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

描述（由申请人提供）：结核病（TB）患者在完成治疗后通常不会进行随访，这些患者的长期结局尚未得到很好的评价。一些研究表明，长期生存可能会减少这一人群。尚未进行基于人群的研究来评估与不良结局相关的风险因素。对影响长期生存的因素进行表征，可以识别出死亡率增加的风险患者，并允许进行干预。除了宿主因素外，结核分枝杆菌复合群（MTB）的菌株特异性差异可能会影响临床结局。MTB的分子基因分型是过去二十年来结核病领域的重要进展。该技术最近的应用是在MTB染色体遗传学领域，或 对进化相关性的研究。越来越多的证据表明，不同的结核分枝杆菌菌株可能在疾病严重程度和传播性方面存在差异。这项建议的目的是：1）记录在大的基于人群的队列中诊断为TB的患者在长的随访期内的存活率，并确定死亡原因，2）鉴定与TB诊断后的结果相关的临床和人口统计学因素，3）描述华盛顿州的MTB的遗传群体结构，并鉴定TB的特定菌株与临床结果之间的关联，4）鉴定MTB的系统发育谱系与近期疾病传播之间的关联，如通过非独特基因型分离株的存在所证明的。结核病仍然是世界范围内的主要死因;在美国，2006年有近14,000例结核病病例。过去对结核病的不重视导致全国结核病发病率急剧上升，耐多药结核病和极端耐药结核病的流行率不断上升，这进一步表明需要在结核病的调查、治疗和控制方面继续投入资源。更好地了解结核病的自然史、结果的差异和传播性的变化将对结核病患者的健康产生直接影响。进一步阐明MTB菌株变异性的重要性对于开发抗TB的诊断测试和治疗剂可能是重要的。

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.