Background
Leprosy, leprosy, infection, chronic infectious disease
LEPROSY, MAY, LEPROSY, INFECTION, CHRONIC INFECTIOUS DISEASE
BE-PEOPLE is a randomized controlled trial assessing the effectiveness of bedaquiline and rifampicin as post-exposure prophylaxis (PEP) for leprosy in Comoros. Leprosy is an ancient chronic infectious disease caused by In 2000, the World Health Organization (WHO) declared leprosy eliminated as public health problem based on a prevalence below 1 per 10,000 worldwide [The BE-PEOPLE trial described in this manuscript is a sequel of the PEOPLE trial conducted between 2019 and 2023 in Comoros and Madagascar. In PEOPLE, three modalities of SDR-PEP were compared to a control arm (arm 1), in which annual door-to-door case finding was conducted yet no PEP provided. Randomization was at the village level. The dosage of SDR-PEP used in the PEOPLE trial was double the WHO-recommended dose, i.e. 20 mg/kg. In arm 2 villages only household contacts received PEP. In arm 3 villages blanket PEP coverage was provided to anyone living within a 100-meter of an index case or to the entire village if more than 50% of the village population were included in this perimeter. In arm 4 villages, screening was accompanied by a serosurvey based on anti-PGL-I IgM (the first serosurvey with UCP-LFA on such a large scale in the field), an antibody marker of infection with BE-PEOPLE was preceded by a phase 2 study to confirm the safety of BE-PEP. For this purpose, a leprosy endemic village that had been part of arm 1 of the PEOPLE trial was selected. In May 2022, the entire population of approximately 900 was screened for leprosy. After the screening, 300 eligible participants divided over three age brackets were randomized to either BE-PEP (rifampicin 600 mg + bedaquiline 800 mg for adults) or SDR-PEP (rifampicin 600 mg for adults) in an age de-escalating design. All participants had an ECG recorded pre-treatment and one day after treatment, and venous blood samples were collected pre-treatment and 14 days after treatment to be tested for liver functions (Aspartate aminotransferase AST/Alanine aminotransferase ALT). No major safety concerns emerged and the independent data safety and management board gave the green light for proceeding to phase 3, which is the subject of the current manuscript.