Epco Hasker, Younoussa Assoumani, Andriamira Randrianantoandro, Stéphanie Ramboarina, Sofie Marijke Braet, Bertrand Cauchoix, Abdallah Baco, Aboubacar Mzembaba, Zahara Salim, Mohammed Amidy, Saverio Grillone, Nissad Attoumani, Sillahi Halifa Grillone, Maya Ronse, Koen Peeters Grietens, Mala Rakoto-Andrianarivelo, Hanitra Harinjatovo, Philip Supply, Rian Snijders, Carolien Hoof, Achilleas Tsoumanis, Philip Suffys, Tahinamandranto Rasamoelina, Paul Corstjens, Nimer Ortuno-Gutierrez, Annemieke Geluk, Emmanuelle Cambau, Bouke Catharina de Jong
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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 109 436 individuals, of whom 95 762 had evaluable follow-up 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><p><strong>Funding: </strong>European and Developing Countries Clinical Trials Partnership.</p><p><strong>Translation: </strong>For the French translation of the abstract see Supplementary Materials section.</p>","PeriodicalId":48783,"journal":{"name":"Lancet Global Health","volume":null,"pages":null},"PeriodicalIF":19.9000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.\",\"authors\":\"Epco Hasker, Younoussa Assoumani, Andriamira Randrianantoandro, Stéphanie Ramboarina, Sofie Marijke Braet, Bertrand Cauchoix, Abdallah Baco, Aboubacar Mzembaba, Zahara Salim, Mohammed Amidy, Saverio Grillone, Nissad Attoumani, Sillahi Halifa Grillone, Maya Ronse, Koen Peeters Grietens, Mala Rakoto-Andrianarivelo, Hanitra Harinjatovo, Philip Supply, Rian Snijders, Carolien Hoof, Achilleas Tsoumanis, Philip Suffys, Tahinamandranto Rasamoelina, Paul Corstjens, Nimer Ortuno-Gutierrez, Annemieke Geluk, Emmanuelle Cambau, Bouke Catharina de Jong\",\"doi\":\"10.1016/S2214-109X(24)00062-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. 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Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.
Background: 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.
Methods: 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.
Findings: Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109 436 individuals, of whom 95 762 had evaluable follow-up 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.
Interpretation: 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.
Funding: European and Developing Countries Clinical Trials Partnership.
Translation: For the French translation of the abstract see Supplementary Materials section.
期刊介绍：
The Lancet Global Health is an online publication that releases monthly open access (subscription-free) issues.Each issue includes original research, commentary, and correspondence.In addition to this, the publication also provides regular blog posts.
The main focus of The Lancet Global Health is on disadvantaged populations, which can include both entire economic regions and marginalized groups within prosperous nations.The publication prefers to cover topics related to reproductive, maternal, neonatal, child, and adolescent health; infectious diseases (including neglected tropical diseases); non-communicable diseases; mental health; the global health workforce; health systems; surgery; and health policy.
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