Tuberculosis Preventive Treatment in High TB-Burden Settings: A State-of-the-Art Review.

Tuberculosis (TB) is the leading cause of death from a single infectious agent. The burden is highest in some low- and middle-income countries. One-quarter of the world's population is estimated to have been infected with TB, which is the seedbed for progressing from TB infection to the deadly and contagious disease itself. Although some individuals may clear their infections through innate and acquired immunity, many do not. People living with HIV, TB-exposed household contacts, other individuals recently infected, and immunosuppressed individuals are at especially high risk of progressing to TB disease. There have been major advances in recent years to support the programmatic management of TB infection. New tests of infection, including those that predict progression to TB disease, have become available. Numerous World Health Organization-recommended TB preventive treatment (TPT) regimens are available for all ages and for both drug-susceptible and drug-resistant TB infection. All regimens are generally safe, efficacious, and cost effective and have a low risk of generating resistance. TPT is recommended for pregnant women who are at risk for developing TB, but some regimens are associated with an increased likelihood of poor obstetric and fetal outcomes, and newer regimens have not yet been tested in pregnancy. New formulations of rifapentine-based TPT have been developed, and the cost has been radically reduced. Innovative models of delivery to support the scale up of TPT have been developed. Modeling suggests that scaling up TPT, especially regimens with optimal target product profile characteristics, can contribute substantially to ending the TB epidemic. The global uptake of TPT has increased substantially, especially for people living with HIV. Implementation gaps remain, particularly for children, pregnant women, and other household contacts. Further innovation is required to support the continued scale up of TPT and to contribute to ending the TB epidemic.