Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis

Retrospective active case finding in Cambodia: an innovative approach to leprosy control in a low-endemic country

Currently, leprosy control relies on the clinical diagnosis of leprosy and the subsequent administration of multidrug therapy (MDT). However, many health workers are not familiar with the cardinal signs of leprosy, particularly in low-endemic settings including Cambodia. In response, a new approach to early diagnosis was developed in the country, namely retrospective active case finding (RACF) through small mobile teams. In the frame of RACF, previously diagnosed leprosy patients are traced and their contacts screened through "drives". According to the available records, 984 of the 1,463 (67.3%) index patients diagnosed between 2001 and 2010 and registered in the national leprosy database were successfully traced in the period 2012-2015. Migration (8.4%), death (6.7%), operational issues (1.6%) and unidentified other issues (16.0%) were the main reasons for non-traceability. A total of 17,134 contacts of traced index patients (average: 2.2 household members and 15.2 neighbors) and another 7,469 contacts of the untraced index patients could be screened. Among them, 264 new leprosy patients were diagnosed. In the same period, 1,097 patients were diagnosed through the routine passive case detection system. No change was observed in the relation between the rate at which new patients were identified and the number of years since the diagnosis of the index patient. Similar to leprosy patients diagnosed through passive case detection, the leprosy patients detected through RACF were predominantly adult males. However, the fraction of PB leprosy patients was higher among the patients diagnosed through RACF, suggesting relatively earlier diagnosis. It appears that RACF is a feasible option and effective in detecting new leprosy patients among contacts of previously registered patients. However, a well-maintained national leprosy database is essential for successful contact tracing. Hence, passive case detection in the frame of routine leprosy surveillance is a precondition for efficient RACF as the two systems are mutually enhancing. Together, the two approaches may offer an interesting option for countries with low numbers of leprosy patients but evidence of ongoing transmission. The impact on leprosy transmission could be further increased by the administration of single dose rifampicin as post-exposure prophylaxis to eligible contacts

Leprosy Post-Exposure Prophylaxis (LPEP) programme: Study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin

Introduction: The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50-60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PE

Minimal essential data to document contact tracing and single dose rifampicin (SDR) for leprosy control in routine settings

In leprosy control there is a renewed interest in active case finding, which is increasingly being combined with chemoprophylactic interventions to try and reduce M. leprae transmission. The Leprosy Post-Exposure Prophylaxis (LPEP) programme, currently ongoing in eight endemic countries, pilots the provision of single-dose rifampicin (SDR) to eligible contacts of leprosy patients. LPEP has developed a surveillance system including data collection, reporting and regular monitoring for every participating country. This system is still largely programmespecific to LPEP. To facilitate continuity after completion of the project phase and start-up in other interested countries, we aim at identifying the minimal set of data required to appropriately document contact tracing activities and SDR administration for leprosy control in a routine setting. We describe four indicators for the index case (plus four already routinely collected) and seven indicators for household/neighbour screening, and community surveys. We propose two generic forms to capture all relevant information required at field and district level to follow-up on individuals or data if needed, provide gu

The long-term impact of the leprosy post-exposure prophylaxis (Lpep) program on leprosy incidence:a modelling study

Background The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. Methodology The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continua-tion of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. Principal findings In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction after-wards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. Conclusions The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.</p

Leprosy post-exposure prophylaxis with single-dose rifampicin

_Objective:_ Leprosy post-exposure prophylaxis with single-dose rifampicin (SDRPEP) has proven effective and feasible, and is recommended by WHO since 2018. This SDR-PEP toolkit was developed through the experience of the leprosy postexposure prophylaxis (LPEP) programme. It has been designed to facilitate and standardise the implementation of contact tracing and SDR-PEP administration in regions and countries that start the intervention. _Results:_ Four tools were developed, incorporating the current evidence for SDRPEP and the methods and learnings from the LPEP project in eight countries. (1) th

The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study.

BackgroundThe Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence.MethodologyThe individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040.Principal findingsIn all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme.ConclusionsThe LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes