Single-dose rifampicin and BCG to prevent leprosy

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., 2019Richardus R. Alam K. Kundu K. Chandra Roy J. Zafar T. Chowdhury A.S. et al.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.Int J Infect Dis. 2019; 88: 65-72Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar). 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. Participants were followed for 2 years. The primary outcome of the RCT recorded in the Netherlands Trial Register, 2019Netherlands Trial Register. Available from: https://www.trialregister.nl/trial/2940. [Accessed 21 October 2019].Google Scholar (NTR3087) and reported in the peer-reviewed protocol was “New cases of leprosy among the contacts of index cases” and “…the number of new leprosy patients emerging from the contact groups” respectively (Richardus et al., 2013Richardus R.A. Alam K. Pahan D. Feenstra S.G. Geluk A. Richardus J.H. The combined effect of chemoprophylaxis with single dose rifampicin and immunoprophylaxis with BCG to prevent leprosy in contacts of newly diagnosed leprosy cases: a cluster randomized controlled trial (MALTALEP study).BMC Infect Dis. 2013; 13: 456Crossref PubMed Scopus (38) Google Scholar). There were no significant differences between the proportions of contacts who developed leprosy following the interventions at one or two years. This is an important negative finding and in keeping with the findings of the COLEP RCT of SDR (Moet et al., 2008Moet F.J. Pahan D. Oskam L. Richardus J.H. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial.BMJ. 2008; 336: 761-764Crossref PubMed Scopus (136) Google Scholar). The COLEP trial identified that the short-term benefits of SDR were only significant in more distant contacts of index cases. A secondary data analysis was planned to “define special groups at risk for developing leprosy” and “No significant differences of interest were found” (Richardus et al., 2013Richardus R.A. Alam K. Pahan D. Feenstra S.G. Geluk A. Richardus J.H. The combined effect of chemoprophylaxis with single dose rifampicin and immunoprophylaxis with BCG to prevent leprosy in contacts of newly diagnosed leprosy cases: a cluster randomized controlled trial (MALTALEP study).BMC Infect Dis. 2013; 13: 456Crossref PubMed Scopus (38) Google Scholar). The authors discuss the non-significant 42% reduction in the number of new cases of paucibacillary leprosy in those who received SDR after one year. We were surprised that the significant number of individuals who developed multibacillary (MB) leprosy in the SDR group by 2 years was not similarly discussed. The odds of having developed MB leprosy at the two year follow up point were 3.68 (95% CI: 1.03–13.21) in the group randomised to receive BCG and SDR compared to BCG alone. Table 6 states that only one of 11 new cases of MB leprosy diagnosed after completion of the intervention was slit-skin smear positive. The clinical relevance of the increased numbers of MB patients should be discussed including information about nerve function impairment. The COLEP trial did not show any significant difference in the amount of MB disease between the SDR and placebo groups during two or four years of follow up (Moet et al., 2008Moet F.J. Pahan D. Oskam L. Richardus J.H. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial.BMJ. 2008; 336: 761-764Crossref PubMed Scopus (136) Google Scholar). The MALTALEP study shows that SDR after BCG does not have a significant protective effect against leprosy in household and next-door neighbour contacts compared to BCG alone. This replicates the finding from the larger COLEP study. Data from the BCG arm of the current study were compared with the placebo arm of the COLEP study to infer that the protective effect of BCG is doubtful in Bangladesh. 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., 2019Richardus R. Alam K. Kundu K. Chandra Roy J. Zafar T. Chowdhury A.S. et al.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.Int J Infect Dis. 2019; 88: 65-72Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar) and with WHO that the evidence for BCG alone is conflicting with no evidence of benefit (Anon, 2018aBCG vaccines: WHO position paper — February 2018.Wkly Epidemiol Rec. 2018; 93: 73-96PubMed Google Scholar). The incomplete understanding of the transmission of Mycobacterium leprae and development of disease hamper the discovery of an effective strategy for prevention. The administration of SDR to contacts of individuals diagnosed with leprosy is recommended by WHO without providing criteria to determine who is a contact (Anon, 2018bGuidelines for the diagnosis, treatment and prevention of leprosy. World Health Organization, Regional Office for South-East Asia, New Delhi2018Google Scholar). The evidence for SDR as a strategy to prevent leprosy or achieve the target of zero transmission of M. leprae remains limited. None. None.