Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial
The Lancet Global Health, vol. 12, pp. e1017–e1026
Abstract
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.
Authors 28
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Epco C. Hasker corresponding
Instituut voor Tropische Geneeskunde
Affiliation as printed
Institute of Tropical Medicine, Antwerp, Belgium. Electronic address: ehasker@itg.be
ITM - Institute of Tropical Medicine [Antwerp] (Nationalestraat 155, 2000 Antwerp - Belgium)
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Affiliation as printed
National Tuberculosis and Leprosy Control Program, Moroni, Comoros
Damien Foundation (Bld Léopold II 263 1081 Bruxelles - Belgium)
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Affiliation as printed
National Leprosy Control Program, Antananarivo, Madagascar
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Institut Pasteur de Madagascar · Fondation Raoul Follereau
Affiliation as printed
Fondation Raoul Follereau, Antananarivo, Madagascar
Institut Pasteur de Madagascar (B.P. 1274 Antananarivo - Madagascar)
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Instituut voor Tropische Geneeskunde
Affiliation as printed
Institute of Tropical Medicine, Antwerp, Belgium
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Affiliation as printed
Fondation Raoul Follereau, Antananarivo, Madagascar
Fondation Raoul Follereau [Paris] (France)
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Affiliation as printed
National Tuberculosis and Leprosy Control Program, Moroni, Comoros
Damien Foundation (Bld Léopold II 263 1081 Bruxelles - Belgium)
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Affiliation as printed
National Tuberculosis and Leprosy Control Program, Moroni, Comoros
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Affiliation as printed
National Tuberculosis and Leprosy Control Program, Moroni, Comoros
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Affiliation as printed
National Tuberculosis and Leprosy Control Program, Moroni, Comoros
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Affiliation as printed
National Tuberculosis and Leprosy Control Program, Moroni, Comoros
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Affiliation as printed
National Tuberculosis and Leprosy Control Program, Moroni, Comoros
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Affiliation as printed
National Tuberculosis and Leprosy Control Program, Moroni, Comoros
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Instituut voor Tropische Geneeskunde
Affiliation as printed
Institute of Tropical Medicine, Antwerp, Belgium
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Nagasaki University · Instituut voor Tropische Geneeskunde
Affiliation as printed
Institute of Tropical Medicine, Antwerp, Belgium
ITM - Institute of Tropical Medicine [Antwerp] (Nationalestraat 155, 2000 Antwerp - Belgium)
Nagasaki University (Nagasaki, Nagasaki Prefecture, Japan - Japan)
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Affiliation as printed
Centre d'Infectiologie Charles Mérieux, Antananarivo, Madagascar
Centre d’Infectiologie Charles-Mérieux, Université d’Antananarivo - Madagascar (Centre d’infectiologie Charles-Mérieux, Ankatso, Université d’Antananarivo, BP 4299, 101 Antananarivo, Madagascar - Madagascar)
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Affiliation as printed
National Leprosy Control Program, Antananarivo, Madagascar
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Centre National de la Recherche Scientifique · Inserm · Institut Pasteur de Lille · Centre Hospitalier Universitaire de Lille · Center for Infection and Immunity of Lille
Affiliation as printed
University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017, Center for Infection and Immunity of Lille, Lille, France
CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (1 Rue du Professeur Calmette - Lille Cedex - 59019 - BP 245 - France)
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Instituut voor Tropische Geneeskunde
Affiliation as printed
Institute of Tropical Medicine, Antwerp, Belgium
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Instituut voor Tropische Geneeskunde
Affiliation as printed
Institute of Tropical Medicine, Antwerp, Belgium
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Instituut voor Tropische Geneeskunde
Affiliation as printed
Institute of Tropical Medicine, Antwerp, Belgium
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Affiliation as printed
Oswaldo Cruz Institute, Fiocruz, Laboratory of Molecular Biology Applied to Mycobacteria, Rio de Janeiro, Brazil
IOC - Instituto Oswaldo Cruz = Oswaldo Cruz Institute [Rio de Janeiro] (Avenida Brasil 4.365 - Manguinhos, Rio de Janeiro, RJ - Brazil)
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Affiliation as printed
Centre d'Infectiologie Charles Mérieux, Antananarivo, Madagascar
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Paul L. A. M. Corstjens Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, Leiden, Netherlands
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Affiliation as printed
Damien Foundation, Brussels, Belgium
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Annemieke Geluk Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, Leiden, Netherlands
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Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Bichat-Claude-Bernard · Infection, Anti-microbiens, Modélisation, Evolution
Affiliation as printed
Inserm, IAME, Université Paris Cité, UMR 1137, Paris, France; AP-HP, Hôpital Bichat, Service de Mycobacteriologie Specialisee et de Reference, Paris, France
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Instituut voor Tropische Geneeskunde
Affiliation as printed
Institute of Tropical Medicine, Antwerp, Belgium
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