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 109436 individuals, of whom 95762 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.
}, year = {2024}, journal = {The Lancet Global Health}, volume = {12}, pages = {e1017-e1026}, publisher = {Elsevier BV}, issn = {2214-109X}, url = {https://www.thelancet.com/action/showPdf?pii=S2214-109X%2824%2900062-7}, doi = {10.1016/s2214-109x(24)00062-7}, language = {ENG}, }