Journal Article Randomized Controlled Trial Ppublish 9 citations
PubMed: 38762282 DOI: 10.1016/S2214-109X(24)00062-7
Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.
Lancet Glob Health 12(6):e1017-e1026
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
Affiliations
- Institute of Tropical Medicine, Antwerp, Belgium.
- National Tuberculosis and Leprosy Control Program, Moroni, Comoros.
- National Leprosy Control Program, Antananarivo, Madagascar.
- Fondation Raoul Follereau, Antananarivo, Madagascar.
- Institute of Tropical Medicine, Antwerp, Belgium.
- Centre d'Infectiologie Charles Mérieux, Antananarivo, Madagascar.
- University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017, Center for Infection and Immunity of Lille, Lille, France.
- Oswaldo Cruz Institute, Fiocruz, Laboratory of Molecular Biology Applied to Mycobacteria, Rio de Janeiro, Brazil.
- Leiden University Medical Center, Leiden, Netherlands.
- Damien Foundation, Brussels, Belgium.
- Inserm, IAME, Université Paris Cité, UMR 1137, Paris, France; AP-HP, Hôpital Bichat, Service de Mycobacteriologie Specialisee et de Reference, Paris, France.
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.
MeSH
Leprosy, Incidence, Global Health, Post-Exposure Prophylaxis, Rifampin
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