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

Liesbeth F Mieras,Hemanta K Kar,Marieke G G Sturkenboom,David M Scollard,Linda Astari,Dejair Caitano Do Nascimento,Wim H Van Brakel,Shinzo Izumi,Paul R Saunderson,Marcos C L Virmond,Laura Gillini,Jacques Grosset,Jacques Grosset,W Cairns S Smith,Emmanuelle Cambau,Cita Rosita S Prakoeswa,Anna T Taal

doi:10.1186/s12879-018-3402-4

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).

Highlights

Possible drugs for enhanced chemoprophylaxis regimen The mechanism of chemoprophylaxis is either killing of the causative organisms before the onset of pathology or killing of the pathogen allowing sub-clinical disease to heal or both
The PEP++ research project will test the enhanced regimen using a cluster-randomised trial design to compare the effectiveness of the enhanced post-exposure prophylaxis regimen with that of Single dose rifampicin (SDR) in close contacts who have a higher risk of developing leprosy [8]
The Expert Meeting agreed that the PEP++ regimen should be comprised of drugs that are available in leprosy endemic countries and are approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA)

Summary

Background

Introduction This is a report of an Expert Meeting to propose an enhanced chemoprophylaxis regimen to be tested in a randomised controlled intervention study for contacts of leprosy patients. Background on the PEP++ research project NLR has prepared a study protocol for a multi-country study on stopping the transmission of M. leprae, in which the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important. The PEP++ research project will test the enhanced regimen using a cluster-randomised trial design to compare the effectiveness of the enhanced post-exposure prophylaxis regimen with that of SDR in close contacts (household contacts, neighbours and social contacts) who have a higher risk of developing leprosy [8]. The PEP++ research project aims to provide evidence that a combination of a large-scale application of the current SDR and PEP++ will be able to prevent the development of leprosy disease among contacts and, as a consequence, stop the transmission of M. leprae in previously high-endemic areas. The interventions will be supported by optimised leprosy case detection and treatment services, including but not limited to health systems strengthening, contextualised community education on leprosy, stigma reduction interventions and involvement of leprosy-affected persons in various roles in their communities

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