Historical review of studies on the effect of treating latent tuberculosis.

Tuberculosis Preventive Therapy (TPT) is widely used in particular among high-risk populations such as close contacts and immunosuppressed people mostly in high-income settings. TPT is widely recommended for high-risk populations including HIV-infected and household contacts globally, but is not widely used. Historical trials on risk groups as well as the general population have documented a marked effect on reductions in incidence of active disease among those treated, as well as on prevalence of latent TB infection (LTBI) in populations where massive roll-out of TPT has previously taken place. This review summarizes the results of large historical trials conducted more than 50 years ago among Inuit and African populations as well as risk groups in the USA and Europe exhibiting similarities with current high-burden populations with current limited use of TPT. The trials demonstrated a 27-95% reduction in incidence of active TB among those receiving preventive treatment compared with placebo, with efficacy depending somewhat on length of treatment but mostly on adherence rates. It was possible to achieve satisfactory adherence rates in most of the trial populations and liver toxicity rates were generally low. The historical trials on preventive treatment for LTBI have documented that large-scale TPT is possible and effective even in high-burden populations in high-incidence areas and is therefore a relevant tool to consider in striving to eliminate the TB epidemic.