Date Published: April 23, 2019
Publisher: Public Library of Science
Author(s): Gavin J. Churchyard, Sue Swindells
Abstract: In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries.
Partial Text: The World Health Organization (WHO) estimated that 10 million people developed tuberculosis (TB) and 1.6 million died of TB globally in 2017 . In contrast, an estimated 1.7 billion people (23% of the world’s population) are latently infected with TB, from whom cases of active TB disease arise . The greatest burden of TB infection is in WHO Southeast Asia, Western Pacific, and sub-Saharan Africa regions . Controlling the large reservoir of latent TB infection will require finding and treating individuals infected with TB who are otherwise well and are at high risk of progressing to TB disease. Recognising that it will not be possible to end the TB epidemic unless we prevent TB, the United Nations High Level Meeting on TB in September 2018 called on the world to treat a target number of 30 million people living with TB infection. People at highest risk of progressing from latent to active TB disease are those who are immunosuppressed because of HIV or from treatment (e.g., tumour necrosis factor [TNF]-α inhibitors), who are preparing for organ or haematological transplant, who are on dialysis, who are household contacts of patients with pulmonary TB (particularly children <5 years of age), and who have silicosis, which occurs from occupational exposure to silica dust. TB preventive therapy (TPT) entails using one or more antituberculous drugs to treat persons with latent TB infection who are at high risk of progressing to TB disease. In this perspective, we provide the justification for scaling up TPT in high-burden countries. The utility of TPT was demonstrated more than 60 years ago, when isoniazid preventive therapy (IPT) was used to reduce the risk of TB among Alaskan villages, household contacts, and persons living in mental health facilities . Nine to 12 months of IPT substantially reduces the risk of TB among HIV-uninfected adults and children. Among people living with HIV, 6–9 months of IPT substantially reduces the risk of TB regardless of CD4 count or whether they are on antiretroviral therapy or not . IPT is effective among all individuals taking antiretroviral therapy, regardless of whether they have a positive or negative test for TB infection. In high-TB–transmission settings, the protective effect of TPT may wane over time because of ongoing TB transmission. However, the benefit of TPT may be prolonged in these settings by interrupting transmission through case finding and extending the duration of treatment for up to 36 months . Small observational studies suggest that treating presumed multidrug-resistant (MDR) TB infection with appropriate drugs may be effective, but evidence-based data are urgently needed . Three large cluster randomised trials are evaluating the use of levofloxacin, a fluoroquinolone that has been repurposed for treating TB infection (TB CHAMP: ISRCTN92634082, V-QUIN: ACTRN12616000215426), and delamanid, a new TB drug (nitroimidazole) (A5300B/I2003B/PHOENIx: NCT03568383), for treating household contacts exposed to MDR TB patients in high-burden countries. Modelling studies suggest that by integrating TPT for persons at high risk of developing TB into a comprehensive epidemic control strategy that implements quality services for finding and treating TB disease, strengthening linkages to HIV and child services will accelerate progress towards TB elimination . Validated biomarkers to help identity those at high risk for disease progression would help reduce the number needed to treat and is an area of ongoing investigation. Source: http://doi.org/10.1371/journal.pmed.1002787