Research Strategy

Latent TB infection (LTBI) and persistence of Mycobacterium tuberculosis (Mtb) after appropriate treatment are two forms of paucibacillary tuberculosis, in which organisms are not cultured. The first represents host control of primary infection with Mtb, while the latter represents persistence of viable Mtb organisms despite treatment. They both constitute hidden reservoirs for future epidemics and pose an obstacle to global elimination of tuberculosis.

The mechanisms that determine latency and persistence of Mtb are not completely understood. Little is known about the pathophysiology of latent tuberculosis infection, the mechanisms that determine it, and the biomarkers that predict progression to active disease. Similarly, there is little information on factors favoring persistence/eradication of persistent foci such as minimal inhibitory concentrations (MIC) of antibiotics, anatomic localization of persisting organisms, and pharmacokinetics of anti-TB drugs at the relevant local sites.

Critical gaps include animal models of paucibacillary TB that resemble human disease and biomarkers for latency and persistence of Mtb in humans; both would facilitate development of new drugs, allow tailored treatment regimens, and promote cure of patients.