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 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.

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.

Domaines

Sciences du Vivant [q-bio]

Liste complète des métadonnées

Format du dépôt	Fichier
Type de dépôt	Article dans une revue
Titre	en Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial
Résumé	en <div xmlns="http://www.tei-c.org/ns/1.0"><p>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.</p></div> <div xmlns="http://www.tei-c.org/ns/1.0"><head>Methods</head><p>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 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>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.</p></div>
Auteur(s)	Epco Hasker ¹ , Younoussa Assoumani ² , Andriamira Randrianantoandro , Stéphanie Ramboarina ³ , Sofie Marijke Braet , Bertrand Cauchoix ⁴ , Abdallah Baco ² , Aboubacar Mzembaba , Zahara Salim , Mohammed Amidy , Saverio Grillone , Nissad Attoumani , Sillahi Halifa Grillone , Maya Ronse , Koen Peeters Grietens ^{1, 5} , Mala Rakoto-Andrianarivelo ⁶ , Hanitra Harinjatovo , Philip Supply ⁷ , Rian Snijders , Carolien Hoof , Achilleas Tsoumanis , Philip Suffys ⁸ , Tahinamandranto Rasamoelina , Paul Corstjens , Nimer Ortuno-Gutierrez , Annemieke Geluk , Emmanuelle Cambau , Bouke Catharina de Jong 1 ITM - Institute of Tropical Medicine [Antwerp] ( 479440 ) - Nationalestraat 155, 2000 Antwerp - Belgique 2 Damien Foundation ( 1074127 ) - Bld Léopold II 263 1081 Bruxelles - Belgique 3 Institut Pasteur de Madagascar ( 55578 ) - B.P. 1274 Antananarivo - Madagascar Pasteur Network (Réseau International des Instituts Pasteur) ( 301247 ) 4 Fondation Raoul Follereau [Paris] ( 535516 ) - France 5 Nagasaki University ( 309339 ) - Nagasaki, Nagasaki Prefecture, Japan - Japon 6 Centre d’Infectiologie Charles-Mérieux, Université d’Antananarivo - Madagascar ( 527931 ) - Centre d’infectiologie Charles-Mérieux, Ankatso, Université d’Antananarivo, BP 4299, 101 Antananarivo, Madagascar - Madagascar Université d'Antananarivo ( 300866 ) 7 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 ( 106189 ) - 1 Rue du Professeur Calmette - Lille Cedex - 59019 - BP 245 - France Institut Pasteur de Lille UMR8204 ( 300166 ) ; Pasteur Network (Réseau International des Instituts Pasteur) ( 301247 ) ; Institut National de la Santé et de la Recherche Médicale U1019 ( 303623 ) ; Université de Lille UMR9017 ( 374570 ) ; Centre Hospitalier Régional Universitaire [CHU Lille] U1019 ( 425779 ) ; Centre National de la Recherche Scientifique UMR9017 ( 441569 ) 8 IOC - Instituto Oswaldo Cruz = Oswaldo Cruz Institute [Rio de Janeiro] ( 520680 ) - Avenida Brasil 4.365 - Manguinhos, Rio de Janeiro, RJ - Brésil Fundação Oswaldo Cruz / Oswaldo Cruz Foundation ( 488707 ) ; Pasteur Network (Réseau International des Instituts Pasteur) ( 301247 )
Langue du document	Anglais
Vulgarisation	Non
Comité de lecture	Oui
Audience	Internationale
Date de publication	2024-06
Nom de la revue	Lancet Glob Health - The Lancet global health (ISSN : 2572-116X, ISSN électronique : 2214-109X) Elsevier Publié par Elsevier http://www.journals.elsevier.com/the-lancet-global-health/
Volume	12
Page/Identifiant	e1017-e1026
Numéro	6
Domaine(s)	Sciences du Vivant [q-bio]
DOI	10.1016/S2214-109X(24)00062-7

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https://cnrs.hal.science/hal-04729751

Soumis le : jeudi 10 octobre 2024 à 10:33:28

Dernière modification le : mardi 15 octobre 2024 à 15:10:21

Dates et versions

hal-04729751, version 1 (10-10-2024)

Identifiants

HAL Id : hal-04729751 , version 1
DOI : 10.1016/S2214-109X(24)00062-7

Citer

Epco Hasker, Younoussa Assoumani, Andriamira Randrianantoandro, Stéphanie Ramboarina, Sofie Marijke Braet, et al.. Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial. The Lancet global health, 2024, 12 (6), pp.e1017-e1026. ⟨10.1016/S2214-109X(24)00062-7⟩. ⟨hal-04729751⟩

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