Effectiveness of single-dose rifampicin after BCG vaccination to prevent leprosy in close contacts of patients with newly diagnosed leprosy: A cluster randomized controlled trial

•For decades, leprosy incidence has remained stable, indicating active transmission.•The MALTALEP trial assessed single-dose rifampicin (SDR) after bacillus Calmette–Guérin (BCG) vaccination to prevent leprosy in contacts.•BCG followed by SDR reduced paucibacillary leprosy by 42% in contacts.•This is a large effect, although non-significant due to the low numbers of patients.•Approximately a third (33.6%) of all new cases appeared within 8–12 weeks after BCG vaccination. To assess the effectiveness of single-dose rifampicin (SDR) after bacillus Calmette–Guérin (BCG) vaccination in preventing leprosy in contacts. This was a single-centre, cluster-randomized controlled trial at a leprosy control programme in northwest Bangladesh. Participants were the 14988 contacts of 1552 new leprosy patients who were randomized into the SDR−arm (n=7379) and the SDR+arm (n=7609). In the intervention group, BCG vaccination was followed by SDR 8–12 weeks later. In the control group, BCG vaccination only was given. Follow-up was performed at 1year and 2 years after intake. The main outcome measure was the occurrence of leprosy. The incidence rate per 10000 person-years at risk was 44 in the SDR−arm and 31 in the SDR+arm at 1year; the incidence rate was 34 in the SDR−arm and 41 in the SDR+arm at 2 years. There was a statistically non-significant (p=0.148; 42%) reduction for paucibacillary (PB) leprosy in the SDR+ arm at 1 year. Of all new cases, 33.6% appeared within 8–12 weeks after BCG vaccination. In the first year, SDR after BCG vaccination reduced the incidence of PB leprosy among contacts by 42%. This was a statistically non-significant reduction due to the limited number of cases after SDR was administered. To what extent SDR suppresses excess leprosy cases after BCG vaccination is difficult to establish because many cases appeared before the SDR intervention. Netherlands Trial Register: NTR3087.