Background The island of Anjouan (Comoros) is highly endemic for leprosy with an annual incidence of 5–10/10,000. In May/June, 2015 single-dose Rifampicin post-exposure prophylaxis (SDR-PEP) was administered to 269 close contacts of 70 leprosy-patients in four villages as a pilot programmatic intervention. Two years later we revisited the villages for follow-up investigations. The main aim of our study was to quantify spatial associations between reported leprosy cases before and after PEP implementation. A secondary aim was to assess the effect of this single round of SDR-PEP at the individual level. Methods We conducted door-to-door leprosy screening in all four villages in August/September, 2017. We screened all consenting individuals for leprosy and recorded geographic coordinates of their household. We also recorded whether they had received SDR-PEP and whether they had been diagnosed with leprosy, before or after the 2015 intervention. We fitted a Poisson model with leprosy as outcome and distance to the nearest pre-intervention case and SDR-PEP as predictors. Results During the survey we found 114 new cases among 5760 contacts screened (2.0% prevalence), in addition to the 39 cases detected in the two preceding years. We found statistically significant associations of incident leprosy with physical distance to index cases ranging from 2.4 (95% confidence interval (95% CI) 1.5–3.6) for household contacts to 1.8 (95% CI 1.3–2.5) for those living at 1–25 m, compared to individuals living at ≥75 m. The effect of SDR-PEP appeared protective but did not reach statistical significance due to the low numbers, with an incidence rate ratio (IRR) of 0.6 (95% CI 0.3–1.2) overall, and 0.5 (95% CI 0.2–1.3) when considering only household contacts. Conclusions This pilot demonstrated an increased risk of leprosy in contacts beyond the household, therefore a wider circle should be considered for chemoprophylaxis. Baseline surveys and extended contact definitions are essential for improving SDR-PEP effectiveness.

BackgroundLeprosy is an ancient infectious disease with a global annual incidence that has plateaued above 200,000 new cases since over a decade. New strategies are required to overcome this stalemate. Post-exposure prophylaxis (PEP) with a single dose of Rifampicin (SDR) has conditionally been recommended by the World Health Organization (WHO), based on a randomized-controlled-trial in Bangladesh. More evidence is required. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial will assess effectiveness of different modalities of PEP on the Comoros and Madagascar.MethodsPEOPLE is a cluster-randomized trial with villages selected on previous leprosy-incidence and randomly allocated to four arms. Four annual door-to-door surveys will be performed in all arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP.Arm-1 is the comparator in which no PEP will be provided. In arms 2, 3 and 4, SDR-PEP will be provided at double the regular dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2 all household-members of incident leprosy patients are eligible. In arm 3 not only household-members but also neighbourhood contacts living within 100-m of an incident case are eligible. In arm 4 such neighbourhood contacts are only eligible if they test positive to anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome.DiscussionDifferent trials on PEP have yielded varying results. The pivotal COLEP trial in Bangladesh showed a 57% reduction in incidence over a two-year period post-intervention without any rebound in the following years. A study in a high-incidence setting in Indonesia showed no effect of PEP provided to close contacts but a major effect of PEP provided as a blanket measure to an entire island population. High background incidence could be the reason of the lack of effect of PEP provided to individual contacts. The PEOPLE trial will assess effectiveness of PEP in a high incidence setting and will compare three different approaches, to identify who benefits most from PEP.Trial registrationClinicaltrials.Gov. NCT03662022. Initial Protocol Version 1.2, 27-Aug-2018.

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In order to determine the duration of follow-up needed to evaluate the efficacy of short-course bactericidal regimens for multibacillary leprosy, information is needed on the incubation time of relapses after stopping treatment. Several groups of patients, who had been on rifampicin-containing regimens, were followed up for periods ranging from 4 to 10 years. Two groups of relapses were observed: early relapses occurring within 3.5 years after stopping treatment, with a median incubation time of 1 year and 10 months (upper limit of 95% confidence interval: 2 years); and late relapses occurring more than 3.5 years after stopping treatment, with a median incubation of 5 years. Early relapses are probably due to insufficient treatment, and late relapses to persisting bacilli or to reinfection. It is concluded that the efficacy of short-course RMP-containing therapeutic regimens can be evaluated by observing the occurrence of early relapses, 50% of which occur before 2 years after the end of therapy.

Although the WHO recommended multidrug therapy regimen for multibacillary (MB) leprosy is highly effective, there is a need from the operational point of viewl to develop regimens of shorter duration.We present here the results of a regimen of 6 weeks duration involving the supervised administration of four drugs, introduced in November 1989. Follow-up from 7 years on has become increasingly difficult as a result of political turmoil in the country. We therefore present the results as available. Patients and methodsAs in our previous studies,z-4 all patients were examined clinically, neurologically and bacteriologically; a copy of the clinical file was sent to Antwerp together with a skin biopsy fixed in 10% formalin. MB leprosy was defined as disease with a bacterial index (BI) of 2 or more at any of three sites from which slit-skin smears were prepared (one earlobe and two skin sites) and confirmed by histopathology .• Yearly follow-up examination identical to those at intake are performed. Patients received daily, 6 days a week, under supervision, rifampicin 600 mg, ofloxacin 400 mg, clofazimin 100 mg and once a week minocycline 100 mg.For follow-up, patients were invited to present to the National Leprosy Centre in the capital or to the regional Health Centres, where they were examined by the mobile teams and actively searched for as far as possible. This became more and more difficult from year 7 on.Relapses were suspected clinically when new active looking lesions appeared. These were