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Frontiers in Immunology 2024Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized...
INTRODUCTION
Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions.
METHODS
In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR.
RESULTS
An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that expression could discriminate ENL from LL. Supernatants of blood cells stimulated with sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly and , were revealed.
DISCUSSION
In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.
Topics: Humans; Erythema Nodosum; Neutrophil Activation; Leprosy, Lepromatous; Adult; Male; Neutrophils; Female; Transcriptome; Middle Aged; Gene Expression Profiling; GPI-Linked Proteins; Thalidomide; Receptors, Cell Surface; Leprostatic Agents; Young Adult; Biomarkers; Isoantigens
PubMed: 38715615
DOI: 10.3389/fimmu.2024.1366125 -
Current Biology : CB May 2024Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year. Although ancient...
Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year. Although ancient DNA (aDNA) approaches on the major causative agent, Mycobacterium leprae, have elucidated the disease's evolutionary history, the role of animal hosts and interspecies transmission in the past remains unexplored. Research has uncovered relationships between medieval strains isolated from archaeological human remains and modern animal hosts such as the red squirrel in England. However, the time frame, distribution, and direction of transmissions remains unknown. Here, we studied 25 human and 12 squirrel samples from two archaeological sites in Winchester, a medieval English city well known for its leprosarium and connections to the fur trade. We reconstructed four medieval M. leprae genomes, including one from a red squirrel, at a 2.2-fold average coverage. Our analysis revealed a phylogenetic placement of all strains on branch 3 as well as a close relationship between the squirrel strain and one newly reconstructed medieval human strain. In particular, the medieval squirrel strain is more closely related to some medieval human strains from Winchester than to modern red squirrel strains from England, indicating a yet-undetected circulation of M. leprae in non-human hosts in the Middle Ages. Our study represents the first One Health approach for M. leprae in archaeology, which is centered around a medieval animal host strain, and highlights the future capability of such approaches to understand the disease's zoonotic past and current potential.
Topics: Animals; Mycobacterium leprae; Sciuridae; Leprosy; Humans; Genome, Bacterial; Phylogeny; England; DNA, Ancient; Archaeology; History, Medieval
PubMed: 38703773
DOI: 10.1016/j.cub.2024.04.006 -
The Brazilian Journal of Infectious... 2024Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007‒2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas.
OBJECTIVES
To estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT.
METHODS
The statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables.
RESULTS
The overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio.
CONCLUSIONS
The relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT00669643.
Topics: Humans; Leprostatic Agents; Recurrence; Drug Therapy, Combination; Male; Female; Clofazimine; Dapsone; Rifampin; Adult; Brazil; Middle Aged; Treatment Outcome; Case-Control Studies; Leprosy; Young Adult; Adolescent; Leprosy, Multibacillary; Time Factors
PubMed: 38697216
DOI: 10.1016/j.bjid.2024.103745 -
Cureus Apr 2024Leprosy is a great mimicker. It is caused by and , together termed the complex. Leprosy can result in systemic manifestations; however, the neurocutaneous syndrome is... (Review)
Review
Leprosy is a great mimicker. It is caused by and , together termed the complex. Leprosy can result in systemic manifestations; however, the neurocutaneous syndrome is the most classic. There is a gap in recognizing the condition leading to misdiagnosis and delays in treatment. Leprosy remains an important cause of aesthetic and functional impairment. In this paper, we provide a practical review of leprosy touching on pathophysiology, clinical manifestation, classification, diagnostic approach and management of the condition in a way that can translate into clinical practice and help physicians better identify and manage potential cases of leprosy.
PubMed: 38694670
DOI: 10.7759/cureus.57374 -
Cureus Mar 2024Erythema nodosum leprosum is a type 3 hypersensitivity reaction that often presents with transient eruptions of red papules, plaques, and nodules. A 52-year-old female...
Erythema nodosum leprosum is a type 3 hypersensitivity reaction that often presents with transient eruptions of red papules, plaques, and nodules. A 52-year-old female presented with multiple joint pain that was being treated as rheumatoid arthritis (RA), but through clinical examination, she was found to have Hansen's disease with a type 2 reaction. Hence, the importance of a thorough clinical examination is a must for the timely and correct diagnosis of patients suffering from Hansen's disease.
PubMed: 38690488
DOI: 10.7759/cureus.57312 -
Microorganisms Apr 2024Different bacterial species have dramatically different generation times, from 20-30 min in to about two weeks in . The translation machinery in a cell needs to...
Different bacterial species have dramatically different generation times, from 20-30 min in to about two weeks in . 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 than in the long-generation . 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.
PubMed: 38674712
DOI: 10.3390/microorganisms12040768 -
Medicina (Kaunas, Lithuania) Mar 2024: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from...
: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. : This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. : The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. : Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.
Topics: Humans; Male; Female; Adult; Middle Aged; Republic of Korea; Spondylarthritis; Incidence; Tuberculosis; Mycobacterium Infections, Nontuberculous; Aged; Cohort Studies; Arthritis, Psoriatic; Spondylitis, Ankylosing
PubMed: 38674225
DOI: 10.3390/medicina60040579 -
Cureus Apr 2024Introduction Leprosy remains a significant cause of preventable disability worldwide. Early diagnosis and treatment of leprosy are critical not only to stop its spread...
Introduction Leprosy remains a significant cause of preventable disability worldwide. Early diagnosis and treatment of leprosy are critical not only to stop its spread but also to prevent physical and social complications and reduce the disease burden. Objectives The study aims to evaluate the factors that lead to a delayed leprosy diagnosis. Methods This study was conducted in the outpatient departments of Leprosy Control Institute and Hospital, Dhaka, Bangladesh, and at Medical College for Women and Hospital, Dhaka, Bangladesh, from March 2023 to June 2023. A total number of 252 male (148) and female (104) patients were selected with any sign of leprosy, including disability, age ranging from 15 to 74 years. Data was collected in a pre-designed structured questionnaire by the researchers. To assess the risk of independent exposures of Grade 2 leprosy disabilities, we used a logistic regression model. A chi-square test showed the association between significant effects and leprosy disabilities. A p-value of 0.05 was considered as significant. For statistical analysis, STATA version 15 (StataCorp LLC, College Station, Texas, USA) was used. Results The study participants exhibited a higher percentage of disability, with a rate of 25.8% for Grade 2 disabilities. In addition to this, males represented a more considerable proportion, 58.7%, than females among leprosy and disability patients across all levels of disability. In our study, lack of money and painless symptoms showed a significant association (p<0.001) with Grade 2 disability. Conclusion The study reveals that Grade 2 disabilities are more common in males and are particularly prevalent in lower socioeconomic groups.
PubMed: 38651088
DOI: 10.7759/cureus.58708 -
Infection and Drug Resistance 2024Leprosy and tuberculosis are two of the oldest and most common mycobacterial infections, caused by and for leprosy and for tuberculosis. Dual infections have been...
BACKGROUND
Leprosy and tuberculosis are two of the oldest and most common mycobacterial infections, caused by and for leprosy and for tuberculosis. Dual infections have been known since ancient times; however, cases remain rarely reported in the literature, even in countries where both diseases are endemic, such as Madagascar.
PURPOSE
We report a case series of simultaneous occurrence of leprosy and tuberculosis.
PATIENTS AND METHODS
In this retrospective study, we reviewed the medical records of patients with leprosy registered at the Department of Dermatology, University Hospital Befelatanana, Antananarivo, Madagascar, between January 2012 and June 2021. Patients with leprosy and diagnosed as coinfected by tuberculosis were included in the study.
RESULTS
Of the 120 leprosy cases observed during the study period, coinfection with leprosy and tuberculosis was found in five patients. The mean age was 43.4 (SD 13.2) ranging, 21-59 years. Male gender was predominant (4/5). Four patients presented with lepromatous leprosy, and one with borderline lepromatous leprosy. Three patients experienced leprosy reaction. Four cases of pulmonary tuberculosis and one case of multifocal tuberculosis were observed. The diagnosis of leprosy preceded tuberculosis in four cases, and a coinfection diagnosis was made simultaneously in one case. The average time to develop tuberculosis was 38.8 (SD 10.2) months. HIV infection, malnutrition, alcohol consumption, and long-term corticosteroid therapy were the immunosuppressive factors reported in our patients. Three patients received concomitant multidrug therapy for leprosy and tuberculosis.
CONCLUSION
Dermatologists should be aware of the importance of screening patients affected by leprosy for latent or active tuberculosis to prevent morbidity and mortality due to coinfection and to reduce the risk of acquired resistance to rifampicin, which is the greatest risk of this association.
PubMed: 38645889
DOI: 10.2147/IDR.S458888 -
Molecular Biology Reports Apr 2024Mycobacterium leprae causes leprosy that is highly stigmatized and chronic infectious skin disease. Only some diagnostic tools are being used for the identification M....
BACKGROUND
Mycobacterium leprae causes leprosy that is highly stigmatized and chronic infectious skin disease. Only some diagnostic tools are being used for the identification M. leprae in clinical samples, such as bacillary detection, and histopathological tests. These methods are invasive and often have low sensitivity. Currently, the PCR technique has been used as an effective tool fordetecting M. leprae DNA across different clinical samples. The current study aims to detect M. leprae DNA in urine samples of untreated and treated leprosy patients using the Rlep gene (129 bp) and compared the detection among Ridley-Jopling Classification.
METHODS
Clinical samples (Blood, Urine, and Slit Skin Smears (SSS)) were collected from leprosy and Non-leprosy patients. DNA extraction was performed using standard laboratory protocol and Conventional PCR was carried out for all samples using Rlep gene target and the amplicons of urine samples were sequenced by Sanger sequencing to confirm the Rlep gene target.
RESULTS
The M. leprae DNA was successfully detected in all clinical samples across all types of leprosy among all the study groups using RLEP-PCR. Rlep gene target was able to detect the presence of M. leprae DNA in 79.17% of urine, 58.33% of blood, and 50% of SSS samples of untreated Smear-Negative leprosy patients. The statistical significant difference (p = 0.004) was observed between BI Negative (Slit Skin Smear test) and RLEP PCR positivity in urine samples of untreated leprosy group.
CONCLUSION
The PCR positivity using Rlep gene target (129 bp) was highest in all clinical samples among the study groups, across all types of leprosy. Untreated tuberculoid and PNL leprosy patients showed the highest PCR positivity in urine samples, indicating its potential as a non-invasive diagnostic tool for leprosy and even for contact screening.
Topics: Humans; Mycobacterium leprae; Skin; Bacillus; Firmicutes; Polymerase Chain Reaction
PubMed: 38616219
DOI: 10.1007/s11033-024-09470-0