Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial

Area of Science:

• Epidemiology
• Infectious Diseases
• Public Health

Background:

• Post-exposure prophylaxis (PEP) with single-dose rifampicin is known to reduce the progression from Mycobacterium leprae infection to leprosy disease.
• This study investigated the effectiveness of different administration modalities of single double-dose rifampicin (SDDR)-PEP, including a higher dosage (20 mg/kg).

Purpose of the Study:

• To compare the effectiveness of various SDDR-PEP administration strategies in reducing leprosy incidence.
• To assess the individual protective effect of SDDR-PEP and explore spatial associations with leprosy transmission.

Main Methods:

• A cluster randomized study was conducted in Madagascar and Comoros over 4 years, involving annual leprosy screening.
• Four study arms were implemented: a control arm with no PEP, and three intervention arms with varying SDDR-PEP distribution (household contacts, proximity within 100m, or proximity with positive serology).
• Participants aged 2 years and older were eligible, with leprosy patients receiving multidrug therapy and asymptomatic contacts receiving SDDR-PEP.

Main Results:

• Overall, SDDR-PEP showed a non-significant reduction in leprosy incidence across intervention arms.
• However, after adjusting for baseline prevalence, arm 3 (SDDR-PEP within 100m) demonstrated a significant reduction (IRR 0.56, p=0.0030).
• Individually, SDDR-PEP was protective (IRR 0.55, p=0.0050), with leprosy risk increasing significantly for individuals living within 75m of an index patient.

Conclusions:

• SDDR-PEP demonstrates protective effects against leprosy, though potentially less than initially anticipated.
• Strong spatial clustering of leprosy cases was observed, highlighting the importance of proximity to infected individuals.
• A combined strategy of targeted door-to-door screening around index patients and widespread SDDR-PEP administration is likely to significantly reduce leprosy transmission.