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ABSTRACT: Objectives: Purulia is one of the high-endemic districts for leprosy in West Bengal (the eastern part of India). The annual new case detection rate (ANCDR) of leprosy in West Bengal is 6.04/100000 (DGHS 2019–20). Our earlier report provided evidence of secondary drug resistance in relapse cases of leprosy. The aim of the current study was to observe primary drug resistance patterns for dapsone, rifampicin, and ofloxacin amongst new leprosy patients from Purulia, West Bengal in order to better understand the emergence of primary resistance to these drugs. Methods: In the present study, slit-skin smear samples were collected from 145 newly diagnosed leprosy cases from The Leprosy Mission (TLM) Purulia hospital between 2017 and 2018. DNA was extracted from these samples and the Mycobacterium leprae genome was analyzed for genes associated with drug resistance by polymerase chain reaction (PCR), followed by Sanger sequencing. Wild-type strain (Thai-53) and mouse footpad-derived drug-resistant strain (Z-4) were used as reference strains. Results: Of 145 cases, 25 cases showed mutations in genes associated with resistance to rifampicin, dapsone, and ofloxacin (as described by the World Health Organization, rpoB, folP, and gyrA, respectively) through Sanger sequencing. Of these 25 cases, 16 cases showed mutations in ofloxacin, two cases showed mutations in combinations of ofloxacin and rifampicin, four cases showed a mutation only in rifampicin, one case showed mutations in combinations of rifampicin and dapsone, and two cases showed mutations only in dapsone. Conclusion: Results from this study indicated the emergence of resistance to antileprosy drugs in new cases of leprosy. As ofloxacin is the alternate drug for the treatment of rifampicin-resistant cases, the emergence of new cases with resistance to ofloxacin indicates that ofloxacin-resistant M. leprae strains are actively circulating in this endemic region (i.e., Purulia, West Bengal), posing challenges for the effective treatment of rifampicin-resistant cases.

Introduction Leprosy occurs among very poor people who may be stigmatised and pushed further to the margins of society. Programmes to improve social integration and stimulate economic development have been implemented to help break the vicious cycle of poverty, reduced quality of life and ulcer recurrence. These involve forming groups of people, with a common concern, to provide mutual support and form saving syndicates—hence the term ‘self-help groups’ (SHGs). While there is literature on the existence and effectiveness of SHGs during the funded periods, little is known about their sustainability. We aim to explore the extent to which SHG programme activities have continued beyond the funding period and record evidence of sustained benefits.Methods and analysis In India, Nepal and Nigeria, we identified programmes funded by international non-governmental organisations, primarily aimed at people affected by leprosy. In each case, financial and technical support was allocated for a predetermined period (up to 5 years).We will review documents, including project reports and meeting minutes, and conduct semistructured interviews with people involved in delivery of the SHG programme, potential beneficiaries and people in the wider environment who may have been familiar with the programme. These interviews will gauge participant and community perceptions of the programmes and barriers and facilitators to sustainability. Data will be analysed thematically and compared across four study sites.Ethics and dissemination Approval was obtained from the University of Birmingham Biomedical and Scientific Research Ethics Committee. Local approval was obtained from: The Leprosy Mission Trust India Ethics Committee; Federal Capital Territory Health Research Ethics Committee in Nigeria and the Health Research Ethics Committee of Niger State Ministry of Health; University of Nigeria Teaching Hospital and the Nepal Health and Research Council. Results will be disseminated via peer-reviewed journals, conference presentations and community engagement events through the leprosy missions.

Abstract Background Plantar ulcers are a leading complication of leprosy that requires frequent visits to hospital and is associated with stigma. The extent of burden of ulcers in leprosy and its risk factors are scant impeding the development of targeted interventions to prevent and promote healing of ulcers. The aim of this review is to generate evidence on the prevalence of plantar ulcer and its risk factors in leprosy. Methods Databases (Medline, Embase, Web of Science, CINAHL, BVS), conference abstracts and reference lists were searched for eligible studies. Studies were included that reported a point prevalence of plantar ulcer and/or its “risk factors” associated with development of ulcers (either causatively or predictively), including individual level, disease related and bio‐mechanical factors. We followed PRISMA guidelines for this review. Random‐effects meta‐analysis was undertaken to estimate the pooled point prevalence of ulcers. Reported risk factors in included studies were narratively synthesised. This review is registered in PROSPERO: CRD42022316726. Results Overall, 15 studies (8 for prevalence of ulcer and 7 for risk factors) met the inclusion criteria. The pooled point prevalence of ulcer was 34% (95% CIs: 21%, 46%) and 7% (95% CIs: 4%, 11%) among those with foot anaesthesia and among all people affected by leprosy, respectively. Risk factors for developing ulcers included: unable to feel 10 g of monofilament on sensory testing, pronated/hyper‐pronated foot, foot with peak plantar pressure, foot with severe deformities, and those with lower education and the unemployed. Conclusions The prevalence of plantar ulceration in leprosy is as high as 34% among those with loss of sensation in the feet. However, the incidence and recurrence rates of ulceration are least reported. The inability to feel 10 g of monofilament appears to be a strong predictor of those at risk of developing ulcers. However, there is a paucity of evidence on identifying those at risk of developing plantar ulcers in leprosy. Prospective studies are needed to estimate the incidence of ulcers. Identifying individuals at risk of ulcers will help design targeted interventions to minimize risk factors, prevent ulcers and promote ulcer healing.

IntroductionPeople affected by leprosy are at increased risk of impairments and deformities from peripheral nerve damage. This mostly occurs if diagnosis and treatment is delayed and contributes to continued transmission within the community. Champa district of Chhattisgarh state in India is an endemic area with the highest national annual case detection and disability rates for leprosy. The Replicability Model is a system strengthening intervention implemented by the Leprosy Mission Trust India in Champa that aims to promote early diagnosis and treatment of leprosy, improve on-going management of the effects of leprosy and improve welfare for the people affected by leprosy. This protocol presents a plan to describe the overall implementation of the Replicability Model and describe the barriers and facilitators encountered in the process. We will also quantify the effect of the program on one of its key aims- early leprosy diagnosis.MethodsThe replicability model will be implemented over four years, and the work described in this protocol will be conducted in the same timeframe. We have two Work Packages (WPs). In WP1, we will conduct a process evaluation. This will include three methods i) observations of replicability model implementation teams' monthly meetings ii) key informant interviews (n = 10) and interviews with stakeholders (n = 30) iii) observations of key actors (n = 15). Our purpose is to describe the implementation process and identify barriers and facilitators to successful implementation. WP2 will be a quantitative study to track existing and new cases of leprosy using routinely collected data. If the intervention is successful, we expect to see an increase in cases (with a higher proportion detected at an early clinical stage) followed by a decrease in total cases.ConclusionThis study will enable us to improve and disseminate the Replicability Model by identifying factors that promote success. It will also identify its effectiveness in fulfilling one of its aims: reducing the incidence of leprosy by finding and tracking cases at an earlier stage in the disease.

BackgroundLeprosy reactions, Type-1 and erythema nodosum leprosum, are immune-mediated complications of leprosy, which play a significant role in the morbidity associated with the disease. A considerable amount of literature has been published on the impact of leprosy in general but few studies focus specifically on leprosy reactions. This study aimed to investigate the impact of leprosy reactions on physical, psychological, and social aspects of the lives of people affected by analysing their life experiences and perspectives about leprosy reactions.Methods/principal findingsThis qualitative study involved people affected by leprosy reactions and their family members in two leprosy endemic countries. The data were collected through 66 interviews and 9 focus group discussions (4-6 participants each) in Surabaya, Indonesia, and Purulia, India. Content analysis and conversational analysis were performed. This study found that both types of leprosy reactions were perceived as an unpredictable and painful condition. Leprosy reactions restricted physical activities of the participants, such as going to bathroom, sleeping, eating, and cooking. In the interviews, the respondents expressed a range of emotions and feelings including confusion, sadness, anxiety, and anger. Some recounted that they felt stigmatized and lost opportunities to socialise and earn money. Differences between the two settings were identified. The majority of Indonesian participants preferred to stay at home, and some concealed the diagnosis of leprosy, while most of the Indian respondents continued working up to the time of hospitalization.ConclusionLeprosy reactions are a distressing complication of leprosy and adversely affect the lives of those affected. Individuals reported physical discomfort, distress, anxiety, stigma, and financial hardship and these negative impacts in the physical, psychological, and social spheres reinforced each other. These findings provide important information about a need for early detection and sustained commitment to follow-up care for people with a history of leprosy reactions. More research on new drugs for reactional episodes, tools to measure knowledge, attitude, and practice, and costing study on leprosy reactions treatment are needed. We recommend the development and testing of holistic strategies to improve the management of leprosy reactions.

BackgroundLeprosy is a Neglected Tropical Diseases (NTDs) known to cause stigma and discrimination in low-and middle-income countries. It often results in visible impairments, thus pre-disposing to poor mental health. Aim of the study was to estimate the prevalence of depression and anxiety among people affected by Leprosy and to determine the associated factors.Methodology/principal findingsA multi-centric, cross-sectional study was carried out in four leprosy endemic states of India-Chhattisgarh, Maharashtra, West Bengal and Tamil Nadu in randomly selected blocks (a sub-unit of district), from one district in each state. From selected blocks those registered for leprosy treatment at public health or referral centres, people above the age of 18 years were interviewed with PHQ-9 and GAD-7 questionnaires for Depression and Anxiety, respectively. Disease profile like leprosy classification, deformity grade, number and site of the patches and socio-economic status were collected along with individual data. Of the total 220 respondents, prevalence of depression and anxiety symptoms was, 33% (73) and 19% (42), respectively. Presence of disability (47%) and Female gender (46%) were significantly associated with depression. Presence of disability (32%), Lower income group (27%) and low education (22%) were significantly associated with symptoms of anxiety. As the severity of disability increased, risk of developing depression and anxiety increased.ConclusionThe study indicates that more than 30% of people affected by leprosy have mental health problems, which emphasizes the importance of mental health care services in leprosy. Women, those who had lower level of education, those belonging to lower socio-economic status and those with any level of disability due to leprosy are at risk of developing depression and/or anxiety. The study concludes more attention to be paid to the categories identified to be at risk.

Introduction Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the ‘MTX and prednisolone study in ENL’ (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL.Methods and analysis MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients’ reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events.Ethics and dissemination Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.

Introduction: Leprosy still remains a public health problem in India. Stigma and associated psychosocial problems are common in leprosy and may affect the quality of life (QoL). This study aimed to assess the QoL of the person affected by leprosy living in Purulia district, West Bengal. Methods: A cross-sectional study was conducted among 358 persons affected by leprosy above the age of 18 years and who were reporting at tertiary leprosy referral hospital, Purulia, West Bengal, from April to July 2017. The World Health Organization QoL (WHOQOL-BREF) scale was used to measure the QoL and the scale had four domain; physical health, psychological health, social relationship, and environmental health. Results: Of the 358 respondents, 41% were female, 60% were aged between 18 and 45 years, and 58% were literate. Half of the participants (55%) were farmer and labor, and 75% of the participants' family income was below Rs. 5000 per month. One hundred and forty-four (40%) participants had physical disability. There was a highly significant difference seen among the person affected by leprosy between those with visible deformity and no deformity in four domains. The participants with visible deformity had lower QoL than the person without deformity. Conclusion: The study observed that the person affected by leprosy with visible deformity had lower QoL. Early detection and management would prevent the deformity and might improve the QoL of persons affected by leprosy.

Background: This study aimed to explore the disease severity perceived by people affected with leprosy reporting at leprosy referral center, Purulia, West Bengal, India. Methods: A cross-sectional study was conducted among 358 persons affected by leprosy above the age of 18 and married who were reporting at tertiary leprosy referral hospital, Purulia, West Bengal, India. A semistructured questionnaire was prepared to collect the demographic profile, disease profile, and perceived severity of the disease. Results: Among the participants, 41% of them were female, 60% were aged between 18 and 45 years, 58% were literate, and 40% of the participants had physical disability. The participants had multiple feelings of fear, anxiety and sorrow when first diagnosed as leprosy affected. Majority (69%) of the participants had fear of the disease. A significant association was present among males and females feeling fear of leprosy and the female feared more than male. Conclusion: The present study emphasizes the need for continuous counseling and health education for persons affected with leprosy to avoid or minimize the psychological problems. Periodical screening and counseling will improve their psychosocial well-being and quality of life.

Purpose: PCR assay is a highly sensitive, specific and reliable diagnostic tool for the identification of pathogens in many infectious diseases. Genome sequencing Mycobacterium leprae revealed several gene targets that could be used for the detection of DNA from clinical and environmental samples. The PCR sensitivity of particular gene targets for specific clinical and environmental isolates has not yet been established. The present study was conducted to compare the sensitivity of RLEP, rpoT, Sod A and 16S rRNA gene targets in the detection of M. leprae in slit skin smear (SSS), blood, soil samples of leprosy patients and their surroundings. Method: Leprosy patients were classified into Paucibacillary (PB) and Multibacillary (MB) types. Ziehl–Neelsen (ZN) staining method for all the SSS samples and Bacteriological Index (BI) was calculated for all patients. Standard laboratory protocol was used for DNA extraction from SSS, blood and soil samples. PCR technique was performed for the detection of M. leprae DNA from all the above-mentioned samples. Results: RLEP gene target was able to detect the presence of M. leprae in 83% of SSS, 100% of blood samples and in 36% of soil samples and was noted to be the best out of all other gene targets (rpoT, Sod A and 16S rRNA). It was noted that the RLEP gene target was able to detect the highest number (53%) of BI-negative leprosy patients amongst all the gene targets used in this study. Conclusion: Amongst all the gene targets used in this study, PCR positivity using RLEP gene target was the highest in all the clinical and environmental samples. Further, the RLEP gene target was able to detect 53% of blood samples as positive in BI-negative leprosy cases indicating its future standardization and use for diagnostic purposes.

OBJECTIVES:We wished to validate our recently devised 16-item ENLIST ENL Severity Scale, a clinical tool for measuring the severity of the serious leprosy associated complication of erythema nodosum leprosum (ENL). We also wished to assess the responsiveness of the ENLIST ENL Severity Scale in detecting clinical change in patients with ENL. METHODS:Participants, recruited from seven centres in six leprosy endemic countries, were assessed using the ENLIST ENL Severity Scale by two researchers, one of whom categorised the severity of ENL. At a subsequent visit a further assessment using the scale was made and both participant and physician rated the change in ENL using the subjective categories of "Much better", "somewhat better", "somewhat worse" and "much worse" compared with "No change" or "about the same". RESULTS:447 participants were assessed with the ENLIST ENL Severity Scale. The Cronbach alpha of the scale and each item was calculated to determine the internal consistency of the scale. The ENLIST ENL Severity Scale had good internal consistency and this improved following removal of six items to give a Cronbach's alpha of 0.77. The cut off between mild ENL and more severe disease was 9 determined using ROC curves. The minimal important difference of the scale was determined to be 5 using both participant and physician ratings of change. CONCLUSIONS:The 10-item ENLIST ENL Severity Scale is the first valid, reliable and responsive measure of ENL severity and improves our ability to assess and compare patients and their treatments in this severe and difficult to manage complication of leprosy. The ENLIST ENL Severity Scale will assist physicians in the monitoring and treatment of patients with ENL. The ENLIST ENL Severity Scale is easy to apply and will be useful as an outcome measure in treatment studies and enable the standardisation of other clinical and laboratory ENL research.

BACKGROUND:Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R. METHODOLOGY:Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome. PRINCIPAL FINDINGS:345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia. CONCLUSIONS:Azathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve damage do not improve. Future studies should test giving azathioprine in the treatment of nerve damage and giving a higher dose for 48 weeks to patients. These findings highlight the difficulty in switching off leprosy inflammation and the need for better treatments for reactions and nerve damage. There is also a research need to identify patients who have recurrences and optimize treatments for them. Patients with recurrences may benefit from combined treatment with steroids and azathioprine. We have also shown that significant numbers of patients treated with steroids develop adverse effects and this needs to be highlighted in leprosy programmes. Research is needed to identify patients who do not respond to steroid treatment and develop alternative treatments for them. TRIAL REGISTRATION:ClinicalTrials.gov This trial was registered with the Indian Council of Medical research clinical Trial register as a clinical trial Number-REFCTRI/2016/12/007558.

Erythema nodosum leprosum (ENL) is a common immune-mediated complication of lepromatous (LL) and borderline lepromatous (BL) leprosy. Most patients experience chronic or multiple acute ENL over many years during an economically active period of their lives. Understanding the economic burden of ENL is essential to provide effective patient support, yet this area has not been investigated.Ninety-one patients with LL or BL leprosy attending a leprosy hospital in Purulia district of West Bengal, India, were interviewed using a structured questionnaire. Cases (n = 53) were identified as those who had one or more episodes of ENL within the last 3 years. Controls (n = 38) had LL or BL leprosy but no history of ENL. Data were collected on household income, direct and indirect costs, and coping strategies.The total household cost was Rs 1543 per month or 27.9% (IQR 13.2-52.6) of monthly household income for cases, and Rs 237 per month or 4.9% (IQR 1.7-13.4) of monthly household income for controls. Indirect costs accounted for 65% of total household costs for cases. Direct costs accounted for the remaining 35% of household costs, and resulted almost entirely from treatment-seeking in the private sector. Total household costs exceeded 40% of household income for 37.7% of cases (n = 20) and 2.6% of controls (n = 1) [1 USD = 59 INR].Households affected by ENL face significant economic burden and are at risk of being pushed further into poverty. Health policy should acknowledge the importance of private sector provision and the significant contribution to total household costs of lost productivity (indirect cost). Further work is needed to explore this area and identify solutions.

Erythema nodosum leprosum (ENL) is a severe multisystem immune mediated complication of borderline lepromatous leprosy and lepromatous leprosy. ENL is associated with skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. The treatment of ENL requires immunosuppression, which is often required for prolonged periods of time and may lead to serious adverse effects. ENL and its treatment is associated with increased mortality and economic hardship. Improved, evidence-based treatments for ENL are needed; however, defining the severity of ENL and outcome measures for treatment studies is difficult because of the multiple organ systems involved. A cross-sectional study was performed, by the members of the Erythema Nodosum Leprosum International STudy (ENLIST) Group, of patients with ENL attending seven leprosy referral centres in Brazil, Ethiopia, India, Nepal, the Philippines and the United Kingdom. We systematically documented the clinical features and type of ENL, its severity and the drugs used to treat it. Patients with chronic ENL were more likely to be assessed as having severe ENL. Pain, the most frequent symptom, assessed using a semi-quantitative scale was significantly worse in individuals with "severe" ENL. Our findings will determine the items to be included in a severity scale of ENL which we are developing and validating. The study also provides data on the clinical features of ENL, which can be incorporated into a definition of ENL and used for outcome measures in treatment studies.