Diagnosis and treatment of latent tuberculosis infections in high burden settings: A Herculean task

India carries the highest share of the global tuberculosis (TB) burden. In 2021, there was a 19% increase in TB patients from 2020. The WHO ‘End TB’ strategy sets a goal to reduce TB deaths by 90% between 2015 and 2035.[1] Although the initiative has been started to achieve this goal, it resulted in a small decline in the disease burden. Hence, efforts need to be increased exponentially. To meet this target, it requires not only improving active TB case diagnosis and their effective treatment but also strategic plans to prevent the development of new infection.[2] Many of the modelling studies from China and India suggested that it is not possible to achieve the 2035 target or even the 2050 elimination goal without combining active TB treatment with the diagnosis and treatment of an individual with latent tuberculosis infection (LTBI).[3] Latent TB is basically defined as a state of persistent immune response to simulation by Mycobacterium tuberculosis antigen without evidence of clinically manifested active TB. It can lead to active TB disease in approximately 5–10% of these individuals during their lifetime. This reactivation risk depends upon various factors like age when they are infected, the presence of many other associated medical conditions like diabetes, HIV, etc.[4] Diagnosis of LTBI is important, and early initiation of prophylaxis treatment for positive patients can prevent the development of active TB. The diagnostics method is a century-old tuberculin skin test (TST) but still being widely used. Newly emerged interferon-gamma release assay (IGRA) can diagnose LTBI more accurately in people vaccinated with Bacillus Calmette-Guerin (BCG). Novel emerging skin tests have been developed in recent years: Diaskintest (Generium Pharmaceutical, Moscow, Russia), C-Tb skin test (Statens Serum Institut, Copenhagen, Denmark), and EC-Test (Zhifei Longcom Biologic Pharmacy Co., Anhui, China).The Diaskintest is a new effective way to identify the initial presentation of TB and developed based on a fusion protein of the early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) antigens present in virulent strains of M. tuberculosis, which are absent in the BCG strain and in most NTMs. The novel C-Tb skin test is based on a mixture of antigens ESAT-6 and CFP10. The EC-Test is the latest skin test for the diagnosis of TB and LTBI. All these tests have higher specificity than that of the TST and are more accurate, acceptable, and cheaper alternatives to IGRAs.[5] Isoniazid (INH) for LTBI treatment has a longer duration of therapy and poor tolerability, while shorter, better-tolerated treatment using rifamycin provides a safe and effective alternative to INH. Hence, CDC recommended once weekly regimen of isoniazid plus rifapentine for three months (3 HP) and a daily rifapentine regimen of one month.[6,7] Even though latent infections are treated in countries having low TB burden such as the United States, various views state that this approach is not possible and cannot be implemented in high-burden countries like India. The main reason lies in the fact that, in India, re-infection due to contact with active disease cases rather than reactivation contributes to a high disease burden.[4] Hence, achieving the WHO pre-defined LTBI target for TB elimination may sound like a ‘colossal task’. In such a situation risk group, prioritisation for LTBI testing and treatment, radiological screening and shorter treatment for LTBI is really worth. For higher TB incidence countries like us, implementing an effective LTBI treatment programme represents both challenge and opportunity. Though many challenges are there in the journey to achieve this target, more research on LTBI in terms of novel biomarkers which can differentiate persons with LTBI at risk for the development of active TB and active steps in their management, cost-effective shorter regimens can definitely direct our path towards the goal. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.