Spatial-temporal trends in leprosy burden and its associations with socioeconomic and physical geographic factors: results from the Global Burden of Disease Study 2019.

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.

Genetic diversity of Mycobacterium leprae: Need to move towards genome-wide approaches.

ABSTRACT: Leprosy, an ancient disease, continues to be a public health concern as it remains endemic in several countries. After reaching the elimination target (1/10,000) as a public health problem in 2005 in India, around 1.2 lakh cases have been detected every year over the last decade indicating active transmission of leprosy bacillus (Mycobacterium leprae). Single-nucleotide polymorphisms (SNPs), genomic insertions/deletions and variable-number tandem repeats (VNTRs) have been identified as genetic markers for tracking M. leprae transmission. As the leprosy bacilli cannot be cultured in vitro, molecular testing of M. leprae genotypes is done by polymerase chain reaction-based sequencing which provides a practical alternative for the identification of strains as well as drug resistance-associated mutations. Whole-genome sequencing (WGS) of M. leprae directly from clinical samples has also proven to be an effective tool for identifying genetic variations which can further help refine the molecular epidemiological schemes based on SNPs and VNTRs. However, the WGS data of M. leprae strains from India are scarce, being responsible for a gross under-representation of the genetic diversity of M. leprae strains present in India and need to be addressed suitably. Molecular studies of leprosy can provide better insight into phylogeographic markers to monitor the transmission dynamics and emergence of antimicrobial resistance. An improved understanding of M. leprae transmission is essential to guide efficient leprosy control strategies. Therefore, this review compiles and discusses the current status of molecular epidemiology, genotyping and the potential of genome-wide analysis of M. leprae strains in the Indian context.

Target product profiles: leprosy diagnostics.

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.

L'Organisation mondiale de la Santé (OMS) vise à réduire le nombre de nouveaux cas de lèpre de 70% d'ici 2030, ce qui nécessite un meilleur diagnostic de la maladie. Dans le présent document, nous évoquons le développement de deux profils de produit cible établis par l'OMS à cette fin. Ces profils définissent des critères en matière d'utilisation, de conception, de performances, de configuration et de distribution du produit, en accordant une attention particulière à l'accessibilité et à l'abordabilité. Le premier profil de produit cible décrit les exigences pour les tests servant à confirmer le diagnostic de la lèpre chez les individus qui présentent des signes cliniques et des symptômes, afin d'orienter l'instauration d'un traitement à base de plusieurs médicaments. Le second profil de produit cible décrit les exigences pour les tests servant à détecter une infection à Mycobacterium leprae ou M. lepromatosis parmi les contacts asymptomatiques de patients lépreux, ce qui contribue à l'adoption de mesures prophylactiques et à la prévention. Nous avons eu recours à une modélisation statistique pour évaluer les exigences de sensibilité et de spécificité de ces tests diagnostiques. Cet article met en évidence les obstacles à l'atteinte d'un niveau élevé de spécificité en raison de l'endémicité variable de M. leprae, et à l'identification d'analytes cibles offrant de bons résultats chez les phénotypes lépreux. Nous concluons qu'un diagnostic reposant sur des caractéristiques de performance et de conception appropriées est essentiel pour détecter rapidement la maladie et intervenir en amont, et nous plaidons pour une prévention plutôt qu'une gestion de la lèpre.

La Organización Mundial de la Salud (OMS) pretende reducir los nuevos casos de lepra en un 70% para 2030, lo que requiere avances en el diagnóstico de la lepra. Aquí se analiza el desarrollo de dos perfiles de productos objetivo de la OMS para este tipo de diagnósticos. Estos perfiles definen los criterios de uso, diseño, rendimiento, configuración y distribución de los productos, centrándose en su accesibilidad y asequibilidad. El primer perfil de producto objetivo describe los requisitos de las pruebas para confirmar el diagnóstico de la lepra en personas con signos y síntomas clínicos, con el fin de orientar el inicio del tratamiento con múltiples fármacos. El segundo perfil de producto objetivo describe los requisitos de las pruebas para detectar la infección por Mycobacterium leprae o M. lepromatosis entre los contactos asintomáticos de los pacientes con lepra, para facilitar las intervenciones profilácticas y la prevención. Se utilizaron modelos estadísticos para evaluar los requisitos de sensibilidad y especificidad de estas pruebas diagnósticas. El artículo destaca las dificultades para lograr una alta especificidad, dada la diferente endemicidad de M. leprae, y para identificar analitos diana con un rendimiento sólido en todos los fenotipos de lepra. Concluimos que los diagnósticos con un diseño de producto y unas características de rendimiento adecuados son fundamentales para la detección precoz y la intervención preventiva, lo que favorece la transición del manejo de la lepra a la prevención.

Mitochondrial variants of complex I genes associated with leprosy clinical subtypes.

Leprosy is a chronic bacterial infection mainly caused by Mycobacterium leprae that primarily affects skin and peripheral nerves. Due to its ability to absorb carbon from the host cell, the bacillus became dependent on energy production, mainly through oxidative phosphorylation. In fact, variations in genes of Complex I of oxidative phosphorylation encoded by mtDNA have been associated with several diseases in humans, including bacterial infections, which are possible influencers in the host response to leprosy. Here, we investigated the presence of variants in the mtDNA genes encoding Complex I regarding leprosy, as well as the analysis of their pathogenicity in the studied cohort. We found an association of 74 mitochondrial variants with either of the polar forms, Pole T (Borderline Tuberculoid) or Pole L (Borderline Lepromatous and Lepromatous) of leprosy. Notably, six variants were exclusively found in both clinical poles of leprosy, including m.4158A>G and m.4248T>C in MT-ND1, m.13650C>A, m.13674T>C, m.12705C>T and m.13263A>G in MT-ND5, of which there are no previous reports in the global literature. Our observations reveal a substantial number of mutations among different groups of leprosy, highlighting a diverse range of consequences associated with mutations in genes across these groups. Furthermore, we suggest that the six specific variants exclusively identified in the case group could potentially play a crucial role in leprosy susceptibility and its clinical differentiation. These variants are believed to contribute to the instability and dysregulation of oxidative phosphorylation during the infection, further emphasizing their significance.

Dermoscopic features of nails in Leprosy patients in a tertiary referral hospital in West Java, Indonesia.

INTRODUCTION: Leprosy is a chronic granulomatous infectious disease, mainly affecting the skin and peripheral nerves, caused by the obligate intracellular bacteria Mycobacterium leprae. The disease has been discussed in several review articles in recent research, but as far as we know, only a few have addressed the effects of leprosy on nails, especially those who examine the dermoscopic features of nails in leprosy patients. PURPOSES: We aimed to document nail changes in leprosy patients and identify any particular findings through dermoscopic examination. METHOD: This was an observational study conducted in the Dermatology and Venereology Clinic of Hasan Sadikin Hospital, West Java, Indonesia, from March 2023 through May 2023. All patients have established cases of leprosy, and the diagnosis is based on clinical and bacteriological examinations. Recruitment was done through total sampling. Dermoscopic examination of all fingernails and toenails was performed at 10x magnification using a handheld dermatoscope (Heine DELTA 20 T Dermatoscope) in polarized mode without the linkage fluid to document the dermoscopic features. RESULT: Of a total of 19 patients, 15 had nail changes due to leprosy. Out of 15 patients, 13 patients were male. Patients below 25 years old had more nail changes. Most of the patients had a duration of disease greater than two years. Both fingers and toes were involved in nine patients. In this study, the most common dermoscopic feature found was the longitudinal ridge. Other dermoscopic features found in this study were transverse lines, onycholysis, longitudinal melanonychia, leukonychia, subungual hemorrhage, subungual hyperkeratosis, anonychia, and onychorrexis. CONCLUSION: Nail changes are found in leprosy patients and have a wide variety of clinical appearances. A dermoscopy should be performed to assess nail changes in leprosy.

Leprosy: treatment, prevention, immune response and gene function.

Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.

Leprosy in Colombia: A look from life experience.

Leprosy continues to be stigmatized, causing harm to fundamental rights, pain and hopelessness in those who have suffered from it and their families. From its relationship with public and mental health, effective strategies must be implemented to reduce stigma and unlearn myths and wrong perceptions, support families, and improve quality of life through early care and detection. This article shows that those affected by leprosy are capable, functional people with much to contribute to society anywhere in the world.

Let them talk and we listen: what are diseases of neglected people?

This article is a reflection from a person with lived experience of leprosy, who has been working as a global advocate and champion for the rights of persons affected by neglected tropical diseases for the last decade. Synthesising learning from the collection of pieces included within this special supplement that are written from the perspective of people affected by neglected tropical diseases, I argue that it is time to centre the lived experiences of people affected by neglected tropical diseases. These are diseases of neglected people, and it is now time to let them talk while we listen.

An evaluation of mental health integration in the neglected tropical diseases program in Zamfara, North-west Nigeria.

BACKGROUND: Mental health and neglected tropical diseases (NTDs) are critical in healthcare systems, especially in low- and middle-income countries. Several policies are planned or designed by health stakeholders to address the mental health needs of people affected by NTDs. Still, the impact of such policies seems to be of no consequence. METHODS: The GAD-7 and PHQ-9 tools were used to determine the rate of depression and anxiety, respectively, among people affected by skin NTDs (leprosy and lymphatic filariasis [LF]) in Zamfara State, North-west Nigeria. The study also evaluated the barriers to the uptake of mental health services for people affected by skin NTDs in the state. We assessed 48 people affected by NTDs (leprosy, 32; lymphatic filariasis, 16) along with a corresponding 48 people who served as controls in the study. Qualitative interviews were carried out with the participants to elicit the barriers to mental health services for people affected by NTDs. Additionally, 48 selected healthcare workers from the state were assessed for their skills and capacity to offer mental health services. RESULTS: We found anxiety disorder present in 100% of the people living with LF and in 62% of the people living with leprosy. Depression was also found in 56% and 75% of the people living with leprosy and LF, respectively. An assessment of the barriers to the uptake of mental health services reveals that most people with NTDs are constrained by a lack of money to visit hospitals, the fear of stigmatisation and discrimination and long distances to health centres. Regarding the healthcare workers, the skills and capacity to offer mental health services were very low. CONCLUSIONS: We conclude that for mental health services to be integrated into the community health system for people with NTDs, there should be a concerted effort by all stakeholders and the intervention should be context specific instead of generalised. CONTEXTE: La santé mentale et les maladies tropicales négligées (MTN) sont des problématiques centrales dans la santé, en particulier dans les pays à revenu faible ou intermédiaire. Plusieurs politiques sont conçues par les acteurs de la santé publique pour répondre aux besoins de soins en santé mentale pour les personnes touchées par les MTN. Pourtant, le bilan reste mitigé quant à l'efficacité de ces soins. MÉTHODES: Les outils GAD-7 et PHQ-9 ont été utilisés pour déterminer le taux de dépression et d'anxiété chez les personnes atteintes de MTN cutanées (lèpre et filariose lymphatique) dans l'État de Zamfara, au nord-ouest du Nigeria. L'étude a également évalué les obstacles à l'utilisation des services de santé mentale pour les personnes atteintes de MTN cutanées dans l'État. Nous avons évalué 48 personnes atteintes de MTN (lèpre : 32, filariose lymphatique : 16) ainsi que 48 personnes correspondantes qui ont servi de témoins dans l'étude. Des entretiens qualitatifs ont été menés avec les participants afin d'identifier les obstacles aux services de santé mentale pour les personnes atteintes de MTN. En outre, 48 professionnels de la santé sélectionnés dans l'État ont été évalués pour déterminer leurs compétences et leur capacité à offrir des services de santé mentale. RÉSULTATS: Nous avons trouvé des troubles anxieux chez 100% des personnes atteintes de filariose lymphatique et chez 62% des personnes atteintes de lèpre. La dépression touche 56% et 75% des personnes vivant avec la lèpre et la filariose lymphatique respectivement. Une évaluation des obstacles à l'utilisation des services de santé mentale révèle que la plupart des personnes atteintes de MTN sont limitées par le manque d'argent pour se rendre à l'hôpital, la peur de la stigmatisation et de la discrimination, et les longues distances à parcourir pour se rendre dans les centres de santé. Les compétences et les capacités des professionnels de la santé à offrir des services de santé mentale sont très faibles. CONCLUSION: L'efficacité d'un protocole de soins pour les patients atteints de MTN (traitant la pathologie physique et d'éventuelles pathologies psychiatriques associées) nécessite une intégration des services de santé mentale dans le système de santé communautaire. ANTECEDENTES: La salud mental y las enfermedades tropicales desatendidas (ETDs), son fundamentales en los sistemas sanitarios, especialmente en los países de renta baja y media. Las partes interesadas en la sanidad planean o diseñan varias políticas para abordar las necesidades de salud mental de las personas afectadas por ETDs. Sin embargo, el impacto de dichas políticas parece ser nulo. MÉTODOS: Se utilizaron las herramientas GAD-7 y PHQ-9 para determinar la tasa de depresión y ansiedad, respectivamente, entre las personas afectadas por ETDs cutáneas (lepra y filariasis linfática) en el Estado de Zamfara, al noroeste de Nigeria. El estudio también evaluó las barreras para la aceptación de los servicios de salud mental por parte de las personas afectadas por ETDs cutáneas en el Estado. Se evaluó a 48 personas afectadas por ETDs (lepra: 32; filariasis linfática: 16) y a otras 48 que sirvieron de control en el estudio. Se llevaron a cabo entrevistas cualitativas con los participantes para determinar las barreras a los servicios de salud mental para las personas afectadas por ETDs. Además, se evaluaron las habilidades y la capacidad para ofrecer servicios de salud mental de 48 profesionales sanitarios del Estado. RESULTADOS: Encontramos trastorno de ansiedad presente en el 100% de las personas que vivían con filariasis linfática y en el 62% de las personas que vivían con lepra. También se encontró depresión en el 56% y el 75% de las personas que vivían con lepra y filariasis linfática respectivamente. Una evaluación de los obstáculos para la utilización de los servicios de salud mental revela que la mayoría de las personas con ETDs se ven limitadas por la falta de dinero para acudir a los hospitales, el miedo a la estigmatización, la discriminación y las largas distancias hasta los centros sanitarios. Por parte del personal sanitario, los conocimientos y la capacidad para ofrecer servicios de salud mental eran muy escasos. CONCLUSIONES: Para que los servicios de salud mental para personas con ETD se integren en el sistema sanitario comunitario, debe haber una concertación entre todas las partes interesadas y la intervención debe ser específica para cada contexto en lugar de generalizada.

Experiences of social stigma of people living with Hansen's disease in Brazil: silencing, secrets and exclusion.

BACKGROUND: Hansen's disease is a chronic, infectious and transmissible disease that is considered a public health problem in Brazil. Hansen's disease is marked by stigma and prejudice, because it carries with it a strong negative social image, reinforced by policies of social isolation in the community. METHODS: A qualitative study was conducted in Ribeirão Preto, an inland city of the state of São Paulo, Brazil. Eleven patients under treatment for the disease were interviewed. The interviews were audio recorded and transcribed in full, then were analyzed through the stages of transcription, transposition and reconstitution, as informed by concepts proposed by Goffman. RESULTS: The results showed that the marks of stigma are still present in the twenty-first century and were presented in two axes: 'Stigma and work for the person affected by Hansen's disease' and 'The experience of stigma in the family'. The participants refer to fears of losing their jobs and of being ridiculed, which stops them talking about the disease. Regarding their families, the participants reported episodes of discrimination, the creation of family secrets and fear of relatives' reactions. CONCLUSIONS: All these aspects interfere in the follow-up and treatment of patients and need to be considered and welcomed by health professionals. It is recommended that these aspects are addressed in the initial training and continuing education of health professionals. CONTEXTE: La maladie de Hansen est une maladie chronique, infectieuse et transmissible, considérée comme un problème de santé publique au Brésil. La maladie de Hansen est marquée par la stigmatisation et les préjugés, car elle véhicule une image sociale fortement négative, renforcée par des politiques d'isolement social au sein de la communauté. MÉTHODES: Étude qualitative menée à Ribeirão Preto, une ville intérieure de l'État de São Paulo, au Brésil. Onze patients traités pour la maladie ont été interrogés. Les entretiens ont été enregistrés et transcrits intégralement, et ont été analysés en suivant les étapes de transcription, de transposition et de reconstitution, selon les concepts proposés par Goffman. RÉSULTATS: Les résultats montrent que les marques de la stigmatisation sont toujours présentes au 21ème siècle et ont été présentées selon deux axes : 'La stigmatisation et le travail pour la personne affectée par la maladie de Hansen' et 'L'expérience de la stigmatisation dans la famille'. Les participants évoquent la peur de perdre leur emploi, la peur d'être ridiculisés, ce qui les pousse à ne pas parler de la maladie. En ce qui concerne les familles, les participants ont rapporté des épisodes de discrimination, la création de secrets de famille et la peur des réactions des proches. CONCLUSIONS: Tous ces aspects interfèrent dans le suivi et le traitement des patients et doivent être pris en compte et accueillis par les professionnels de la santé. Il est recommandé que ces aspects soient abordés dans la formation initiale et la formation continue des professionnels de la santé. ANTECEDENTES: La enfermedad de Hansen es una enfermedad crónica, infecciosa y transmisible, considerada un problema de salud pública en Brasil. La enfermedad de Hansen está marcada por el estigma y el prejuicio, ya que conlleva una fuerte imagen social negativa, reforzada por políticas de aislamiento social en la comunidad. MÉTODOS: Estudio cualitativo realizado en Ribeirão Preto, una ciudad del interior del estado de São Paulo, Brasil. Se entrevistaron a once pacientes en tratamiento para la enfermedad. Las entrevistas fueron grabadas en audio, transcritas en su totalidad y analizadas a través de etapas de transcripción, transposición y reconstitución, según los conceptos propuestos por Goffman. RESULTADOS: Los resultados muestran que las marcas del estigma siguen presentes en el siglo XXI y se presentaron en dos ejes: 'Estigma y trabajo para la persona afectada por la enfermedad de Hansen' y 'La experiencia del estigma en la familia'. Los participantes mencionan el miedo a perder sus trabajos, el temor a ser ridiculizados, lo que les impide comentar sobre la enfermedad. En cuanto a las familias, los participantes reportaron episodios de discriminación, la creación de secretos familiares y el miedo a las reacciones de los familiares. CONCLUSIONES: Todos estos aspectos interfieren en el seguimiento y tratamiento de los pacientes y deben ser considerados y acogidos por los profesionales sanitarios. Se recomienda abordar estos aspectos en la formación inicial y la educación continua de los profesionales sanitarios.

Epidemiological, clinical, and geographical characterization of Leprosy in the County of Santarém-Pará: Insights for effective control and targeted intervention.

Leprosy is an infectious disease characterized by slow and chronic evolution, caused by Mycobacterium leprae and or Mycobacterium lepromatosis, an intracellular alcohol-acid-resistant (BAAR) bacillus. The objective of this study was to provide an epidemiological, clinical, and geographic characterization of leprosy in the city of Santarém-Pará during the period 2011-2020. A cross-sectional, descriptive, and quantitative approach was used, employing maps and tables to illustrate clinical and epidemiological variables, including: sex, age, race, area of residence, operational classification, clinical form, number of skin lesions, number of affected nerves, and health units. During the analyzed period, 581 cases of leprosy were diagnosed, resulting in the following cumulative incidence rates: male (60%); age over 15 years (94%); urban area (73%); multibacillary (74%); borderline form (46%); skin lesions greater than 5 (34%); and no nerves affected (68%). In the urban perimeter, a higher cumulative incidence of cases was observed in the central area with 133 cases. However, the health unit reporting the largest number of cases belonged to the southern area, specifically the Basic Health Unit of Nova República, with 48 cases. This study highlights the need to characterize the nuances of leprosy and its variability within the urban environment, according to different areas. Further research is essential to inform the implementation of public policies aimed at addressing the population with the highest vulnerability index, thereby reducing leprosy rates in Santarém.

Navigating diagnostic and therapeutic challenges in ocular manifestations of Hansen's disease and trachoma: A narrative review.

Neglected tropical diseases (NTDs) encompass a group of approximately 20 diseases prevalent in tropical and subtropical regions, closely associated with poverty, affecting over a billion people in low-income countries. This manuscript aims to explore the ocular manifestations and burden of two significant NTDs, namely Hansen's disease and trachoma while addressing gaps in understanding and management. Hansen's disease, caused by Mycobacterium leprae , has a long history and presents with diverse neurological and ocular manifestations. Despite the availability of treatment, ocular complications persist, leading to significant visual impairment in some cases. The manuscript emphasizes the importance of early diagnosis, regular ophthalmic examinations, and follow-ups to prevent and control ocular complications, reducing the burden of visual impairment and blindness. Trachoma, caused by Chlamydia trachomatis , remains the leading infectious cause of blindness in underdeveloped and remote areas. The manuscript highlights the clinical diagnosis and implementation of the World Health Organization's (WHO's) SAFE (surgery, antibiotics, facial hygiene, and environmental sanitation) strategy to prevent transmission and associated blindness. However, challenges in health surveillance tools and underreporting of trachoma cases are addressed, emphasizing the need for improved strategies to combat the disease effectively. Through a comprehensive review of the ocular manifestations and management of Hansen's disease and trachoma, this manuscript contributes to the existing knowledge base and enhances a deeper understanding of these NTDs. Addressing gaps in understanding and management emphasizes the importance of implementing WHO's strategies and collaborative efforts to achieve the global goal of reducing the burden of NTDs and improving community health and well-being. The manuscript underscores the significance of early intervention, preventive measures, and technological advancements, providing valuable insights for policymakers, healthcare professionals, and researchers working in the field of NTDs.

From periphery to center, untold story of pure neuritic leprosy: an electrophysiological study.

BACKGROUND: Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. METHODS: We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. RESULTS: Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35 years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. DISCUSSION: This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

Spatiotemporal pattern of leprosy in southwest China from 2010 to 2020: an ecological study.

BACKGROUND: Despite many efforts to control leprosy worldwide, it is still a significant public health problem in low- and middle-income regions. It has been endemic in China for thousands of years, and southwest China has the highest leprosy burden in the country. METHODS: This observational study was conducted with all newly detected leprosy cases in southwest China from 2010 to 2020. Data were extracted from the Leprosy Management Information System (LEPMIS) database in China. The Joinpoint model was used to determine the time trends in the study area. Spatial autocorrelation statistics was performed to understand spatial distribution of leprosy cases. Spatial scan statistics was applied to identify significant clusters with high rate. RESULTS: A total of 4801 newly detected leprosy cases were reported in southwest China over 11 years. The temporal trends declined stably. The new case detection rate (NCDR) dropped from 4.38/1,000,000 population in 2010 to 1.25/1,000,000 population in 2020, with an average decrease of 12.24% (95% CI: -14.0 to - 10.5; P < 0.001). Results of global spatial autocorrelation showed that leprosy cases presented clustering distribution in the study area. Most likely clusters were identified during the study period and were frequently located at Yunnan or the border areas between Yunnan and Guizhou Provinces. Secondary clusters were always located in the western counties, the border areas between Yunnan and Sichuan Provinces. CONCLUSIONS: Geographic regions characterized by clusters with high rates were considered as leprosy high-risk areas. The findings of this study could be used to design leprosy control measures and provide indications to strengthen the surveillance of high-risk areas. These areas should be prioritized in the allocation of resources.

The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission.

BACKGROUND: Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. METHODS: The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 - 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 - 600 mg) and clarithromycin (150 - 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox' proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. DISCUSSION: Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. TRIAL REGISTRATION: NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060.

Different profiles of chemokines, cytokines and cell growth factors in plasma samples from patients with leprosy, leprosy reactions and households contacts.

BACKGROUND: Leprosy is a highly neglected disease that is considered a serious public health problem in many countries. This illness is characterised by a variety of clinical and histopathological manifestations that are related to the patient immune response. OBJECTIVES: This work aimed evaluate the profile of circulating immune mediators in the plasma from patients classified clinically as paucibacillary (PB), multibacillary (MB), households contacts (HHC), type1 leprosy reaction (T1R), type2 leprosy reaction (T2R) and control individuals without medical history of leprosy (CTL). METHODS: To assessment of the plasma immune mediators was used multiplex microbeads immunoassay "Luminex". FINDINGS: The results showed that patients (PB) had a regulatory-biased profile, while MB revealed a pro-inflammatory trend of highly expressed biomarkers. HHC display conspicuously increased levels in the plasma of the chemokines (CCL2, CCL3, CCL4, CCL5 and CXCL8), pro-inflammatory cytokines (IFN-γ,TNF and IL-1ß), modulating cytokines (IL-9 and IL-1Ra) and growth factors (PDGF, G-CSF and IL-2). Interestingly, HHC displayed superior production of IFN-γ as compared to other leprosy groups, indicating a putative protective role for this cytokine during chronic Mycobacterium leprae exposure. MAIN CONCLUSION: Further investigations are currently underway to elucidate the potential of these mediators as biomarkers applicable to the diagnosis/prognosis of leprosy and also T1R and T2R leprosy reactions.

Half a Century in Hiding: A Unique Case of Tuberculoid Leprosy with an Unprecedented Incubation Period.

BACKGROUND Leprosy, also known as Hansen's disease, is a neglected tropical disease with low prevalence in the United States. The disease's long incubation period can cause delayed presentation, and most affected individuals have a history of travel or work in leprosy-endemic regions. The immune response to Mycobacterium leprae determines the clinical characteristics of leprosy, with tuberculoid leprosy being characterized by well-defined granulomas and involvement of peripheral nerves. The recommended treatment is a combination of dapsone and rifampin for 12 months. CASE REPORT A 78-year-old man with a history of extensive travel to Africa and Asia 50 years ago, presented with a non-tender, non-pruritic, and hypopigmented skin lesion on his left knee. Biopsy results confirmed granulomatous inflammation and the presence of Mycobacterium leprae, leading to a diagnosis of tuberculoid/paucibacillary leprosy. The patient received dapsone and rifampin treatment, which resulted in symptom improvement. CONCLUSIONS The patient's long incubation period of 50 years between exposure and symptom onset is remarkable and possibly one of the longest reported for tuberculoid leprosy. It emphasizes the importance of considering leprosy in cases with an extensive travel history and long incubation periods. Our patient's case presented contradictory staining results, suggesting potential sampling variation or a rare mixed leprosy form. Based on his clinical findings, he was diagnosed with tuberculoid leprosy. Early diagnosis and treatment are crucial to prevent irreversible nerve damage and improve patient outcomes. Healthcare providers should be vigilant in acquiring a detailed travel history to facilitate early diagnosis and appropriate management of leprosy cases.