Project 1

Biomarkers to stratify risk of progression from latent TB infection to disease

Goal: To identify and validate biomarkers that can predict which patients are at high risk of progressing from LTBI to active disease.

Questions addressed:

  • What are the risk factors for progression to TB disease after infection with Mtb?
  • Are there early markers of bacterial clearance in response to chemotherapy?
  • Which immunological markers can indicate the presence (or absence) of live Mtb?
  • What are the correlates of protection from active TB disease?

Specific aims:

  1. To characterize and validate biomarkers of high risk of progression.
  2. To characterize and validate biomarkers of low risk of progression and of cure.
  3. To identify correlates of protection in tetramer-isolated antigen-specific T cells from household contacts who self-cure.

Significance:

Biomarkers of latency progression would transform TB control by allowing the targeting of preventive therapy to those who would benefit most. Biomarkers of cure can be used as surrogate endpoints in future trials of therapeutic drugs and vaccines and for treatment shortening.