Predictors of short-term and long-term outcome after a diagnosis of tuberculosis

描述(申请人提供)：结核病患者在完成治疗后通常不会被跟踪，这些患者的长期结果没有得到很好的评估。几项研究表明，这一人群的长期存活率可能会降低。尚未开展以人群为基础的研究，以评估与不良结局相关的风险因素。对影响长期存活率的因素进行表征可导致确定有可能增加死亡率的患者，并允许采取干预措施。除了宿主因素外，结核分枝杆菌复合体(MTB)的菌株特异性差异可能会影响临床结果。在过去的二十年里，结核分枝杆菌的分子基因分型已经成为结核病领域的一项重要进展。这项技术的最新应用是在结核分枝杆菌系统发育领域，或 进化论对进化关联性的研究越来越多的证据表明，不同的结核分枝杆菌菌株在疾病严重性和传播性方面可能有所不同。这项建议的目的是：1)记录被诊断为结核病的患者在大规模人群队列中长期随访的存活情况，并确定死亡原因；2)确定与结核病诊断结果相关的临床和人口学因素；3)描述华盛顿州结核杆菌的遗传种群结构，确定特定结核菌株与临床结果之间的联系；4)确定结核杆菌的系统发展谱系与最近疾病传播之间的关联，如存在非独特的基因分离株所证明的那样。结核病仍然是世界范围内主要的死亡原因；2006年美国有近14,000例结核病病例。过去对结核病的忽视导致全国结核病发病率急剧上升，多药耐药(MDR)和极端耐药结核病的流行率不断上升，进一步表明需要继续投入资源进行结核病的调查、治疗和控制。更好地了解结核病的自然历史、结果的差异和传播率的变化将对公众健康产生直接影响。进一步阐明结核分枝杆菌菌株变异性的重要性可能对发展结核病的诊断检测和治疗方法很重要。

DESCRIPTION (provided by applicant): Patients with tuberculosis (TB) are not usually followed after they have completed treatment and long-term outcomes in these patients have not been well evaluated. Several studies suggest that long-term survival may be reduced in this population. Population-based studies to assess risk factors that are associated with poor outcomes have not been performed. Characterization of factors that impact long-term survival could lead to the identification of patients at risk for increased mortality and allow for interventions. In addition to host factors, strain specific differences of Mycobacterium tuberculosis complex (MTB) may impact clinical outcome. Molecular genotyping of MTB has been an important advancement in the field of TB over the last two decades. A more recent application of this technology has been in the area of MTB phylogenetics, or the study of evolutionary relatedness. There is growing evidence that different strains of MTB may differ in disease severity and transmissibility. The aims of this proposal are to: 1) document survival of patients diagnosed with TB in a large population based cohort over a long follow-up period and determine cause of death, 2) identify clinical and demographic factors associated with outcome after a diagnosis of TB, 3) describe the genetic population structure of MTB in Washington State and identify associations between specific strains of TB and clinical outcome, 4) identify associations between phylogenetic lineage of MTB and recent disease transmission as demonstrated by the presence of non-unique genotype isolates. TB remains a leading cause of death world-wide; in the U.S. there were almost 14,000 cases of TB in 2006. Past inattention to TB in resulted in a dramatic increase in national rates and the increasing prevalence of multi-drug resistant (MDR) and extremely drug resistant TB have further demonstrated the need for continued investment of resources in the investigation, treatment, and control of TB. A better understanding of the natural history of TB, differences in outcomes and variations in transmissibility would have direct impacts on publich health. Further elucidation of the importance of MTB strain variability could be important in the development of diagnostic tests and therapeutics in the fight against TB.