An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP++

Abstract

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80–90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

Prototype multi-biomarker test for point-of-care leprosy diagnostics

“…The NUM score provides a quick interpretation of the test result suitable for large-scale screening studies, for instance, to identify M. leprae -infected individuals that contribute to the perpetuating transmission. HCs of patients with MB leprosy are at the highest risk of acquiring M. leprae infection ( Bakker et al., 2006 ; Goulart et al., 2008 ; Sales et al., 2011 ) and thus represent candidates for preventive drug administration in multiple studies ( Barth-Jaeggi et al., 2016 ; Mieras et al., 2018 ; Ortuno-Gutierrez et al., 2019b ; Richardus et al., 2020 ; Tiwari et al., 2020 ) to prevent progress to leprosy disease, as well as decrease transmission. Since June 2018, the WHO guidelines for leprosy control have included single-dose rifampicin as PEP for leprosy prevention ( World Health Organization, 2018 ).…”

Risk factor for <em>Mycobacterium leprae</em> detection in household contacts with leprosy patients: a study in Papua, East Indonesia

“…For future studies, accurate prediction of risk for developing leprosy in household contacts might be a useful tool for deciding priority for chemoprophylaxis blanket area and providing early treatment before any spread out of leprosy manifestation. 26 The transmission of leprosy can be greatly curbed by providing necessary treatment at early stages.…”

Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): a cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts

“…In the COLEP trial a 50–60% reduction in incidence was achieved after administering a single dose of Rifampicin at 10 mg/kg [6]. An expert committee convened in preparation of the PEP++ trial, which is to start soon, drafted a reinforced PEP regimen based on three monthly doses of Rifampicin plus Clarithromycin [19]. In the PEOPLE trial we choose to adopt a regimen that includes only one single dose of PEP for logistical and cost reasons.…”