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Virulence Dec 2022Leprosy is caused by (. ) and , an obligate intracellular organism, and over 200,000 new cases occur every year. parasitizes histiocytes (skin macrophages) and Schwann... (Review)
Review
Leprosy is caused by (. ) and , an obligate intracellular organism, and over 200,000 new cases occur every year. 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 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 and have been investigated. Our laboratory has been focused on the metabolism of lipids which constitute the cell wall of . Our findings may be useful for the development of future treatments.
Topics: Animals; Mycobacterium leprae; Virulence; Drug Therapy, Combination; Leprostatic Agents; Leprosy
PubMed: 36326715
DOI: 10.1080/21505594.2022.2141987 -
Actas Dermo-sifiliograficas Sep 2013Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium leprae. It primarily affects the skin and peripheral nerves and is still endemic in... (Review)
Review
Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium leprae. It primarily affects the skin and peripheral nerves and is still endemic in various regions of the world. Clinical presentation depends on the patient's immune status at the time of infection and during the course of the disease. Leprosy is associated with disability and marginalization. Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal signs specified by the World Health Organization: hypopigmented or erythematous macules with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy with loss of adnexa at affected sites. Leprosy is treated with a multidrug combination of rifampicin, clofazimine, and dapsone. Two main regimens are used depending on whether the patient has paucibacillary or multibacillary disease.
Topics: Antibodies, Bacterial; Antigens, Bacterial; BCG Vaccine; Bacterial Vaccines; Drug Therapy, Combination; Global Health; Glycolipids; Humans; Intradermal Tests; Lepromin; Leprostatic Agents; Leprosy; Mycobacterium leprae; Serologic Tests; Skin; Species Specificity
PubMed: 23870850
DOI: 10.1016/j.adengl.2012.03.028 -
Indian Journal of Dermatology,... 2020With the worldwide implementation of WHO multidrug therapy in the 1980s, the global burden of leprosy has decreased. However, the annual new case detection rate around... (Review)
Review
With the worldwide implementation of WHO multidrug therapy in the 1980s, the global burden of leprosy has decreased. However, the annual new case detection rate around the world has remained nearly static over the past decade with India, Brazil, and Indonesia contributing the majority of these new cases. This has been attributed to the ongoing transmission of Mycobacterium leprae from existing untreated cases and partly to the intensive new case detection programs operative in endemic areas. The WHO has called for a "global interruption of transmission of leprosy by 2020". Targeted chemoprophylaxis of contacts may help bring down the number of new cases. The single-dose rifampicin currently in use for post-exposure prophylaxis (PEP) has limitations and so newer antileprosy drugs and regimens have been trialed for chemoprophylaxis. BCG re-vaccination in combination with chemoprophylaxis for the prevention of leprosy transmission has not been very encouraging. The use of the anti-phenolic glycolipid-1 (PGL-1) antibody test to detect subclinical cases and administer targeted chemoprophylaxis was unsuccessful owing to its low sensitivity and technical difficulties in a field setup. There is a pressing need for newer multidrug chemoprophylactic regimens using second-line antileprosy drugs. The Netherlands Leprosy Relief has proposed an enhanced PEP++ regimen. A simple but highly sensitive and specific serological test to detect subclinical cases at the field level needs to be developed. Although there are a number of challenges in the large-scale implementation of strategies to halt leprosy transmission, it is important to overcome these in order to move towards a "leprosy-free world."
Topics: Clinical Trials as Topic; Drug Therapy, Combination; Humans; Immunotherapy; Leprostatic Agents; Leprosy; Mycobacterium leprae
PubMed: 31975697
DOI: 10.4103/ijdvl.IJDVL_326_19 -
Frontiers in Immunology 2018Leprosy is an infectious disease that may present different clinical forms depending on host immune response to . Several studies have clarified the role of various T... (Review)
Review
Leprosy is an infectious disease that may present different clinical forms depending on host immune response to . Several studies have clarified the role of various T cell populations in leprosy; however, recent evidences suggest that local innate immune mechanisms are key determinants in driving the disease to its different clinical manifestations. Leprosy is an ideal model to study the immunoregulatory role of innate immune molecules and its interaction with nervous system, which can affect homeostasis and contribute to the development of inflammatory episodes during the course of the disease. Macrophages, dendritic cells, neutrophils, and keratinocytes are the major cell populations studied and the comprehension of the complex networking created by cytokine release, lipid and iron metabolism, as well as antimicrobial effector pathways might provide data that will help in the development of new strategies for leprosy management.
Topics: Animals; Humans; Immunity, Innate; Leprosy; Mycobacterium leprae
PubMed: 29643852
DOI: 10.3389/fimmu.2018.00518 -
Emerging Infectious Diseases Mar 2022The treatment of leprosy is long and complex, benefiting from the development of sterilizing, rapidly-acting drugs. Reductive evolution made Mycobacterium leprae...
The treatment of leprosy is long and complex, benefiting from the development of sterilizing, rapidly-acting drugs. Reductive evolution made Mycobacterium leprae exquisitely sensitive to Telacebec, a phase 2 drug candidate for tuberculosis The unprecedented potency of Telacebec against M. leprae warrants further validation in clinical trials.
Topics: Imidazoles; Mycobacterium leprae; Piperidines; Pyridines
PubMed: 35202539
DOI: 10.3201/eid2803.210394 -
Frontiers in Cellular and Infection... 2021, the causative agent of leprosy, is an obligate intracellular pathogen primarily residing within host macrophages and Schwann cells. Whole genome sequencing predicts a...
, the causative agent of leprosy, is an obligate intracellular pathogen primarily residing within host macrophages and Schwann cells. Whole genome sequencing predicts a highly degraded genome with approximately one third of the coding capacity resulting in the loss of many catabolic pathways. Therefore, it can be assumed that obtains many of the necessary metabolites for intracellular survival and growth from the host cells. In this study, global transcriptomic analyses were done on freshly harvested growing in athymic mouse footpads for five months (MFP5) and compared to those held in axenic medium for 48 (ML48) and 96 (ML96) hours. Results show that all of the genes and pseudogenes were transcribed under both and conditions. 24% and 33% of gene transcript levels were significantly altered in ML48 and ML96 respectively, compared to MFP5. Approximately 45% (39/86) of lipid metabolism genes were significantly downregulated in ML96 compared to MFP5, majority of which are in the β-oxidation pathway. Cholesterol oxidase, acyl-CoA dehydrogenase, and coenzyme F420-dependent oxidoreductase, were significantly upregulated in both ML48 and ML96 compared to MFP5. 30% of cell wall and cell processes functional category genes had altered gene transcription at 96hr compared to MFP5. 40% of 57 genes associated with mycobacterial virulence showed significantly altered transcript levels with 52% significantly downregulated in ML96, including most of the Pro-Glu/Pro-Pro-Glu genes. All 111 hypothetical protein genes with unknown function were expressed. Adenosine triphosphate (ATP) synthesis in appears to be significantly downregulated under conditions. This is the first study comparing global gene expression during growth and stationery phase in axenic medium confirming that during the growth phase in the footpads of experimentally infected mice, is metabolically active and its primary source of energy production is probably lipids.
Topics: Animals; Gene Expression Profiling; Leprosy; Macrophages; Mice; Mycobacterium leprae; Transcriptome
PubMed: 35096659
DOI: 10.3389/fcimb.2021.817221 -
Nature Oct 2021Humans are considered as the main host for Mycobacterium leprae, the aetiological agent of leprosy, but spillover has occurred to other mammals that are now maintenance...
Humans are considered as the main host for Mycobacterium leprae, the aetiological agent of leprosy, but spillover has occurred to other mammals that are now maintenance hosts, such as nine-banded armadillos and red squirrels. Although naturally acquired leprosy has also been described in captive nonhuman primates, the exact origins of infection remain unclear. Here we describe leprosy-like lesions in two wild populations of western chimpanzees (Pan troglodytes verus) in Cantanhez National Park, Guinea-Bissau and Taï National Park, Côte d'Ivoire, West Africa. Longitudinal monitoring of both populations revealed the progression of disease symptoms compatible with advanced leprosy. Screening of faecal and necropsy samples confirmed the presence of M. leprae as the causative agent at each site and phylogenomic comparisons with other strains from humans and other animals show that the chimpanzee strains belong to different and rare genotypes (4N/O and 2F). These findings suggest that M. leprae may be circulating in more wild animals than suspected, either as a result of exposure to humans or other unknown environmental sources.
Topics: Animals; Autopsy; Cote d'Ivoire; Feces; Genotype; Guinea-Bissau; Humans; Leprosy; Mycobacterium leprae; Pan troglodytes; Phylogeny
PubMed: 34646009
DOI: 10.1038/s41586-021-03968-4 -
BMC Biology Oct 2021Hansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually....
BACKGROUND
Hansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease's complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period.
RESULTS
Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae's genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria.
CONCLUSIONS
Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease's global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy's global history and can contribute to current models of M. leprae's worldwide dissemination, including interspecies transmissions.
Topics: Europe; Genome, Bacterial; Humans; Leprosy; Mycobacterium leprae; Population Dynamics
PubMed: 34610848
DOI: 10.1186/s12915-021-01120-2 -
Clinical Microbiology Reviews Jul 1988Leprosy affects over 10 million people in the world. The disease is a model of graded cell-mediated immunity, in this case to the causative organism, Mycobacterium... (Review)
Review
Leprosy affects over 10 million people in the world. The disease is a model of graded cell-mediated immunity, in this case to the causative organism, Mycobacterium leprae. The clinical manifestations are due to (i) bacterial progression, (ii) immunologic responses of the host, (iii) peripheral nerve damage due to either or both bacterial progression and immunologic responses of the host, and (iv) preventable secondary deformities following nerve damage, which account for most of the stigma of the disease. Treatment modalities are now available to control or minimize the effects of bacterial progression, harmful immunologic responses of the host, peripheral nerve damage, and secondary deformities. Unique biochemical characteristics of M. leprae reside in the cell wall and associated macromolecules. Some of these molecules are potent immunogens in humans, while others constitute the structural integrity of the bacillus. Proteins of M. leprae are currently under intensive investigation as a result of deoxyribonucleic acid cloning of M. leprae genes. Structure-function and antigenic relationships of M. leprae proteins should become available by using recombinant deoxyribonucleic acid procedures coupled with T- and B-cell cloning to advance our understanding of the immunologic reactions encountered in Hansen's disease. Until recently, the study of the immunology of leprosy has been stymied by the lack of immunologically specific M. leprae antigens. The definition of specific antigens and production of recombinant and synthetic immunologic reagents have fostered state-of-the-art research efforts into new immunodiagnostic procedures and development of a leprosy vaccine. Also discussed is progress in understanding of the mechanism(s) underlying the M. leprae-specific immunodeficiency associated with lepromatous leprosy, including the role of suppressor T cells and defective macrophage function. Metabolic studies of M. leprae suggest intact catabolic pathways and energy generation with purine bases and catalase as possible growth factors. Special attention may also need to be given to biophysical parameters for eventual in vitro cultivation. Rapid in vitro systems, using quantitation of bacillary metabolic activity, may soon replace the lengthy mouse footpad test for determining the viability and drug susceptibility of the leprosy bacillus.
Topics: Animals; Humans; In Vitro Techniques; Leprostatic Agents; Leprosy; Mice; Microbial Sensitivity Tests; Mycobacterium leprae
PubMed: 3058299
DOI: 10.1128/CMR.1.3.330 -
Future Microbiology Jan 2011Leprosy, which has afflicted human populations for millenia, results from infection with Mycobacterium leprae, an unculturable pathogen with an exceptionally long... (Review)
Review
Leprosy, which has afflicted human populations for millenia, results from infection with Mycobacterium leprae, an unculturable pathogen with an exceptionally long generation time. Considerable insight into the biology and drug resistance of the leprosy bacillus has been obtained from genomics. M. leprae has undergone reductive evolution and pseudogenes now occupy half of its genome. Comparative genomics of four different strains revealed remarkable conservation of the genome (99.995% identity) yet uncovered 215 polymorphic sites, mainly single nucleotide polymorphisms, and a handful of new pseudogenes. Mapping these polymorphisms in a large panel of strains defined 16 single nucleotide polymorphism-subtypes that showed strong geographical associations and helped retrace the evolution of M. leprae.
Topics: Base Composition; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Genetic Variation; Genome, Bacterial; Humans; Leprosy; Mycobacterium leprae; Polymorphism, Single Nucleotide; Pseudogenes
PubMed: 21162636
DOI: 10.2217/fmb.10.153