03577nas a2200469   4500000000100000008004100001260001600042100001300058700001600071700002400087700001700111700001300128700001500141700001100156700001500167700001200182700001200194700001500206700001600221700001600237700001200253700002300265700002800288700001800316700001300334700001500347700001100362700001600373700001300389700001800402700001600420700002500436700001200461700001300473700001500486245007800501856007500579300001600654490000700670520241600677022001403093       2024                            d  bElsevier BV1 aHasker E1 aAssoumani Y1 aRandrianantoandro A1 aRamboarina S1 aBraet SM1 aCauchoix B1 aBaco A1 aMzembaba A1 aSalim Z1 aAmidy M1 aGrillone S1 aAttoumani N1 aGrillone SH1 aRonse M1 aPeeters Grietens K1 aRakoto-Andrianarivelo M1 aHarinjatovo H1 aSupply P1 aSnijders R1 aHoof C1 aTsoumanis A1 aSuffys P1 aRasamoelina T1 aCorstjens P1 aOrtuño-Gutiérrez N1 aGeluk A1 aCambau E1 ade Jong BC00aPost-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial  uhttps://www.thelancet.com/action/showPdf?pii=S2214-109X%2824%2900062-7  ae1017-e10260 v123 a<p><strong>Background:</strong> Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. We compared effectiveness of different administration modalities, using a higher (20 mg/kg) dose of rifampicin—single double-dose rifampicin (SDDR)-PEP.</p>

<p><strong>Methods:</strong> We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed.</p>

<p><strong>Findings:</strong> Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109436 individuals, of whom 95762 had evaluable followup data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0∙95), arm 3 (IRR 0∙80), and arm 4 (IRR 0∙58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0∙56, p=0∙0030). At an individual level SDDR-PEP was also protective with an IRR of 0∙55 (p=0∙0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline.</p>

<p><strong>Interpretation:</strong> SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission.</p>
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