The spectrum of latent tuberculosis: rethinking the biology and intervention strategies.
Immunological tests provide evidence of latent tuberculosis in one third of the global population, which corresponds to more than two billion individuals. Latent tuberculosis is defined by the absence of clinical symptoms but carries a risk of subsequent progression to clinical disease, particularly in the context of co-infection with HIV. In this Review we discuss the biology of latent tuberculosis as part of a broad range of responses that occur following infection with Mycobacterium tuberculosis, which result in the formation of physiologically distinct granulomatous lesions that provide microenvironments with differential ability to support or suppress the persistence of viable bacteria. We then show how this model can be used to develop a rational programme to discover effective drugs for the eradication of M. tuberculosis infection.
Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Clifton E
CE
Barry
Helena I
HI
Boshoff
Véronique
V
Dartois
Thomas
T
Dick
Sabine
S
Ehrt
JoAnne
J
Flynn
Dirk
D
Schnappinger
Robert J
RJ
Wilkinson
Douglas
D
Young
D000942:Antigens, Bacterial / Q000276:immunology; D000995:Antitubercular Agents / Q000627:therapeutic use; D019295:Computational Biology; D016503:Drug Delivery Systems; D015195:Drug Design; D055985:Latent Tuberculosis / Q000188:drug therapy; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology*; D011933:Reagent Kits, Diagnostic; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D011933:Reagent Kits, Diagnostic