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Japanese Journal of Infectious Diseases Jul 2022The causative agents of leprosy are Mycobacterium leprae and M. lepromatosis. Mycobacterium lepromatosis was found in 2008 to cause diffuse lepromatous leprosy in...
The causative agents of leprosy are Mycobacterium leprae and M. lepromatosis. Mycobacterium lepromatosis was found in 2008 to cause diffuse lepromatous leprosy in Mexican patients. This study aimed to identify M. leprae and M. lepromatosis in paraffin-embedded skin samples from Caribbean patients with leprosy. A total of six skin samples were obtained from the Dominican Republic. All cases presented the multibacillary form; five were nodular lepromatous leprosy, and one was borderline lepromatous leprosy. All patients received multidrug therapy. Molecular identification was achieved using the M. leprae-specific repetitive element for M. leprae and the hemN gene for M. lepromatosis. Mycobacterium leprae was identified in two lepromatous leprosy cases, and one borderline lepromatous leprosy case; M. lepromatosis was found in one nodular lepromatous leprosy case. Both Mycobacterium species were present in two nodular lepromatous leprosy cases. This is the first report of M. lepromatosis in the Dominican Republic.
Topics: Dominican Republic; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Leprosy, Lepromatous; Mycobacterium; Mycobacterium leprae
PubMed: 35354704
DOI: 10.7883/yoken.JJID.2021.709 -
The American Journal of Tropical... Aug 2014
Topics: Aged, 80 and over; Clofazimine; Dapsone; Humans; Leprostatic Agents; Leprosy; Male; Mycobacterium leprae; Rifampin; Skin; Treatment Outcome
PubMed: 25100789
DOI: 10.4269/ajtmh.13-0668 -
PLoS Neglected Tropical Diseases May 2020Leprosy urgently needs a precise and early diagnostic tool. The sensitivity of the direct (bacilli staining, Mycobacterium leprae DNA) and indirect (antibody levels, T...
Leprosy urgently needs a precise and early diagnostic tool. The sensitivity of the direct (bacilli staining, Mycobacterium leprae DNA) and indirect (antibody levels, T cell assays) diagnostics methods vary based on the clinical form. Recently, PCR-based M. leprae DNA detection has been shown to differentially diagnose leprosy from other dermatological conditions. However, accuracy can still be improved, especially for use with less invasive clinical samples. We tested different commercial DNA extraction kits: DNeasy Blood & Tissue, QIAamp DNA Microbiome, Maxwell 16 DNA Purification, PowerSoil DNA Isolation; as well as in-house phenol-chloroform and Trizol/FastPrep methods. Extraction was performed on M. leprae-infected mouse footpads and different clinical samples of leprosy patients (skin biopsies and scrapings, lesion, oral and nasal swabs, body hair, blood on FTA cards, peripheral whole blood). We observed that the Microbiome kit was able to enrich for mycobacterial DNA, most likely due the enzymatic digestion cocktail along with mechanical disruption involved in this method. Consequently, we had a significant increase in sensitivity in skin biopsies from paucibacillary leprosy patients using a duplex qPCR targeting 16S rRNA (M. leprae) and 18S rRNA (mammal) in the StepOnePlus system. Our data showed that the presence of M. leprae DNA was best detected in skin biopsies and skin scrapings, independent of the extraction method or the clinical form. For multibacillary patients, detection of M. leprae DNA in nasal swabs indicates the possibility of having a much less invasive sample that can be used for the purposes of DNA sequencing for relapse analysis and drug resistance monitoring. Overall, DNA extracted with the Microbiome kit presented the best bacilli detection rate for paucibacillary cases, indicating that investments in extraction methods with mechanical and DNA digestion should be made.
Topics: Animals; DNA, Bacterial; Humans; Mice; Mycobacterium leprae; Polymerase Chain Reaction; RNA, Bacterial; RNA, Ribosomal, 16S; Sensitivity and Specificity
PubMed: 32453754
DOI: 10.1371/journal.pntd.0008325 -
Clinical Microbiology and Infection :... Nov 2021The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to... (Review)
Review
BACKGROUND
The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to diagnose AMR in M. leprae to provide reliable data concerning mutations and their impact. Fluoroquinolones (FQs) are efficient for the treatment of leprosy and the main second-line drugs in case of multidrug resistance.
OBJECTIVES
This study aimed at performing a systematic review (a) to characterize all DNA gyrase gene mutations described in clinical isolates of M. leprae, (b) to distinguish between those associated with FQ resistance or susceptibility and (c) to delineate a consensus numbering system for M. leprae GyrA and GyrB.
DATA SOURCES
Data source was PubMed.
STUDY ELIGIBILITY CRITERIA
Publications reporting genotypic susceptibility-testing methods and gyrase gene mutations in M. leprae clinical strains.
RESULTS
In 25 studies meeting our inclusion criteria, 2884 M. leprae isolates were analysed (2236 for gyrA only (77%) and 755 for both gyrA and gyrB (26%)): 3.8% of isolates had gyrA mutations (n = 110), mostly at position 91 (n = 75, 68%) and 0.8% gyrB mutations (n = 6). Since we found discrepancies regarding the location of substitutions associated with FQ resistance, we established a consensus numbering system to properly number the mutations. We also designed a 3D model of the M. leprae DNA gyrase to predict the impact of mutations whose role in FQ-susceptibility has not been demonstrated previously.
CONCLUSIONS
Mutations in DNA gyrase are observed in 4% of the M. leprae clinical isolates. To solve discrepancies among publications and to distinguish between mutations associated with FQ resistance or susceptibility, the consensus numbering system we proposed as well as the 3D model of the M. leprae gyrase for the evaluation of the impact of unknown mutations in FQ resistance, will provide help for resistance surveillance.
Topics: DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae
PubMed: 34265461
DOI: 10.1016/j.cmi.2021.07.007 -
Drug Discovery Today Jul 2021Hansen's disease (HD), or leprosy, continues to be endemic in many parts of the world. Although multidrug therapy (MDT) is successful in curing a large number of... (Review)
Review
Hansen's disease (HD), or leprosy, continues to be endemic in many parts of the world. Although multidrug therapy (MDT) is successful in curing a large number of patients, some of them abandon it because it is a long-term treatment. Therefore, identification of new drug targets in Mycobacterium leprae is considered of high importance. Here, we introduce an overview of in silico and in vitro studies that might be of help in this endeavor. The essentiality of M. leprae proteins is reviewed with discussion of flux balance analysis, gene expression, and knockout articles. Finally, druggability techniques are proposed for the validation of new M. leprae protein targets (see Fig. 1).
Topics: Animals; Bacterial Proteins; Computer Simulation; Drug Design; Gene Ontology; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae
PubMed: 33798649
DOI: 10.1016/j.drudis.2021.03.026 -
Memorias Do Instituto Oswaldo Cruz 2022Leprosy is curable by multidrug therapy (MDT) treatment regimen ranging from six to 12 months. The variable levels of tolerance and adherence among patients can,...
BACKGROUND
Leprosy is curable by multidrug therapy (MDT) treatment regimen ranging from six to 12 months. The variable levels of tolerance and adherence among patients can, however, result in treatment failure and the emergence of drug-resistant strains.
OBJECTIVES
Describe the impact of MDT over Mycobacterium leprae viability in patient's oral and nasal mucosa along treatment.
METHODS
Mycobacterium leprae viability was monitored by quantitative polymerase chain reaction (qPCR) quantification of 16S rRNA in lateral and contralateral scrapings of oral and nasal mucosa of 10 multibacillary patients along the initial five months of treatment.
FINDINGS
The results demonstrated high heterogenicity of M. leprae viability among patients and between nasal and oral samples. Of six patients who presented good adherence and tolerance to the treatment, only four displayed absence of M. leprae viability in both samples three months after the first MDT dose, while for the other two, the absence of M. leprae viability in the oral and nasal cavities was only detected five months after the first dose.
MAIN CONCLUSIONS
We concluded that qPCR of 16S rRNA for the determination of M. leprae viability in nasal and oral scraping samples could represent an interesting approach to monitor treatment efficacy.
Topics: Humans; Mycobacterium leprae; RNA, Ribosomal, 16S; Leprostatic Agents; Drug Therapy, Combination; Nasal Mucosa; DNA, Bacterial
PubMed: 36259791
DOI: 10.1590/0074-02760220058 -
Future Microbiology Feb 2011Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical... (Review)
Review
Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae-host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed.
Topics: Genetic Predisposition to Disease; Host-Pathogen Interactions; Humans; Leprosy; Mycobacterium leprae
PubMed: 21366421
DOI: 10.2217/fmb.10.173 -
Scandinavian Journal of Immunology Apr 2012Although Mycobacterium leprae was the first bacterial pathogen identified causing human disease, it remains one of the few that is non-cultivable. Understanding the... (Review)
Review
Although Mycobacterium leprae was the first bacterial pathogen identified causing human disease, it remains one of the few that is non-cultivable. Understanding the biology of M. leprae is one of the primary challenges in current leprosy research. Genomics has been extremely valuable, nonetheless, functional proteins are ultimately responsible for controlling most aspects of cellular functions, which in turn could facilitate parasitizing the host. Furthermore, bacterial proteins provide targets for most of the vaccines and immunodiagnostic tools. Better understanding of the proteomics of M. leprae could also help in developing new drugs against M. leprae. During the past nearly 15 years, there have been several developments towards the identification of M. leprae proteins employing contemporary proteomics tools. In this review, we discuss the knowledge gained on the biology and pathogenesis of M. leprae from current proteomic studies.
Topics: Animals; Bacterial Proteins; Humans; Leprosy; Mycobacterium leprae; Proteome; Proteomics
PubMed: 22229831
DOI: 10.1111/j.1365-3083.2012.02677.x -
Microbiology and Immunology 2001Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which was discovered by G.H.A. Hansen in 1873. M. leprae is an exceptional bacterium because of... (Review)
Review
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which was discovered by G.H.A. Hansen in 1873. M. leprae is an exceptional bacterium because of its long generation time and no growth in artificial media. Entire sequencing of the bacterial genome revealed numerous pseudogenes (inactive reading frames with functional counterparts in M. tuberculosis) which might be responsible for the very limited metabolic activity of M. leprae. The clinical demonstration of the disease is determined by the quality of host immune response. Th1-type immune response helps to kill the bacteria, but hosts are encroached upon when Th2-type response is predominant. The bacteria have affinity to the peripheral nerves and are likely to cause neuropathy. M. leprae/laminin-alpha2 complexes bind to alpha/beta dystroglycan complexes expressed on the Schwann cell surface. WHO recommends a chemotherapy protocol [multidrug therapy (MDT)] which effectively controls the disease and contributes to the global elimination program. Leprosy has been stigmatized throughout history, and recent topics regarding the disease in Japan are also discussed.
Topics: Animals; Humans; Leprosy; Leprosy, Lepromatous; Leprosy, Tuberculoid; Mycobacterium leprae; Peripheral Nervous System; Prevalence; Pseudogenes; Zoonoses
PubMed: 11791665
DOI: 10.1111/j.1348-0421.2001.tb01308.x -
Emerging Infectious Diseases Jun 2021Mycobacterium leprae was detected by optical microscopy, fluorescent in situ hybridization, and molecular detection in feces collected for the diagnosis of Entamoeba...
Mycobacterium leprae was detected by optical microscopy, fluorescent in situ hybridization, and molecular detection in feces collected for the diagnosis of Entamoeba coli enteritis in a leprosy patient in Burkina Faso. This observation raises questions about the role of fecal excretion of M. leprae in the natural history and diagnosis of leprosy.
Topics: Burkina Faso; Humans; In Situ Hybridization, Fluorescence; Leprosy; Mycobacterium leprae
PubMed: 34013859
DOI: 10.3201/eid2706.200748