Background
The Maltalep trial in Bangladesh assessed whether single-dose rifampicin (SDR) given 8–12 weeks after bacillus Calmette–Guérin (BCG) vaccination was able to prevent excess leprosy cases due to BCG in contacts of newly diagnosed leprosy patients. After previous publication of the two years follow-up results of the trial, we now review the results after five years. Furthermore, to better understand the long-term protective effects of BCG against leprosy, we conduct post-hoc in-depth secondary statistical analyses based on the prospective interventional (randomized) Maltalep trial and a non-interventional (non-randomized) cohort study that was conducted simultaneously in the same project area.
Methodology
The Maltalep trial is a single center, cluster-randomized controlled trial consisting of two arms. In one arm, SDR was given 8–12 weeks after BCG vaccination (SDR+), in the other arm no SDR was given after BCG revaccination (SDR-).
Results
The Maltalep trial included 1,552 index patients. Of these, 14,986 eligible contacts were randomized into two arms SDR- and SDR+ of the trial. During the 5-year observation period, 95 and 100 new cases appeared among the contacts in two arms SDR- and SDR+ , respectively. Overall, there was no statistically significant difference in the leprosy incidence between the contacts of two arms of the trial. The non-intervention cohort included 554 index patients and 4,216 eligible contacts, with a total of 82 new leprosy cases appearing during the 5-year observation period. After adjustment for risk factors, the leprosy incidence was statistically significantly 1.70 [95% CI (1.03-2.80)] times higher in the contacts of the non-intervention cohort as compared to the contacts in the Maltalep trial. In the Maltalep trial, adjusted for both observed and unobserved differences, SDR- arm contacts of MB, slit skin smear (SSS) positive, blood-related (brother/sister, child, parent), and ‘blood-related other’ to index patients had higher risks for leprosy (AOR 2.35; 95% CI: 1.20-4.60; AOR: 6.35; CI: 2.42-16.72; AOR: 4.34; 95% CI: 1.83-10.26 and AOR: 3.07; 95% CI: 1.37-7.90) compared to PB, SSS negative, and not blood-related index patients. Household members of index patients had an increased risk (AOR: 2.60; 95% CI: 1.30-7.27) for leprosy. In the SDR+ arm, leprosy incidences were statistically significantly less in the contacts of MB, SSS positive, and ‘blood-related other’ index patients as compared to the same kind of contacts in the SDR- arm. Leprosy incidence increased with age of contacts, with a peak at age group 45+ years (AOR:3.45; 95% CI: 1.44-8.23).
Conclusions and recommendations
BCG vaccination of contacts is effective in preventing leprosy, overall there is no clear benefit of adding SDR after BCG to reduce the number of excess leprosy cases after vaccination. SDR after BCG, however, appears effective to prevent leprosy in contacts of MB patients, smear positive index patients, and second degree blood-related contacts of index patients. Genetic relationship is a more profound risk factor for leprosy in contacts than being a household contact only. Leprosy incidence is clustered at levels of index patients and contacts, and this should be taken into account when assessing the effect of risk factors.
a1935-2735