Lepra Society

[This corrects the article DOI: 10.1016/j.metop.2025.100416.].

Background: Leprosy, or Hansen’s disease, is a chronic infectious condition caused by Mycobacterium leprae or Mycobacterium lepromatosis, predominantly affecting the skin, peripheral nerves, and mucous membranes. Despite being curable, it continues to result in significant morbidity due to delayed diagnosis, stigma, and complications such as chronic trophic ulcers (CTUs). While multiple treatment options exist ranging from debridement and protective footwear to growth factor therapies but their comparative effectiveness remains unclear. Methods: This systematic review and meta-analysis aim to evaluate the effectiveness of various ulcer care practices for individuals affected by leprosy, focusing on outcomes such as healing rates and ulcer recurrence. This systematic review will follow the PRISMA-P 2015 guidelines and is registered in PROSPERO (CRD420251010372). A thorough search will be conducted in databases such as PubMed, Google Scholar, and grey literature from 2005 to 2024. Studies included will be randomized controlled trials (RCTs) and cross-sectional studies that report on ulcer care practices in people affected by leprosy. We will include interventions like wound dressings, debridement, medications, use of footwear, and traditional methods. The quality of the studies will be assessed using standard tools: the Cochrane RoB 2 tool for randomized trials and the Joanna Briggs Institute (JBI) checklist for cross-sectional studies. Data will be analysed using R software. Conclusions: The review will synthesize evidence on the effectiveness of ulcer care interventions in leprosy, guiding clinical decision-making and informing policy to improve healing outcomes and quality of life among affected individuals. Trial Registration: Current control trial registration number is CRD420251010372.

On May 23–25, 2024, a multidisciplinary expert group met in Bergen, Norway, the site of the first description of Mycobacterium leprae (M. leprae) in 1873, to discuss advancements and remaining knowledge gaps in the transmission of M. leprae at the Global Partnership for Zero Leprosy Zero Transmission Symposium. Research and operational approaches to interruption of transmission were identified; the research approaches from the symposium are described here. Updates since a previous symposium at the National School of Tropical Medicine, Baylor College of Medicine in Houston (USA), in 2014 from these fields of research are presented here: epidemiology; microbiological diagnosis; immunodiagnostics; genotyping; geospatial mapping; leprosy elimination monitoring and transmission under low-endemic circumstances; leprosy post-exposure prophylaxis (PEP); modelling relevant to interruption of transmission of M. leprae; OneHealth; environmental transmission of M. leprae; social determinants; control programmes relevant to interruption of transmission of M. leprae; and organizations of persons affected. Progress and outstanding gaps since 2014 are identified, and recommendations for relevant research in these areas to achieve interruption of transmission are presented. These include research into human reservoirs, including platforms for field-friendly diagnostics; routes of entry/exit of M. leprae; the roles of animals or vectors in transmission; the role of social determinants in transmission; host-pathogen interactions; transmission networks; and enhanced epidemiological data. Fulfilment of these research recommendations and further understanding of which settings require intensified control efforts, will help to advance the aim of achieving complete interruption of transmission of M. leprae and the elimination of leprosy disease.

The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect Mycobacterium leprae or M. lepromatosis infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of M. leprae, and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.

India is thought to harbour the origins of leprosy based on evidence of the disease dating back to 2000 BC and is described in ancient Indian scripts. However, some studies have suggested a migration of this disease from Africa to India. India has fought a long battle against leprosy with a good amount of success. This has been both in terms of the progress of leprology as a science and achievements in terms of the management of leprosy at clinical and public health levels1-3. After the introduction of multi-drug treatment (MDT) in 1983 in India, remarkable success was witnessed in the first two decades1. From more than 40 lakh cases in 1982, the patient load was reduced to less than two lakhs (nearly 97% reduction) by 2005 when it was declared to have been eliminated as a major public health concern (with a national prevalence <1/10,000)1,2. Similarly, more than 90 per cent reduction was observed in dapsone (DDS) resistance. Since then, there has been some decline in the number of new cases and disabilities4. However, this reduction has been slow and the situation has generally been considered as stagnating. Except for the period of the COVID-19 pandemic, over 100,000 new cases of leprosy have been annually reported for several years. Whenever active surveillance such as leprosy case detection campaigns have been conducted, the proportion of hidden cases has been found to be significant; nearly three times higher numbers of leprosy affected person (LAPs) with as compared to those self-reporting to the healthcare system (27.7 vs. 10.48/100,000) were detected in a national sample survey conducted in 2011-20125. Overall, the new case detection, disability rates and child leprosy trends did not show appreciable reduction6. Analysis of the distribution of caseload across the country shows that India's success is patchy and not uniform. Globally there are some high leprosy endemic countries. There are pockets of endemicity within such countries that may be, however, be overall in good position in terms of leprosy disease burden. Low endemic States/countries with weakening expertise and closure of vertical programme(s) have possibly reduced access to early and timely leprosy diagnosis and management services thereby contributing to higher disability rates. Standard guidelines for management as well as prevention have been developed by the WHO7 and followed by most countries including India. Diagnostic tools are available; however, access is limited; even slit skin smears are not available in most of the places. Although molecular tests have been established since years, these are not being used in health systems to confirm the diagnosis in doubtful cases. This indicates the need for introspection both about the research ecosystem and public health aspects related to service provision. Historical landmarks The science of leprology has several landmarks linked to India1-3,8. These landmarks include a description of two types of leprosy in the late eighteenth/early nineteenth century (Hamilton 1762-1825)8. In the second half of nineteenth century, there were many landmarks – successful use of Chaulmoogra oil/ Hydnocarpus oil for leprosy treatment, the first leprosy survey was conducted in India, Dr. Henry Van Dyke Carter advocated the 'contagion theory' leading to segregation of leprosy sufferers in leprosy homes and colonies. The Lepers Act, 1898, segregated leprosy victims based on gender to restrict reproduction. A report on the lepra bacilli present in the nasal smears of the LAPs from Mumbai was presented at the first leprosy Congress which was held in Berlin in 18971. During 1915-1920, Sir Leonard Rogers started treatment of leprosy with Chaulmoogra oil; almost around the same time, Ernest Muir advocated the use of this oil in the management of leprosy. The Indian Council of the British Empire Leprosy Relief Association (ICBELRA) which was established in 1925 became the precursor of HindKusth Nivaran Sangh, and since 1929, it has been publishing the national Journal on Leprosy –Indian Journal of Leprosy (erstwhile Leprosy in India). In 1941, Dharmendra described 'Lepromin' antigen3. In 1945-1946, Dr. RG Cochrane administered DDS for the treatment of leprosy and this was initiated in the Acworth Leprosy Home. Mahatma Gandhi himself proved to be a catalyst in synergizing the modern medical efforts of missionaries and Indian institutions combined with compassion/empathy2. After our independence in 1947, the National Leprosy Control Programme was launched in 1954-1955 which later evolved to become the National Eradication Programme (NLEP)1,2. By the second half of 20th century, nearly 30 government organizations and non-governmental organizations (NGO) (national/international) were working on leprosy contributing to services and research. Many of these are less active now but still exist and can contribute if supported adequately and tasked with filling the gaps in knowledge/implementation. Medical treatment of leprosy While the use of DDS was a major advancement, prolonged treatment was required for lepromatous disease and by the 1970s there was increasing evidence of relapses and the development of DDS resistance. The WHO then recommended MDT for leprosy in 1982. Worldwide more than 15 million LAPs have been reported to be cured of the disease with MDT9. It is estimated that MDT has contributed to the prevention of disabilities in about three million individuals. The WHO7 recommended a uniform MDT (U-MDT) comprising of the same combination of rifampin, clofazimine (CLF) and DDS for six months for paucibacillary (PB) and 12 months for multibacillary leprosy, respectively. The addition of CLF to the PB regimen initially emerged from ICMR-JALMA, Agra which showed its beneficial effects10, later accepted by the WHO after multi-centric studies on U-MDT. Alternate regimens comprising same drugs with varying durations, combinations and other drugs such as different quinolones, clarithromycin and minocycline. MDT plus immunotherapy regimens have improved the therapy of leprosy significantly. The development of Mw (Mycobacterium indicus pranii, MIP) vaccine in India and its use as immunoprophylaxis to contacts as well as an adjunct to MDT in new cases to improve the outcomes of chemotherapy in a cost-effective manner are important contributions from India11,12. Reconstructive surgery In 1958, reconstructive surgery (RCS) for correction of deformities of LAPs was started in Vellore by Dr. Paul Brand. Over the past 6-7 decades, several surgical procedures have been developed for the prevention of nerve damage, correction of disabilities of hands and feet, nasal deformities, lagophthalmos and protection of eyes and post-operative physiotherapy and self-care. Many of these procedures have been developed by Indian surgeons/ surgeons working in India1-3. These have contributed to the enablement of these affected persons. NSP (2023-2027)4 has advocated a well-defined referral system for DPMR services. Promoting centres for skill development for meaningful employment of disabled LAPs is needed. Looking at future To eradicate the disease from India, we need to prioritize and introduce/implement new tools for diagnosis and treatment as well as prophylactic strategies which are well developed and tested in tertiary care centres and the programme. Despite dwindling interest and expertise even today there are many institutions in the government and NGO sector that are actively working on leprosy. There is thus a need to prioritize our efforts. Important priority areas: The areas which deserve priority in research-cum-action in the immediate and long-term future: (i) improving/strengthening the health systems at various levels, (ii) improving access for early detection, appropriate management of leprosy cases including surveillance of drug resistance, (iii) prevention strategies, (iv) stigma reduction – both community as well as self-stigma and community participation, (v) improving management of cases, aftercare and surveillance, (vi) environmental factors, (vii) data management, mobile health (mHealth), electronic health (eHealth) and use of artificial intelligence. Strengthening of health systems: While there has been an overall dilution of expertise to diagnose and treat leprosy early, we need to understand the issues at local a level and train/re-train and deploy our human resource for contact examination, monitor treatment and surveillance for late complications. Leprosy situation varies from area to area with sociocultural factors playing an important role. Thus, the strengthening of health systems must be understood, and solutions provided according to local needs. Technologies for early diagnosis and management of cases: Molecular tests for early diagnosis, especially confirmation of leprosy in early /atypical cases as well as monitoring disease activity have been available for a long time. Some are also under development using newer platforms which are feasible in district, peripheral healthcare settings as seen for tuberculosis programme using cartridge-based nucleic acid amplification test (Truenat for tuberculosis in India). Strengthening of network(s) for Diagnostics – Network of molecular laboratory services should be a priority for ensuring early diagnosis for all types of cases, especially atypical presentations. These need to be included in the algorithm in a gradual manner with priority for difficult-to-diagnose cases. Antimicrobial resistance (AMR) surveillance for anti-leprosy drugs and strain typing for studying the epidemiology of disease can be undertaken by molecular methods and should receive due priority. Prevention strategies: chemoprophylaxis and immunoprophylaxis: Both chemoprophylaxis (single-dose rifampicin as well as post-exposure prophylaxis++ using multiple-dose regimens) and immunoprophylaxis have different mechanisms of protection; these would be complementary to each other and should not always be considered in isolation. MIP (Mw) has demonstrable protective efficacy at five years and even up 8-10 yr in India11. Bacillus Calmette–Guérin (BCG) at birth is recommended7 and has shown good effects in some countries, however, may not be adequate for India as high endemicity of leprosy has continued despite BCG as part of the universal immunization programme. LepVax, a new vaccine candidate is still being developed1,12. Evidence suggests that appropriate implementation of chemoprophylaxis (SDR) and immunoprophylaxis using MIP (Mw) vaccine among all eligible contacts will be of help in decreasing the burden of leprosy transmission in society and sustain the same12. MIP also has protective efficacy against tuberculosis. Thus, considering the state of present knowledge, the approach of using both chemoprophylaxis and immunoprophylaxis (MIP vaccine) deserves serious attention and urgency. Stigma reduction and community participation: Stigma in various forms affects the physical, mental and social well-being of any individual including LAPs. Although the social stigma in leprosy has been reduced due to the curability of the disease, reduction in disabilities and better treatment outcomes, self-stigma in patients appears to be an issue5. Information, Education, Communication (IEC) and knowledge empowerment activities, both for patients and the community which have a profound healing as well as destigmatizing effect on both the patients and the community at large and are required. Wherever possible LAPs should be included in such activities. Improving management of cases and aftercare: There could be several ways to improve the therapy by considering the use of known as well as novel immunotherapy (MIP vaccine) and chemotherapy regimens. Attention also needs to be given to the development of methods for early identification of non-responders to MDT. The development of newer diagnostic algorithm(s) in difficult-to-diagnose cases and the use of technologies for monitoring treatment response would be useful. Further, the repurposing of drugs such as bedaquiline especially for non-responders and drug-resistant cases should be considered. Surgical care remains important and timely appropriate interventions should be available. Advances in ulcer care including platelet-rich-plasma and use of antibiotics as per susceptibility profile merit investigations. Environmental factors: Understanding the role of environmental factors and suggesting policy measures to address their role in continued transmission will be important in ultimate eradication of disease. Focused research and interventions on this aspect are important as viable M. leprae in the environment may be responsible for transmission of leprosy. Currently, there are no tools to eradicate M. leprae from nature13. Endemicity has been shown to be linked to environmental factors and housing conditions in Indonesia14. Measures to improve environmental health (housing, sanitation, nutrition, programmes like expanded Swatchh Bharat mission in India) would not only be relevant for leprosy but also add to a life free from many diseases. Data management, mobile health, electronic health and artificial intelligence: Improving data management for research and development as well as for targeted interventions will be important in the final battle and has been a priority in NSP 2023-20274. Detection of type 1 reactions and their timely management could be facilitated by appropriate data capture tools and will be important in reducing the morbidity including disabilities. The optimum use of eHealth tools is known to improve the access. mHealth has also not been optimally used in leprosy and other neglected tropical diseases in developing countries. Artificial intelligence tools have immense potential in providing quality services in areas where trained/specialist services will not be available in the near future15. National Strategic Plan and Roadmap of Leprosy 2023-2027 NSP 2023-2027 is aligned with global strategy 2021-203016 and has a vision of Leprosy free India4. It has a goal of accelerating the programme for interruption of transmission of leprosy by 2027 – three years ahead of sustainable development goal 3.3. Knowledge and tools exist that can be considered to further improve the management of LAPs/lives of persons affected by leprosy and overcome the public health challenges still posed by leprosy. In a scenario of competing priorities and limited human and financial resources available for leprosy, the issue is: 'can we set some timelines?' Or these remain just aspirational goals with no predictions and a hazy distant future? Finite game plan creates confusion among stakeholders13. NLEP is committed to end leprosy using various innovative approaches17. However, it would be advisable to set realistic milestones and provide complete information about likely scenarios rather than use words like elimination/eradication which should be fully explained. Targets of zero disabilities and zero transmission are largely achievable but intense efforts are needed. In 2006 (at the end of December 2005), India celebrated the elimination of leprosy as a public health problem (<1/10,000) at the national level. However, let us hope that with a mass screening approach we will be able to connect with all cases by the end of 2027 and treat the hidden cases plus provide chemoprophylaxis and immunoprophylaxis for all contacts. The outcome of transmission will, however, be known only in 2037 – a long incubation period. Disability prevention, management and care of LAPs will need attention for a long time at least 20 years till 2047 or beyond. For future both basic as well as applied research remain important to cover several aspects which include health systems, mental health, urban leprosy, improved regimens especially for non/poor responders; molecular diagnosis, molecular epidemiology, detection of anti-microbial drug resistance (AMR), stigma reduction, prevention strategies, chemoprophylaxis, immunoprophylaxis, environmental health aspects, teaching and training of different type of health professionals. Providing robust medical care in low endemic settings, sustaining the interruption in transmission, disability prevention and management as well as aftercare for socioeconomic well-being of LAPs should remain the long-term goals. Acknowledgement: This editorial is based on the 7th Dr. P.P. Talwar Oration delivered at ICMR Headquarters on December 12, 2023. Financial support & sponsorship: None. Conflicts of Interest: None.

BackgroundIL-17 and IL-22 cytokines play an important role in protective immune responses against Mycobacterium tuberculosis (Mtb) infection. Information on the production of these cytokines and the factors that regulate their production in the context of human immunodeficiency virus (HIV) and latent tuberculosis infection (LTBI) or active tuberculosis disease (ATB) is limited. In the current study, we compared the production of these two cytokines by PBMC of HIV-LTBI+ and HIV + LTBI+ individuals in response to Mtb antigens CFP-10 (culture filtrate protein) and ESAT-6 (Early Secretory Antigenic Target). We also determined the mechanisms involved in their production.MethodsWe cultured Peripheral Blood Mononuclear Cells (PBMCs) from HIV- individuals and HIV+ patients with latent tuberculosis and active disease with CFP-10 and ESAT-6. Production of IL-17, IL-22 and PD1 (Programmed Death 1), ICOS (Inducible T-cell Costimulator), IL-23R and FoxP3 (Forkhead box P3) expression on CD4+ T cells was measured.ResultsIn response to Mtb antigens CFP-10 and ESAT-6, freshly isolated PBMCs from HIV+ LTBI+ and HIV+ active TB patients produced less IL-17 and IL-22 and more IL-10, expressed less IL-23R, and more PD1 and expanded to more FoxP3+ cells. Active TB infection in HIV+ individuals further inhibited antigen specific IL-17 and IL-22 production compared to those with LTBI. Neutralization of PD1 restored IL-23R expression, IL-17 and IL-22 levels and lowered IL-10 production and reduced expansion of FoxP3 T cells.ConclusionsIn the current study we found that increased PD1 expression in HIV + LTBI+ and HIV+ active TB patients inhibits IL-17, IL-22 production and IL-23R expression in response to Mtb antigens CFP-10 and ESAT-6.