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.

Evaluating active leprosy case identification methods in six districts of Nepal.

BACKGROUND: Nepal has achieved and sustained the elimination of leprosy as a public health problem since 2009, but 17 districts and 3 provinces with 41% (10,907,128) of Nepal's population have yet to eliminate the disease. Pediatric cases and grade-2 disabilities (G2D) indicate recent transmission and late diagnosis, respectively, which necessitate active and early case detection. This operational research was performed to identify approaches best suited for early case detection, determine community-based leprosy epidemiology, and identify hidden leprosy cases early and respond with prompt treatment. METHODS: Active case detection was undertaken in two Nepali provinces with the greatest burden of leprosy, Madhesh Province (40% national cases) and Lumbini Province (18%) and at-risk prison populations in Madhesh, Lumbini and Bagmati provinces. Case detection was performed by (1) house-to-house visits among vulnerable populations (n = 26,469); (2) contact examination and tracing (n = 7608); in Madhesh and Lumbini Provinces and, (3) screening prison populations (n = 4428) in Madhesh, Lumbini and Bagmati Provinces of Nepal. Per case direct medical and non-medical costs for each approach were calculated. RESULTS: New case detection rates were highest for contact tracing (250), followed by house-to-house visits (102) and prison screening (45) per 100,000 population screened. However, the cost per case identified was cheapest for house-to-house visits [Nepalese rupee (NPR) 76,500/case], followed by contact tracing (NPR 90,286/case) and prison screening (NPR 298,300/case). House-to-house and contact tracing case paucibacillary/multibacillary (PB:MB) ratios were 59:41 and 68:32; female/male ratios 63:37 and 57:43; pediatric cases 11% in both approaches; and grade-2 disabilities (G2D) 11% and 5%, respectively. Developing leprosy was not significantly different among household and neighbor contacts [odds ratios (OR) = 1.4, 95% confidence interval (CI): 0.24-5.85] and for contacts of MB versus PB cases (OR = 0.7, 95% CI 0.26-2.0). Attack rates were not significantly different among household contacts of MB cases (0.32%, 95% CI 0.07-0.94%) and PB cases (0.13%, 95% CI 0.03-0.73) (χ2 = 0.07, df = 1, P = 0.9) and neighbor contacts of MB cases (0.23%, 0.1-0.46) and PB cases (0.48%, 0.19-0.98) (χ2 = 0.8, df = 1, P = 0.7). BCG vaccination with scar presence had a significant protective effect against leprosy (OR = 0.42, 0.22-0.81). CONCLUSIONS: The most effective case identification approach here is contact tracing, followed by house-to-house visits in vulnerable populations and screening in prisons, although house-to-house visits are cheaper. The findings suggest that hidden cases, recent transmission, and late diagnosis in the community exist and highlight the importance of early case detection.

Epidemiology and grade 2 disability of leprosy among migrant and resident patients in Guangdong: an unignorable continued transmission of leprosy.

Introduction: Leprosy remains a major public health concern worldwide and one of the leading causes of disability. New cases of leprosy with grade 2 disability (G2D) often reflect delayed detection due to the limited capacity of the health system to recognize leprosy early. This study aimed to describe the epidemiology and G2D of leprosy among migrant and resident patients with leprosy in Guangdong province, China. Methods: Data on newly diagnosed cases of leprosy were collected from the leprosy management information system in China. Descriptive statistical analysis was used to describe the status of G2D. Joinpoint regression model and logistic regression were performed to analyze the temporal trends and influencing factors for G2D. Results: The G2D rate among migrant, resident, and total patients with leprosy was 17.5%, 18.7%, and 18.4%, respectively. The total G2D rate increased significantly from 18.0% in 2001 to 25.7% in 2021 (average annual per cent change: 2.5%). Multivariate analysis revealed that factors that negatively influence G2D between migrant and resident patients included delayed discovery time (migrants: OR = 2.57; residents: OR = 4.99) and nerve damage when diagnosed (migrants: OR = 9.40; residents: OR = 21.28). Discussion: Our findings indicate that the targeted intervention measures implemented by our health system are urgently needed to improve the current situation, such as programs to promote early detection, strengthen awareness and skills of healthcare workers, and rehabilitation for disabled patients to improve their quality of life.

Systemic lupus erythematosus mimicking leprosy: A challenge to early diagnosis.

We describe a case of a male patient with systemic lupus erythematosus (SLE) and lupus nephritis. A patient who was initially diagnosed with multibacillary leprosy, an infectious disease, with clinical symptoms for two years. However, after hospitalization and investigation, his diagnosis was revoked and replaced with SLE. The aim of this study is to emphasize the importance of knowing the most important and significant clinical changes in SLE and thus allowing an accurate diagnosis, preventing disease progression with target organ involvement, and allowing better clinical management.

Negligência no diagnóstico precoce de hanseníase na atenção primária: um relato de caso / Negligence in the early diagnosis of leprosy in primary care: a case report

A hanseníase é uma doença infecciosa, transmissível, de caráter crônico, com potencial grau de incapacidade, que ainda persiste como problema de saúde pública no Brasil. A demora e a falta de conhecimento técnico para realizar o diagnóstico resulta em inúmeros prejuízos aos pacientes acometidos pela doença, sendo que, a prevenção das incapacidades está relacionada diretamente com o diagnóstico precoce da doença. Com a finalidade de evitar a negligência diagnóstica e o desenvolvimento de incapacidades físicas, ressaltamos a importância do conhecimento técnico sobre o diagnóstico e o manejo da hanseníase por profissionais da saúde em qualquer nível de atenção à saúde ou especialidade.

Hansen is an infectious disease, transmissible, of a chronic nature, with serious potential for disability, which still persists as a public health problem in Brazil. The delay and the lack of technical knowledge to carry out the diagnosis with numerous prejudices to the patients affected by the disease, since the prevention of disabilities is directly related to the early diagnosis of the disease. In order to avoid diagnostic negligence and the development of physical disabilities, we highlight the importance of technical knowledge about the diagnosis and management of training by health professionals at any level of health care or special care.

High-resolution ultrasonography for early diagnosis of neural impairment in seropositive leprosy household contacts.

Leprosy household contacts (HC) represent a high-risk group for the development of the disease. Anti-PGL-I IgM seropositivity also increases the risk of illness. Despite significant advances in leprosy control, it remains a public health problem; and early diagnosis of this peripheral neuropathy represents one of the main goals of leprosy programs. The present study was performed to identify neural impairment in leprosy HC by analyzing differences in high-resolution ultrasonographic (US) measurements of peripheral nerves between leprosy HC and healthy volunteers (HV). Seventy-nine seropositive household contacts (SPHC) and 30 seronegative household contacts (SNHC) underwent dermato-neurological examination and molecular analysis, followed by high-resolution US evaluation of cross-sectional areas (CSAs) of the median, ulnar, common fibular and tibial nerves. In addition, 53 HV underwent similar US measurements. The US evaluation detected neural thickening in 26.5% (13/49) of the SPHC and only in 3.3% (1/30) among the SNHC (p = 0.0038). The CSA values of the common fibular and tibial nerves were significantly higher in SPHC. This group also had significantly greater asymmetry in the common fibular and tibial nerves (proximal to the tunnel). SPHC presented a 10.5-fold higher chance of neural impairment (p = 0.0311). On the contrary, the presence of at least one scar from the BCG vaccine conferred 5.2-fold greater protection against neural involvement detected by US (p = 0.0184). Our findings demonstrated a higher prevalence of neural thickening in SPHC and support the role of high-resolution US in the early diagnosis of leprosy neuropathy. The combination of positive anti-PGL-I serology and absence of a BCG scar can identify individuals with greater chances of developing leprosy neuropathy, who should be referred for US examination, reinforcing the importance of including serological and imaging methods in the epidemiological surveillance of leprosy HC.

Early detection of sensory nerve function impairment in leprosy under field conditions.

AIM: To assess the fine sensation of palms and soles in field conditions, to enable early detection of nerve function impairment before the loss of protective sensation, thus preventing the development of disability. METHODS: A cross-sectional descriptive study was conducted at seven tertiary referral hospitals located in different states in India. This study included all newly diagnosed patients affected by leprosy, who were registered during the period between March 2011 and April 2012. A detailed history was taken along with charting and voluntary muscle testing /sensory testing (VMT/ST) for the diagnosed patients. The sensation was measured using 0.2 gm Semmes-Weinstein filaments for palms and 4 gm for soles first, followed by 2 gm Semmes-Weinstein filaments for palms and 10 gm for soles. RESULTS: Among the 374 patients, 106 were identified with sensory nerve function impairment. Of the 106 patients, 84 were identified with absence of both fine and protective sensation and 22 patients had a loss of fine touch sensation with protective sensation intact. LIMITATION: This study was conducted only among patients who were newly diagnosed with leprosy. Hence, future longitudinal studies in a larger population will add more validity to the study. CONCLUSION: The patients who had loss of fine sensation would have been missed by the normal leprosy programme protocol which uses 2 gm and 10 gm filaments for testing sensory loss before initiating steroid therapy. Further research is needed to determine whether testing for fine sensation with 0.2 gm Semmes-Weinstein filaments for palms and 4 gm for soles can be introduced at all specialized leprosy centres to detect nerve function impairment at an earlier stage followed by steroid therapy.

Suspicious symptom monitoring for leprosy: an optimal practice for early detection under a low endemic situation in Zhejiang Province, China.

BACKGROUND: Leprosy is a chronic infectious disease that causes disabilities and deformities. Early detection is a major strategy for leprosy control. This study reported a new practice of suspicious symptom monitoring for early detection of leprosy. METHODS: A descriptive and comparative analysis between a non-strategy group of pre-implementation of suspicious symptom monitoring in 2005-2011 and a strategy group of strategy implementation in 2012-2018 was conducted through indicators of the number of times of misdiagnoses, delayed period, proportion of early detected cases, and proportion of disabilities. RESULT: Compared with the non-strategy group in 2005-2011, the median number of times of misdiagnoses was decreased from two times to zero times (z = 4.387, P < 0.001), and the median delayed period of newly detected cases were shortened from 24 months to 13 months (z = 2.381, P < 0.001), the proportion of early detected cases was increased from 43.7% to 75.2% (χ2 = 29.464, P < 0.001), the proportion of grade 2 disabilities was decreased from 28.6% in the highest year of 2005 to 4.0% in the lowest year of 2014, and the average proportion of disabilities was decreased from 33.5% to 17.6% (χ2 = 9.421, P = 0.002) in the strategy group in 2012-2018, respectively. CONCLUSION: Suspicious symptom monitoring promoted early detection of cases by reducing the number of times misdiagnosis of leprosy patients, shortening the delayed period, increasing the proportion of early detection, and decreasing the proportion of disabilities. It is an important and recommendable public health strategy for leprosy prevention and control in a low epidemic condition.

Role of diffusion tensor imaging in the evaluation of ulnar nerve involvement in leprosy.

OBJECTIVE: Early detection of peripheral neuropathy is extremely important as leprosy is one of the treatable causes of peripheral neuropathy. The study was undertaken to assess the role of diffusion tensor imaging (DTI) in ulnar neuropathy in leprosy patients. METHODS: This was a case-control study including 38 patients (72 nerves) and 5 controls (10 nerves) done between January 2017 and June 2019. Skin biopsy proven cases of leprosy, having symptoms of ulnar neuropathy (proven on nerve conduction study) were included. MRI was performed on a 3 T MR system. Mean cross-sectional area, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of ulnar nerve at cubital tunnel were calculated. Additional ancillary findings and appearance of base sequences were evaluated. RESULTS: Ulnar nerve showed thickening with altered T2W signal in all the affected nerves, having an average cross-sectional area of 0.26 cm2. Low FA with mean of 0.397 ± 0.19 and high ADC with mean of 1.28 ± 0.427 x 10 -3 mm2/s of ulnar nerve in retrocondylar groove was obtained. In the control group, mean cross-sectional area was 0.71cm2 with mean FA and ADC of 0.53 ± 0.088 and 1.03 ± 0.24 x 10 -3 mm2/s respectively. Statistically no significant difference was seen in diseased and control group. Cut-off to detect neuropathy for FA and ADC is 0.4835 and 1.1020 × 10 -3 mm2/s respectively. CONCLUSION: DTI though is challenging in peripheral nerves, however, is proving to be a powerful complementary tool for assessment of peripheral neuropathy. Our study validates its utility in infective neuropathies. ADVANCES IN KNOWLEDGE: 1. DTI is a potential complementary tool for detection of peripheral neuropathies and can be incorporated in standard MR neurography protocol.2. In leprosy-related ulnar neuropathy, altered signal intensity with thickening or abscess of the nerve is appreciated along with locoregional nodes and secondary denervation changes along with reduction of FA and rise in ADC value.3. Best cut-offs obtained in our study for FA and ADC are 0.4835 and 1.1020 × 10 -3 mm2/s respectively.

Revisão sistemática: acurácia dos testes laboratoriais complementares para o diagnóstico precoce de hanseníase / Scope review: therapeutic alternatives for the treatment of leprosy in drug-resistant patients

Realizar revisão sistemática avaliando a acurácia de exames laboratoriais complementares para o diagnóstico precoce da hanseníase. Foram incluídos estudos de acurácia que avaliaram exames laboratoriais complementares para diagnóstico precoce de casos de hanseníase. Não houve restrição de língua e foram aplicados os seguintes critérios de inclusão: ƒ Estudos transversais ou caso-controle de acurácia. ƒ Comparação a padrão-ouro: diagnóstico clínico e/ou baciloscopia positiva para M. leprae. ƒ Teste-índice: exames laboratoriais com mais de dois artigos de acurácia publicados. ƒ Artigos com dados suficientes para extração numérica de verdadeiro-positivos (VP), falso-negativos (FN), verdadeiro-negativos (VN) e falso-positivos (FP). ƒ Estudos que forneçam dados separados de forma multibacilar e paucibacilar.

Hanseníase em gêmeos de 3 anos em Mato Grosso, Brasil: a importância da baciloscopia no diagnóstico / Leprosy in 3-year-old twin children in Mato Grosso, Brazil: the importance of bacilloscopy in the diagnosis

Introdução: o diagnóstico clínico da hanseníase em crianças é particularmente difícil. Relato de Caso: crianças gêmeas bivitelinas, com três anos de idade, eram contactantes de pai com hanseníase Virchowiana. Os dois pacientes têm lesões cutâneas bem definidas e irregulares, anteriormente tratadas como micoses e uma cicatriz de BCG. Foram confirmados positivos para Mycobacterium por análise histopatológica da pele. Discussão: especialmente, com menos de cinco anos, os diagnósticos de hanseníase são raros e difíceis porque simulam outras doenças. Esses diagnósticos são alarmes epidemiológicos para áreas endêmicas e mostram a importância dos sintomas em crianças e o rastreamento nos contactantes dos pacientes.

Introduction: the clinical diagnosis of leprosy in children is particularly difficult. Case Report: fraternal twins, three years old, were in contact with a father with Virchowian leprosy. Both patients have well-defined and irregular skin lesions previously treated as mycoses and a BCG scar. They were confirmed positive for Mycobacterium by histopathological analysis of the skin. Discussion:especially, with less than five years, leprosy diagnoses are rare and difficult because they simulate other diseases. These diagnoses are epidemiological alarms for endemic areas and show the importance of symptoms in children and tracking of patients' contacts.

O uso do teste Ml flow entre casos de hanseníase recém-diagnosticados e contatos intradomiciliares / The use of the Ml flow test between newly diagnostic leprosy cases and in-home contacts / El uso de la prueba de flujo Ml entre casos de lepra recientemente diagnósticos y contactos en el hogar

Objetivo: identificar o resultado de teste Ml Flow entre casos de hanseníase recém-diagnosticados e contatos intradomiciliares.Métodos: estudo transversal, descritivo, com abordagem quantitativa realizado no município de Caxias, Maranhão, Brasil, onde recrutou-se casos recém-diagnosticados, virgens de tratamento e contatos intradomiciliares. Resultados: recrutou-se 324 contatos de casos de hanseníase, no período de 2015 a 2018. Nos casos recém-diagnosticados o teste Ml Flow foi negativo em 87,5% (7/8) dos paucibacilares e positivo em 70% (21/30) dos multibacilares, ambos concordantes com a baciloscopia do raspado intradérmico. Identificou-se 30 (9%) contatos intradomiciliares com alto risco de adoecer. Conclusão: o teste Ml Flow constitui-se uma ferramenta útil para correta detecção de contatos com alta chance de adoecer da hanseníase, bem como para classificar corretamente os casos novos

Objective: to identify the Ml Flow test result between newly diagnosed leprosy cases and household contacts. Methods: cross-sectional, descriptive study with a quantitative approach carried out in the city of Caxias, Maranhão, Brazil, where newly diagnosed cases, treatment virgins and intra-household contacts were recruited. Results: 324 contacts of leprosy cases were recruited from 2015 to 2018. In newly diagnosed cases, the Ml Flow test was negative in 87.5% (7/8) of paucibacillary patients and positive in 70% (21/ 30) of the multibacillary, both in agreement with the bacilloscopy of the intradermal smear. Thirty (9%) household contacts with high risk of illness were identified. Conclusion: the Ml Flow test is a useful tool for the correct detection of contacts with a high chance of getting sick from leprosy, as well as for correctly classifying new cases

Objetivo: identificar el resultado de la prueba Ml Flow entre casos de lepra recién diagnosticados y contactos domésticos. Métodos: estudio descriptivo transversal con abordaje cuantitativo realizado en la ciudad de Caxias, Maranhão, Brasil, donde se reclutaron casos recién diagnosticados, vírgenes en tratamiento y contactos intrafamiliares. Resultados: se reclutaron 324 contactos de casos de lepra entre 2015 y 2018. En los casos recién diagnosticados, la prueba Ml Flow fue negativa en el 87,5% (7/8) de los pacientes paucibacilares y positiva en el 70% (21/30) de los multibacilares, ambos de acuerdo con la baciloscopia del frotis intradérmico. Identificamos 30 (9%) contactos dentro del hogar con alto riesgo de enfermarse. Conclusión: la prueba Ml Flow es una herramienta útil para la correcta detección de contactos con alta probabilidad de enfermarse de lepra, así como para clasificar correctamente nuevos casos

A comparison of three types of targeted, community-based methods aimed at promoting early detection of new leprosy cases in rural parts of three endemic states in India.

BACKGROUND: India achieved elimination of leprosy nationally in 2005, but since then the number of patients with grade 2 disability at diagnosis increased steadily indicating delay in diagnosis. Therefore, there was a need for public health interventions which can increase case finding in their earlier stage. The objective of this study is to compare the effectiveness of three such community-based interventions; 1) Enhancement of community awareness on leprosy; 2) Education and motivation of "Index" leprosy cases; and 3) Involvement of Non-Formal Health Practitioners (NFHPs) to promote early detection of new cases of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: Three community-based interventions were implemented between April 2016 and March 2018, embedded within the National Leprosy Eradication Program (NLEP) of India. Interventions were 1) increasing awareness through involvement of Gram Panchayat (local government) in the community regarding early signs of leprosy (Awareness), 2) providing health education and motivating newly diagnosed leprosy patients to bring suspects from their contacts (Index) and 3) training local non-formal health practitioners (NFHP). Each intervention was implemented in a group of ten blocks (sub-division of district) with an additional ten blocks as control (with no intervention). The main outcomes were number of new cases detected and number of grade 2 disability among them. They were obtained from the routine NLEP information system and compared between these interventions. On an average, there was an addition of 1.98 new cases in Awareness blocks, 1.13 in NFHP blocks and 1.16 cases in Index intervention blocks per month per block after adjusting for changes in control blocks during the same period. In terms of ratio, there was a 61%, 40% and 41% increase in case notification in awareness, Index and NFHP intervention, respectively. Overall, the percentage of grade 2 disability across intervention blocks declined. CONCLUSION: The Awareness intervention appears to be more effective in detection of new cases, compared to Index case motivation and sensitization of NFHPs. However, it is important to stress that while selecting strategies to increase early diagnosis it is important to determine, which is the most appropriate for each context or area and must be decided depending on the local context.

Hanseníase: Endemia Oculta na Floresta Amazônica

Acompanhe neste documentário uma das viagens de especialistas ao interior do Estado do Pará em uma região isolada da Floresta Amazônica, acessível apenas de barco ou avião. Na viagem apresentada neste vídeo, acompanhamos o grupo de especialistas/pesquisadores na busca ativa de casos de Hanseníase no município de Breves.

Temporal-spatial distribution characteristics of leprosy: A new challenge for leprosy prevention and control in Zhejiang, China.

BACKGROUND: After the elimination of leprosy in 1995, there were 10-30 newly detected leprosy cases every year in Zhejiang Province, and the epidemiological characteristics of the newly detected leprosy cases have changed. While most of the newly detected cases came from other provinces in China, not Zhejiang, it brought a new challenge for leprosy prevention and control in post- elimination era in Zhejiang, China. This study was aimed to understand the temporal-spatial distribution characteristics of newly detected leprosy cases, and provide the scientific rationales for the development of leprosy control strategy. METHODS: Data on the demographic of Zhejiang Province from 2011 to 2019 were obtained from the China Information System for Disease Control and Prevention, and the epidemiological data on leprosy cases newly detected in Zhejiang Province from 2011 to 2019 were obtained from the LEPROSY MANAGEMANT INFORMATION SYSTEM IN CHINA (LEPMIS), and temporal-spatial distributions were described. The geographic information system software-ArcGIS 10.4 was used to draw the statistical maps, and Geoda 1.14.0 was used for local spatial autocorrelation analysis (local Getis coefficient method). Ridley-Jopling classification was used to classify the clinical types into I, TT, BT, BB, BL or LL. Two-group classification system developed by the World Health Organization (WHO) was used and cases were classified into multibacillary (MB) type or paucibacillary (PB) type. RESULTS: A total of 167 leprosy cases were reported in Zhejiang Province during 2011-2019, including 107 cases in males and 60 in females. The mean age at diagnosis was 37.99±14.81 years, and 94.01% of the cases were detected through the examination at skin-clinics. The number of workers, MB cases, G2D cases were 81 (48.50%), 159 (94.01%), 24 (14.37%) respectively, and the rate of early detection increased from 45.16% in 2011 to 90.91% in 2019. Leprosy cases were reported in all the prefectures of Zhejiang except Zhoushan City. The cases in local population accounted for 23.35% (39 cases), and the cases in floating population (especially coming from high epidemic provinces in China) accounted for 76.65% (128 cases). The annual number of newly detected cases showed a decreasing trend, from 31 cases in 2011 to 11 in 2019. Time of the floating population living in Zhejiang Province ranged from several months to more than 10 years. The annual proportion of new cases with G2D declined from 22.58% in 2011 to 9.09% in 2019. The results of local indicators of autocorrelation (LISA) analysis showed that the high-high areas were mainly concentrated in the middle and northeast of Zhejiang Province, while the low-low areas were in the east and southwest. CONCLUSION: A few scattered cases still can be seen in post-elimination era, and there was a spatial clustering of the newly detected leprosy cases in Zhejiang Province. Most of the cases in Zhejiang Province were from other high epidemic provinces in China, which brought a new challenge for leprosy control and prevention in post- elimination era in Zhejiang, and it is also necessary to strengthen the early detection and standard management of the leprosy cases in floating population in Zhejiang.

Transcriptomic Analysis of Mycobacterium leprae-Stimulated Response in Peripheral Blood Mononuclear Cells Reveal Potential Biomarkers for Early Diagnosis of Leprosy.

We aimed to identify an unique host transcriptional signature in peripheral blood mononuclear cells (PBMCs) in response to Mycobacterium leprae antigens to distinguish between patients with leprosy and non-leprosy controls for early diagnosis of the disease. Sixteen individuals were enrolled in the discovery cohort [eight patients with leprosy, comprising four multibacillary (MB) and four paucibacillary (PB); and eight non-leprosy controls, comprising four healthy house contacts (HHCs) and four endemic controls (ECs)]. The differences in the transcriptome response of PBMCs to M. leprae sonicate antigen were evaluated between leprosy patients and non-leprosy controls, and 12 differentially expressed genes (CCL2/MCP-1, IL-8, JAKM, ATP, ND1, SERP, FLJ10489, LINC00659, LOC34487, LOC101928143, MIR22, and NCF1C) were identified. The accuracy of the 12 differentially expressed genes was further validated for the diagnosis of leprosy using real-time quantitative PCR in 82 individuals (13 MB, 10 PB, 37 HHCs, and 22 ECs) in the validation cohort. We found that a 5 gene signature set IL-8, CCL2/MCP-1, SERP, LINC00659 and FLJ10489 had a suitable performance in discriminating leprosy from ECs. In addition, elevated expression of IL-8, CCL2/MCP-1, SERP and LINC00659 was associated with MB diagnosis compared with ECs, whereas increased expression of IL-8, CCL2/MCP-1, SERP and FLJ10489 was found to be useful biomarkers for PB diagnosis from ECs. Moreover, we found decreased expression of NCF1C among leprosy patients could distinguish leprosy from HHCs, whereas higher expression of CCL2 among MB than PB could distinguish different leprosy patients. In conclusion, among the 12 candidate host genes identified, a three gene signature IL-8, CCL2/MCP-1, and SERP showed the best performance in distinguishing leprosy patients from healthy controls. These findings may have implications for developing a rapid blood-based test for early diagnosis of leprosy.

Peripheral nerve biopsy: a tool still needed in the early diagnosis of neural leprosy?

BACKGROUND: The early recognition of neural impairment in leprosy, especially in primary neural forms, represents a challenge in clinical practice and a peripheral nerve biopsy may be required for diagnostic confirmation. This study aims to characterize the epidemiological, clinical, electroneuromyographic, laboratory and histopathological aspects of patients undergoing peripheral nerve biopsy during investigation of primary neural cases in leprosy. METHODS: A total of 104 patients with peripheral neuropathy who were referred to a national reference centre for leprosy were biopsied from 2014 to 2018. All cases underwent clinical, laboratory, histopathological and electroneuromyographic evaluations. RESULTS: Of 104 biopsied patients, leprosy was confirmed in 89.4% (93/104). The biopsied nerves were the ulnar (67.8% [63/93]), superficial fibular (21.5% [20/93]), sural (8.6% [8/93]), radial (1.1% [1/93]) and deep fibular (1.1% [1/93]). Twenty-nine percent (27/93) presented histopathological abnormalities and 4.4% (4/93) presented acid-fast bacilli. Nerve and superjacent skin quantitative polymerase chain reaction were positive in 49.5% (46/93) and 24.8% (23/93) of cases, respectively. Patients with multiple mononeuropathy had a higher frequency of histopathological abnormalities (p=0.0077). CONCLUSIONS: This study reinforces peripheral nerve biopsy's role as an important tool in the investigation of primary neural cases, contributing to the early diagnosis and also reducing diagnostic errors and the need for empirical treatment.

Nutritional status and morbidity profile of children with leprosy contact in a rural community.

An observational pilot study was conducted to assess the nutritional status and morbidity profile of childhood contacts of leprosy in an endemic area (Chengalpattu) in India. A total of 70 such children were included in the study. Sociodemographic data were collected using a one-to-one interview method and the children were evaluated by dermatologists qualified in paediatric leprosy. The obtained data were computed. Three children were diagnosed to have leprosy through this study. Nutritional status assessment in these children demonstrated malnutrition, a common finding. Regular contact screening of children in endemic areas for early case detection, disability prevention and thereby prevention of community transmission is mandatory. Further research is needed concerning the role of malnutrition in children and its relation to morbidity in leprosy. The closeness and duration of contact of leprosy is also an important risk factor. Effective strategies to diagnose subclinical infection are needed.

Barreras y facilitadores relacionados con el diagnóstico de la lepra en Costa Rica / Barriers and facilitators related to leprosy detection in Costa Rica

Resumen Objetivo: Analizar barreras y facilitadores relacionados con el diagnóstico de la lepra en Costa Rica, desde la perspectiva de la persona con la enfermedad y en el contexto de la vida cotidiana. Métodos: Se llevó a cabo un estudio cualitativo de carácter exploratorio a partir de 25 entrevistas semiestructuradas, a personas con lepra o con antecedente de haberla padecido, de entre 23 y 88 años, atendidos en el sistema de salud público costarricense. A partir del análisis de los datos cualitativos, las barreras y facilitadores se agruparon en factores personales, culturales y la oferta de los servicios de salud. Resultados: En relación con los factores personales, la mayoría de los participantes reportó no poseer conocimiento ni conciencia previa a la enfermedad. El temor a ser estigmatizado, la sintomatología intermitente, sentirse bien, compromisos laborales y familiares, fueron percibidos como barreras. Entre los factores culturales, algunas creencias religiosas fueron percibidas como barreras, y la historia familiar de lepra como facilitador en términos de la búsqueda de atención y diagnóstico. Con respecto a los servicios de salud, el acceso oportuno a citas con personal de salud informado, la telemedicina y médicos de la familia, fueron citados como facilitadores. Conclusiones: Las principales barreras y facilitadores descritos en los resultados del estudio deben ser tomados en cuenta a fin de contribuir a la detección y tratamiento oportuno de la lepra, para curar la enfermedad, evitar la discapacidad y eliminar la transmisión.

Abstract Objective: To analyze barriers and facilitators related to the diagnosis of leprosy in Costa Rica from the perspective of the person with the disease and in the context of everyday life. Methods: A qualitative exploratory study was carried out from 25 semi-structured interviews, with people with leprosy or with a history of having it, aged between 23 - 88 years, treated in the Costa Rican public health system. From the analysis of the qualitative data, the barriers and facilitators were classified into personal, cultural factors and the offer of health services. Results: In relation to personal factors, most of the participants reported having no knowledge or awareness prior to the disease. Fear of being stigmatized, intermittent symptoms, feeling good, work and family commitments were perceived as barriers. Among the cultural factors, some religious beliefs were perceived as barriers and the family history of leprosy as a facilitator in terms of seeking care and diagnosis. With respect to health services, timely access to appointments with informed health personnel, telemedicine and family doctors were cited as facilitators. Conclusions: The main barriers and facilitators described in the results of the study should be considered in order to contribute to the detection and timely treatment of leprosy to cure the disease avoid disability and eliminate transmission.