The results of a randomized controlled trial in China suggest that an antibiotic used for tuberculosis treatment can protect household contacts from leprosy, researchers reported yesterday in the New England Journal of Medicine.
In the cluster-randomized trial, counties or districts of Southwest China with at least two household contacts of patients with leprosy were assigned to one of three intervention groups. One group received a single post-exposure dose of the anti-tuberculosis antibiotic rifapentine, one received a single dose of the anti-tuberculosis antibiotic rifampin, and a control group received no intervention.
Follow-up visits were conducted annually. The primary outcome was the 4-year incidence of leprosy among household contacts.
Promising results for rifapentine
Rifampin is one of the drugs in the multidrug regimen used to treat new leprosy cases, and in a previous trial showed an overall protective effect of 57% over 2 years in neighbors and social contacts of people with leprosy, which isn't highly contagious but spreads through extensive contact. That result led the World Health Organization to recommend a single dose of rifampin as post-exposure prophylaxis (prevention). But rifapentine has shown greater activity against Mycobacterium leprae—the bacterium that causes leprosy—than rifampin in mouse models.
Of the 207 clusters that underwent randomization, 68 (2,331 household contacts) were assigned to the rifapentine group, 71 (2,760) to the rifampin group, and 68 (2,359) to the control group.
In the per-protocol analysis, the cumulative incidence at 4 years was 0.05% in the rifapentine group (1 new case among 2,004 household contacts), 0.19% in the rifampin group (5 new cases among 2,609 contacts), and 0.63% in the control group (18 new cases among 2,837 contacts. The cumulative incidence was 92% lower in the rifapentine group than in the control group (cumulative incidence ratio, 0.08; 95% confidence interval [CI], 0.01 to 0.63), with no severe adverse events reported.
Our trial provides evidence for an additional approach to the prevention of leprosy.
Cumulative incidence was 79% lower in the rifampin group compared with the control group, but that difference was not considered statistically significant.
Leprosy can lead to damage of the nerves, skin, eyes, and respiratory tract. While it is treatable, the authors say current interventions are not sufficient to address the 200,000 new cases reported annually.
Exploring post-exposure prevention more thoroughly
"Our trial provides evidence for an additional approach to the prevention of leprosy among household contacts," the study authors wrote. They added, however, that post-exposure prophylaxis in household contacts along may not reduce incidence in countries with higher endemic levels of leprosy than China.
In an accompanying editorial, David Scollard, MD, PhD, of the National Hansen's Disease Programs, said providing protection for close contacts is a "game changer."
"Rifapentine should now be considered in planning future trials of postexposure prophylaxis for leprosy and possibly also in any potential new version of multidrug therapy," he wrote. "Much remains to be done, but these new findings with rifapentine provide additional energy in the implementation of postexposure prophylaxis for leprosy."
Rifapentine should now be considered in planning future trials of postexposure prophylaxis for leprosy.