Controlling latent TB tuberculosis infection in high-burden countries: A neglected strategy to end TB

Latent TB infection: Global burden and risk factors for progressing to TB diseaseThe World Health Organization (WHO) estimated that 10 million people developed tuberculosis (TB) and 1.6 million died of TB globally in 2017 [1].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 [2].The greatest burden of TB infection is in WHO Southeast Asia, Western Pacific, and sub-Saharan Africa regions [2].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]- 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. TPTThe 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 [3].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 [4].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 [5].Small observational studies suggest that treating presumed multidrug-