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.

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.

Cross-cultural validation of two scales to assess mental wellbeing in persons affected by leprosy in Province 1 and 7, Nepal.

To assess mental wellbeing among persons affected by leprosy, this study aimed to validate the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) and the Patient Health Questionnaire (PHQ-9, depression tool) in Province 1 and 7, Nepal. Using purposive and convenience sampling, cross-cultural equivalences were assessed through semi-structured interviews with persons affected by leprosy (>18 years). Data were transcribed, translated, analysed and discussed with experts before revising the tools. Psychometric properties of the scales were assessed using an interviewer-administered questionnaire with cases affected by leprosy and controls not affected by leprosy (>18 years). Statistical analysis included internal consistency, construct validity, floor and ceiling effects, and interpretability. The qualitative study included 20 respondents of whom eleven were female. The statements in the original tools were rephrased to questions as participants had difficulties understanding the statements. Six additional changes were made to ensure items were understood well. The quantitative study included 90 cases (46% female) and 50 controls (54% female). The WEMWBS and PHQ-9 had adequate psychometric properties. Cronbach's alphas were 0.85 and 0.76, respectively, indicating good internal consistency, 75% of hypotheses for construct validity were confirmed, no floor and ceiling effects were found, and data to help users interpret results are presented. Our study provides evidence that the adapted versions of the WEMWBS and PHQ-9 have good cultural validity to measure mental wellbeing and depression among persons affected by leprosy in Province 1 and 7, Nepal.

Impact of basic psychological support on stigma and the mental well-being of people with disabilities due to leprosy and lymphatic filariasis: a postintervention evaluation study.

BACKGROUND: A peer support intervention, called basic psychological support for people affected by neglected tropical diseases (BPS-N), was piloted in India to improve mental well-being and social participation and to reduce stigma among people with disabilities due to leprosy or lymphatic filariasis. Preintervention and postintervention assessments showed improvements in mental well-being and reductions in depression and stigma. This study aimed to further evaluate this intervention at approximately 2 mo after its completion. METHODS: Scales were administered to 62 clients to measure stigma, depression, mental well-being and participation levels. Interviews with 13 clients and six peer supporters were conducted. RESULTS: Stigma scores were significantly reduced at 2 mo postintervention compared with preintervention and postintervention. The improvement in mental well-being detected at immediate postintervention had not changed significantly 2 mo later. Depression levels were higher than at postintervention, but lower than at preintervention levels. No significant differences were found in median participation scores, but the number of clients with moderate and severe participation restrictions reduced significantly from postintervention to 2 mo follow-up. Qualitative results showed that clients received information about their condition and treatment, and that some experienced positive effects on their emotions and self-esteem. CONCLUSIONS: This study provides additional evidence on the proof of concept of BPS-N. CONTEXTE: Une intervention de soutien par les pairs, appelée Soutien psychologique de base pour les personnes atteintes de maladies tropicales négligées (BPS-N), a été pilotée en Inde afin d'améliorer le bien-être mental et la participation sociale, et de réduire la stigmatisation, chez les personnes souffrant d'incapacités dues à la lèpre ou à la filariose lymphatique. Les évaluations avant et après l'intervention ont montré une amélioration du bien-être mental et une réduction de la dépression et de la stigmatisation chez ces personnes. Cette étude avait pour but d'évaluer cette intervention environ 2 mois après son achèvement. MÉTHODES: Des échelles ont été administrées à 62 clients pour mesurer la stigmatisation, la dépression, le bien-être mental et les niveaux de participation. Des entretiens ont été menés avec 13 clients et 6 pairs aidants. RÉSULTATS: Les scores de stigmatisation ont été significativement réduits deux mois après l'intervention par rapport à la situation avant et après l'intervention. L'amélioration du bien-être mental détectée immédiatement après l'intervention n'a pas changé de manière significative deux mois plus tard. Les niveaux de dépression étaient plus élevés qu'après l'intervention, mais plus bas qu'avant l'intervention. Aucune différence significative n'a été constatée dans les scores médians de participation, mais le nombre de clients ayant des restrictions de participation modérées et sévères a diminué de manière significative entre la période post-intervention et les deux mois de suivi. Les résultats qualitatifs ont montré que les clients ont reçu des informations sur leur état et leur traitement, et que certains ont ressenti des effets positifs sur leurs émotions et leur estime de soi. CONCLUSIONS: Cette étude a fourni des preuves supplémentaires de l'efficacité de la BPS-N. INTRODUCCIÓN: Una intervención de apoyo entre iguales, denominada Apoyo Psicológico Básico para personas afectadas por enfermedades tropicales desatendidas (BPS-N), se puso a prueba en la India para mejorar el bienestar mental y la participación social y reducir el estigma entre las personas con discapacidades debidas a la lepra o la filariasis linfática. Las evaluaciones previas y posteriores a la intervención mostraron mejoras en el bienestar mental y reducciones en la depresión y el estigma. El objetivo de este estudio era seguir evaluando esta intervención ∼2 meses después de su finalización. MÉTODOS: Se administraron escalas a 62 clientes para medir el estigma, la depresión, el bienestar mental y los niveles de participación. Se realizaron entrevistas con 13 clientes y 6 compañeros de apoyo. RESULTADOS: Las puntuaciones de estigma se redujeron significativamente a los 2 meses de la intervención, en comparación con antes y después de la misma. La mejora del bienestar mental detectada inmediatamente después de la intervención no había cambiado significativamente 2 meses después. Los niveles de depresión eran más altos que en el postintervención, pero más bajos que en el preintervención. No se encontraron diferencias significativas en las puntuaciones medias de participación, pero el número de clientes con restricciones de participación moderadas y graves se redujo significativamente entre el periodo posterior a la intervención y los 2 meses de seguimiento. Los resultados cualitativos mostraron que los clientes recibieron información sobre su enfermedad y tratamiento, y que algunos experimentaron efectos positivos en sus emociones y autoestima. CONCLUSIONES: Este estudio aportó pruebas adicionales sobre la prueba de concepto de la BPS-N.

Impact of basic psychological support on stigma and mental well-being of people with disabilities due to leprosy and lymphatic filariasis: a proof-of-concept study.

BACKGROUND: People with leprosy and lymphatic filariasis (LF)-related disabilities experience higher levels of poor mental well-being compared with the general community. Mental health services are often not available. This study was conducted to provide proof of concept that basic psychological support for people affected by neglected tropical diseases (BPS-N) can be given by peer supporters to reduce stigma, improve mental well-being and participation among clients. METHODS: The BPS-N approach was tested in a quasi-experimental design using mixed methods. To provide psychological support using the BPS-N, peer supporters were selected and trained. They supported people with leprosy- and LF-related disabilities. Preintervention and postintervention, stigma, mental well-being, depression and participation were measured through standard scales within 4 wk of the intervention; differences were tested using standard tests of significance. RESULTS: After 3 mo of intervention, the mean level of stigma had decreased (30.3 to 24, p<0.001); high mental well-being increased (0% to 13.3%, p<0.001); and moderate to severe depression decreased (88% to 47%, p<0.001). No significant change occurred in participation restrictions (87% to 92%, p=0.497). CONCLUSIONS: Psychological peer support using the BPS-N guideline appears effective in reducing stigma and improving mental well-being and can be operationalised. However, this should be confirmed through a randomised controlled trial. CONTEXTE: Les personnes atteintes de lèpre et de handicaps liés à la filariose lymphatique (FL) souffrent davantage d'un manque de bien-être mental que le reste de la population. Les services de santé mentale ne sont souvent pas disponibles hors des zones urbaines. Cette étude a été menée pour démontrer que le soutien psychologique de base pour les personnes atteintes de MTN (BPS-N) peut être dispensé par des pairs (dans une logique de transfert de tâches) afin de réduire la stigmatisation et d'améliorer le bien-être mental et la participation des clients. MÉTHODES: L'approche du BPS-N a été testée dans le cadre d'un modèle quasi-expérimental utilisant des méthodes mixtes. Pour fournir un soutien psychologique à l'aide du BPS-N, des pairs ont été sélectionnés et formés. Ils sont venus en aide aux personnes atteintes de lèpre et de déficiences liées à la FL. Avant et après l'intervention, les éléments suivants ont été mesurés à l'aide d'échelles standardisées: niveau de stigmatisation, bien-être mental, symptômes dépressifs, et enfin, la participation sociale. Les différences ont été testées à l'aide de tests de signification standardisés. RÉSULTATS: Après 3 mois d'intervention, le niveau moyen de stigmatisation a diminué (30,3 à 24, p<0 001) ; le niveau de bien-être mental a augmenté (0% à 13,3%, p<0 001) et la dépression modérée à sévère a diminué (88% à 47%, p<0 001). Aucun changement significatif n'a été observé en ce qui concerne les restrictions de participation (87% contre 92%, p=0 497). CONCLUSIONS: Le soutien psychologique par les pairs utilisant la ligne directrice BPS-N semble efficace pour réduire la stigmatisation et améliorer le bien-être mental. Toutefois, cette efficacité doit être confirmée par un essai contrôlé randomisé. ANTECEDENTES: Las personas con lepra y discapacidades relacionadas con la filariasis linfática (FL) sufren niveles más altos de malestar mental en comparación con la comunidad en general. Los servicios de salud mental no suelen estar disponibles a nivel periférico. Este estudio se llevó a cabo para proporcionar una prueba de concepto de que el Apoyo Psicológico Básico para personas afectadas por NTDs (BPS-N) puede ser dado por compañeros de apoyo (rotación de tareas) para reducir el estigma, mejorar el bienestar mental y la participación entre los clientes. MÉTODOS: El enfoque BPS-N se probó en un diseño cuasi-experimental utilizando métodos mixtos. Para proporcionar apoyo psicológico con el BPS-N, se seleccionaron y formaron compañeros de apoyo. Apoyaron a personas con lepra y discapacidades relacionadas con la FL. El estigma, el bienestar mental, la depresión y la participación se midieron antes y después de la intervención, mediante escalas estándar; las diferencias se comprobaron mediante pruebas estándar de significación. RESULTADOS: Después de 3 meses de intervención, el nivel medio de estigma disminuyó (30,3 a 24, p<0 001); el bienestar mental alto aumentó (0% a 13,3%, p<0 001) y la depresión moderada a grave disminuyó (88% a 47%, p<0 001). No se produjeron cambios significativos en las restricciones de participación (87% frente a 92%, p=0 497)). CONCLUSIONES: El apoyo psicológico entre iguales, utilizando la guía BPS-N, parece eficaz para reducir el estigma y mejorar el bienestar mental. Sin embargo, esto debe confirmarse mediante un ensayo controlado aleatorizado.

A global call for action to tackle skin-related neglected tropical diseases (skin NTDs) through integration: An ambitious step change.

On 8 June 2022, the World Health Organization (WHO) released pivotal guidance, "Ending the neglect to attain the Sustainable Development Goals: A strategic framework for integrated control and management of skin-related neglected tropical diseases." Skin-related neglected tropical diseases, or skin NTDs, comprise a group of NTDs that produce signs and symptoms on the skin and include at least 9 diseases or disease groups. Moving away from disease-specific approaches, it is anticipated that synergies will be identified and integrated building on this shared feature, where possible, to achieve a greater health impact. This paper intends to draw attention to the prospects created by this scheme. The framework is a key basis for a proposal produced by WHO dedicated to skin NTD integration and describes the practical opportunities for this evolving strategy. It underlines the wider health benefits that will follow, thus working towards Universal Health Coverage and skin health for all.

Identifying clusters of leprosy patients in India: A comparison of methods.

BACKGROUND: Preventive interventions with post-exposure prophylaxis (PEP) are needed in leprosy high-endemic areas to interrupt the transmission of Mycobacterium leprae. Program managers intend to use Geographic Information Systems (GIS) to target preventive interventions considering efficient use of public health resources. Statistical GIS analyses are commonly used to identify clusters of disease without accounting for the local context. Therefore, we propose a contextualized spatial approach that includes expert consultation to identify clusters and compare it with a standard statistical approach. METHODOLOGY/PRINCIPAL FINDINGS: We included all leprosy patients registered from 2014 to 2020 at the Health Centers in Fatehpur and Chandauli districts, Uttar Pradesh State, India (n = 3,855). Our contextualized spatial approach included expert consultation determining criteria and definition for the identification of clusters using Density Based Spatial Clustering Algorithm with Noise, followed by creating cluster maps considering natural boundaries and the local context. We compared this approach with the commonly used Anselin Local Moran's I statistic to identify high-risk villages. In the contextualized approach, 374 clusters were identified in Chandauli and 512 in Fatehpur. In total, 75% and 57% of all cases were captured by the identified clusters in Chandauli and Fatehpur, respectively. If 100 individuals per case were targeted for PEP, 33% and 11% of the total cluster population would receive PEP, respectively. In the statistical approach, more clusters in Chandauli and fewer clusters in Fatehpur (508 and 193) and lower proportions of cases in clusters (66% and 43%) were identified, and lower proportions of population targeted for PEP was calculated compared to the contextualized approach (11% and 11%). CONCLUSION: A contextualized spatial approach could identify clusters in high-endemic districts more precisely than a standard statistical approach. Therefore, it can be a useful alternative to detect preventive intervention targets in high-endemic areas.

Correction: The role of perceptions and knowledge of leprosy in the elimination of leprosy: A baseline study in Fatehpur district, northern India.

[This corrects the article DOI: 10.1371/journal.pntd.0007302.].

Erratum: Psychosocial burden of neglected tropical diseases in eastern Colombia: an explorative qualitative study in persons affected by leprosy, cutaneous leishmaniasis and Chagas disease - ERRATUM.

[This corrects the article DOI: 10.1017/gmh.2021.18.].

Changing perception and improving knowledge of leprosy: An intervention study in Uttar Pradesh, India.

INTRODUCTION: Since ancient times leprosy has had a negative perception, resulting in stigmatization. To improve the lives of persons affected by leprosy, these negative perceptions need to change. The aim of this study is to evaluate interventions to change perceptions and improve knowledge of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a pre-post intervention study in Fatehpur and Chandauli districts, Uttar Pradesh, India. Based on six steps of quality intervention development (6SQuID) two interventions were designed: (1) posters that provided information about leprosy and challenged misconceptions, and (2) meetings with persons affected by leprosy, community members and influential people in the community. The effect of the interventions was evaluated in a mixed-methods design; in-depth interviews, focus group discussions, and questionnaires containing a knowledge measure (KAP), two perception measures (EMIC-CSS, SDS) and an intervention evaluation tool. 1067 participants were included in Survey 1 and 843 in Survey 2. The interventions were effective in increasing knowledge of all participant groups, and in changing community and personal attitudes of close contacts and community members (changes of 19%, 24% and 13% on the maximum KAP, EMIC-CSS and SDS scores respectively, p<0.05). In Survey 1, 13% of participants had adequate knowledge of leprosy versus 53% in Survey 2. Responses showed stigmatizing community attitudes in 86% (Survey 1) and 61% (Survey 2) of participants and negative personal attitudes in 37% (Survey 1) and 19% (Survey 2). The number of posters seen was associated with KAP, EMIC-CSS and SDS scores in Survey 2 (p<0.001). In addition, during eight post-intervention focus group discussions and 48 interviews many participants indicated that the perception of leprosy in the community had changed. CONCLUSIONS/SIGNIFICANCE: Contextualized posters and community meetings were effective in changing the perception of leprosy and in increasing leprosy-related knowledge. We recommend studying the long-term effect of the interventions, also on behavior.

Psychosocial burden of neglected tropical diseases in eastern Colombia: an explorative qualitative study in persons affected by leprosy, cutaneous leishmaniasis and Chagas disease.

BACKGROUND: Leprosy, cutaneous leishmaniasis (CL) and Chagas disease (CD) are neglected tropical diseases (NTDs) with a high psychosocial burden in Norte de Santander and Arauca in Colombia. This study provides insights into affected persons' feelings, perceptions and experiences to better understand the nature of this burden. METHODS: In 2018, 34 leprosy, CD and CL patients participated in four focus groups discussing the influence of the disease on mental well-being, social participation and stigma. Additionally, 13 leprosy patients participated in semi-structured interviews to further explore the health-related stigma related to this disease. Audio recordings were transcribed verbatim, and open coding was used to identify the most relevant categories and themes. RESULTS: Persons suffering from CD reported that their mental distress was mainly caused by impairments and stress related to the progressive and incurable nature of the disease. Persons affected by CL perceived the treatment for the disease as having the most impact on their psychosocial well-being. Persons affected by leprosy reported suffering most from anticipated and experienced stigma. CONCLUSIONS: The findings indicate that these diseases are likely to impose a significant psychosocial burden on patients in the studied regions, even though these vary per condition. Consistent data collection on the psychosocial burden and the sharing of knowledge of effective interventions can contribute to the holistic approach needed to win the fight against NTDs.

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

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

Number of people requiring post-exposure prophylaxis to end leprosy: A modeling study.

BACKGROUND: Worldwide, around 210,000 new cases of leprosy are detected annually. To end leprosy, i.e. zero new leprosy cases, preventive interventions such as contact tracing and post-exposure prophylaxis (PEP) are required. This study aims to estimate the number of people requiring PEP to reduce leprosy new case detection (NCD) at national and global level by 50% and 90%. METHODOLOGY/PRINCIPAL FINDINGS: The individual-based model SIMCOLEP was fitted to seven leprosy settings defined by NCD and MB proportion. Using data of all 110 countries with known leprosy patients in 2016, we assigned each country to one of these settings. We predicted the impact of administering PEP to about 25 contacts of leprosy patients on the annual NCD for 25 years and estimated the number of contacts requiring PEP per country for each year. The NCD trends show an increase in NCD in the first year (i.e. backlog cases) followed by a significant decrease thereafter. A reduction of 50% and 90% of new cases would be achieved in most countries in 5 and 22 years if 20.6 and 40.2 million people are treated with PEP over that period, respectively. For India, Brazil, and Indonesia together, a total of 32.9 million people requiring PEP to achieve a 90% reduction in 22 years. CONCLUSION/SIGNIFICANCE: The leprosy problem is far greater than the 210,000 new cases reported annually. Our model estimates of the number of people requiring PEP to achieve significant reduction of new leprosy cases can be used by policymakers and program managers to develop long-term strategies to end leprosy.

Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme.

BACKGROUND: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. METHODS: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. FINDINGS: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. INTERPRETATION: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. FUNDING: Novartis Foundation.

The State of Affairs in Post-Exposure Leprosy Prevention: A Descriptive Meta-Analysis on Immuno- and Chemo-Prophylaxis.

OBJECTIVE: Annually, over 200,000 people are diagnosed with leprosy, also called Hansen's disease. This number has been relatively stable over the past years. Progress has been made in the fields of chemoprophylaxis and immunoprophylaxis to prevent leprosy, with a primary focus on close contacts of patients. In this descriptive meta-analysis, we summarize the evidence and identify knowledge gaps regarding post-exposure prophylaxis against leprosy. METHODS: A systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was conducted by searching the medical scientific databases Cochrane, Embase, Pubmed/MEDLINE, Research Gate, Scopus and Web of Science on Jan. 22, 2020, using a combination of synonyms for index terms in four languages: "leprosy" and "population" or "contacts" and "prevention" or "prophylaxis." Subsequently, Infolep.org and Google Scholar were searched and the "snowball method" was used to retrieve other potentially relevant literature. The found articles were screened for eligibility using predetermined inclusion and exclusion criteria. RESULTS: After deduplication, 1,515 articles were screened, and 125 articles were included in this descriptive meta-analysis. Immunoprophylaxis by bacillus Calmette-Guérin (BCG) vaccination is known to provide protection against leprosy. The protection it offers is higher in household contacts of leprosy patients compared with the general population and is seen to decline over time. Contact follow-up screening is important in the first period after BCG administration, as a substantial number of new leprosy patients presents three months post-vaccination. Evidence for the benefit of re-vaccination is conflicting. The World Health Organization (WHO) included BCG in its Guidelines for the Diagnosis, Treatment and Prevention of Leprosy by stating that BCG at birth should be maintained in at least all leprosy high-burden regions. Literature shows that several vaccination interventions with other immunoprophylactic agents demonstrate similar or slightly less efficacy in leprosy risk reduction compared with BCG. However, most of these studies do not exclusively focus on post-exposure prophylaxis. Two vaccines are considered future candidates for leprosy prophylaxis: Mycobacterium indicus pranii (MiP) and LepVax. For chemoprophylaxis, trials were performed with dapsone/acedapsone, rifampicin, and ROM, a combination of rifampicin, ofloxacin, and minocycline. Single-dose rifampicin is favored as post-exposure prophylaxis, abbreviated as SDR-PEP. It demonstrated a protective effect of 57% in the first two years after administration to contacts of leprosy patients. It is inexpensive, and adverse events are rare. The risk of SDR-PEP inducing rifampicin resistance is considered negligible, but continuous monitoring in accordance with WHO policies should be encouraged. The integration of contact screening and SDR-PEP administration into different leprosy control programs was found to be feasible and well accepted. Since 2018, SDR-PEP is included in the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. CONCLUSION: Progress has been made in the areas of chemoprophylaxis and immunoprophylaxis to prevent leprosy in contacts of patients. Investing in vaccine studies, like LepVax and MiP, and increasing harmonization between tuberculosis (TB) and leprosy research groups is important. SDR-PEP is promising as a chemoprophylactic agent, and further implementation should be promoted. More chemoprophylaxis research is needed on: enhanced medication regimens; interventions in varying (epidemiological) settings, including focal mass drug administration (fMDA); specific approaches per contact type; combinations with screening variations and field-friendly rapid tests, if available in the future; community and health staff education; ongoing antibiotic resistance surveillance; and administering chemoprophylaxis with SDR-PEP prior to BCG administration. Additionally, both leprosy prophylactic drug registration nationally and prophylactic drug availability globally at low or no cost are important for the implementation and further upscaling of preventive measures against leprosy, such as SDR-PEP and new vaccines.

Depression and mental wellbeing in people affected by leprosy in southern Nepal.

BACKGROUND: Leprosy, a leading cause of disability, remains endemic in southern Nepal. Alongside physical impairment and stigmatization, many people affected by leprosy suffer from mental health problems. OBJECTIVES: This study had two objectives: (a) Establishing a baseline level of mental wellbeing and depression among people affected by leprosy in southern Nepal, and (b) Examining factors that influence mental wellbeing and depression in this target group. METHODS: A cross-sectional survey was conducted using three interview-administered questionnaires measuring level of depression (PHQ-9), mental wellbeing status (WEMWBS) and level of stigma (5-QSI-AP). Random clustering sampling was used to include leprosy-affected people from Self Help Groups (SHGs) and the reference group was matched based on socio-demographic characteristics. All participants were adults with no additional major morbidities. A sample of 142 persons affected by leprosy and 54 community controls were included. RESULTS: People affected by leprosy participating in SHGs had a significantly lower level of mental wellbeing and higher level of depression than the general population. Both mental wellbeing and depression were influenced by gender and the level of stigma. In addition, the level of depression was associated with the disability grade of leprosy-affected people. CONCLUSION: Leprosy-affected people need mental health-care interventions at different organizational levels, with attention to identifying individuals at increased risk for mental health problems or with additional needs. These findings highlight the demand for further research on specific interventions to improve the mental health of leprosy-affected people.

Stigma, participation restriction and mental distress in patients affected by leprosy, cutaneous leishmaniasis and Chagas disease: a pilot study in two co-endemic regions of eastern Colombia.

BACKGROUND: Leprosy, cutaneous leishmaniasis (CL) and Chagas disease (CD) are neglected tropical diseases with a high psychosocial burden (PSB). These conditions are endemic in Norte de Santander and Arauca in Colombia, but data on the related PSB are scarce. Therefore, we assessed mental distress, participation restriction and stigma among CD, CL and leprosy patients. METHODS: In 2018, 305 leprosy, CD or CL patients were interviewed using a self-report questionnaire to assess mental distress, participation scale for participation restriction and explanatory model interview catalogue (EMIC) for stigma. Descriptive statistics and the significance of median score differences were compared. RESULTS: Fifty percent of CD patients and 49% of leprosy patients exhibited mental distress, percentages which were significantly higher than that of CL (26%). Twenty-seven percent of leprosy patients experienced participation restriction, which was lower for CL (6%) and CD (12%). Median EMIC scores were significantly higher for leprosy patients than for CD (27%) and CL (17%) patients. CONCLUSIONS: We found high levels of PSB among leprosy, CD and CL patients. Mental distress was highest among CD patients. Participation restriction and stigma were more prevalent in leprosy patients. Rural residence or lower educational status may impact PSB. Further investigation is needed to formulate evidence-based, holistic interventions.

Validation of a cross-NTD toolkit for assessment of NTD-related morbidity and disability. A cross-cultural qualitative validation of study instruments in Colombia.

BACKGROUND: Many neglected tropical diseases (NTDs) are not fatal, but they are disabling, disfiguring and stigmatizing. More accurate data on these aspects would benefit planning, monitoring and evaluation of interventions, as well as provision of appropriate services for the often life-long consequences. In 2015, a cross-NTD toolkit was developed, consisting of a variety of existing questionnaires to measure morbidity, disability and health-related quality of life. The toolkit covers the domains of the International Classification of Functioning, Disability and Health (ICF) framework. These tools have been developed in a source country, however, it was intended for the cross-NTD toolkit to be applicable across NTDs in many countries with different cultures and languages in order to generate universally comparative data. Therefore; the present study aimed to validate several tools of the toolkit among people affected by leprosy or leishmaniasis in the cultural settings of Cartagena and Cúcuta, Colombia. METHODOLOGY: This study aimed to validate the following tools among 55 participants between 18-85 years old, affected by leprosy and leishmaniasis: (I) Clinical Profile, (II) Self-Reporting Questionnaire (SRQ), (III) WHO Quality of Life assessment-abbreviated version (WHOQOL-BREF), and (IV) WHO Quality of Life assessment-Disability (WHOQOL-DIS). The tools were administered during face-to-face interviews and were followed by open questions about the respondents' thoughts on format of the tool and the understanding, relevance and acceptability of the items. The tools were validated using a qualitative method approach based on the framework for cultural equivalence, measured by the cultural, item, semantic and operational equivalences. RESULTS: The Clinical Profile was seen as acceptable and relevant, only the semantic equivalence was not as satisfying and needs a few adaptations. The SRQ was very well understood and shows to reach the equivalences for the population of Colombia without any additional changes. Several items of the WHOQOL-BREF and the WHOQOL-DIS were not well understood and changes are recommended due to semantic difficulties. Operational equivalence of both questionnaires was not as desired in relation to the used response scales. The participants shared that the tools are relevant and important for their particular situation. CONCLUSIONS/SIGNIFICANCE: The SRQ is found to be a valid tool for Colombia and can be included in the cross-NTD toolkit. The Clinical Profile, WHOQOL-BREF & WHOQOL-DIS need changes and retesting among Colombian people affected by an NTD. The toolkit as a whole is seen as useful to show the effects leprosy and leishmaniasis have on the participants. This cultural validation will contribute to a universally applicable cross-NTD toolkit.