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Project Topic
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Global control of leprosy, an ancient infectious disease caused by Mycobacterium leprae (M. leprae), has stalled and needs new interventions. Post exposure prophylaxis (PEP) is one of the key interventions suggested to overcome the stalemate. Currently single dose Rifampicin (SDR) is the regimen of choice but new strategies and tools are required to target individuals at risk of developing leprosy or transmitting the bacterium. We initiated the PEOPLE community randomized trial to evaluate the impact of three different approaches to SDR PEP on new leprosy case detection rates in highly endemic villages on the Comoros and Madagascar, assessing the effectiveness of inclusion of different sets of contacts. Highly endemic villages were randomized to one of four study arms, comparing the current baseline, i.e. no PEP (arm 1), to intervention arms in which SDR PEP is provided to household contacts only (arm 2), to all contacts within a radius of 100 meters (arm 3), or to household contacts plus individuals seropositive for anti-M. leprae PGL-I antibodies living within a radius of 100 meters (arm 4). Rather than the standard dose for Rifampicin of 10 mg/kg, we offer 20 mg/kg (single double dose of rifampicin (SDDR)) in all three intervention arms. Ethical approvals were obtained at all study sites and in Antwerp. In the Comoros’ islands of Anjouan and Moheli, we selected highly endemic villages based on data for the period 2013-2017. In these villages we are completing the first of four annual door-to-door surveys. Preliminary findings include a leprosy prevalence of 0.66% among 56,623 population screened on the Comoros, and 0.45% among 11,906 population screened in Madagascar. The first survey serves as a baseline and is also used to outline high risk zones within the villages allocated to study arms 3 and 4 by applying a 100m radius buffer around each household with an incident case in the preceding five years. PEP is then provided in arms 2-4. Surveys will be repeated once yearly. After the second and third survey, risk zones will be redrawn based on cases reported over the preceding five-year period and PEP will be provided accordingly. The fourth and final survey will be used to calculate cumulative incidence rates per study arm since baseline. In Madagascar, the first survey serves to document baseline prevalence in endemic villages, based on which they will be randomized to the four different arms in year 2. In addition, we conduct a qualitative study to identify optimal ways of implementation, avoiding possible obstacles related mainly to acceptability. In order to correlate patterns of clustering of leprosy at village and island level with the results observed in the four study arms, a molecular study based on genotyping of M. leprae bacteria is performed. Validation of a new tool, the Deeplex MycLep, based on target deep sequencing, is ongoing. The design of the study, as well as preliminary findings, were presented at the Leprosy Research Initiative meeting in Veenendaal in April 2019, as well as at the ILEP conference in Manilla in September 2019. The outcomes of this project will have important programmatic implications for leprosy control and will likely show how to turn off the tap of ongoing M. leprae transmission. More information on the project can be found at: https://www.people-project.be/.
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