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.

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.

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.

Neural leprosy investigation using electroneuromyography and the ML Flow rapid test: a case report.

Neural leprosy, which is characterized by nerve involvement without visible skin lesions, presents a diagnostic challenge. This case report examined the significance of diverse diagnostic modalities in the identification of pure neural leprosy. A 28-year-old patient with symptoms of edema, pain, paresthesia, and diminished sensitivity in the lower limbs underwent various tests. A stilt skin smear yielded negative results on bacilloscopy, whereas a Fast ML Flow leprosy test and electroneuromyography supported the diagnosis. This discussion highlights the importance of accessible methods for early investigation. This study emphasizes the multidisciplinary approach and value of the Fast ML Flow leprosy test and electroneuromyography for diagnosing neural leprosy.

Leprosy mimicking autoimmune diseases: a case series.

OBJECTIVES: Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Less frequently, there is involvement of the musculoskeletal system, and occurrence of systemic manifestation with non-specific symptoms such as fever, fatigue and myalgia. Therefore, leprosy can often mimic autoimmune diseases such as arthritis, vasculitis, or collagenosis and be mis-diagnosed. METHODS: This study describes a series of cases of leprosy mimicking autoimmune diseases in patients treated in the Rheumatology Department of our centre in the period 2019 to 2023. All patients were investigated regarding leprosy criteria and had clinical evaluation, serum markers, and histopathological analyses recorded. The diagnosis of leprosy was confirmed using skin biopsy followed by testing for acid-fast bacillus (AFB) or smear microscopy. RESULTS: Six patients who were initially investigated for autoimmune diseases were identified as diagnosed as leprosy cases, fulfilling both clinical and histopathologic criteria, two of whom presented with symptoms of polyarthritis with an inflammatory characteristic, two diffuse erythematous-violaceous lesions, three recurrent fever, three arthralgia, and one Raynaud's phenomenon, which are all characteristics present most frequently in rheumatologic diseases. CONCLUSIONS: We must consider the bacillary infection as a differential diagnosis of autoimmune diseases. Histopathological analysis is an important tool and the gold standard for diagnostic confirmation.

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.

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.

A cost-effectiveness analysis of a novel algorithm to sequentially diagnose leprosy based on manufactured tests under the SUS perspective.

Brazil has the second largest number of leprosy cases (a disease with a significant burden) in the world. Despite global and local efforts to eliminate this public health problem, inadequate or late diagnosis contribute to perpetuate its transmission, especially among household contacts. Tests such as the rapid IgM antibody detection (RT) and real-time polymerase chain reaction (RT-PCR) were developed to overcome the challenges of early diagnosis of leprosy. This study aimed to analyze the cost-effectiveness of a new diagnostic algorithm recommended by the Brazilian government to diagnose leprosy in household contacts of confirmed leprosy cases, which includes the RT and RT-PCR tests. A decision tree model was constructed and the perspective of the Brazilian Unified National Health System (SUS) and a 1-year time horizon were adopted. Only direct medical costs related to diagnostic tests were included. Effectiveness was measured as the number of avoided undiagnosed leprosy cases. Different scenarios were analyzed. The sequential use of RT, slit-skin smear (SSS) microscopy, and RT-PCR as recommended by the Brazilian Ministry of Health was compared to a base case (isolated SSS microscopy), yielding an incremental cost-effectiveness ratio of USD 616.46 per avoided undiagnosed leprosy case. Univariate sensitivity analysis showed that the prevalence of leprosy among household contacts was the variable that influenced the model the most. This is the first economic model to analyze a diagnostic algorithm of leprosy. Results may aid managers to define policies and strategies to eradicate leprosy in Brazil.

Factors associated with delayed diagnosis of leprosy in an endemic area in Northeastern Brazil: a cross-sectional study.

This study aimed to investigate the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy in an endemic area in the Northeastern Brazil. This is a cross-sectional study of 120 individuals with leprosy. Demographic and clinical data and information on the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy were obtained. Delayed diagnosis in months was estimated for each participant by interviews. A multivariate Poisson's regression analysis was performed between the outcome and the independent variables. The median delay in the diagnosis of leprosy was 10.5 (4.0-24.0) months. Approximately 12.6% of participants had grade 2 disability (G2D) at the time of diagnosis. In the multivariate Poisson regression analysis, males, older age, low schooling level, residing in urban areas, multibacellar or tuberculoid leprosy, not seeking healthcare immediately after symptom onset, suspected leprosy, excessive referrals, and the need for three or more consultations to confirm the diagnosis were associated with longer diagnostic delay. This study found a significant delay in the diagnosis of leprosy in Arapiraca, Northeastern Brazil, which may explain the continuously high rate of G2D among new cases. Factors related to the individual and the health system were associated with longer diagnostic delay. Interventions to raise awareness of the disease among the general population and strengthen primary health care are urgently needed.

Characterization of cases and epidemiological and operational indicators of leprosy: analysis of time series and spatial distribution, Piauí state, Brazil, 2007-2021.

OBJECTIVE: To analyze epidemiological characteristics, temporal trends and spatial distribution of leprosy cases and indicators in the state of Piauí, 2007-2021. METHODS: This was an ecological time-series study using data from the Notifiable Health Conditions Information System, describing the spatial distribution and the temporal trend of leprosy using Prais-Winsten regression. RESULTS: A total of 17,075 new cases of leprosy were reported. There was a falling trend in the overall detection rate [annual percentage change (APC) = -6.3; 95%CI -8.1;-4.5)], detection in children under 15 years of age (APC = -8,6; 95%CI -12,7;-4,3) and detection of cases with grade 2 physical disability (APC = -4,4; 95%CI -7,0;-1,8). There was a rising trend in the proportion of multibacillary cases. Spatial distribution of the average detection rate identified hyperendemic areas in the Carnaubais, Entre Rios, Vale dos Rios Piauí e Itaueiras regions. CONCLUSION: High leprosy detection rates were found, despite the falling trend of indicators, except the proportion of multibacillary cases. MAIN RESULTS: Between 2007 and 2021, Piauí showed an improving trend in all indicators analyzed, except the proportion of new multibacillary cases. Spatial distribution identified hyperendemic areas in different regions of the state. IMPLICATIONS FOR SERVICES: This study provides health services with a broad overview of the epidemiological situation of leprosy in Piauí, with evidence of the populations and locations most affected by the disease, whereby public authorities need to reinforce the promotion of health actions. PERSPECTIVES: It is expected that actions to prevent and control the disease will be adopted, such as offering early diagnosis, ensuring correct treatment and implementing measures to prevent physical disabilities.

The spectrum of central nervous system manifestations in leprosy: a systematic review of published case reports and case series.

BACKGROUND: This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, Scopus and Embase databases were searched up to 8 July 2023, using a predefined search strategy. Inclusion criteria included patients diagnosed with leprosy with evidence of CNS involvement. The quality of the included cases was evaluated using the Joanna Briggs Institute checklist. RESULTS: A total of 34 records were identified, including 18 cohort studies and 16 reports describing 27 isolated cases. Autopsies revealed macroscopic changes in the spinal cord, neurofibrillary tangles and senile plaques. Mycobacterium leprae was detected in neurons of the medulla oblongata and spinal cord using PCR and phenolic glycolipid 1 staining. Cerebrospinal fluid (CSF) analysis showed inflammatory changes, increased gamma globulins and detection of Mycobacterium leprae antigens and antibodies. In 21 patients (78%), spinal cord/brachial plexus abnormities were detected. In the majority, MRI revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the cervical cord. In patients with brainstem involvement, T2/FLAIR hyperintensity was noted in the cerebellar peduncles, facial nerve nuclei and/or other cranial nerve nuclei. Brain parenchymal involvement was noted in three patients. CONCLUSIONS: This systematic review provides evidence of CNS involvement in leprosy, based on autopsy findings, neuroimaging, CSF analysis and neurophysiological studies.

Challenges and advances in serological and molecular tests to aid leprosy diagnosis.

Leprosy is a neglected chronic infectious disease caused by obligate intracellular bacilli, Mycobacterium leprae and Mycobacterium lepromatosis. Despite multidrug therapy (MDT) success, leprosy accounts for more than 200,000 new cases yearly. Leprosy diagnosis remains based on the dermato-neurologic examination, but histopathology of skin biopsy and bacilloscopy of intradermal scraping are subsidiary diagnostic tests that require expertise and laboratory infrastructure. This minireview summarizes the state of the art of serologic tests to aid leprosy diagnosis, highlighting enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (POCT) biotechnologies. Also, the impact of the postgenomic era on the description of new recombinantly expressed M. leprae-specific protein antigens, such as leprosy Infectious Disease Research Institute (IDRI) diagnostic (LID)-1 is summarized. Highly specific and sensitive molecular techniques to detect M. leprae DNA as the quantitative polymerase chain reaction (qPCR) and the loop-mediated isothermal amplification (LAMP) are briefly reviewed. Serology studies using phenolic glycolipid-I (PGL-I) semi-synthetic antigens, LID-1 fusion antigen, and the single fusion complex natural disaccharide-octyl (NDO)-LID show high sensitivity in multibacillary (MB) patients. However, serology is not applicable to paucibacillary patients, as they have weak humoral response and robust cell-mediated response, requiring tests for cellular biomarkers. Unlike ELISA-based tests, leprosy-specific POCT based on semi-synthetic PGL-I antigens and NDO-LID 1 antigen is easy to perform, cheaper, equipment-free, and can contribute to early diagnosis avoiding permanent incapacities and helping to interrupt M. leprae transmission. Besides its use to help diagnosis of household contacts or at-risk populations in endemic areas, potential applications of leprosy serology include monitoring MDT efficacy, identification of recent infection, especially in young children, as surrogate markers of disease progression to orient adult chemoprophylaxis and as a predictor of type 2 leprosy reactions. Advances in molecular biology techniques have reduced the complexity and execution time of qPCR confirming its utility to help diagnosis while leprosy-specific LAMP holds promise as an adjunct test to detect M. leprae DNA.

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.

Simulation-based training in Leprosy: development and validation of a scenario for community health workers.

OBJECTIVES: To build and validate a clinical simulation scenario designed to instruct community health workers (CHWs) in active leprosy case detection. METHODS: Methodological study involving the development of a simulated clinical scenario and content validation by experts. The Content Validity Index (CVI) was used to determine the level of agreement among the judging commitee, and a descriptive analysis of their recommendations was performed. RESULTS: A simulated scenario with a simulated participant was developed - a simulation characterized by low complexity, moderate physical/environmental fidelity, moderate to high psychological fidelity, and high conceptual fidelity, lasting 50 minutes and capable of training up to 10 CHWs simultaneously. The scenario was validated by 14 experts, with a CVI exceeding 80% for all components. CONCLUSIONS: The validated clinical simulation possesses attributes that make it highly reproducible in various national health contexts, thereby contributing to the global "Towards Zero Leprosy" strategy.

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.