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

Abstract

To assess the effectiveness of single-dose rifampicin (SDR) after bacillus Calmette-Guérin (BCG) vaccination in preventing leprosy in contacts. Methods: This was a single-centre, cluster-randomized controlled trial at a leprosy control programme in northwest Bangladesh. Participants were the 14 988 contacts of 1552 new leprosy patients who were randomized into the SDR À 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 1 year and 2 years after intake. The main outcome measure was the occurrence of leprosy. Results: The incidence rate per 10 000 person-years at risk was 44 in the SDR À arm and 31 in the SDR + arm at 1 year; the incidence rate was 34 in the SDR À 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. Conclusions: 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. Trial registration: Netherlands Trial Register: NTR3087.

<p>The State of Affairs in Post-Exposure Leprosy Prevention: A Descriptive Meta-Analysis on Immuno- and Chemo-Prophylaxis</p>

“…This made it impossible to determine whether excess cases in the first year after immunoprophylaxis (with BCG) could be prevented with SDR-PEP without affecting the protective effect of BCG. 126 This increase of cases after immunoprophylaxis administration in the first year is consistent with other studies. 48,51,[127][128][129] Therefore, Richardus et al concluded that BCG vaccination followed by SDR as a routine intervention is not recommended in leprosy control.…”

Single-dose rifampicin and BCG to prevent leprosy

“…We agree with Richardus et al that the current evidence does not support the use of BCG followed by SDR for the contacts of leprosy patients (Richardus et al, 2019) and with WHO that the evidence for BCG alone is conflicting with no evidence of benefit (2018a).…”

“…The MALTALEP trial compared the efficacy of bacillus Calmette-Guérin (BCG) vaccination followed by single-dose rifampicin (SDR) with BCG vaccination alone in preventing leprosy in household contacts and next-door neighbours of newly diagnosed leprosy patients in Bangladesh (Richardus et al, 2019). It was a large, well designed cluster randomised controlled trial (RCT) and 14,988 contacts of 1552 new leprosy patients were randomised to receive either BCG alone (7378) or BCG followed by SDR (7609) 8-12 weeks later.…”

Geospatial Epidemiology of Leprosy in Northwest Bangladesh: A 20-year Retrospective Observational Study

“…Geospatial methods are proven to be important for targeting active case nding strategies and public health interventions at hotspot areas, as this strategy could yield a high proportion of new cases (8). In these areas, innovations could be implemented to halt transmission and address underlying inequalities, such as early detection of cases by contract-tracing (5) and single-dose rifampicin prophylaxis for close contacts of leprosy cases (24,49), but also conditional cash transfers (50) and local campaigns to increase knowledge and awareness about leprosy and reduce leprosy-related stigma (51). Although the current de nition of 'hotspots' and accompanied geospatial methodologies are valuable as precision public health tools, nding areas where leprosy is signi cantly spatially clustered does not seem su cient to identify underlying drivers of leprosy transmission.…”