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Leprosy, caused by the bacterium Mycobacterium leprae, is known to primarily affect the skin and peripheral nerves. We present a rare case of leprosy initially manifesting as demyelinating polyneuropathy. A 46-year-old female presented with progressive weakness, tingling, and numbness in her extremities. Nerve conduction studies revealed evidence of demyelination, prompting further investigations. Skin slit-skin smears confirmed the diagnosis of leprosy, with the presence of acid-fast bacilli. The patient was subsequently started on multidrug therapy, leading to significant clinical improvement. This case highlights the importance of considering leprosy as a differential diagnosis in patients presenting with demyelinating polyneuropathy, especially in endemic regions. [ABSTRACT FROM AUTHOR]

Leprosy is an infectious disease primarily caused by the obligate intracellular parasite Mycobacterium leprae. Although it has been considered eradicated in many countries, leprosy continues to be a health issue in developing nations. Besides the social stigma associated with it, individuals affected by leprosy may experience nerve damage leading to physical disabilities if the disease is not properly treated or early diagnosed. Leprosy is recognized as a complex disease wherein socioenvironmental factors, immune response, and host genetics interact to contribute to its development. Recently, a new field of study called epigenetics has emerged, revealing that the immune response and other mechanisms related to infectious diseases can be influenced by noncoding RNAs. This review aims to summarize the significant advancements concerning non-coding RNAs in leprosy, discussing the key perspectives on this novel approach to comprehending the pathophysiology of the disease and identifying molecular markers. In our view, investigations on non-coding RNAs in leprosy hold promise and warrant increased attention from researches in this field.

Objective: To evaluate the annual number of skin smear microscopies for leprosy performed in the Unified Health System (SUS) in the last decade. Methods: An ecological, longitudinal, retrospective, and quantitative study was conducted using data from the Ambulatory Information System (SIA/SUS). The number of skin smear microscopies for leprosy per 100,000 residents was estimated for Brazil and its five macroregions, between 2013 and 2022, with a significance level (a) of 5%. Results: More than 1.3 million skin smear microscopies were reported in the last decade in the SUS. The median annual incidence was 67 skin smear microscopies for leprosy per 100,000 residents, with the maximum observed in 2013 (82) and the minimum in 2022 (46). Annual incidences in the North, Central-West, and Northeast macro-regions were significantly higher than the national estimate, whereas in the South and Southeast, they were lower (p

Background: Bedaquiline (BDQ), by targeting the electron transport chain and having a long half-life, is a good candidate to simplify leprosy treatment. Our objectives were to (i) determine the minimal effective dose (MED) of BDQ administered orally, (ii) evaluate the benefit of combining two inhibitors of the respiratory chain, BDQ administered orally and clofazimine (CFZ)) and (iii) evaluate the benefit of an intramuscular injectable long-acting formulation of BDQ (intramuscular BDQ, BDQ-LA IM), in a murine model of leprosy. Methodology/Principal findings: To determine the MED of BDQ administered orally and the benefit of adding CFZ, 100 four-week-old female nude mice were inoculated in the footpads with 5x103 bacilli of M. leprae strain THAI53. Mice were randomly allocated into: 1 untreated group, 5 groups treated with BDQ administered orally (0.10 to 25 mg/kg), 3 groups treated with CFZ 20 mg/kg alone or combined with BDQ administered orally 0.10 or 0.33 mg/kg, and 1 group treated with rifampicin (RIF) 10 mg/kg. Mice were treated 5 days a week during 24 weeks. To evaluate the benefit of the BDQ-LA IM, 340 four-week-old female swiss mice were inoculated in the footpads with 5x103 to 5x101 bacilli (or 5x100 for the untreated control group) of M. leprae strain THAI53. Mice were randomly allocated into the following 11 groups treated with a single dose (SD) or 3 doses (3D) 24h after the inoculation: 1 untreated group, 2 treated with RIF 10 mg/kg SD or 3D, 8 treated with BDQ administered orally or BDQ-LA IM 2 or 20 mg/kg, SD or 3D. Twelve months later, mice were sacrificed and M. leprae bacilli enumerated in the footpad. All the footpads became negative with BDQ at 3.3 mg/kg. The MED of BDQ administered orally against M. leprae in this model is therefore 3.3 mg/kg. The combination of CFZ and BDQ 10-fold lower than this MED did not significantly increase the bactericidal activity of CFZ. The BDQ-LA IM displayed similar or lower bactericidal activity than the BDQ administered orally. Conclusion: We demonstrated that the MED of BDQ administered orally against M. leprae was 3.3 mg/kg in mice and BDQ did not add significantly to the efficacy of CFZ at the doses tested. BDQ-LA IM was similar or less active than BDQ administered orally at equivalent dosing and frequency but should be tested at higher dosing in order to reach equivalent exposure in further experiments. Author summary: The current multidrug therapy is effective against leprosy but remains long and difficult to observe for patients supporting the need of monthly -based treatment. Bedaquiline (BDQ), a diarylquinoline with a long half-life, is a candidate drug to shorten leprosy treatment by targeting the electron transport chain and inhibiting the ATP synthesis. In this work, we demonstrated that (i) the minimal effective dose of BDQ administered orally against M. leprae is 3.3 mg/kg, (ii) BDQ did not add significantly to the efficacy of CFZ at the doses tested, and (iii) BDQ long acting formulation was similar or less active than BDQ administered orally at equivalent dosing and frequency but should be tested at higher dosing in order to reach equivalent exposure in further experiments. [ABSTRACT FROM AUTHOR]

Background: Leprosy is rare within non-endemic countries such as Canada, where cases are almost exclusively imported from endemic regions, often presenting after an incubation period of as many as 20 years. Due to its rarity and prolonged incubation period, diagnosis is often delayed, which may result in neurologic impairment prior to the initiation of treatment. In this report we describe a case that is novel in its incubation period, which is the longest reported to-date and may have contributed to diagnostic delay. The case also uniquely demonstrates the challenges of distinguishing leprosy reactions from new rheumatologic manifestations in a patient with established autoimmune disease. Case presentation: We describe an 84-year-old male patient with rheumatoid arthritis on methotrexate and hydroxychloroquine, with no travel history outside Canada for 56 years, who presented in 2019 with new-onset paresthesias and rash. His paresthesias persisted despite a short course of prednisone, and his rash recurred after initial improvement. He underwent skin biopsy in May 2021, which eventually led to the diagnosis of leprosy. He was diagnosed with type 1 reaction and was started on rifampin, dapsone, clofazimine and prednisone, with which his rash resolved but his neurologic impairment remained. Conclusion: This case report serves to highlight the potential for leprosy to present after markedly prolonged incubation periods. This is especially relevant in non-endemic countries that is home to an aging demographic of individuals who migrated decades ago from endemic countries. The importance of this concept is emphasized by the persistent neurologic impairment suffered by our case due to untreated type 1 reaction. We also demonstrate the necessity of skin biopsy in distinguishing this diagnosis from other autoimmune mimics in a patient with known autoimmune disease. [ABSTRACT FROM AUTHOR]

Mycobacterium indicus pranii (MIP), previously called Mw vaccine, is a one-of-a-kind immunomodulatory vaccine. It was indigenously developed in India for use in leprosy. MIP is heat-killed Mycobacterium w, which is a non-pathogenic atypical mycobacterium belonging to Class IV of Runyon classification. It shares epitopes with Mycobacterium leprae and Mycobacterium tuberculosis, which forms the rationale behind its use in leprosy and tuberculosis. MIP activates both innate and acquired immunity. It induces a Th1 and Th17 immune response along with downregulation of Th2 pathway and activates macrophages and dendritic cells. MIP vaccine is safe with adverse effects such as local site erythema, swelling, and rarely fever and other systemic reactions. Apart from leprosy, MIP has been used in dermatological diseases such as warts and psoriasis. Clinical trials have evaluated the efficacy of MIP in a plenitude of non-dermatological conditions such as category II tuberculosis, Gram-negative sepsis, non-small cell lung cancer, human immunodeficiency virus (HIV), muscle-invasive bladder cancer, and very recently, coronavirus 2019 (COVID-19). In vitro and animal studies have also demonstrated its utility in leishmaniasis, melanoma, and as a vaccine for the prevention of pregnancy. The PubMed database was searched using "Mycobacterium indicus pranii, MIP, Mycobacterium w" as the keyword in title. This comprehensive review provides useful information for healthcare professionals about immunotherapeutic potential of MIP vaccine, its composition, dosing schedule, administration, and side effects besides its efficacy in various indications other than leprosy. [ABSTRACT FROM AUTHOR]

Background: Considering the cross-regulation of Th1 and Th2 responses, we hypothesised that atopic diseases (Th2) inhibit the protective Th1 immune response to Mycobacterium leprae and exacerbates leprosy. Objective: In this study, we aimed to evaluate the association between leprosy and atopic diseases. Methods: To evaluate the association of atopic diseases with leprosy, we conducted a case-control study that included leprosy patients (n = 333) and their household contacts (n = 93). The questionnaire from the International Study of Asthma and Allergies in Childhood, which is validated in several countries for epidemiological diagnosis of atopic diseases, was applied to determine the occurrence of atopic diseases, allergic rhinitis, asthma, and atopic dermatitis among leprosy patients and the household contacts. Results: Considering clinical and epidemiological data, among the leprosy group 51.6% (n = 172) were determined to have at least one atopic disease, while atopy was observed less frequently at 40.86% among household contacts (n = 38). When two or more atopic diseases were assessed, the frequency was significantly higher among the leprosy patients than in the household contacts (21.9% vs. 11.8%; P-value = 0.03). Likewise, the frequency of asthma was significantly higher among leprosy patients (21%) than in the household contacts (10.8%; P-value = 0.02). Thus, our analyses revealed an association of atopic diseases with leprosy, with a significant linear increase in the occurrence of leprosy with an increase in the number of atopic diseases (P-value = 0.01). Limitation: Due to the difficulties in recruiting household contacts that have prolonged contact with patients, but are not genetically related to the patient, the household contacts group is smaller than the leprosy patient group. Conclusion: The data reveal an association between atopic diseases and leprosy outcomes. This knowledge could improve the treatment of leprosy patients with co-incident atopic diseases. [ABSTRACT FROM AUTHOR]

Macrophages respond against Mycobacterium leprae infection through interacting with vitamin D and vitamin D receptor (VDR). There has been no study analyzing the association between vitamin D and VDR with bacteriological index (BI) in leprosy patients in Indonesia. To analyze the serum level of 25-hydroxyvitamin D (25(OH)D) and plasma level of VDR as well as their association with BI in leprosy patients in Indonesia. This is a cross-sectional study. Serum level of 25(OH)D was assessed with in vitro chemiluminescent immunoassay. Plasma level of VDR was assessed with enzyme linked immunosorbent assay method. Median serum level of 25(OH)D was 12.68 ng/mL. There was no correlation between serum level of 25(OH)D and BI (r=0.033; p=0.869). Median plasma level of VDR was 1.36 ng/mL. There was no correlation between plasma level of VDR and BI (r=-0.063; p=0.749) and no significant association between BI and serum level of 25(OH) and plasma level of VDR (R²=0.055). There was no association between serum level of 25(OH)D and plasma level of VDR with BI in leprosy patients. [ABSTRACT FROM AUTHOR]

The early diagnosis of leprosy serves as an important tool to reduce the incidence of this disease in the world. Phage display (PD) technology can be used for mapping new antigens to the development of immunodiagnostic platforms. Our objective was to identify peptides that mimic Mycobacterium leprae proteins as serological markers using phage display technology. The phages were obtained in the biopanning using negative and positive serum from household contacts and leprosy patients, respectively. Then, the peptides were synthesized and validated in silico and in vitro for detection of IgG from patients and contacts. To characterize the native protein of M. leprae, scFv antibodies were selected against the synthetic peptides by PD. The scFv binding protein was obtained by immunocapture and confirmed using mass spectrometry. We selected two phase-fused peptides, MPML12 and MPML14, which mimic the HSP60 protein from M. leprae. The peptides MPML12 and MPML14 obtained 100% and 92.85% positivity in lepromatous patients. MPML12 and MPM14 detect IgG, especially in the multibacillary forms. The MPML12 and MPML14 peptides had positivity of 11.1% and 16.6% in household contacts, respectively. There was no cross-reaction in patient's samples with visceral leishmaniasis, tuberculosis and other mycobacteriosis for both peptides. Given these results and the easy obtainment of mimetic antigens, our peptides are promising markers for application in the diagnosis of leprosy, especially in endemic and hyperendemic regions. Key points: PD technology could be used to get and characterize M. leprae mimetic peptides; MPML12 and MPM14 peptides detect IgG antibody in leprosy patients; HSP60 mimetic peptides are specific for leprosy diagnosis. [ABSTRACT FROM AUTHOR]

Despite the great diversity of malonate semialdehyde decarboxylases (MSADs), one of five subgroups of the tautomerase superfamily (TSF) found throughout the biosphere, their distribution among strains within the genus Mycobacterium remains unknown. In this study, we sought to investigate the phylogenetic distribution of MSAD genes of mycobacterial species via genome analysis of 192 different reference Mycobacterium species or subspecies retrieved from NCBI databases. We found that in a total of 87 of 192 strains (45.3%), MSAD-1 and MSAD-2 were distributed in an exclusive manner among Mycobacterium species except for 12 strains, including Mycobacterium chelonae members, with both in their genome. Of note, Mycobacterium strains better adapted to the host and of high virulence potential, such as the Mycobacterium tuberculosis complex, Mycobacterium leprae, Mycobacterium marinum, Mycobacterium ulcerans, and Mycobacterium avium subsp. paratuberculosis, had no orthologs of MSAD in their genome, suggesting MSAD loss during species differentiation in pathogenic slow growing Mycobacterium. To investigate the MSAD distribution among strains of M. avium subspecies, the genome sequences of a total of 255 reference strains from the four subspecies of M. avium (43 of subspecies avium, 162 of subspecies hominissuis, 49 of subspecies paratuberculosis, and 1 of subspecies silvaticum) were further analyzed. We found that only 121 of 255 strains (47.4%) had MSADs in their genome, with none of the 49 M. avium subsp. paratuberculosis strains having MSAD genes. Even in 13 of 121 M. avium strains with the MSAD-1 gene in their genome, deletion mutations in the 98th codon causing premature termination of MSAD were found, further highlighting the occurrence of MSAD pseudogenization during species or subspecies differentiation of M. avium. In conclusion, our data indicated that there are two distinct types of MSADs, MSAD1 and MSAD-2, among strains in the Mycobacterium genus, but more than half of the strains, including pathogenic mycobacteria, M. tuberculosis and M. leprae, have no orthologs in their genome, suggesting MSAD loss during host adaptation of pathogenic mycobacteria. In the future, the role of two distinct MSADs, MSAD-1 and MSAD-2, in mycobacterial pathogenesis or evolution should be investigated. [ABSTRACT FROM AUTHOR]

Background: Hansen's disease, caused by the bacteria Mycobacterium leprae, is a chronic illness that poses various challenges to affected individuals. This study aimed to assess the prevalence and types of psychiatric illnesses among leprosy patients receiving care at a tertiary health care facility in Odisha, while also examining the association between these conditions and sociodemographic and clinical factors. Methodology: A cohort of 100 leprosy patients aged 18 to 60, diagnosed and seeking treatment at the Fakhir Mohan Medical College and Hospital, Balasore, was enrolled in the study. Mental health evaluations were conducted using a specifically designed pro-forma based on the ICD-10 Mental Illness Checklist. Result: Our findings revealed that 34% of leprosy patients exhibited co-existing mental disorders. Depression emerged as the most prevalent mental illness, closely followed by anxiety. Notably, urban residents exhibited a lower prevalence of mental illness compared to their semiurban and rural counterparts. Among leprosy patients, psychiatric issues were more common in the older adult group (51–60 years), with women being more susceptible to mental health challenges than men. Additionally, patients with the lepromatous stage of leprosy demonstrated a higher likelihood of experiencing mental disorders. Conclusion: In our study underscores the significant occurrence of serious mental co-morbidities, particularly depression and anxiety, among leprosy patients. Beyond impacting patient well-being, psychiatric comorbidities also exert a detrimental influence on prognosis and overall morbidity. Timely diagnosis and intervention for these mental health conditions can play a crucial role in improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background Mycobacterium leprae is the primary causative agent of the chronic infectious illness leprosy, can affect peripheral nerves and the skin. Vitamin E, a fat-soluble antioxidant, is essential in the body and can modulate various immune responses. Previous study showed reduced vitamin E levels in leprosy patients. This study evaluated vitamin E levels, differences in paucibacillary and multibacillary type leprosy subjects, and the correlation between bacterial index and vitamin E levels. Methods In this study, 24 leprosy subjects have been included in this analytical investigation using a cross-sectional methodology. Between March and October 2018, the study was carried out in the Dermatology and Venerology Department of the Leprosy Division at the Haji Adam Malik General Hospital in Medan, Pirngadi General Hospital in Medan, Belidahan Leprosy Hospital, Sicanang Leprosy Hospital, and Lau Simomo Leprosy Hospital. Results Leprosy was found primarily in males (70.8%), 16-35 years old (50%). The mean value of vitamin E levels in MB leprosy (9.62±3.91 mg/L) was lower than in PB leprosy (10.55±2.12 mg/L). This study showed a statistically significant correlation between bacterial index and vitamin E levels (r=0.284, p=0.043). Conclusion There is a correlation between bacterial index and vitamin E levels. [ABSTRACT FROM AUTHOR]

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-β, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy. [ABSTRACT FROM AUTHOR]

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Background: Mycobacterium leprae (ML) is the pathogen that causes leprosy, which has a long history and still exists today. ML is an intracellular mycobacterium that dominantly induces leprosy by causing permanent damage to the skin, nerves, limbs and eyes as well as deformities and disabilities. Moreover, ML grows slowly and is nonculturable in vitro. Given the prevalence of leprosy, a highly sensitive and rapid method for the early diagnosis of leprosy is urgently needed. Results: In this study, we devised a novel tool for the diagnosis of leprosy by combining restriction endonuclease, real-time fluorescence analysis and multiple cross displacement amplification (E-RT-MCDA). To establish the system, primers for the target gene RLEP were designed, and the optimal conditions for E-RT-MCDA at 67 °C for 36 min were determined. Genomic DNA from ML, various pathogens and clinical samples was used to evaluate and optimize the E-RT-MCDA assay. The limit of detection (LoD) was 48.6 fg per vessel for pure ML genomic DNA, and the specificity of detection was as high as 100%. In addition, the detection process could be completed in 36 min by using a real-time monitor. Conclusion: The E-RT-MCDA method devised in the current study is a reliable, sensitive and rapid technique for leprosy diagnosis and could be used as a potential tool in clinical settings. [ABSTRACT FROM AUTHOR]

Leprosy (Hansen's disease) is an infectious, neglected tropical skin disease caused by the bacterium Mycobacterium leprae (M. leprae). It is crucial to note that the dynamic behavior of any living microorganism such as M. leprae not only depends on the conditions of its current state (e.g., substrate concentration, medium condition, etc.) but also on those of its previous states. In this article, we have developed a three-dimensional mathematical model involving concentrations of healthy Schwann cells, infected Schwann cells, and M. leprae bacteria in order to predict the dynamic changes in the cells during the disease dissemination process; additionally, we investigated the effect of memory on system cell populations, especially on the M. leprae bacterial population, by analyzing the Caputo–Fabrizio fractionalized version of the model. Most importantly, we developed and investigated a fractionalized optimal-control-induced system comprising the combined drug dose therapy of Ofloxacin and Dapsone intended to achieve a more realistic treatment regime for leprosy. The main goal of our research article is to compare this fractional-order system with the corresponding integer-order model and also to distinguish the rich dynamics exhibited by the optimal-control-induced system based on different values of the fractional order ζ ∈ (0 , 1) . All of the analytical results are validated through proper numerical simulations and are compared with some real clinical data. [ABSTRACT FROM AUTHOR]

Introduction: Leprosy also widely known by the name Hansen's disease is a chronic disease caused by Mycobacterium leprae affecting mankind with various clinico-pathological forms. It remained a major public health issue due to associated case load, morbidity and stigma attached to it. India declared elimination of leprosy in the year 2005. However, it is surprising to see that in some parts of the country, the prevalence is still significant. The objective of the study is to describe the spectrum of histopathological profile of leprosy and compare its correlation with clinical diagnosis in this post elimination era. Methods: A 24-months prospective study was conducted with clinically diagnosed leprosy cases in a tertiary care hospital in eastern India. Lesions were graded and the histopathological slides along with its bacteriological index (BI) on slit skin smears where possible was reviewed and analyzed. Agreement of histopathological finding with clinical finding was established. Results: A total of 220 cases were included in the study. On histopathology, borderline category was the most frequently reported with borderline tuberculoid the most common subtype. Most common clinical feature was hypopigmented plaque, followed by erythematous skin lesions, nodules, macules etc. Bacteriological index was studied in 192 slit skin smears. Moderate agreement between clinical and histopathological diagnosis with kappa measure of inter-rater agreement as 0.457 was noted. Conclusion: Clinico-histopathological correlation is pivotal in the accurate diagnosis of leprosy to prevent, treat, and control the resurgence of the disease in the post-elimination era. [ABSTRACT FROM AUTHOR]

Leprosy is a chronic infectious disease primarily affecting the skin and peripheral nerves and is caused by Mycobacterium leprae. Although effective control measures have significantly reduced its global incidence in recent years, its insidious onset and diverse skin manifestations pose considerable challenges to early diagnosis, particularly among young medical practitioners. This study reports a case of tuberculoid leprosy accompanied by a type I reaction (T1R) to leprosy, aiming to contribute to the broader understanding and management of the disease. The patient came from a leprosy-endemic region and had a family history of leprosy. They first presented with neuritis, characterised by numbness in the left upper limb, which is an early-stage symptom often overlooked. This case accentuates the importance of comprehensive examination techniques, including bacteriological and histological investigations, ultrasound and magnetic resonance imaging, to identify early nerve damage, which is critical for prompt diagnosis and intervention. According to World Health Organization data, approximately 200,000 new cases of leprosy are reported worldwide each year, with a prevalence rate of 0.2 cases per 10,000 individuals. The disease exhibits two clinical forms based on the host's immune response: tuberculoid leprosy in a well-immunised population and lepromatous leprosy in a poorly immunised host. The patient in this study demonstrated signs of tuberculoid leprosy, marked by isolated skin papules and plaques, and a T1R, a tissue-destructive, immune-driven inflammatory process. This case underscores the need for ongoing education and updated diagnostic tools to facilitate the early detection of leprosy, particularly in endemic areas. Moreover, attention must be given to the comprehensive care of patients, encompassing both physical and psychological aspects, to improve their quality of life and mitigate social discrimination and prejudice. [ABSTRACT FROM AUTHOR]

We examined armadillos from museum collections in the United States using molecular assays to detect leprosy-causing bacilli. We found Mycobacterium leprae bacilli in samples from the United States, Bolivia, and Paraguay; prevalence was 14.8% in nine-banded armadillos. US isolates belonged to subtype 3I-2, suggesting long-term circulation of this genotype.

Leprosy is a chronic infectious disease caused by M. leprae with a primary lesion of the skin and peripheral nervous system. Currently, clinicians using bacterioscopic studies of scarification and skin biopsy mainly diagnose leprosy. However, the development and application of new diagnostic criteria, especially those associated with damage to nerve fibers, remains an urgent task of modern leprology. This review considers the important role of neurotrophic factor (nerve growth factor, NGF) in the pathogenesis of nervous system damage in leprosy and establishes the relationship between NGF levels and forms of the disease. The review includes data from foreign and domestic articles; the search was carried out using the “Scopus”, “PubMed”, “Web of Science”, “elIBRARY” databases.

Florida, USA, has witnessed an increased incidence of leprosy cases lacking traditional risk factors. Those trends, in addition to decreasing diagnoses in foreign-born persons, contribute to rising evidence that leprosy has become endemic in the southeastern United States. Travel to Florida should be considered when conducting leprosy contact tracing in any state.

Background: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae or Mycobacterium lepromatosis and mainly affects the skin and peripheral nerves. Although treatable, its early intervention can significantly reduce the occurrence of disability. India accounts for more than half of new cases globally. This study was undertaken to better understand the clinical traits of newly diagnosed cases in a tertiary facility of Western Uttar Pradesh, and a few from Madhya Pradesh and Uttarakhand. Methods: The observational prospective study was carried out on all the newly diagnosed leprosy cases who visited the Outpatient Department of ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, during October 2019–December 2022. After obtaining answers to a prestructured questionnaire with their consent, participants were enrolled in the study and underwent clinical examination and a slit-skin smear test. Results: A total of 56 cases were investigated, and among them, 20 (35.7%) and 36 (64.3%) women and men, respectively, had positive contact with persons affected by leprosy either within family, friends, or neighbors. It is observed that due to the delayed detection of leprosy cases, paucibacillary (PB) patients converted into multibacillary (MB) patients, and the number of MB cases is much higher compared to PB cases. Conclusion: Leprosy instances continue to spread frequently from sick to healthy people indicating continued transmission of leprosy in society. Multidrug therapy in the management of leprosy cases is effective; however, early diagnosis of PB cases is still a challenge and needs to be addressed on priority.

Objectives: As the only bactericidal drug in multidrug therapy is rifampicin, monitoring of antimicrobial resistance is important in leprosy patients. Therefore, we conducted a meta-analysis on the resistance of Mycobacterium leprae (M. leprae) to rifampicin and estimated drug resistance in different therapeutic states and regions. Methods: Embase, Medline, PubMed, and Web of Science were searched to identify studies between 1 January 1993 and 1 January 2022. Two independent reviewers extracted study data. Pooled cumulative incidences were computed using random-effects meta-analyses. Results: We included 32 papers describing the resistance of M. leprae to rifampicin (pooled cumulative incidences, 11% [95% confidence interval {CI}, 7% to 15%]). Therapeutic states and regional distribution were obtained for subgroup analyses. A total of 51 of 1135 new cases (pooled incidence, 10% [95% CI, 5% to 16%]) and 81 of 733 relapsed cases (pooled incidence, 20% [95% CI, 13% to 27%]) had rifampicin resistance. A total of 139 participants, including 11 patients with rifampicin resistance (pooled incidence, 42% [95% CI, −21% to 105%]), were nonresponsive and intractable cases. The incidence of rifampicin resistance was highest in the Western Pacific (pooled incidence, 21% [95% CI, 13% to 29%]) and lowest in the Americas (pooled incidence, 4% [95% CI, 1% to 7%]). Conclusions: Drug resistance testing and a robust and rigorous surveillance system are recommended to detect the prevalence of drug resistance in leprosy.

Leprosy is caused by Mycobacterium leprae (M. leprae) and M. lepromatosis, an obligate intracellular organism, and over 200,000 new cases occur every year. M. leprae parasitizes histiocytes (skin macrophages) and Schwann cells in the peripheral nerves. Although leprosy can be treated by multidrug therapy, some patients relapse or have a prolonged clinical course and/or experience leprosy reaction. These varying outcomes depend on host factors such as immune responses against bacterial components that determine a range of symptoms. To understand these host responses, knowledge of the mechanisms by which M. leprae parasitizes host cells is important. This article describes the characteristics of leprosy through bacteriology, genetics, epidemiology, immunology, animal models, routes of infection, and clinical findings. It also discusses recent diagnostic methods, treatment, and measures according to the World Health Organization (WHO), including prevention. Recently, the antibacterial activities of anti-hyperlipidaemia agents against other pathogens, such as M. tuberculosis and Staphylococcus aureus have been investigated. Our laboratory has been focused on the metabolism of lipids which constitute the cell wall of M. leprae. Our findings may be useful for the development of future treatments.

Leprosy, a chronic granulomatous disease generally caused by Mycobacterium leprae and Mycobacterium lepromatosis, remains a serious public health concern, particularly in developing countries. With the introduction of multi-drug therapy (MDT) by the World Health Organization in 1980, the prevalence of leprosy has declined globally. In the past, acid-fast bacilli frequently developed resistance to both first-line (dapsone, rifampicin and clofazimine) and second-line drugs (fluoroquinolones, minocycline and clarithromycin). According to previous research, it is reported that genes like rpoB, gyrA and folP play a role in drug resistance. Considering its exceptionally modest pace of growth, it is challenging to cultivate M. leprae in a laboratory environment on a synthetic medium. Thus, studies on animal models have assisted in evaluating anti-leprosy drugs and documentation of drug-resistant strains, as well as other basic immunological investigations examining the efficacy of vaccinations. In addition to the conventionally administered MDT treatments, several newly developed drugs have shown more impressive results, along with combinational therapies of moxifloxacin-based regimens, having much better efficacy. This review focuses on the increscent journey of anti-leprosy drugs to treat the disease and highlights the relevance of animal models in the research and development of anti-leprosy drugs. [ABSTRACT FROM AUTHOR]

Background: Individuals with leprosy are at risk of leprosy reactions, T-cell mediated immunological complications, which lead to nerve function impairment. Leprosy reactions require systemic immunosuppression which is a risk factor for severe COVID-19. Vaccination for SARS-CoV-2 infection is recommended in the UK and became widely available in 2021 with individuals at increased risk of severe disease, including the immunosuppressed, prioritised. Vaccines for SARS-CoV-2 may provoke a T cell response. The latter poses a theoretical risk of provoking an immunological response to latent Mycobacterium leprae infection leading to clinical disease or in those with clinical disease triggering a leprosy reaction. BCG vaccination is associated with the development of leprosy in a small proportion of healthy contacts of people with leprosy within twelve weeks of administration. BCG causes a Th1 immune response. Methodology/Principal findings: We performed a retrospective cohort study to determine the SARS-CoV-2 vaccination status of individuals diagnosed with leprosy attending the Leprosy Clinic in 2021 and whether any had developed leprosy or experienced a new leprosy reaction within twelve weeks of receiving a dose of a SARS-CoV-2 vaccine. The electronic patient records were used to retrieve data. Fifty-two individuals with leprosy attended the clinic in 2021 of which five people were newly diagnosed with leprosy. Thirty-seven (71%) were male and the median age was 48.5 years old (Range 27–85 years). Eight (15.4%) individuals were taking multi-drug therapy (MDT) and eight (15.4%) had completed MDT within three years of the study. Twenty-two (41.5%) individuals were prescribed a systemic immunosuppressant drug during 2021. Ten (18.9%) individuals have one or more risk factors for severe COVID-19. The SARS-CoV-2 vaccination status of fifty (96%) were recorded of which forty-nine were vaccinated (98%). One individual had declined vaccination. One individual was diagnosed with borderline tuberculoid (BT) leprosy having developed red skin lesions with reduced sensation (which increased in size and number) and thickened peripheral nerves one week after a second dose of BNT162b2 vaccine. Another individual who had completed MDT more than three years earlier developed red plaques and tender thickened nerves consistent with a leprosy Type 1 reaction eight weeks after a single dose of BNT162b2 vaccine (having received two doses of CoronaVac vaccine three months earlier). Conclusions/Significance: The development of BT leprosy and a Type 1 reaction in another individual shortly after a dose of BNT162b2 vaccine may be associated with vaccine mediated T cell responses. The benefits of vaccination to reduce the risk of severe COVID-19 outweigh these unwanted events but data from leprosy endemic countries may provide further information about potential adverse effects of augmented T cell responses in individuals with leprosy or latent M. leprae infection. Author summary: Leprosy is a neglected tropical disease caused by Mycobacterium leprae. The clinical presentation varies depending on the immune response of the affected person. The infection is curable with antimicrobial therapy but individuals with leprosy can experience immune-mediated complications known as leprosy reactions. There are reports of vaccines, including those for SARS-CoV-2 being associated with the development of leprosy or leprosy reactions. We performed a retrospective study to determine the vaccination status of all individuals diagnosed with leprosy attending the Leprosy Clinic in 2021 and whether any individual had developed leprosy or a new leprosy reaction within 12 weeks of receiving a dose of a SARS-CoV-2 vaccine. Fifty-two individuals with leprosy attended the clinic, five newly diagnosed and eight individuals were on antimicrobial treatment. Twenty-two individuals were prescribed an immunosuppressant drug during 2021. Forty-nine individuals had at least one vaccine dose, one was unvaccinated There was no vaccination record for two individuals. Two individuals met our criteria for a SARS-CoV-2 vaccine associated new leprosy adverse event. We have reviewed other cases of vaccine associated leprosy adverse events and conclude that the benefits of vaccination to reduce the risk of severe COVID-19 outweigh these unwanted events. It is important for clinicians to be aware of the potential leprosy adverse events associated with SARS-CoV-2 vaccination and to advise leprosy affected individuals to report any new symptoms immediately. [ABSTRACT FROM AUTHOR]

Neglected tropical diseases are those caused by infectious agents or parasites and are considered endemic in low-income populations. These diseases also have unacceptable indicators and low investment in research, drug production, and control. Tropical diseases such as leishmaniasis are some of the main causes of morbidity and mortality around the globe. Electrochemical immunosensors are promising tools for diagnostics against these diseases. One such benefit is the possibility of assisting diagnosis in isolated regions, where laboratory infrastructure is lacking. In this work, different peptides were investigated to detect antibodies against Leishmania in human and canine serum samples. The peptides evaluated (395-KKG and 395-G) have the same recognition site but differ on their solid-binding domains, which ensure affinity to spontaneously bind to either graphene oxide (GO) or graphene quantum dots (GQD). Cyclic voltammetry and differential pulse voltammetry were employed to investigate the electrochemical behavior of each assembly step and the role of each solid-binding domain coupled to its anchoring material. The graphene affinity peptide (395-G) showed better reproducibility and selectivity when coupled to GQD. Under the optimized set of experimental conditions, negative and positive human serum samples responses were distinguished based on a cut-off value of 82.5% at a 95% confidence level. The immunosensor showed selective behavior to antibodies against Mycobacterium leprae and Mycobacterium tuberculosis, which are similar antibodies and potentially sources of false positive tests. Therefore, the use of the graphene affinity peptide as a recognition site achieved outstanding performance for the detection of Leishmania antibodies. [ABSTRACT FROM AUTHOR]

IntroductionLeprosy, one of the oldest known human diseases, continues to pose a global challenge for disease control due to an incomplete understanding of its transmission pathways. Ticks have been proposed as a potential contributor in leprosy transmission due to their importance as vectors for other infectious diseases.MethodsIn 2010, a sampling of ticks residing on cattle was conducted on the islands Grande Comore, Anjouan, and Mohéli which constitute the Union of the Comoros where leprosy remains endemic. To investigate the potential role of ticks as a vector in transmission of leprosy disease, molecular analyses were conducted.ResultsOut of the 526 ticks analysed, none were found to harbour Mycobacterium leprae DNA, as determined by a quantitative polymerase chain reaction (qPCR) assay targeting a family of dispersed repeats (RLEP) specific to M. leprae.DiscussionTherefore, our results suggest that in the Union of the Comoros, ticks are an unlikely vector for M. leprae.

Introduction: Leprosy is a slowly progressive chronic granulomatous disease caused by Mycobacterium Leprae (M. leprae) and predominantly affects skin and peripheral nerves. Leprosy is a leading cause of physical disability in India and poses a major public health challenge for the country. Histopathological evaluation and demonstration of Lepra bacilli by special stain is gold standard for definitive diagnosis and subtyping of leprosy. Aim: To study the common histological subtypes of leprosy on the basis of microscopic features and bacteriological index. Materials and Methods: A cross-sectional study was conducted in the Department of Pathology at Dr. S.N. Medical College, Jodhpur, Rajasthan, India. The duration of the study was two years and 11 months, from January 2019 to December 2021. A total of 55 skin biopsies which were histologically diagnosed as different types of leprosy were included. Patients data of age, gender, skin examination and other investigations were collected from the requisition forms and analysed. After proper fixation and processing of biopsy samples, Haematoxylin and Eosin (H&E) stained sections were examined for epidermal atrophy, presence of grenz zone, granulomas, infiltrates of lymphocytes, histiocytes, foam cells, infiltration of nerves and adnexa. The sections stained with Fite-Faraco stain were studied for the assessment of bacteriological index. On the basis of microscopic features, cases were categorised into tuberculoid leprosy, borderline tuberculoid leprosy, indeterminate leprosy, borderline leprosy, lepromatous leprosy and histoid leprosy as per Ridley-Jopling classification and percentage is calculated for each category. Data was entered and analysed by using Microsoft Excel version 2008 and Statistical Package for Social Sciences (SPSS) version 23.0. Results: The mean age of the study participants was 39.6 years. Male to female ratio was 2.92:1. There were 33 (60%) cases with erythematous lesions followed by 15 (27.27%) hypopigmented lesions and 7 (12.73%) nodules. Out of 55 there were 21 (38.18%) cases of tuberculoid leprosy followed by 11 (20%) cases of borderline tuberculoid leprosy, 8 (14.55%) cases of indeterminate leprosy, 6 (10.91%) cases of borderline leprosy, 5 (9.09%) cases of lepromatous leprosy and 4 (7.27%) cases of histoid leprosy. Bacteriological index was negative in 35 (63.64%) cases followed by 2+ in 6 (10.91%) cases, 5 (9.09%) had index of 4+, 4 (7.27%) cases had index of 3+, 3 (5.45%) had index of 1+, and 1 (1.82%) case had index of 5+ and 6+ each. Conclusion: Skin biopsy is easy, simple, inexpensive and outpatient procedure which provides adequate material for confirmation of the clinical diagnosis and further management. Histopathological examination including microscopic features of H&E stained sections, along with assessment of bacteriological index on Fite-Faraco stained sections remain the gold standard for diagnosis and subtyping of leprosy cases.

Introduction: Chronic plantar ulcers in leprosy are lesions resulting from motor and sensory alterations caused by Mycobacterium leprae. They are lesions refractory to conventional dressings and present high recurrence rates. Objective: To evaluate the epidemiological clinical profile of patients with chronic plantar ulcers associated with bony prominences in the lesion bed and to evaluate the efficacy of orthopedic surgical treatment of these lesions. Methods: This is a descriptive and analytical retrospective study with the evaluation of medical records of patients undergoing surgical treatment of chronic plantar ulcers from 2008 to 2018. The surgical technique applied consisted of corrective resection of bone prominences and the primary closure of the lesion with bipediculated local flap. Results: 234 patients were submitted to surgery, 55.1% male with an average age of 69.5 years old. Of these, 82.9% were illiterate; and 88.5% with open lesions over 10 years. After surgical treatment, total wound healing occurred in an average time of 12 weeks. The variables that contributed to shorter healing time were: Patients' lower age group; regular use of orthopedic shoes and insoles and dressings performed by nurse aides in health units before surgery. Obesity was the factor that correlated with the delay of healing time. Conclusion: A higher incidence was observed in males and male and female illiterate patients. The regular use of shoes and insoles and dressings performed by nurse aides in health units contributed to shorter postoperative healing time. Orthopedic surgical treatment with corrective resection of bony prominences proved to be an efficient therapeutic method for the closure of chronic plantar ulcers. It is a reproducible method, justifying the importance of the orthopedic surgeon in the context of the multidisciplinary team to cope with these complex lesions. [ABSTRACT FROM AUTHOR]

The case report of a patient infected by the human immunodeficiency virus in early symptomatic phase is described, who was seen at the Dermatology Service of the Dr. León Cuervo Rubio Teaching Clinical Surgical Hospital of Pinar del Río for presenting infiltrated erythematous lesions of three months of evolution in the right lower limb, with altered pain and thermal sensation. A basiloscopic and histopathologic study was indicated, which confirmed the presumptive diagnosis of borderline tuberculoid leprosy, and therefore polychemotherapy combined with antiretroviral therapy was started, which favored the patient's evolution. [ABSTRACT FROM AUTHOR]

Introduction: Leprosy is an infectious and chronic disease caused by Mycobacterium leprae. Despite the great worldwide progress after the introduction of multidrug therapy (MDT), leprosy is still considered a major public health problem. The analysis of epidemiological data is important for the implementation of public health policies that allow for breaking the cycle of leprosy transmission and facilitating early diagnosis. Methods: This is an observational, cross-sectional, and descriptive epidemiological study. Data were obtained from the Notifiable Diseases Information System (SINAN), the official information system for leprosy in the country. Results: During this period, 338,904 cases of leprosy were reported. The northeast region, the one with the most cases, is considered the poorest in the country, with many inhabitants in an unfavorable socioeconomic situation. The majority of multibacillary (MB) patients were associated with late diagnosis, and therefore it maintains the transmission and worsens neurological damage. Discussion: The probability of occurrence and reactivation of leprosy was higher in patients with a low level of education, as this class has a low level of knowledge. Conclusion: Leprosy has a long incubation period, which increases in adult and elderly cases. Despite the improvements in leprosy control, the disease persists as a public health problem. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae or Mycobacterium lepromatosis and mainly affects the skin and peripheral nerves. Although treatable, its early intervention can significantly reduce the occurrence of disability. India accounts for more than half of new cases globally. This study was undertaken to better understand the clinical traits of newly diagnosed cases in a tertiary facility of Western Uttar Pradesh, and a few from Madhya Pradesh and Uttarakhand. Methods: The observational prospective study was carried out on all the newly diagnosed leprosy cases who visited the Outpatient Department of ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, during October 2019-December 2022. After obtaining answers to a prestructured questionnaire with their consent, participants were enrolled in the study and underwent clinical examination and a slit-skin smear test. Results: A total of 56 cases were investigated, and among them, 20 (35.7%) and 36 (64.3%) women and men, respectively, had positive contact with persons affected by leprosy either within family, friends, or neighbors. It is observed that due to the delayed detection of leprosy cases, paucibacillary (PB) patients converted into multibacillary (MB) patients, and the number of MB cases is much higher compared to PB cases. Conclusion: Leprosy instances continue to spread frequently from sick to healthy people indicating continued transmission of leprosy in society. Multidrug therapy in the management of leprosy cases is effective; however, early diagnosis of PB cases is still a challenge and needs to be addressed on priority. [ABSTRACT FROM AUTHOR]

Introduction: Leprosy also known as Hansen's Disease (HD), is a chronic infectious granulomatous disease caused by Mycobacterium leprae. It affects the skin and peripheral nerves. It is characterised by the formation of nodules or macules that enlarge and spread with loss of sensation due to nerve involvement which can progress to paralysis and eventually lead to deformities. Aim: To describe the clinical and epidemiological pattern of leprosy patients in a tertiary care hospital in Bareilly, Uttar Pradesh, India. Materials and Methods: This retrospective study was conducted at a tertiary level, Military Hospital in Bareilly, Uttar Pradesh, India, from June 2022 to August 2022. Medical records of 263 Leprosy patients, who were diagnosed as HD clinically and histopathologically were part of the study. All their data pertaining to the history, onset, time of detection, clinical features in the form, type and number of patches, presence of peripheral nerve thickenings, investigations which included skin slit smear for Acid Fast Bacilli (AFB) (Lepra) and histopathological examination, duration of drug therapy, reactions encountered and the disabilities were collected. Results: A total of 263 case records of leprosy patients (225 males (85.55%) and 38 females (14.45%), mean age of 35.36±13.79 years) were analysed. Majority of the cases were Borderline Tuberculoid (BT) Hansen's 113 (42.96%). Average time taken by the patients before reporting to the Leprosy centre from onset of symptoms was 18 months. The most common clinical manifestation was multiple light coloured numb patches in 169 patients. A total of 245 patients had peripheral nerve thickening with Ulnar nerve 205 (77.95%) being the most commonly affected nerve. A total of 98 patients had Type-1 reaction and 13 had Type-2 reaction. The Grade-2 disability was seen in 22 cases with claw hand deformity being the commonest 10 (45.45%). Conclusion: In present study, majority patients were male with the most common clinical manifestation being multiple numb patches all over the body. The most common type of leprosy which presented was BT HD. [ABSTRACT FROM AUTHOR]

Mycobacteria form some of the most notorious and difficult-to-treat bacterial pathogens. As a group, they are intrinsically resistant to many commonly used antibiotics, such as tetracyclines and beta-lactams. In addition to intrinsic resistances, acquired multidrug resistance has also been observed and documented in Mycobacterium tuberculosis (MTB), Mycobacterium leprae and non-tuberculous mycobacteria (NTM). To combat multidrug resistant infections by these pathogens, innovative antimicrobials and treatment regimens are required. In this regard, linezolid, an oxazolidinone introduced for clinical use just two decades ago, was added to the therapeutic armamentarium for drug-resistant mycobacteria. It exhibits antibacterial activity by binding to the 50S ribosomal subunit and inhibiting protein synthesis. Unfortunately, linezolid resistance has now been documented in MTB and NTM, in many parts of the world. Most linezolid-resistant mycobacterial strains show mutations in the ribosome or related genes, such as in the rplC, rrl and tsnR genes. Non-ribosomal mechanisms appear to be rare. One such mechanism was associated with a mutation in fadD32, which encodes a protein that plays an important role in mycolic acid synthesis. Mycobacterial efflux proteins have also been implicated in linezolid resistance. This review summarises current knowledge of genetic determinants of linezolid resistance in mycobacteria, with the aim of contributing information that could facilitate the discovery of new therapeutic approaches to overcome, delay or avoid further developments of drug resistance among these important pathogens. [ABSTRACT FROM AUTHOR]

The two polar clinical forms of leprosy, termed tuberculoid and lepromatous, have polarized cellular immune responses with complex immunological distinctions. The predominance of DCs in tuberculoid leprosy has been reported, while the lepromatous pattern of illness is associated with weak activation of local populations of DCs. TiO2 nanoparticles have previously been shown to induce maturation of these cells, leading to an inflammatory response similar to adjuvant usage in vaccine administration. We aimed to evaluate the effect of potassium-incorporated Ti oxide nanostructures, namely KTiOxs, in the response of human monocyte-derived DCs to live M. leprae. Human monocytic cell line dual THP-1, which harbors two inducible reporter plasmid systems for transcription factor activation of NF-κB and interferon regulating factor (IRF), was treated with titanium control or with 1 mol/L KOH-treated Ti or 10 mol/L KOH for 24 h. Subsequently, cells were infected with M. leprae. KTiOx nanoparticles increase DC phagocytic activity without inflammation. KTiOx exposure of DCs led to an increase in IRF activation with modulation of the inflammatory response to live M. leprae. It also led to differential secretion of the critical components of innate immune response and the development of cell-mediated immunity against intracellular pathogens. This study demonstrates the effect of nanostructures of KTiOxs and the usefulness of nanoparticle technology in the in vitro activation of human DCs against an infectious disease with a puzzling immune spectrum. Our findings may prompt future therapeutic strategies, such as DC immunotherapy for disseminated and progressive lepromatous lesions. [ABSTRACT FROM AUTHOR]

Background: Leprosy, a chronic infectious peripheral neuropathy, is caused by Mycobacterium leprae. This bacterium produces triacylated lipopeptides that can induce the immune system via the Toll-like receptor 2/1 (TLR 2/1) complex. Activation of TLR 2/1 produces proinflammatory cytokines and antimicrobial peptides (AMPs), including human beta-defensin-3 (HBD-3) and cathelicidin. Purpose: To analyze differences in gene expression of HBD-3 and cathelicidin in the skin of leprosy patients, household contacts, and healthy individuals. Patients and Methods: An analytic observational study was conducted at the Outpatient Clinic of Dermatology and Venereology of Dr Mohammad Hoesin General Hospital, Palembang, Indonesia, from January 2021 to June 2022. In each group of 18 subjects, 72 samples were collected, including skin lesion in leprosy patients, normal skin in leprosy patients, household contacts, and healthy individuals. A comparison of HBD-3 and cathelicidin gene expression between the four groups was analyzed using Pearson Chi Square, Kruskal–Wallis, and Mann–Whitney Test. Results: The median value of HBD-3 gene expression on skin lesion in leprosy patients was 260.61 (0.19– 3734.10); normal skin in leprosy patients was 1.91 (0.01– 151.17); household contacts skin was 7.93 (0.27– 121.10); and healthy individuals' skin was 1.00 (1.00– 1.00) is highly significant difference (p < 0.0001). The median value of cathelicidin gene expression on skin lesion in leprosy patients was 38.72 (0.28– 1852.17); normal skin in leprosy patients was 0.48 (0.01– 15.83); household contacts skin was 9.8 (0.04– 128.0); and healthy individual skin was 1.00 (1.00– 1.00), also highly significant difference (p < 0.0001). Conclusion: Gene expression of HBD-3 and cathelicidin increased in skin lesions of leprosy patients and household contacts. [ABSTRACT FROM AUTHOR]

IntroductionLeprosy, an infectious disease caused by Mycobacterium leprae, remains a public health concern in endemic countries, particularly in Brazil. In this study, we conducted an active surveillance campaign in the hyperendemic city of Castanhal in the northeastern part of the state of Pará using clinical signs and symptoms combined with serological and molecular tools to diagnose new cases and to identify drug resistance of circulating M. leprae strains and their distribution in the community.MethodsDuring an active surveillance of one week, we enrolled 318 individuals using three different strategies to enroll subjects for this study: (i) an active survey of previously treated cases from 2006 to 2016 found in the Brazil National Notifiable Disease Information System database (n = 23) and their healthy household contacts (HHC) (n = 57); (ii) an active survey of school children (SC) from two primary public schools in low-income neighborhoods (n = 178), followed by visits to the houses of these newly diagnosed SC (n = 7) to examine their HHC (n = 34) where we diagnosed additional new cases (n = 6); (iii) and those people who spontaneously presented themselves to our team or the local health center with clinical signs and/or symptoms of leprosy (n = 6) with subsequent follow-up of their HHC when the case was confirmed (n = 20) where we diagnosed two additional cases (n = 2). Individuals received a dermato-neurological examination, 5 ml of peripheral blood was collected to assess the anti-PGL-I titer by ELISA and intradermal earlobe skin scrapings were taken from HHC and cases for amplification of the M. leprae RLEP region by qPCR.ResultsAnti-PGL-I positivity was highest in the new leprosy case group (52%) followed by the treated group (40.9%), HHC (40%) and lowest in SC (24.6%). RLEP qPCR from SSS was performed on 124 individuals, 22 in treated cases, 24 in newly diagnosed leprosy cases, and 78 in HHC. We detected 29.0% (36/124) positivity overall in this sample set. The positivity in treated cases was 31.8% (7/22), while in newly diagnosed leprosy cases the number of positives were higher, 45.8% (11/23) and lower in HHC at 23.7% (18/76). Whole genome sequencing of M. leprae from biopsies of three infected individuals from one extended family revealed a hypermutated M. leprae strain in an unusual case of primary drug resistance while the other two strains were drug sensitive.DiscussionThis study represents the extent of leprosy in an active surveillance campaign during a single week in the city of Castanhal, a city that we have previously surveyed several times during the past ten years. Our results indicate the continuing high transmission of leprosy that includes fairly high rates of new cases detected in children indicating recent spread by multiple foci of infection in the community. An unusual case of a hypermutated M. leprae strain in a case of primary drug resistance was discovered. It also revealed a high hidden prevalence of overt disease and subclinical infection that remains a challenge for correct clinical diagnosis by signs and symptoms that may be aided using adjunct laboratory tests, such as RLEP qPCR and anti-PGL-I serology.

Leprosy is an infectious and contagious disease of slow evolution, triggered by Mycobacterium leprae. Arthritis is its third most common manifestation, after cutaneous and peripheral nerve involvement. Since musculoskeletal symptoms may be the initial presentation of the disease, it is important for health professionals to recognize its rheumatic manifestations for early diagnosis and appropriate treatment, especially in endemic areas. In addition, cases of leprosy have increased globally, notably in patients undergoing treatment with TNF-α blockers and due to the increase in migration and travel of people from developing countries to developed countries. This review proposes to discuss the main scenarios of mimicry of different rheumatic diseases by leprosy, as well as the role of immunosuppressive drugs used in rheumatology practice in the treatment of reactional states and in the risk of developing the infection.

Different bacterial species have dramatically different generation times, from 20–30 min in Escherichia coli to about two weeks in Mycobacterium leprae. The translation machinery in a cell needs to synthesize all proteins for a new cell in each generation. The three subprocesses of translation, i.e., initiation, elongation, and termination, are expected to be under stronger selection pressure to optimize in short-generation bacteria (SGB) such as Vibrio natriegens than in the long-generation Mycobacterium leprae. The initiation efficiency depends on the start codon decoded by the initiation tRNA, the optimal Shine–Dalgarno (SD) decoded by the anti-SD (aSD) sequence on small subunit rRNA, and the secondary structure that may embed the initiation signals and prevent them from being decoded. The elongation efficiency depends on the tRNA pool and codon usage. The termination efficiency in bacteria depends mainly on the nature of the stop codon and the nucleotide immediately downstream of the stop codon. By contrasting SGB with long-generation bacteria (LGB), we predict (1) SGB to have more ribosome RNA operons to produce ribosomes, and more tRNA genes for carrying amino acids to ribosomes, (2) SGB to have a higher percentage of genes using AUG as the start codon and UAA as the stop codon than LGB, (3) SGB to exhibit better codon and anticodon adaptation than LGB, and (4) SGB to have a weaker secondary structure near the translation initiation signals than LGB. These differences between SGB and LGB should be more pronounced in highly expressed genes than the rest of the genes. We present empirical evidence in support of these predictions.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, an SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases retrospectively (2010–2017) and prospectively (2018–2022). We conducted a retrospective audit to determine the comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,641 household contacts were identified (9791 in the retrospective and 3850 in the prospective cohort). In the retrospective cohort, 1044 (11%) contacts were absent, 403 (4%) were ineligible for SDR, and 42 new cases were detected (0.4%) Overall, SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR, and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were 23 SDR refusals. The median time to SDR administration was 220 days (IQR 162–468) and 120 days (IQR 36–283) for the retrospective and prospective cohorts, respectively. SDR was readily accepted in both cohorts. The new case detection rate (0.5%) is consistent with that in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.