Leprae Infection Research Articles

Leprosy.

Leprosy, a neglected tropical disease, causes significant morbidity in marginalized communities. Before the COVID-19 pandemic, annual new case detection plateaued for over a decade at ~200,000 new cases. The clinical phenotypes of leprosy strongly parallel host immunity to its causative agents Mycobacterium leprae and Mycobacterium lepromatosis. The resulting spectrum spans from paucibacillary leprosy, characterized by vigorous pro-inflammatory immunity with few bacteria, to multibacillary leprosy, harbouring large numbers of bacteria with high levels of seemingly non-protective, anti-M. leprae antibodies. Leprosy diagnosis remains clinical, leaving asymptomatic individuals with infection undetected. Antimicrobial treatment is effective with recommended multidrug therapy for 6 months for paucibacillary leprosy and 12 months for multibacillary leprosy. The incubation period ranges from 2 to 6 years, although longer periods have been described. Given this lengthy incubation period and dwindling clinical expertise, there is an urgent need to create innovative, low-complexity diagnostic tools for detection of M. leprae infection. Such advancements are vital for enabling swift therapeutic and preventive interventions, ultimately transforming patient outcomes. National health-care programmes should prioritize early case detection and consider post-exposure prophylaxis for individuals in close contact with affected persons. These measures will help interrupt transmission, prevent disease progression, and mitigate the risk of nerve damage and disabilities to achieve the WHO goal 'Towards Zero Leprosy' and reduce the burden of leprosy.

Leprosy as a cause of nasolacrimal duct obstruction.

Leprosy, also known as Hansen disease, is an airborne spread disease caused by Mycobacterium leprae (M. leprae) which commonly presents with skin lesions, peripheral neuropathy, and ocular involvement. This report describes a patient who presented with epiphora secondary to chronic nasolacrimal duct obstruction four years after completing antimicrobial treatment for tuberculoid leprosy. At the time of endoscopic dacryocystorhinostomy (DCR), the lacrimal sac demonstrated chronic dacryocystitis with granulomatous inflammation and a Fite positive staining bacterial rod-like structure. Pathological examination of the surgical specimen demonstrated numerous non-necrotizing granulomas in a perivascular and neural distribution, compatible with sequelae of previously treated M. leprae infection. The patient has remained symptom free six months after surgery.

A case report and literature review: Mycobacterium leprae infection diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid

BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that is responsible for deformities and irreversible peripheral nerve damage and has a broad spectrum of clinical and serological manifestations. Leprosy primarily affects the peripheral nerves and rarely presents with central nervous system involvement. Diagnosing leprosy can still be difficult in some cases, especially when the infection involves uncommon clinical manifestations and extracutaneous sites. Delayed diagnosis and treatment of leprosy may lead to irreversible damage and death.Case PresentationWe report a case of a 30-year-old female presenting with “repeated high fever with symptoms of headache for 14 days”. On the day of admission, physical signs of lost eyebrows and scattered red induration patches all over her body were observed. The patient’s diagnosis was based on the clinical characteristics using a combination of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and slit-skin smear. After confirming Listeria meningitis and multibacillary leprosy with erythema nodosum leprosum (ENL), a type 2 reaction, she was treated with ampicillin sodium, dapsone, rifampicin, clofazimine, methylprednisolone, and thalidomide. At the 1-year follow-up, the frequency and severity of headaches have significantly decreased and a good clinical response with improved skin lesions was found.ConclusionThis case highlights the importance of considering leprosy, which is a rare and underrecognized disease, in the differential diagnosis of skin rashes with rheumatic manifestations, even in areas where the disease is not endemic, and physicians should be alerted about the possibility of central nervous system infections. In addition, mNGS can be used as a complementary diagnostic tool to traditional diagnostic methods to enhance the diagnostic accuracy of leprosy.

Type II Reaction Erythema Nodosum Leprosum: A Case Report

Leprosy, or Hansen's disease, is a chronic granulomatous infectious disease caused by Mycobacterium leprae. This is a case of a 25-year-old male from Micronesia who presented to a hospital in the Midwest with a two-week history of a widespread, nodular, erythematous, painful rash most severe on his lower extremities and sparing only his hands and feet. In addition to the cutaneous manifestations, the patient met the criteria for Systemic Inflammatory Response Syndrome (SIRS) due to his presentation of tachycardia, tachypnea, leukocytosis, and elevated inflammatory markers. A short course of antibiotics, including Piperacillin-Tazobactam and Vancomycin, and IV steroids were started on admission. A skin biopsy taken from the center and edge of a lesion on the patient’s right arm demonstrated acute and chronic granulomatous superficial and deep inflammation with abundant acid-fast bacilli consistent with lepromatous leprosy from a Mycobacterium leprae infection. Once the National Hansen's Disease Center was contacted previous therapies were stopped and a multidrug therapy, consisting of Rifampin, Moxifloxacin, Minocycline, Methotrexate, and Prednisone was started. The multidrug therapy promptly resulting in substantial clinical improvement over the subsequent months. This case emphasizes the significance of early recognition, accurate diagnosis, and timely initiation of appropriate treatment in leprosy management, even in unlikely regions such as the Midwestern United States.

DETERMINING FACTORS OF LEPROSY: A CASE-CONTROL STUDY IN A HYPERENDEMIC AREA OF THE BRAZILIAN LEGAL AMAZON

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It can result in permanent physical disabilities if not diagnosed early. A case-control study was conducted to identify the factors associated with the occurrence of leprosy in individuals living in a region of high incidence of the disease in the Tocantins state in northern Brazil. Sixty cases were diagnosed between 2016 and 2018, and 120 controls were included in the study. The control group consisted of residents from the same area as the cases, the same sex, and with an age variation of up to 5 years. Data were collected through interviews with each participant. Associations were assessed by univariate analysis, followed by logistic regression analysis. The following factors were associated with leprosy in the logistic regression model: households with no more than four rooms (OR = 4.01), absence of a BCG vaccination scar (OR = 2.16), and a previous case of leprosy in the family (OR = 4.32). The data indicated that a close relationship between individuals of the same family in small households, without any immunological protection, and with a history of leprosy cases, significantly increased the risk of M. leprae infection and development of leprosy.

RELATIONSHIP BETWEEN BCG VACCINATION HISTORY AND THE INCIDENCE OF LEPROSY IN CHILDREN: A LITERATURE REVIEW

Background: Globally, 9,052 new cases of leprosy in children were reported, with a corresponding rate of 4.5 per million child population. Children are believed to be the most vulnerable group to M. leprae infections due to their immature immunity. Purpose: This study aims to determine the relationship between the history of BCG vaccination and leprosy incidence in children. Methods: This study used a literature review method that involved a systematic search. The data sources were obtained using several databases, namely Google Scholar, Proquest, Science Direct, and Pubmed. Keywords were built using the PICOS protocol and Boolean Operators, so the keywords used were "relationship" AND "BCG vaccine" AND "leprosy" AND "children". The research selection and search procedures were explained using the PRISMA 2020 method and research included in this study following the inclusion and exclusion criteria that have been set. Results: There were eight studies suitable for inclusion in this literature review. Five articles concluded that there was a relationship between the history of BCG vaccine and the incidence of leprosy in children, while three articles concluded that there was no relationship between the two variables. Conclusion: The BCG vaccine is useful as an effort to prevent the transmission and spread of leprosy in children. Children who do not receive BCG immunization are more susceptible to leprosy than those who receive immunization. The BCG vaccine has a protective effect to prevent children from contracting and transmitting leprosy to other people.

Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions

BackgroundC–C motif chemokine ligand 2, a gene that codes for a protein involved in inflammation. Certain SNPs in the CCL2 gene have been studied for their potential associations with susceptibility to various diseases. These SNPs may affect the production and function of the CCL2 protein, which is involved in the recruitment of immune cells to the site of inflammation. Variations in CCL2 may influence the immune response to Mycobacterium leprae infection. ObjectiveTo investigate the association of the C–C motif chemokine ligand-2 single nucleotide polymorphisms with leprosy. MethodsCCL2 single nucleotide polymorphisms were analyzed in a total of 975 leprosy patients and 357 healthy controls. Of those, 577 leprosy and 288 healthy controls were analyzed by PCR-RFLP for CCL2 -2518 A>G, 535 leprosy and 290 controls for CCL2 -362 G>C, 295 leprosy and 240 controls for CCL2 -2134 T>G, 325 leprosy and 288 controls for CCL2 -1549 A>T SNPs by melting curve analysis using hybridization probe chemistry and detection by fluorescence resonance energy transfer (FRET) technique in Realtime PCR. The levels of CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β were estimated in sera samples and correlated with CCL2 genotypes. ResultsThe frequency of the GCT (-2518 A>G, -362 G>C, -2134 T>G) haplotype is observed to be higher in leprosy patients compared to healthy controls (P = 0.04). There was no significant difference observed in genotypic frequencies between leprosy patients and healthy controls {(-2518A>G, p = 0.53), (-362 G>C, p = 0.01), (-2134 T>G, p = 0.10)}. G allele at the -2134 site is predominant in leprosy (borderline) without any reaction (8 %) compared to borderline patients with RR reactions (2.1 %) (P = 0.03). GG genotype (p = 0.008) and G allele at -2518 (p = 0.030) of the CCL 2 gene were found to be associated with patients with ENL reaction. An elevated level of serum CCL2 was observed in leprosy patients with the -2518 AA and AG genotypes (p = 0.0001). ConclusionsG allele and GG genotype at the CCL2 -2518 site are associated with a risk of ENL reactions.

Leprosy in Children with a Focus on the Asian Region: A Narrative Review

Abstract Children are often more susceptible to contracting Mycobacterium leprae infection because of their immature immunity as well as their exposure to intrafamily interactions. The percentage of children among newly identified leprosy cases serves as a robust indicator of the ongoing transmission of the disease. Globally, the number of new cases fell by 19.3% between 2013 and 2022. A reduction of over 50% in the incidence of leprosy among children was seen, with rates declining from 10.4 cases per million children in 2013 to 5.1 per million in 2022. Children may exhibit atypical clinical symptoms, and the clinical presentation of leprosy in children can often be misdiagnosed as differential diagnoses such as pityriasis alba, nevus depigmentosus, pityriasis versicolor, among others, contributing to diagnostic difficulties. The cultural stigma surrounding leprosy may also discourage parents from seeking medical help promptly, prolonging the time to diagnosis. Furthermore, health-care systems in some regions may lack adequate training or resources for diagnosing pediatric leprosy. These challenges underscore the importance of increased awareness, early detection, and improved health-care infrastructure to effectively diagnose and treat leprosy in children. Stakeholders must give top priority in policy making and interventions to lower the prevalence of leprosy and its consequences in children and adolescents. The present article is an attempt to review the epidemiological, clinical, and therapeutic dimensions of childhood leprosy cases in Asia.

CYBB-Mediated Ferroptosis Associated with Immunosuppression in Mycobacterium leprae–Infected Monocyte-Derived Macrophages

Mycobacterium leprae- infected macrophages preferentially exhibit the regulatory M2 phenotype in vitro, which help the immune escape unabated growth of M. leprae in host cells. The mechanism that triggers macrophages polarization is still unknown. Herein, we performed single-cell RNA- sequencing (scRNA- seq) to determine the initial responses of human monocyte-derived macrophages (MDMs) against M. leprae infection of 4 healthy individuals and found an increase in a major alternative-activated macrophage type that overexpressed NEAT1, CCL2 and CD163. Importantly, further functional analysis showed that ferroptosis was positively correlated with M2 polarization of macrophages and in vitro experiments have shown that inhibition of ferroptosis promote the survival of M. leprae within macrophages. In addition, further joint analysis of our results with muti sequencing data from leprosy patients and in vitro validation identified that Cytochrome B-245 Beta Chain (CYBB) was the pivotal molecule for ferroptosis which could promote the M2 polarization of M. leprae infected macrophages, resulting to the immune escape and unabated growth of pathogenic bacteria. Overall, our results suggest that M. leprae facilitated its survival by inducing CYBB-mediated macrophage ferroptosis leading to its alternative activation and might reveal the potential for new therapeutic strategy of leprosy.

Trend of pediatric leprosy in an endemic area in Northeast of Brazil, 2008–2018

BackgroundThe incidence of leprosy in children is an important indicator of the disease's tendency in the general population and suggests intense circulation and transmission of Mycobacterium leprae. ObjectivesTo describe the clinical, epidemiological characteristics and temporal dynamics of leprosy cases in children under 15 years of age from 2008 to 2018 in an endemic municipality. MethodsA descriptive study with an analytical approach was carried out with data from leprosy cases registered in the Brazilian Information System on Notifiable Diseases for the municipality of Cabo de Santo Agostinho, Pernambuco, Brazil. ResultsBetween 2008 and 2018, 112 new cases of leprosy were registered. Most cases were classified as paucibacillary leprosy and occurred in children living in urban areas. There was no significant difference in the incidence of leprosy during the study period. Only 4.5% of the sample presented reactional episodes, but a high number of cases were not evaluated for the occurrence of reactions. ConclusionsThe findings of this study show a high incidence of paucibacillary leprosy in children and adolescents, which reveals active transmission in the community and failures in the detection of new multibacillary cases among adults. Children between 10 and 14 years old are more vulnerable to M. leprae infection and mainly develop paucibacillary leprosy.

The Role of Innate Immunity against Mycobacterium Leprae: A Systematic Literature Review

Introduction: Innate immunity is the body's defense system that exists from birth and is the body's first defense against infection. This system involves multiple defense mechanisms that work together to recognize, deter, and respond to pathogens such as bacteria, viruses, and fungi. In the context of Mycobacterium leprae, the role of the innate immune system is very important because this bacterium has unique pathogenic properties and is capable of infecting human body cells in complex ways.
 Methods: The literature search process was carried out on various databases (PubMed, Web of Sciences, EMBASE, Cochrane Libraries, and Google Scholar) regarding the role of innate immunity against Mycobacterium leprae. This study follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) recommendations.
 Results: One of the main aspects of the role of the innate immune system against Mycobacterium leprae is the recognition of this pathogen by phagocytic cells, such as macrophages. Mycobacterium leprae evades recognition and destruction by these cells in a number of ways, including cell surface modification of the immune response.
 Conclusion: The innate immunity response plays a significant role in the response to Mycobacterium leprae infection. Innate immunity acts as an initial and fast response to mitigate the Mycobacterium leprae infection from getting more massive.

COVID-19 vaccination and leprosy-A UK hospital-based retrospective cohort study.

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. 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). 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.

Trend of pediatric leprosy in an endemic area in Northeast of Brazil, 2008–2018

BackgroundThe incidence of leprosy in children is an important indicator of the disease's tendency in the general population and suggests intense circulation and transmission of Mycobacterium leprae. ObjectivesTo describe the clinical, epidemiological characteristics and temporal dynamics of leprosy cases in children under 15 years of age from 2008 to 2018 in an endemic municipality. MethodsA descriptive study with an analytical approach was carried out with data from leprosy cases registered in the Brazilian Information System on Notifiable Diseases for the municipality of Cabo de Santo Agostinho, Pernambuco, Brazil. ResultsBetween 2008 and 2018, 112 new cases of leprosy were registered. Most cases were classified as paucibacillary leprosy and occurred in children living in urban areas. There was no significant difference in the incidence of leprosy during the study period. Only 4.5% of the sample presented reactional episodes, but a high number of cases were not evaluated for the occurrence of reactions. ConclusionsThe findings of this study show a high incidence of paucibacillary leprosy in children and adolescents, which reveals active transmission in the community and failures in the detection of new multibacillary cases among adults. Children between 10 and 14 years old are more vulnerable to M. leprae infection and mainly develop paucibacillary leprosy.

Polyunsaturated Fatty Acid-Derived Lipid Mediators as Potential Biomarkers for Leprosy Among Individuals with Asymptomatic Mycobacterium leprae Infection.

Intra-household contacts (HCs) of leprosy patients are at increased risk of infection by Mycobacterium leprae and about ∼5-10% will develop active disease. A prognostic tool to identify HCs with the greatest risk of progressing to active disease would enhance early leprosy diagnosis and optimize prophylactic intervention. Previous metabolomics studies suggest that host lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are potential biomarkers for leprosy. In this study, we investigated retrospective sera of leprosy HCs by liquid chromatography-mass spectrometry and enzyme-linked immunoassay to determine whether circulating levels of ω-3 and ω-6 PUFA metabolites were altered in HCs that developed leprosy (HCDL) in comparison to those that did not (HCNDL). Sera were collected from HCs at the time of index case diagnosis and before clinical signs/symptoms of leprosy. Our findings showed that HCDL sera exhibited a distinct metabolic profile in comparison to HCDNL. Specifically, arachidonic acid, leukotriene B4, 11-hydroxyeicosatetraenoic acid, prostaglandin D2, and lipoxin A4 were elevated in HCDL. In contrast, prostaglandin E2 levels were reduced in HCDL. The ω-3 PUFAs, docosahexaenoic acid, eicosapentaenoic acid, and the docosahexaenoic acid-derived resolvin D1 and maresin-1 were also elevated in HCDL individuals compared to HCNDL. Principal component analyses provided further evidence that lipid mediators could serve as an early biomarker for progression to active leprosy. A logistic model identified resolvin D1 and D2, and prostaglandin D2 as having the greatest potential for early detection of HCs that will manifest leprosy.

Single-cell sequencing analysis reveals development and differentiation trajectory of Schwann cells manipulated by M. leprae.

M. leprae preferentially infects Schwann cells (SCs) in the peripheral nerves leading to nerve damage and irreversible disability. Knowledge of how M. leprae infects and interacts with host SCs is essential for understanding mechanisms of nerve damage and revealing potential new therapeutic strategies. We performed a time-course single-cell sequencing analysis of SCs infected with M. leprae at different time points, further analyzed the heterogeneity of SCs, subpopulations associated with M. leprae infection, developmental trajectory of SCs and validated by Western blot or flow cytometry. Different subpopulations of SCs exhibiting distinct genetic features and functional enrichments were present. We observed two subpopulations associated with M. leprae infection, a stem cell-like cell subpopulation increased significantly at 24 h but declined by 72 h after M. leprae infection, and an adipocyte-like cell subpopulation, emerged at 72 h post-infection. The results were validated and confirmed that a stem cell-like cell subpopulation was in the early stage of differentiation and could differentiate into an adipocyte-like cell subpopulation. Our results present a systematic time-course analysis of SC heterogeneity after infection by M. leprae at single-cell resolution, provide valuable information to understand the critical biological processes underlying reprogramming and lipid metabolism during M. leprae infection of SCs, and increase understanding of the disease-causing mechanisms at play in leprosy patients as well as revealing potential new therapeutic strategies.

Association between serum level of vitamin D (25-hydroxyvitamin D) and plasma level of vitamin D receptor with bacteriological index in leprosy patients.

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.

Protocol, rationale and design of BE-PEOPLE (Bedaquiline enhanced exposure prophylaxis for LEprosy in the Comoros): a cluster randomized trial on effectiveness of rifampicin and bedaquiline as post-exposure prophylaxis of leprosy contacts

BackgroundLeprosy is an ancient infectious disease with an annual global incidence of around 200,000 over the past decade. Since 2018, the World Health Organization (WHO) recommends single-dose rifampicin as post-exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial evaluated PEP with a double dose of rifampicin in Comoros and Madagascar. Preliminary results of this trial show some reduction in leprosy incidence in intervention villages but a stronger regimen may be beneficial. The objective of the current Bedaquiline Enhanced ExpOsure Prophylaxis for LEprosy trial (BE-PEOPLE) is to explore effectiveness of a combination of bedaquiline and rifampicin as PEP.MethodsBE-PEOPLE is a cluster-randomized trial in which 44 clusters in Comoros will be randomized to two study arms. Door-to-door screening will be conducted annually during four years, leprosy patients identified will be offered standard of care treatment. Based on study arm, contacts aged five years and above and living within a 100-meter radius of an index case will either receive bedaquiline (400-800 mg) and rifampicin (150-600 mg) or only rifampicin (150–600 mg). Contacts aged two to four years will receive rifampicin only. Household contacts randomized to the bedaquiline plus rifampicin arm will receive a second dose four weeks later. Incidence rate ratios of leprosy comparing contacts who received either of the PEP regimens will be the primary outcome. We will monitor resistance to rifampicin and/or bedaquiline through molecular surveillance in all incident tuberculosis and leprosy patients nationwide. At the end of the study, we will assess anti-M. leprae PGL-I IgM seropositivity as a proxy for the population burden of M. leprae infection in 8 villages (17,000 individuals) that were surveyed earlier as part of the PEOPLE trial.DiscussionThe COLEP trial on PEP in Bangladesh documented a reduction of 57% in incidence of leprosy among contacts treated with SDR-PEP after two years, which led to the WHO recommendation of SDR-PEP. Preliminary results of the PEOPLE trial show a lesser reduction in incidence. The BE-PEOPLE trial will explore whether reinforcing SDR-PEP with bedaquiline increases effectiveness and more rapidly reduces the incidence of leprosy, compared to SDR-PEP alone.Trial registrationNCT05597280. Protocol version 5.0 on 28 October 2022.

B lymphocytes deficiency results in altered immune response and increased susceptibility to Mycobacterium leprae in a murine leprosy model

Leprosy is a chronic and infectious disease that primarily affects the skin and peripheral nervous system, presenting a wide spectrum of clinical forms with different degrees of severity. The distinct host immune response patters developed in the response to the bacillus Mycobacterium leprae, the leprosy etiologic agent, are associated with the spectral clinical forms and outcome of the disease. In this context, B cells are allegedly involved in the disease immunopathogenesis, usually as antibody-producing cells, but also as potential effector or regulatory elements. In order to determine the regulatory B cells role in experimental leprosy, this study evaluated the outcome of M. leprae infection in B cell deficient mice (BKO) and WT C57Bl/6 control, by means of microbiological/bacilloscopic, immunohistochemical and molecular analysis, performed 8 months after M. leprae inoculation. The results demonstrated that infected BKO showed a higher bacilli number when compared with WT animals, demonstrating the importance of these cells in experimental leprosy. The molecular analysis demonstrates that the expression of IL-4, IL-10 and TGF-β was significantly higher in the BKO footpads when compared to WT group. Conversely, there was no difference in IFN-γ, TNF-α and IL-17 expression levels in BKO and WT groups. IL-17 expression was significantly higher in the lymph nodes of WT group. The immunohistochemical analysis revealed that M1 (CD80+) cells counts were significantly lower in the BKO group, while no significant difference was observed to M2 (CD206+) counts, resulting a skewed M1/M2 balance. These results demonstrated that the absence of B lymphocytes contribute to the persistence and multiplication of M. leprae, probably due to the increased expression of the IL-4, IL-10 and TGF-β cytokines, as well as a decrease in the number of M1 macrophages in the inflammatory site.

Leprosy among new child cases in China: Epidemiological and clinical analysis from 2011 to 2020.

Leprosy, caused by Mycobacterium leprae infection, mainly affects skin and peripheral nerves and may further lead to disability and deformity if not treated timely. The new case detection rate of leprosy in children reflects the active transmission of leprosy infection. This study aims to present the epidemiology and clinical characteristics of new leprosy cases in children in China from 2011 to 2020. All data from leprosy patients younger than 15 years old were extracted from the Leprosy Management Information System in China (LEPMIS). Statistical Package for the Social Sciences (SPSS) version 12.0 was used for descriptive and analytical statistics of the epidemiological and clinical indicators by the Mann-Whitney test, Kruskal-Wallis test, and Fisher's exact test. And geographical distribution was analyzed by ArcGIS 10.5. A total of 152 pediatric new cases of leprosy were found over the last decade. The new case detection rate of pediatric leprosy cases decreased from 0.13 to 0.02 per 1,000,000 population over the last ten years. New pediatric cases had a higher new case detection rate in Guizhou, Sichuan, and Yunnan Provinces. All but 7 provinces in China achieved zero new child case for consecutive five years. The onset of leprosy peaked between 10 and 14 years of age, and the male to female ratio was 1.71:1. Pediatric patients were predominantly infected from symptomatic household adult contacts HHCs. Multibacillary leprosy (MB) was the most common. However, a low proportion of patients developed leprosy reaction and grade 2 disability. The new case detection rate of pediatric leprosy cases has decreased over the past ten years in China. Spatial analysis indicated clusters in high-endemic areas. Leprosy transmission has stopped in the majority of provinces in China. However, sporadic cases may continue to exist for a long time. Active surveillance especially contact tracing should be focused on in future plan for management of leprosy, and interventions in leprosy clusters should be prioritized.

Issue Information

Front cover Axonopathy is considered a hallmark of leprosy neuropathy, a chronic infectious disease caused by Mycobacterium leprae infection in Schwann cells. Leprosy neuropathy is associated with irreversible motor and sensory loss seen in infected patients. In the present work, immortalized human Schwann cell line ST8814 were infected with M.leprae. The neurotoxicity of infected Schwann cell-conditioned medium (SCCM) was then evaluated in a human neuroblastoma cell lineage and mouse neurons. ST8814 Schwann cells exposed to M. leprae affected neuronal viability by deviating glial 14C-labeled lactate, important fuel of neuronal central metabolism, to de novo lipid synthesis. We observed that transgenic M. bovis (BCG) cells expressing the M. leprae phenolic glycolipid-1 (PGL-1), a specific cell wall antigen proposed to mediate bacterial-Schwann cell interaction - (BCG-PGL-1) - was able to induce a phenotype similar to M. leprae, unlike the wild type BCG strain. This Schwann cell neurotoxic phenotype, induced by M. leprae PGL-1, occurs through the protein kinase B (Akt) pathway. The pharmacological inhibition of Akt by triciribine significantly reduced free fatty acid content in the SCCM from M. leprae- and BCG-PGL-1-infected Schwann cells and, hence, prevented neuronal death. Overall, these findings provide novel evidence that both M. leprae and PGL-1 induce a toxic Schwann cell phenotype, by modifying the host lipid metabolism, resulting in profound implications for neuronal loss as a basis of leprosy neuropathy. Image content Sensory neurons dissociated from mouse dorsal root ganglion, visualized by immunofluorescence using anti-ß-III tubulin evidencing neurotoxicity of M. leprae-infected Schwann cells conditioned medium over arborization. Read the full article ‘Phenolic glycolipid-1 of Mycobacterium leprae is involved in human Schwann cell line ST8814 neurotoxic phenotype’ by K. do Carmo de Vasconcelos Girardi, B. S. Mietto, K. dos Anjos Lima, G. C. Atella, D. S. da Silva, A. M. R. Pereira, P. S. Rosa, F. A. Lara. 2023, vol.164 (2), pp. 158–171) on doi:10.1111/jnc.15722