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

University Of Washington, Seattle WA

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Abstract

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.