Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.

Autor:	Hasker E; Institute of Tropical Medicine, Antwerp, Belgium. Electronic address: ehasker@itg.be., Assoumani Y; National Tuberculosis and Leprosy Control Program, Moroni, Comoros., Randrianantoandro A; National Leprosy Control Program, Antananarivo, Madagascar., Ramboarina S; Fondation Raoul Follereau, Antananarivo, Madagascar., Braet SM; Institute of Tropical Medicine, Antwerp, Belgium., Cauchoix B; Fondation Raoul Follereau, Antananarivo, Madagascar., Baco A; National Tuberculosis and Leprosy Control Program, Moroni, Comoros., Mzembaba A; National Tuberculosis and Leprosy Control Program, Moroni, Comoros., Salim Z; National Tuberculosis and Leprosy Control Program, Moroni, Comoros., Amidy M; National Tuberculosis and Leprosy Control Program, Moroni, Comoros., Grillone S; National Tuberculosis and Leprosy Control Program, Moroni, Comoros., Attoumani N; National Tuberculosis and Leprosy Control Program, Moroni, Comoros., Grillone SH; National Tuberculosis and Leprosy Control Program, Moroni, Comoros., Ronse M; Institute of Tropical Medicine, Antwerp, Belgium., Peeters Grietens K; Institute of Tropical Medicine, Antwerp, Belgium., Rakoto-Andrianarivelo M; Centre d'Infectiologie Charles Mérieux, Antananarivo, Madagascar., Harinjatovo H; National Leprosy Control Program, Antananarivo, Madagascar., Supply P; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017, Center for Infection and Immunity of Lille, Lille, France., Snijders R; Institute of Tropical Medicine, Antwerp, Belgium., Hoof C; Institute of Tropical Medicine, Antwerp, Belgium., Tsoumanis A; Institute of Tropical Medicine, Antwerp, Belgium., Suffys P; Oswaldo Cruz Institute, Fiocruz, Laboratory of Molecular Biology Applied to Mycobacteria, Rio de Janeiro, Brazil., Rasamoelina T; Centre d'Infectiologie Charles Mérieux, Antananarivo, Madagascar., Corstjens P; Leiden University Medical Center, Leiden, Netherlands., Ortuno-Gutierrez N; Damien Foundation, Brussels, Belgium., Geluk A; Leiden University Medical Center, Leiden, Netherlands., Cambau E; Inserm, IAME, Université Paris Cité, UMR 1137, Paris, France; AP-HP, Hôpital Bichat, Service de Mycobacteriologie Specialisee et de Reference, Paris, France., de Jong BC; Institute of Tropical Medicine, Antwerp, Belgium.
Jazyk:	angličtina
Zdroj:	The Lancet. Global health [Lancet Glob Health] 2024 Jun; Vol. 12 (6), pp. e1017-e1026.
DOI:	10.1016/S2214-109X(24)00062-7
Abstrakt:	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. Competing Interests: Declaration of interests We declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)
Databáze:	MEDLINE
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