Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.
Lancet Glob Health
; 12(6): e1017-e1026, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38762282
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 109â436 individuals, of whom 95â762 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Rifampina
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Profilaxia Pós-Exposição
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Hansenostáticos
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Hanseníase
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle aged
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article