Large-scale field application of a fingerstick blood test for Mycobacterium leprae infection: Monitoring population-wide effects of case finding and post-exposure prophylaxis on transmission in the Comoros and Madagascar

Since 2018, the WHO recommends provision of single-dose rifampicin post-exposure prophylaxis (SDR-PEP) to contacts of leprosy patients. In the Post-ExpOsure Prophylaxis for LEprosy (PEOPLE) trial that took place in the Comoros (Anjouan and Mohéli) and Madagascar (2019-2023), single double-dose rifampicin (SDDR)-PEP administration modalities were compared. Additionally, in 16/64 villages, anti-M. leprae phenolic glycolipid-I (anti-PGL-I) IgM levels were measured for three consecutive years, in newly diagnosed leprosy patients and more than 17,000 household- and neighbourhood contacts who had been screened for signs of leprosy. To study the impact of active case finding and SDDR-PEP on M. leprae infection rates in the population, fingerstick blood of contacts was sampled before, during and after the administration of SDDR-PEP. In this serosurvey, anti-PGL-I IgM levels were measured for the first time at such large scale by local staff using a field-friendly, quantitative lateral flow assay based on the UCP-platform (UCP-LFA). Out of 53 multibacillary patients with a bacterial index of 1 or higher, 92.5% (n = 49) tested seropositive for anti-M. leprae PGL-I IgM, confirming excellent performance of the test when executed by local staff. Before SDDR-PEP administration, seroprevalence among contacts in the different villages ranged from 21.9% to 27.4% across the three study sites. After two years of active case finding and SDDR-PEP, seroprevalence was significantly lower in the population in all three study sites (11.6% to 22.8%). Longitudinal serological monitoring in initially seropositive contacts showed significant reductions in anti-PGL-I IgM levels at an individual level. This reduction in seropositivity was observed irrespective of administration of SDDR-PEP. These serological data suggest that the implemented combination of active case finding with SDDR-PEP, led to a reduction in infection levels in the population in these study sites. This large-scale field serosurvey demonstrates the usefulness of the anti-PGL-I UCP-LFA to evaluate and monitor at a population level the effects of leprosy control interventions on M. leprae transmission.