传播的基本生物学的几个关键假设仍然没有得到解决。 从我们目前的ICIDR项目和我们从事的其他工作中获得的结果使我们假设，在一个良好运作的DOTS项目的背景下，1）仅仅依靠痰液显微镜检查（AFB涂片）用于诊断提供了对结核病流行病学的偏见，2）AFB涂片阴性的患者，但培养阳性（称为“少杆菌性”）对疾病传播有显著贡献3）耐药M的持续传播率令人担忧。结核病，和4）从M的完整基因组序列的可用性获得的见解。结核病的研究可为临床和流行病学提供相关的了解M。结核病群体遗传学 我们现在建议使用“最先进的”分子流行病学技术来验证这些假设。这些结果将对许多热带国家的结核病控制计划产生直接影响。 此外，从本研究中获得的完全特征化的菌株将使我们能够检查M种群内遗传多样性的性质和后果。结核病，并开始利用这些信息来改进基因分型和诊断系统。

Considerable efforts are being expended to implement "Directly Observed Therapy, Short course" (DOTS) globally. However, several key assumptions about the basic biology of tuberculosis transmission, upon which this strategy is based, remain unresolved. Results obtained from our current ICIDR project and other work in which we are engaged have lead us to hypothesize that, in the context of a well functioning DOTS based program, 1) relying solely on sputum microscopy (AFB smear) for diagnosis provides a biased underestimate of TB epidemiology, 2) that patients who are AFB smear negative, but culture positive (termed "paucibacillary") contribute significantly to disease transmission 3) that there are concerning rates of ongoing transmission of drug resistant M. tuberculosis, and 4) insight gained from the availability of the complete genomic sequence of M. tuberculosis can be exploited to provide clinically and epidemiologically relevant understanding of M. tuberculosis population genetics. We now propose to use "state of the art" molecular epidemiologic techniques to test these hypotheses. These results will have immediate implications for tuberculosis control programs in many tropical countries. In addition, the availability of fully characterized strains from this study will allow us to examine the nature and consequence of genetic diversity within populations of M. tuberculosis and begin to exploit this information for improved genotyping and diagnostic systems.