Glycosylation profile of Mycobacterium leprae-specific antibodies associated with disseminated infection.

Genotyping of Mycobacterium leprae in humans and six-banded armadillos suggest lack of inter-species transmission in Rio Grande do Norte, northeast Brazil.

Improved detection of paucibacillary and multibacillary leprosy using a novel recombinant chimeric protein.

Mycobacterial infections such as leprosy and tuberculosis can induce autoimmune responses by disrupting host immune homeostasis. We previously identified eight mimicking B cell epitopes (BCEs) with elevated autoantibody levels in Type 1 Reaction (T1R). In this study, we longitudinally evaluated BCE-specific antibody responses and standardized a dot blot assay for T1R detection. A total of 150 untreated leprosy patients were enrolled: 50 each with T1R, Type 2 Reaction (T2R), and non-reactional (NR) cases; however, follow-up of T2R patients was not feasible. Patients were monitored every 3-4 months for changes in antibody profiles. ELISA quantified antibodies against 15 BCEs derived from Mycobacterium leprae (M. leprae) (HSP65, 50S ribosomal protein, lysyl tRNA synthetase) and host proteins (keratin, myelin basic protein). Dot blot analysis was performed with pooled sera from each group, and cut-off values were derived from NR intensities. Elevated antibodies against HSP2, HSP4-HSP6, KER1, KER2, KER4, MBP50SB1, and MBPLMB2 were strongly associated with T1R and correlated with disease progression in longitudinal analyses. Blot analyses confirmed higher intensities in T1R and T2R compared to NR and healthy controls (HC). Furthermore, future studies with larger longitudinal cohorts and longer follow-up periods are needed to validate these findings and to better characterize changes in autoantibody levels throughout disease progression and treatment, while the identification of these BCEs as potential prognostic biomarkers may also support the adaptation of the dot blot assay into cost-effective lateral flow platforms for clinical screening.

Factors associated with incomplete treatment among leprosy patients in Sabah, Malaysia, between 2012 and 2016

Factors affecting the health-seeking behaviour of leprosy patients in a tertiary referral hospital in the Philippines

Leprosy remains an important cause of peripheral neuropathy in endemic regions, with nerve involvement being the major determinant of long-term disability. The ulnar nerve is commonly affected. Conventional clinical assessment has limited ability to objectively quantify nerve damage. High-resolution ultrasonography (HRUS) enables structural evaluation of peripheral nerves in a non-invasive manner. The objective of the study was to assess ulnar nerve involvement using HRUS in patients with leprosy and to compare ultrasonographic findings with clinical examination. This prospective observational study was conducted at a tertiary care center from March 2024 to August 2025 and included 49 clinically diagnosed leprosy patients. All patients underwent clinical examination and HRUS of the ulnar nerve using a 12-18 MHz linear transducer. Cross-sectional area (CSA), fascicular pattern, echogenicity, and intraneural vascularity on power Doppler were evaluated. The mean age was 43.86 ± 15.20 years, with male predominance (65.3%). Borderline tuberculoid (30.6%) and borderline lepromatous (26.5%) types were most frequent. HRUS detected ulnar nerve thickening in 89.8% of patients compared with 77.6% by clinical examination. Mean CSA was 11.90 ± 4.58 mm2. Loss of fascicular pattern was seen in 63.3%, altered echogenicity in 87.8%, and increased intraneural vascularity in 57.1%. HRUS showed sensitivity 93.6%, specificity 50.0%, positive predictive value 97.8%, negative predictive value 25.0%, and overall accuracy 91.8% for detecting ulnar nerve involvement. HRUS is a useful, noninvasive adjunct for objective detection and characterization of ulnar nerve involvement in leprosy and complements clinical assessment.

Leprosy causes nerve damage which may be clinical or subclinical. Leprosy-associated peripheral neuropathy (LPN) has an unpredictable course despite treatment with multi drug therapy, and results in significant disabilities and stigma. There are no reliable biomarkers to quantify nerve damage in leprosy or predict impending clinical neuropathy. We conducted a cross-sectional observational study over 1 year. Leprosy patients with peripheral neuropathy (LPN, n = 30), leprosy patients without detectable peripheral neuropathy (L, n = 20) and healthy controls (HC, n = 20) were included. Patients with other known causes of peripheral neuropathy were excluded. The primary outcome was to estimate serum neurofilament light chain (NfL) levels using the Single Molecular Assay (SiMoA) HD-X analyzer. NfL concentrations were compared across the three groups and correlated with disease spectrum, bacterial load and severity of nerve function impairment (NFI). The median NfL level in the LPN group was 12.1 pg/mL (range: -1.68 to 224), in the L group was 17.25 pg/mL (range: 4.43-53.8) and in HCs was 4.85 pg/mL (range: 0.252-23.7). Leprosy patients had significantly higher NfL levels than healthy controls (p = 0.008), with a cut-off value of 7.48 pg/mL using ROC analysis (sensitivity 76%; specificity 25%). NfL levels between the LPN and L groups were comparable (p = 0.56). No significant correlation was found between NfL levels and severity of clinical neuropathy, although a non-significant positive trend with the bacterial index was noted. Serum NfL levels were significantly higher in leprosy patients compared to healthy controls, suggesting prominent axonal damage. NfL may serve as a minimally invasive biomarker of nerve damage in leprosy, but further longitudinal studies are needed to validate its predictive and therapeutic utility in LPN. CTRI/2024/04/081960.

Cytokine polarized natural killer T cells modulate effector T cell function in leprosy.

Identification of leprosy reactions using Fourier transform infrared (FTIR) spectroscopy supervised by clinical evaluation.

Lewis Y (Ley) orchestrates leukocyte trafficking and inflammatory remodeling in leprosy patients from the Brazilian Amazon.

Introduction The psychological sequelae of leprosy extend beyond the course of disease, yet systematic mental health evaluation in post-treatment populations remains limited, particularly within urban Indian contexts. This study examined the prevalence and determinants of depression and anxiety among leprosy patients after treatment completion in South West Delhi. Methods A community-based cross-sectional study was conducted among 93 leprosy patients released from treatment between April 2021 and March 2024 in South West Delhi. The Patient Health Questionnaire-9 (PHQ-9) scale and the Generalized Anxiety Disorder-7 (GAD-7) scale were used to assess depression and anxiety, respectively. Impairment levels were graded by the WHO Disability Grading Classification, functional status through the Screening of Activity Limitation and Safety Awareness Scale, and the Participation Scale. Results The study population comprised 57 (61.3%) males and 36 (38.7%) females with a median age of 40 years. Most participants exhibited minimal psychiatric morbidity (depression: n = 73, 78.5 %; anxiety: n = 77, 82.8 %). Nevertheless, clinically meaningful depression (PHQ-9 ≥ 10) was seen in nine (9.7%) participants and clinically meaningful anxiety (GAD-7 ≥ 10) in seven (7.5%) participants. In multivariate linear regression, female gender (B = 1.70, 95% CI: 0.12 to 3.28, t = 2.14, p = 0.035); lower education levels: classes 9-12 (B = 2.80, 95% CI: 0.51 to 5.09, t = 2.43, p = 0.017), classes 1-8 (B = 2.32, 95% CI: 0.06 to 4.58, t = 2.04, p = 0.044), and no formal education (B = 2.78, 95% CI: 0.20 to 5.37, t = 2.14, p = 0.035); and participation restrictions (B = 5.97, 95% CI: 4.20 to 7.74, t = 6.70, p < 0.001) were significantly associated with higher depression scores (adjusted R²= 0.53, F = 11.27, p < 0.001), while just young age (< 40 years) (B = 1.51, 95% CI: 0.14 to 2.88, t = 2.19, p = 0.031) and participation restrictions (B = 4.23, 95% CI: 2.31 to 6.14, t = 4.40, p < 0.001) significantly predicted higher anxiety scores (adjusted R²= 0.31, F = 5.18, p < 0.001). Conclusion This study found that although most post-multi-drug therapy (MDT) leprosy patients reported minimal psychiatric morbidity, a notable proportion experienced clinically relevant depression and anxiety. Participation restrictions emerged as the strongest predictor of higher PHQ-9 and GAD-7 scores. Female gender, lower education, and activity limitations further increased depression risk, while younger age predicted higher anxiety. These findings underscore the need to integrate mental health services into the existing leprosy management protocols.

Alterations in the vitamin D axis have been implicated in chronic wounds, but their role in leprosy-related trophic ulcers (TU) is unclear. This study compared serum vitamin D levels and VDR FokI (rs2228570) polymorphism between leprosy patients with and without TU, assessed their association with ulcer presence, and examined the correlation between vitamin D levels and ulcer severity. This case-control study involved 82 adult leprosy patients (41 with TU, 41 without) treated at a tertiary referral hospital in Jakarta, Indonesia. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using chemiluminescence assay, and FokI polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Ulcer severity was evaluated using the Pressure Ulcer Scale for Healing (PUSH). Associations were assessed through bivariate and multivariate analyses. Patients with TU had significantly lower mean serum 25(OH)D levels than those without TU (13.14 vs. 20.18 ng/mL, p < 0.001). The homozygous mutant FokI genotype (ff) was more frequent in the TU group (p = 0.043). In multivariable analysis, both low vitamin D status (adjusted odds ratio [aOR] 4.15; 95% confidence interval [CI] 1.41-12.24; p = 0.010) and the FokI polymorphism (aOR 7.86; 95% CI 1.80-34.36; p = 0.006) remained independently associated with TU. Vitamin D levels showed a weak inverse correlation with PUSH scores (r = -0.312, p = 0.047). Lower serum vitamin D status and the FokI polymorphism were independently associated with TU in leprosy, and a weak inverse correlation was observed between serum vitamin D levels and ulcer severity. While genetic variation is non-modifiable, vitamin D status represents a potentially modifiable factor; hence, these findings suggest that assessment of vitamin D status may be considered as part of comprehensive ulcer care in leprosy.

Autophagy is a crucial host defense mechanism against intracellular pathogens, including Mycobacterium leprae. Genetic variants in autophagy-related genes have been associated with susceptibility to leprosy, but their functional relevance remains incompletely understood. We investigate the association of single nucleotide polymorphisms (SNPs) in three genes involved in autophagy, CACNA2D3, LRRK2 and IRGM. A total of 3,480 individuals from three Brazilian populations were included in a case-control design. We confirmed that the SNP rs1449325 in CACNA2D3 was associated with leprosy per se protection in the overdominant model (ORoverdTC = 0.70; p = 0.00443) in Rio de Janeiro, which was then replicated in samples from Manaus and Rondonópolis. Curiously, CC genotype of rs1449325 was associated with leprosy per se risk in the recessive model in Rio de Janeiro (ORrecCC = 1.51; p = 0.00476), Manaus (ORrecCC = 3.06; p = 1.44E-07) and Rondonópolis (ORrecCC = 1.50; p = 0.0240). Data from public eQTLs databases and gene expression analysis from whole blood samples suggested increasing CACNA2D3 expression levels with TT < CT < CC genotypes. In the literature, CACNA2D3 mRNA levels are positively correlated with calcium influx levels. Taken together, the genetic and expression data support the hypothesis that either low or high levels of calcium leads to M. leprae susceptibility. Associations of SNPs in LRRK2 and IRGM genes were also observed in the Rio de janeiro population, although not confirmed in replication cohorts. However, a protective effect of the LRRK2 haplotype C/G/G/T/G (rs7308720/rs7133914/rs10878434/rs3761863/rs7962370), apparently driven by rs3761863 T allele, was observed in Rio de Janeiro (ORhap = 0.44; p = 0.0121). This allele was associated with lower levels of LRRK2 mRNA expression in skin biopsy samples from leprosy patients, as well as in tibial nerve and fibroblast samples of healthy individuals from public databases. Our results highlight a dual role of calcium signaling and autophagy gene regulation in leprosy susceptibility. Variants in CACNA2D3 and LRRK2 modulate host response to M. leprae infection and represent potential targets for improved therapeutic and preventive approaches.

Background: Leprosy is a chronic infectious disease that can lead to permanent disability if not properly managed, especially due to non-adherence to the Multi-Drug Therapy (MDT) regimen. Medication adherence plays a crucial role in preventing disease progression and the onset of disability. Purpose: This study aimed to examine the relationship between medication adherence and the level of disability among leprosy patients in Kunir Public Health Center, Lumajang. Methods: This research employed a quantitative, correlational design to examine the relationship between medication adherence and disability level among leprosy patients. The study population comprised all leprosy patients in Kunir Public Health Center, with a total of 14 respondents selected using total sampling. The research instruments used were the MMAS-8 questionnaire to assess adherence and the POD scale to assess disability. Data were analyzed using the Spearman Rank test with a significance level of p &lt; 0.05. Results: Most patients had moderate medication adherence (50%), and the majority experienced Grade 1 disability (42.9%). The Spearman test revealed a significant relationship between medication adherence and disability level (p = 0.000; r = 0.930), indicating that higher adherence is associated with lower levels of disability. Conclusions: Regular and timely MDT treatment can suppress disease progression and prevent nerve damage leading to disability. Therefore, improving medication adherence should be a priority in primary healthcare-based leprosy control programs.

ABSTRACT Stigmatization of leprosy remains a major obstacle in the recovery process leading to isolation, discrimination and adversely affecting their mental and emotional health. This study aims to explore how leprosy patients in the Palue Health Center working area build resilience in the face of such stigma. Qualitative with a case study design, involving leprosy patients who have achieved resilience referring to The Resilience Scale. Data were collected through in-depth interviews and analyzed using thematic analysis techniques according to Braun & Clarke’s frameworks. Three main themes were identified from the experiences of leprosy patients: (1) forms of stigma against leprosy patients; (2) stages of achieving resilience, and (3) aspects that support the development of resilience. Resilience is the key that helps leprosy patients overcome psychological and social stress, maintain mental health, and improve quality of life. Physical rehabilitation alone is not enough; a holistic approach must be applied, which includes psychological support to help leprosy patients deal with the emotional and social stress of stigma. Social support from family, community and health workers is essential in strengthening the support system for leprosy patients and reducing feelings of isolation. Public education about leprosy needs to be improved to reduce stigma and discrimination, so that people with leprosy can more easily reintegrate into society. The involvement of families and health workers in the rehabilitation process plays an important role in helping leprosy patients build resilience, so that they can better cope with stigma and life challenges. This study is quite limited in capturing resilience and can only offers a snapshot of resilience at a single time point and recommend future longitudinal research to better capture its development over time.

Background: Multibacillary leprosy management is frequently complicated by severe immunological reactions and adverse drug events. Erythema nodosum leprosum is an immune-complex-mediated complication, while dapsone hypersensitivity syndrome is an idiosyncratic, potentially life-threatening drug reaction. The concomitant presentation of these distinct entities, especially with bullous eruptions, creates a profound diagnostic and therapeutic dilemma. Case presentation: A 42-year-old male with a history of relapsed borderline lepromatous leprosy and rheumatoid arthritis presented with exquisitely painful erythematous nodules, high-grade fever, and bullous eruptions exactly 72 hours after the re-initiation of multidrug therapy. Physical examination recorded a Visual Analog Scale pain score of 9. Expanded histopathological evaluation confirmed a dual pathology: extensive dermal neutrophilic infiltration characteristic of Erythema Nodosum Leprosum, occurring alongside pronounced subepidermal blistering and marked eosinophilic exocytosis indicative of a dapsone-induced bullous eruption. Standard multidrug therapy was immediately discontinued. A modified regimen comprising rifampicin, clarithromycin, and carefully titrated immunosuppressants (methylprednisolone and azathioprine) was initiated. Conclusion: The substitution of dapsone with clarithromycin facilitated rapid clinical resolution of both the bullous eruptions and recurrent immune reactions. This case underscores the critical need for precise temporal tracking, individualized therapeutic modifications, and comprehensive histopathological evaluation in leprosy patients demonstrating complex, overlapping hypersensitivity syndromes.

BackgroundIn HLA-B*13:01-positive multibacillary (MB) leprosy patients, dapsone-containing multidrug therapy (MDT) carries a high risk of dapsone hypersensitivity syndrome (DHS). Alternative regimens (dapsone-free) are adopted, but their long-term efficacy compared with standard MDT in HLA-B*13:01-negative patients remains inadequately characterized.MethodologyThis retrospective cohort study analyzed MB patients (2015–2023) from the National Leprosy Prevention and Control Management Information System (LEPMIS) with ≥1-year follow-up. Primary outcomes (cure/relapse rates, bacterial index (BI), leprosy reactions, and disability progression) and secondary outcomes (adverse events and treatment duration) were compared between HLA-B*13:01-positive patients receiving alternative therapy (rifampicin + clofazimine ± clarithromycin/ofloxacin/minocycline) and negative patients receiving standard MDT (rifampicin + clofazimine + dapsone).FindingsAmong the 271 enrolled MB patients (120 HLA-B*13:01-positive, 151 negative), alternative therapy showed comparable efficacy to standard MDT in cure rates (67.6% vs. 65.8% at Year 5), the rate of BI decline (89.92% vs. 95.11% at Year 5), smear negativity rates (71.43% vs. 75.00% at Year 5) and relapse rates (0.46 vs. 0.20 per 100 person-years). Kaplan-Meier survival functions revealed no significant differences in leprosy reactions or disability progression. Additionally, alternative therapy demonstrated comparable safety to MDT (1.67% vs. 2.65%, P = 0.70).ConclusionsIn our study, dapsone-free alternative regimens demonstrated comparable clinical efficacy and safety to standard MDT in MB patients, providing a viable option for HLA-B*13:01 carriers. These findings, limited by the observational design and regimen heterogeneity, warrant further investigation in prospective trials.

Leprosy reaction is inflammation caused by the body’s immune system attacking the leprosy bacteria. If left untreated or improperly managed, it may lead to irreversible nerve damage, causing mortality, disability, and physical deformities. Oral prednisolone is a recommended drug to manage these reactions. Despite this, the treatment outcome and safety of prednisolone in treating leprosy reactions in clinical practices have not studied well. Thus, this study aimed to assess the status and factors of treatment outcomes and safety of prednisolone in the treatment of leprosy reactions. A hospital-based retrospective cohort study was conducted. Data were collected using a data abstract form, entered into Epi-Data version 4.0, and then exported to SPSS version 25 for further analysis. Descriptive statistics were computed to get summary results, and binary and multinomial logistic regression analyses were used to predict factors that affect the treatment outcome and safety of prednisolone. In this study, 262 patients’ record files were reviewed. The median age of patients was 30 (IQR 25–42.5) years. Two-thirds (66.8%) of patients were males. Of 262, only 62.2% of the patients improved from the leprosy reactions with prednisolone treatment. Patients with WHO disability grade-0 showed more improvement than those with higher grades. Furthermore, out of 262 patients, 79.4% experienced at least one adverse event during the course of treatment. The starting dose of prednisolone and treatment duration were significantly associated with the occurrence of the adverse events. A considerable proportion of the patients didn’t show improvement in their reaction status with prednisolone for both type one and two reactions. The prevalence of adverse events was higher, and the magnitude was proportional to duration and dose of prednisolone, suggesting the need to optimize treatment strategies. Not applicable.

ABSTRACT Introduction Leprosy remains a major public health challenge in countries like India, Brazil, and Indonesia. The materiovigilance program was established to monitor the safety of medical devices and helps to protect health-care workers and patients from device-related injuries. Leprosy patients suffer from sensory loss and are at high risk of developing injuries with medical devices. Therefore, integrating materiovigilance program with the national leprosy care program is essential to improve the safety and wellbeing of leprosy patients. Areas covered This critical perspective covers the role of materiovigilance in India, the classification of medical devices based on their risk status, devices used in leprosy management, the Indian and international target goals for leprosy elimination, and emphasis on the integration of materiovigilance programs with leprosy programs in leprosy treating hospitals. Expert opinion There is a significant gap existing in the leprosy elimination policies regarding the safety concerns with the use of medical devices. Successful integration of materiovigilance framework with leprosy elimination policies will influence the treatment outcomes in a positive manner. The key challenges to overcome are lack of awareness, training, and funding. Implementing the integration strategy in a stage-wise manner will help to identify the lacunae, operational issues, and further strengthen the program.