Single-dose rifapentine may prevent leprosy spread in household contacts: NEJM

"As a feasible preventive intervention for household contacts of leprosy patients, both single-dose rifampin and single-dose rifapentine are being considered in the national program to eradicate leprosy in China," the researchers noted. They found that single-dose rifapentine, administered orally, has a protective effect in household contacts; the leprosy incidence was 92% lower with one dose of rifapentine than with no intervention.

Leprosy is a chronic infectious disease resulting from Mycobacterium leprae; more than 200,000 new cases were detected annually between 2016 and 2019. With the discovery of antileprosy drugs, mainly since the multidrug therapy introduction in the early 1980s, leprosy has been treatable. Current interventions are, however, inadequate to address the global number of new leprosy cases, despite the remarkable achievements in the treatment.

Previous studies have reported that a single rifampin dose is protective against leprosy in close contact with patients with the disease. Rifapentine was demonstrated to have higher bactericidal activity against Mycobacterium leprae versus rifampin in murine models of leprosy. Still, more data is needed on its effectiveness in leprosy prevention.

To fill this knowledge gap, Hongsheng Wang, the National Center for Leprosy Control, the Chinese CDC, China, and colleagues aimed to investigate the safety and efficacy of single-dose rifapentine and single-dose rifampin in leprosy prevention among household contacts of patients with the disease in a cluster-randomized, controlled trial.

The clusters (districts or counties in Southwest China) were allocated to one of the three trial groups: single-dose rifampin, single-dose rifapentine, or control (no intervention). The 4-year cumulative leprosy incidence was determined among household contacts (primary outcome).

A total of 207 clusters consisting of 7450 household contacts underwent randomization; 68 sets (2331 household contacts) were allocated to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group.

The study revealed the following findings:

· Over the 4-year follow-up, A total of 24 new cases of leprosy occurred, for a cumulative incidence of 0.09% with rifapentine (2 cases), 0.33% with rifampin (9 cases), and 0.55% with no intervention (13 cases).

· In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59).

· In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% without intervention.

· No severe adverse events were observed.

"Our data show that rifapentine can protect household contacts from leprosy in areas in which the endemic level of the disease is low," the researchers concluded.

Reference:

The study "Single-Dose Rifapentine in Household Contacts of Patients with Leprosy" was published in the New England Journal of Medicine. DOI: 10.1056/NEJMoa2205487.