Background: Leprosy is an infectious disease caused byMycobacterium leprae. As incidence begins to decline, the characteristics of new cases shifts away from those observed in highly endemic areas, revealing potentially important insights into possible ongoing sources of transmission. We aimed to investigate whether transmission is driven mainly by undiagnosed and untreated new leprosy cases in the community, or by incompletely treated or relapsing cases.Methodology/Principal findings: A literature search of major electronic databases was conducted in January, 2020 with 134 articles retained out of a total 4318 records identified (PROSPERO ID: CRD42020178923). We presented quantitative data from leprosy case records with supporting evidence describing the decline in incidence across several contexts. BCG vaccination, active case finding, adherence to multidrug therapy and continued surveillance following treatment were the main strategies shared by countries who achieved a substantial reduction in incidence. From 3950 leprosy case records collected across 22 low endemic countries, 48.3% were suspected to be imported, originating from transmission outside of the country. Most cases were multibacillary (64.4%) and regularly confirmed through skin biopsy, with 122 cases of suspected relapse from previous leprosy treatment. Family history was reported in 18.7% of cases, while other suspected sources included travel to high endemic areas and direct contact with armadillos. None of the countries included in the analysis reported a distinct increase in leprosy incidence in recent years.Conclusions/Significance: Together with socioeconomic improvement over time, several successful leprosy control programmes have been implemented in recent decades that led to a substantial decline in incidence. Most cases described in these contexts were multibacillary and numerous cases of suspected relapse were reported. Despite these observations, there was no indication that these cases led to a rise in new secondary cases, suggesting that they do not represent a large ongoing source of human-to-human transmission.

The ALERT MDT Field Evaluation Study (AMFES) began in 1988 and followed patients prospectively for up to 10 years after release from treatment (RFT). This paper presents the findings from this cohort with regard to neuropathy and nerve damage. Five hundred and ninety-four new cases of leprosy are included in the study, 300 multibacillary (MB) and 294 paucibacillary (PB) cases. Fifty-five percent of patients had some degree of impairment at diagnosis and a further 73 (12%) developed new nerve function impairment (NFI) after starting multiple drug therapy (MDT). The overall incidence rate for neuropathy was 39 episodes per 100 PYAR in the first year after diagnosis, gradually declining to 12 episodes per 100 PYAR in the sixth year. In those patients without impairment at diagnosis, the incidence rate of neuropathy was 25 episodes per 100 PYAR for MB cases and 11 per 100 PYAR for PB cases in the first year; in 33% of MB cases whose first episode of neuropathy occurred after diagnosis, that first episode took place after the first year, or after the normal period of treatment with MDT. Seventy-three patients with neuropathy developing after diagnosis are reported more fully: 34 (47%) had only one nerve involved and of these 25 (73%) had a single, acute episode of neuropathy. Nine (27%) had further episodes. Thirty-nine (53%) had more than one nerve involved and of these 16 (41%) had a single, acute episode, while 23 (59%) had further episodes. The terms 'chronic' and 'recurrent' neuropathy are defined and used to describe the pattern of neuropathy in those with repeated attacks. In patients with no impairment at the start of the study, treatment with steroids resulted in full recovery in 88% of nerves with acute neuropathy but only 51% of those with chronic or recurrent neuropathy. The median time to full recovery from acute neuropathy was approximately 6 months, but in a few cases recovery occurred gradually over 2-3 years. Severe neuropathy was less likely to be followed by a complete recovery than mild or moderate neuropathy. Forty-two percent of nerves with acute neuropathy that were not treated with steroids also fully recovered. In the group of patients who were thought to have old, permanent impairments at diagnosis, full recovery of nerve function occurred in 87/374 (23%) of the nerves involved. The overall outcome is illustrated by examining the average EHF score for groups of patients. Patients with no new neuropathy after diagnosis show a gradual improvement in their EHF score, while those with any episodes of neuropathy after diagnosis show a gradual deterioration after completion of MDT. Possible explanations for these findings are discussed. Risk factors for neuropathy, for chronic and recurrent neuropathy, and for a poor outcome 5 years after release from treatment, are examined. Impairment at diagnosis was the main risk factor for a poor outcome, accompanied by the occurrence of chronic/recurrent neuropathy or a reversal reaction.

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.

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).

Objectives To identify patients with typical symptoms of neuropathic pain in a well-defined cohort of multibacillary patients being followed up as part of a relapse study in Ethiopia; to identify risk factors for the development of neuropathic pain. Design 96 patients who had completed MDT more than 10 years previously participated in the study, through a questionnaire. Results 28 (29%) had symptoms of neuropathic pain and it was reported as severe in 12. Because the past history of these subjects is well documented, a risk factor analysis was carried out. The presence of leprosy-related impairment was the only significant risk factor for neuropathic pain that was identified. Conclusions Neuropathic pain is an important problem in a proportion of people previously treated for leprosy. Further research into the management of the condition is required.

(1) Background: The global burden of leprosy is not shared equally; with the majority of cases being diagnosed in Brazil, India, and Indonesia. Understanding the methods of active case detection (ACD) used in high and low endemic regions is vital for the development of future screening programs. (2) Methods: A systematic search of three databases, PubMed, Embase and Web of Science, was conducted for English language papers, published since the year 2000, which discussed the use of active case detection methods for leprosy screening. The paper utilised the Integrated Screening Action Model (I-SAM) as a tool for the analysis of these methods. (3) Results: 23 papers were identified from 11 different countries. The papers identified 6 different methods of active case detection: Household contact/social contact identification; door-to-door case detection; screening questionnaire distribution; rapid village surveys; school-based screening; and prison-based screening. 15 were located in high endemic regions and 8 of these were located in low endemic regions. (4) Conclusions: For selecting the appropriate methods of active case finding, the leprosy endemicity must be taken into consideration. The findings contribute to policy decision making allowing for more successful future leprosy case detection programs to be designed, ultimately reducing the global burden of the disease, and achieving the WHO’s aim of zero leprosy.