Probing the in-vivo reservoir of latent tuberculosis infection

Abstract

For decades the unanswered question of where viable bacilli reside in latently infected individuals has been a central conundrum in tuberculosis. The hitherto insurmountable challenge of identifying dormant Mycobacterium tuberculosis bacilli in asymptomatic latently infected individuals is why diagnosis of latent tuberculosis infection relies on measurement of the cell-mediated immune response to M tuberculosis, by tuberculin skin test or interferon-γ release assay (IGRA).1 The first clues about M tuberculosis's anatomical niche in latent infection stretch back a century when it was shown that post-mortem cadaveric tissue homogenates, from healthy lung as well as fibrotic and granulomatous lesions, could propagate tuberculosis in challenged guinea pigs, a finding replicated in several subsequent studies.