title: Preventive therapy for latent tuberculosis infection-the promise and the challenges.
abstract: Around one third of the world's population may harbour latent tuberculosis infection (LTBI), an asymptomatic immunological state that confers a heightened risk of subsequently developing tuberculosis (TB). Effectively treating LTBI will be essential if the End TB Strategy is to be realized. This review evaluates the evidence in relation to the effectiveness of preventive antibiotic therapy to treat LTBI due to both drug-susceptible and drug-resistant bacteria. Current national and international preventive therapy guidelines are summarized, as well as ongoing randomized trials evaluating regimens to prevent drug-resistant TB. Populations that may benefit most from screening and treatment for LTBI include close contacts of patients with TB (particularly children under 5 years of age) and individuals with substantial immunological impairment. The risks and benefits of treatment must be carefully balanced for each individual. Electronic decision support tools offer one way in which clinicians can help patients to make informed decisions. Modelling studies indicate that the expanded use of preventive therapy will be essential to achieving substantial reductions in the global TB burden. However, the widespread scale-up of screening and treatment will require careful consideration of cost-effectiveness, while ensuring the drivers of ongoing disease transmission are also addressed.
authors.affiliation: Sydney Medical School, Room 574 Blackburn Building, University of Sydney, Sydney, 2006, Australia. Electronic address: greg.fox@sydney.edu.au.
authors.forename: G J
authors.initials: GJ
authors.lastname: Fox
authors.affiliation: Sydney Medical School, Room 574 Blackburn Building, University of Sydney, Sydney, 2006, Australia; South Western Sydney Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: C C
authors.initials: CC
authors.lastname: Dobler
authors.affiliation: The Children's Hospital at Westmead and the Marie Bashir Institute for Infectious Diseases and Biosecurity (MBI), University of Sydney, Sydney, Australia.
authors.forename: B J
authors.initials: BJ
authors.lastname: Marais
authors.affiliation: Victorian Tuberculosis Program, Melbourne Health, Victoria, Australia; Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: J T
authors.initials: JT
authors.lastname: Denholm
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D006801:Humans; D007108:Immune Tolerance; D055985:Latent Tuberculosis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D008403:Mass Screening; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents
keywords: Drug therapy; Latent tuberculosis; Mass screening; Mycobacterium tuberculosis; Risk factors; Tuberculosis