Literature about the discovery of the leprosy bacterium Mycobacterium leprae usually mentions the Hansen-Neisser controversy. It is an established narrative that Neisser tried to present himself as the discoverer of the leprosy bacterium. However, Neisser's first publication on Mycobacterium leprae refers explicitly to Hansen's original discovery. How did the notion of Neisser trying to claim Hansen's discovery emerge? A thorough source-critical examination of Hansen's and Neisser's scientific and popular publications between 1874 and 1897 as well as of the literature dealing with the so-called controversy brought interesting new results. The notion that Neisser tried to steal Hansen's discovery is based on a misreading of Neisser's publications by Hansen's biographer. But Neisser tried indeed to bypass Hansen in trying to prove that Mycobacterium leprae was the contagion causing leprosy. The competition between the two scientists resulted in a personal enmity. This study shows how the history of modern science is prone to myths and underlines the importance of source criticism when dealing with established narratives.

Langerhans cells express the nonpolymorphic antigen-presenting molecule CD1a, positioning them as contributors to host immunity against Mycobacterium leprae in human leprosy. CD1a was originally shown to present non-canonical lipopeptide antigens such as dideoxymycobactin and chemically diverse hydrophobic ligands. Here, we generated CD4⁺ T cell lines from leprosy lesions that recognized M. leprae in a CD1a-restricted manner. Unexpectedly, antigen recognition was protease-sensitive, prompting biochemical purification that identified two microbial protein antigens: LppX, a 25-kDa lipoglycoprotein, and Ag85A, a 30-kDa secreted protein with no known lipid modification. Recombinant proteins activated the corresponding T cell lines in a CD1a-dependent manner. Epitope mapping identified 12-mer peptides that fully reconstituted antigenicity, were conserved between M. leprae and M. tuberculosis , and elicited robust, dose-dependent IFN-γ production and T cell proliferation, establishing that DNA-encoded, ribosomally translated peptides serve as CD1a-restricted cognate antigens. Biochemical analyses showed peptide binding to CD1a, supported by isoelectric focusing and surface plasmon resonance ( K D ∼75 μM for Ag85A). CD1a-peptide tetramers specifically stained cognate T cells, soluble CD1a was sufficient to present peptide antigen, and transfer of the LppX-specific TCR into naïve T cells restored antigen responsiveness. Using CD1a-peptide tetramers, we identified antigen-specific T cells enriched in patients undergoing reversal reactions compared with patients with lepromatous leprosy and healthy donors. The CD1a-restricted T cell lines secreted IFN-γ and IL-26, cytokines with established antimicrobial activity. Together, these findings demonstrate that CD1a can present canonical microbial peptides as part of a cell-mediated immune response in leprosy, extending the known spectrum of CD1a ligands. Because CD1a is nonpolymorphic and presents antigens to antimicrobial T cells, CD1a-peptide complexes may provide a broadly applicable platform for studying, detecting, and potentially targeting mycobacterial immunity.

Hansen's disease (HD, leprosy) had a global incidence of approximately 200000 new cases per annum over the last decade. Armadillos are recognized reservoirs of Mycobacterium leprae in the Americas and HD is considered a zoonosis in the USA. Our aim was to evaluate the association between armadillo meat consumption and HD in Brazil. We conducted a case-control study (n=59 patients with HD, n=59 controls) in the state of Espírito Santo, Brazil, between February and December 2025. Data collected included clinical and sociodemographic, armadillo meat consumption and known (human) case contacts (KCCs). Armadillo meat consumption was much more frequent among cases (59.3%) than controls (8.5%). Consumption was the strongest independent predictor of HD, with 15-fold higher odds of exposure (adjusted odds ratio [aOR] 16.5 [95% confidence interval {CI} 5.2 to 52.5], p<0.001) among cases. Odds of KCCs were five-fold higher among cases (aOR 6.0 [95% CI 2.2 to 16.8], p=0.001). This study provides evidence that armadillo meat consumption is an independent transmission pathway for human M. leprae infection in Brazil. Zoonotic transmission likely accounts for some of the HD 'contact gap' in this setting, supporting the need for a paradigm shift towards One Health surveillance of HD in the Americas.

Background: Hansen's disease (Leprosy), caused by Mycobacterium leprae, is a chronic granulomatous condition with varied clinical presentations reflecting the host's immune response. Clinical and histological classifications may differ, leading to diagnostic errors. Histopathology offers definitive information on granulomas, bacillary load, and tissue changes. Thus, clinico-histopathological correlation is crucial for accurate diagnosis and appropriate treatment. Objectives: To study the clinic-histopathological comparison in patients with Hansen's disease and evaluate the concordance between clinical and histopathological findings. Materials and Methods: This retrospective observational study analyzed records of patients with Hansen’s disease who underwent skin biopsy at a tertiary care center in Nepal during a two-year study period. Cases with complete clinical and histopathological data were included. Clinical and histopathological classifications were performed according to the Ridley-Jopling spectrum. H&amp;E staining and Fite-Faraco stain for bacilli was done. Clinico-histopathological correlation was assessed by comparing clinical and histopathological diagnoses. Data were analyzed using SPSS, with categorical variables expressed as frequencies, percentages and means. Clinicopathological correlation between clinical and histopathological classification of leprosy was assessed using Cohen’s kappa statistic. Results: A total of 150 patients aged 11-85 years were included, with a mean age of 43.75 ± 15.89 years and male predominance. Clinically, lepromatous leprosy was most common, while histopathology most often showed tuberculoid leprosy. The overall agreement was moderate (κ = 0.48) and was statistically significant (p &lt; 0.001). The observed agreement between the two methods was 57.3%.The agreement of tuberculoid leprosy was 76.66% and lepromatous leprosy 75.75%, while it was moderate in borderline tuberculoid (54.83%); and low in borderline (30%) and borderline lepromatous (33.33%). Substantial reclassification occurred particularly within the borderline spectrum, with BB being clinically overestimated and IL being underestimated. Conclusion: A combined clinic-histopathological approach is essential for accurate classification, especially in borderline cases. While clinical features provide an initial impression, histopathology remains the gold standard for confirmation. A combined approach enhances diagnostic precision, ensures appropriate therapy, and contributes to better patient outcomes.

Leprosy, caused by Mycobacterium leprae, frequently leads to neuropathic trophic ulcers and ulcerative lesions associated with type II lepra reactions. These ulcers are difficult to treat due to sensory loss, repeated trauma, and poor vascularity, often responding inadequately to conventional therapies. Topical insulin has recently gained attention for its potential to enhance local wound healing by stimulating angiogenesis, collagen deposition, and re-epithelialization without systemic adverse effects. This case series included five male patients with Hansen’s disease who presented with chronic trophic ulcers or ulcerative lesions of lepra reaction. A solution of 0.1 ml Actrapid insulin diluted with 0.9 ml normal saline was irrigated directly to the ulcer surface twice daily and covered with sterile gauze for five minutes. The intervention was continued for four to six weeks. Ulcer size, depth, tissue quality, and granulation were assessed clinically and documented photographically at baseline and follow-up. All patients showed significant improvement within two weeks, with marked reduction in ulcer dimensions and healthy granulation tissue formation. Complete epithelization was achieved in four to six weeks. No local or systemic adverse effects were observed, and compliance was excellent. Topical insulin is a safe, economical, and effective therapeutic option for leprosy-associated ulcers, meriting further evaluation in larger controlled studies.

Hansen's disease is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae and Mycobacterium lepromatosis. Recently, only a few new cases have been reported in Japan. Diagnosis is based on the demonstration of the bacillus through skin smears, histopathology, or polymerase chain reaction, as well as other clinical and laboratory findings. Nerve conduction studies can detect subclinical neuropathy. Clinical classification is determined by variations in the host's cell-mediated immunity. The World Health Organization divides leprosy into paucibacillary (PB) and multibacillary (MB) forms. Ridley and Jopling classified the disease along a continuous spectrum from tuberculoid to lepromatous. Leprosy reactions, both type 1 and type 2, can lead to rapid nerve deterioration, necessitating immediate anti-inflammatory treatment and the continuation of multidrug therapy. The standard multidrug therapy regimen includes dapsone, rifampicin, and clofazimine, with typical durations of 6 months for PB and 12 months for MB. Peripheral nerve damage is irreversible once it occurs, making prevention the most effective strategy. Neuropathic pain is treated with agents such as pregabalin and amitriptyline. Rehabilitation is provided for muscle atrophy, and orthoses and prostheses are used to address deformities of the fingers and toes as well as limb deficiencies. Collaboration between dermatologists and physiatrists is essential.

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

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

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an obligate intracellular bacterium that affects the skin, peripheral nerves, upper respiratory mucosa, and eyes. Type 2 diabetes mellitus (T2DM) is a comorbidity that can worsen the course of leprosy. The female patient, Mrs. D, aged 55 years came to the emergency room of Cut Meutia Hospital with the main complaint of red bumps accompanied by pain on the face, hands, chest, and back since 3 days ago and additional complaints such as fever, joint pain, and numbness and loss of feeling in the legs, weakness, frequent thirst, and frequent urination. Dermatologic status is obtained in the facial region in the form of erythema nodules with firm boundaries with numular size, multiple. Laboratory examination showed anemia and leukocytosis. The therapy given was MDT MB package, ferrous sulfate 1x325 mg and PRC transfusion 3 kolf. Complaints arose acutely after the patient resumed taking MDT (multidrug therapy) leprosy drugs which had previously been stopped for more than 3 months. Based on the time of onset of symptoms, history of leprosy treatment, and the manifestation of systemic inflammatory lesions with signs of neurotropism, it can be suspected that the patient is experiencing a type 2 leprosy reaction or Erythema Nodosum Leprosum (ENL).

Kiribati has one of the highest rates of leprosy worldwide. A nationwide screening and chemoprophylaxis program for household leprosy contacts was introduced in 2018. In 2022, population-wide screening and rifamycin-based treatment or chemoprophylaxis for leprosy and tuberculosis was introduced as part of the PEARL and COMBINE studies. Largescale rifamycin use theoretically risks selection of resistant Mycobacterium leprae strains. This study aimed to elucidate the baseline antimicrobial resistance (AMR) profile of M. leprae isolates in Kiribati using a novel molecular method. Mycobacterium leprae genomes from skin biopsies of patients clinically diagnosed with leprosy in Kiribati between 2017 and 2024 were analysed. We used an M. leprae specific repetitive element (RLEP) PCR to confirm the presence of M. leprae DNA. Samples with sufficient DNA (cycle threshold (CT) value < 30) proceeded for resistance testing. A combination of nested and heminested PCR assays was used to amplify the drug resistance determining regions (DRDR's) for dapsone (folP1), rifampicin (rpoB) and fluoroquinolones (gyrA) followed by DNA Sanger sequencing. 216 skin biopsies (multibacillary [MB], n = 155, paucibacillary [PB], n = 61) underwent confirmatory testing. 192/216 (89%) samples were PCR positive (median Ct value 24.5 [range 12.0-44.4]), including 145 MB cases (median CT 21.1 [range 12.0-42.0]) and 47 PB cases (median CT 34.0 [range 14.8-37.0]). Twenty-four (11%) samples were PCR negative and 21 of these underwent histopathological testing, with 12 (57%) showing changes consistent with leprosy. 116 (60%) positive samples proceeded to AMR testing (MB, n = 106; PB, n = 10). In 10 cases (9%), dapsone resistance-conferring mutations were identified in the folP1 region. No mutations were identified in the rpoB or gyrA genes. Molecular analysis of skin biopsies revealed moderate-level dapsone resistance but no rifampicin resistance in Kiribati. Establishing this baseline AMR profile will enable a before-versus-after intervention analysis of antimicrobial resistance in M. leprae isolates in Kiribati.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which affects the skin and peripheral nerves. Despite being declared eliminated as a public health problem globally in 2000, atypical presentations can still pose diagnostic challenges, leading to delayed treatment and complications. This case series highlights unusual clinical presentations of leprosy to emphasize the importance of vigilance and timely diagnosis, even in the post-elimination era. Three patients with varied and atypical dermatological manifestations of leprosy were evaluated. Uncommon presentations of leprosy highlight the need for heightened awareness and early diagnostic tools to prevent morbidity and transmission.

Definitively diagnosing Hansen's disease (HD) is challenging, but molecular methods can provide species identification of the causative mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). Most studies have investigated targeted assays, and the performance of broad-range molecular approaches remains unknown. This study evaluated a multilocus (hsp65, 16S ribosomal RNA, and rpoB) broad-range polymerase chain reaction (PCR) assay in detecting HD-associated mycobacteria at a single large reference laboratory in the United States from 2009 to 2024. We identified 148 positive samples from 137 patients submitted from 26 states. Mycobacterium lepromatosis was identified in 8 of 137 patients (5.8%), and M. leprae was identified in the rest. Although most samples were skin biopsies (∼90%), 10 samples (7.9%) represented atypical locations, including bone marrow and liver. Half of all samples were identified by only a single target (n = 72/146 samples, 49.3%), and rpoB was the most likely to be positive (n = 123/146 samples, 84.2%). Overall, broad-range PCR successfully identified HD-associated mycobacteria, including M. lepromatosis, from skin and atypical anatomic sites, and it should be considered more frequently in the evaluation of suspected cases.

Brazil has the second-highest leprosy burden worldwide, with approximately 20,000 new cases reported annually, many diagnosed with advanced disease and disability. To support earlier detection, the Ministry of Health recently approved the ML Flow rapid test for contact evaluation. ML Flow detects immunoglobulin M antibodies against phenolic glycolipid-I of Mycobacterium leprae, can be performed at the point of care using finger-prick blood, and yields results within minutes. ML Flow offers important operational advantages. It enables same-visit counseling and may support risk-stratified household-contact follow-up. However, its value is context-dependent. Because anti-phenolic glycolipid-I immunoglobulin M responses correlate with bacillary burden, positivity is more frequent in multibacillary disease, whereas many paucibacillary and pure neural cases have absent or low antibody levels. A seronegative result therefore does not exclude disease. Among asymptomatic contacts, seropositivity varies widely across studies, and in previously treated individuals antibodies may remain detectable for years. Available evidence suggests that seropositive contacts are at increased risk of incident leprosy, although predictive performance varies across settings. Serology alone is not diagnostic, and misuse may lead to stigma, anxiety, unnecessary referrals, and diversion of resources. The contribution of ML Flow is therefore implementation-dependent. In settings with standardized counseling, scheduled re-examination, and reliable referral pathways, it may support risk-stratified follow-up. In settings where these elements are weak, benefits may be limited. Brazil offers an important programmatic setting in which to evaluate this strategy, but only with safeguards: integration with dermato-neurological examination, clear protocols stating that seropositivity is not diagnostic, structured follow-up pathways, quality-controlled training, and systematic recording in the Brazilian Unified Health System information systems. Under these conditions, ML Flow may contribute to earlier diagnosis and disability reduction; without them, it risks adding workload without improving care.

Previous studies have examined prevalence of leprosy-causing bacteria, Mycobacterium leprae and Mycobacterium lepromatosis, in rural Mexican long-nosed armadillo (Dasypus mexicanus) populations of the southeastern USA. However, few prevalence studies have been conducted in Alabama nor in urbanized, human-dominated areas where potential zoonotic transmission may be a public health concern. This study evaluated the prevalence of leprosy-causing bacteria in armadillos from rural, suburban, and urban zones in Lee and Mobile County, Alabama, USA. This study detected the first evidence of M. leprae-infection in a wild juvenile armadillo, from an individual sampled in a suburban zone of Mobile County, indicating potential vertical or environmental transmission. Additionally, 15/83 adult armadillos were infected in the Mobile County population, giving a total population prevalence of 16/93 (17%). Of the adults, more females were infected with M. leprae (11/36), especially lactating females, compared to males (4/47), despite more adult males being sampled overall. In Lee County, 64 adults were sampled and only one, a male, was M. leprae-positive, resulting in a total population prevalence of 1/94 (1%). The significantly lower occurrence than in Mobile County may be a result of environmental conditions, as the counties predominantly exist in two different ecoregions, the Piedmont and Southeastern Plains. Therefore, this study presents findings that may support an ecological-constraints hypothesis, previously applied to the northward expansion of M. leprae. Although no significant difference in prevalence was observed among the residential zones in this study, future research should investigate the prevalence of leprosy-causing bacteria in armadillos across different ecoregions and land use types to elucidate transmission dynamics and zoonotic risk, and inform public health strategies and wildlife management efforts in the southeastern USA.

In this study, we propose a novel machine learning-based simulation framework for evaluating biomedical compound efficacy under biosafety constraints. Focusing on antileprotic compounds, the system integrates QSAR-derived descriptors and a Random Forest surrogate model to predict inhibitory responses without requiring live Mycobacterium leprae cultures. The simulation achieved an R² of 0.87 and RMSE of 0.15, accurately estimating inhibition levels at multiple concentrations. A compound prioritization matrix was constructed using performance metrics, drug-likeness filters, and structural novelty scores. The framework demonstrates how signal-driven modeling and surrogate learning can accelerate screening processes in biomedical engineering where experimental validation is limited by infrastructure constraints.

The relative sensitivity of three Mycobacterium Leprae specific probes targeting ribosomal genes sequence has been compared in clinical specimens along with DNA. This analysis was carried out in diluted biopsy homogenates of lepromatous (LL) cases. The overall sensitivity of targeting rRNA vs DNA in specimens from paucibacillary ( PB ) and multibacillary ( MB ) was also accessed. The biopsies / slit smears were collected and nucleic acids were extracted by an improved integrated physio – chemical procedure. DNA and RNA were fractionated and measured quantities from similar bacterial populations were blotted on nitro – cellulose membrane. Three probes were synthesized, end – labeled and hybridization with blotted DNA as well as RNA was done. It was observed that rRNA targeting was 10 – 100 fold more sensitive as compared to DNA detection. The sensitivity of targeting rRNA was significantly higher in specimens with low bacillary numbers. These observations indicate greater potential for clinical application for rRNA targeting as compared to DNA for detection of Mycobacterium Leprae from various clinical specimens. Key words:- Diagnosis, rRNA, DNA, Probes, Sensitivity, M. leprae.

To develop an in-house reference control DNA standard targeting the RLEP region of Mycobacterium leprae for use in quantitative polymerase chain reaction (qPCR) diagnostics, aiming to reduce dependence on animal models and external sources. Previously characterized DNA samples from patients with leprosy were used to amplify and sequence the 450-base pair RLEP region. A specific 131-base pair segment within this region was targeted for qPCR assay development. The amplified products were purified; sequenced using Illumina next-generation sequencing technology; and validated through bioinformatics analyses, including Basic Local Alignment Search Tool (BLAST; National Institutes of Health) alignment and copy number assessment. The consensus sequence aligned perfectly with the known RLEP region. The BLAST analysis revealed 37 copies of the target sequence throughout the genome, confirming the sequence's utility as a sensitive diagnostic marker. The qPCR assay successfully detected the target in both reference and clinical samples, with melting curve analysis indicating high specificity. An in-house M leprae RLEP control standard was successfully developed that provides a reliable, ethical, and resource-efficient alternative to traditional animal-derived controls for leprosy diagnosis using qPCR.

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.

BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and Mycobacterium lepromatosis (M. lepromatosis), primarily affecting the skin and peripheral nervous system. Leprosy is complicated by immune-mediated reactions which are risk factors for nerve damage and disability. Systemic corticosteroids are the mainstay of therapy; however, prolonged use in chronic or recurrent reactions carries significant risks but the evidence on the short- and long-term adverse effects of corticosteroids in leprosy is limited. We conducted a systematic review to evaluate corticosteroid-associated adverse effects in leprosy affected individuals.MethodologyEight electronic databases were searched (including PubMed, Embase and LILACS) without language or year restriction for studies reporting adverse effects associated with systemic corticosteroid use in individuals with leprosy. Eligible studies included randomised controlled trials, observational studies, case series and case reports. Data variability was assessed using Stata software.Main findingsA total of 111 studies were included; of which 22 were randomised controlled trials. Due to heterogeneity, findings were synthesised narratively. The most frequently reported adverse effects were metabolic complications, with approximately one-third of individuals developing corticosteroid-induced lipodystrophy. Infections were the second most common adverse effect (15.5%), followed by gastritis (12.6%). Infections accounted for three-quarters of corticosteroid-associated mortality, predominantly due to tuberculosis, with 88.2% of corticosteroid-associated mortalities occurring in individuals with erythema nodosum leprosum (ENL). There was an association between ENL and the development of cataract and osteoporosis, with 69.7% of cataract cases and 84.4% of osteoporosis cases occurring among individuals with ENL.ConclusionThis systematic review illustrates the range and severity of adverse effects affecting individuals with leprosy who received systemic corticosteroids. Although this review is limited by study heterogeneity, publication bias, and the scarcity of long-term data, it highlights the need for corticosteroid stewardship, structured pharmacovigilance and further research for safer therapeutic alternatives to corticosteroids for leprosy reactions.

Ibiza, an island in present-day Spain, was conquered in 902 CE by the Umayyad Emirate of Córdoba. The island remained under Islamic rule until 1235. Here, we analyse the genetic and metagenomic profiles of 13 individuals from an Islamic cemetery in Ibiza, dated to 950-1150 CE. Genome-wide analyses reveal heterogeneity, with ancestry components from Europe, North Africa, and Sub-Saharan Africa. Our analyses estimate that North African gene flow occurred two to seven generations before these individuals lived, suggesting admixture following the Islamic conquest of Iberia and potentially on Ibiza itself. Notably, two individuals trace their Sub-Saharan origins to distinct regions, Senegambia and present-day southern Chad, providing direct evidence of trans-Saharan connections via military and slave networks documented in contemporary Arabic sources. Metagenomic analyses detect several pathogens in this community, with one individual carrying Mycobacterium leprae, offering insight into the presence of leprosy in Ibiza. Our findings align with the historically documented two-pulse demographic model, indicating an initial settlement following the early tenth-century conquest and a second influx associated with Almoravid movements in the twelfth century. These securely dated genomes offer insights into medieval population dynamics and health in the Balearics.