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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 -
Microbial Pathogenesis Dec 2020Mycobacterium leprae is known to cause leprosy, a neurological and dermatological disease. In the past 20 years, 16 million leprosy cases have been recorded and more... (Review)
Review
Mycobacterium leprae is known to cause leprosy, a neurological and dermatological disease. In the past 20 years, 16 million leprosy cases have been recorded and more than 200,000 new cases were registered each year, indicating that the disease is still progressing without hindrance. M. leprae, an intracellular bacterium, infects the Schwann cells of the peripheral nervous system. Several types of leprosy have been described, including indeterminate, tuberculoid, borderline tuberculoid, mid-borderline, borderline lepromatous and lepromatous, and three different forms of leprosy reactions, namely type 1, 2 and 3, have been designated. Microscopic detection, serological diagnostic test, polymerase chain reaction and flow tests are employed in the diagnosis of leprosy. The recommended treatment for leprosy consists of rifampicin, dapsone, clofazimine, ofloxacin and minocycline and vaccines are also available. However, relapse may occur after treatment has been halted and hence patients must be educated on the signs of relapse to allow proper treatment and reduce severity. In this review, we depict the current understanding of M. leprae pathogenicity, clinical aspects and manifestations. Transmission of leprosy, diagnosis and treatment are also discussed.
Topics: Humans; Leprosy; Mycobacterium leprae; Polymerase Chain Reaction; Rifampin; Serologic Tests
PubMed: 32931893
DOI: 10.1016/j.micpath.2020.104475 -
Anais Brasileiros de Dermatologia 2022Leprosy, a disease caused by Mycobacterium leprae, has polymorphic neurocutaneous manifestations strongly correlated with the host immune response. Peripheral neural... (Review)
Review
Leprosy, a disease caused by Mycobacterium leprae, has polymorphic neurocutaneous manifestations strongly correlated with the host immune response. Peripheral neural damage can lead to sensory and motor losses, as well as deformities of the hands and feet. Both innate and acquired immune responses are involved, but the disease has been classically described along a Th1/Th2 spectrum, where the Th1 pole corresponds to the more limited presentations and the Th2 to the multibacillary ones. The aim of this review is to discuss this dichotomy in light of the current knowledge of the cytokines, T helper subpopulations, and regulatory T cells involved in each presentation of leprosy. The text will also address leprosy reactions related to increased inflammatory activity in both limited and multibacillary presentations, leading to exacerbation of chronic signs and symptoms and/or the development of new ones. Despite the efforts of many research groups around the world, there is no standardized serological test/biological marker for diagnosis so far, even in endemic areas, which could contribute to the eradication of leprosy.
Topics: Cytokines; Humans; Leprosy; Mycobacterium leprae; T-Lymphocytes, Regulatory
PubMed: 35379512
DOI: 10.1016/j.abd.2021.08.006 -
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 -
PLoS Neglected Tropical Diseases Apr 2020Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two...
Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar pathologic conditions. They primarily target the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease, being endemic in specific locations within countries of the Americas, Asia, and Africa, while in Europe it is only rarely reported. The reason for a spatial inequality in the prevalence of leprosy in so-called endemic pockets within a country is still largely unexplained. A systematic review was conducted targeting leprosy transmission research data, using PubMed and Scopus as sources. Publications between January 1, 1945 and July 1, 2019 were included. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. The transmission of this disease is probably much more complicated than was thought before. In the Americas, the nine-banded armadillo (Dasypus novemcinctus) has been established as another natural host and reservoir of M. leprae. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. More recently, in red squirrels (Sciurus vulgaris) with leprosy-like lesions in the British Isles M. leprae and M. lepromatosis DNA was detected. This finding was unexpected, because leprosy is considered a disease of humans (with the exception of the armadillo), and because it was thought that leprosy (and M. leprae) had disappeared from the United Kingdom. Furthermore, animals can be affected by other leprosy-like diseases, caused by pathogens phylogenetically closely related to M. leprae. These mycobacteria have been proposed to be grouped as a M. leprae-complex. We argue that insights from the transmission and reservoirs of members of the M. leprae-complex might be relevant for leprosy research. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady global incidence of leprosy despite effective and widespread multidrug therapy. A reduction in transmission cannot be expected to be accomplished by actions or interventions from the human healthcare domain alone, as the mechanisms involved are complex. Therefore, to increase our understanding of the intricate picture of leprosy transmission, we propose a One Health transdisciplinary research approach.
Topics: Animals; Armadillos; Disease Reservoirs; Disease Transmission, Infectious; Global Health; Humans; Incidence; Leprosy; Mycobacterium; Mycobacterium leprae; Prevalence; Sciuridae
PubMed: 32339201
DOI: 10.1371/journal.pntd.0008276 -
Methods in Molecular Biology (Clifton,... 2021Building upon the foundational research of Robert Koch, who demonstrated the ability to grow Mycobacterium tuberculosis for the first time in 1882 using media made of...
Building upon the foundational research of Robert Koch, who demonstrated the ability to grow Mycobacterium tuberculosis for the first time in 1882 using media made of coagulated bovine serum, microbiologists have continued to develop new and more efficient ways to grow mycobacteria. Presently, all known mycobacterial species can be grown in the laboratory using either axenic culture techniques or in vivo passage in laboratory animals. This chapter provides conventional protocols to grow mycobacteria for diagnostic purposes directly from clinical specimens, as well as in research laboratories for scientific purposes. Detailed protocols used for production of M. tuberculosis in large scale (under normoxic and hypoxic conditions) in bioreactors and for production of obligate intracellular pathogens such as Mycobacterium leprae and "Mycobacterium lepromatosis" using athymic nude mice and armadillos are provided.
Topics: Animals; Armadillos; Bacteriological Techniques; Bioreactors; Disease Models, Animal; Humans; Mice, Nude; Microbial Viability; Mycobacterium; Mycobacterium Infections; Mycobacterium leprae; Time Factors; Mice
PubMed: 34235647
DOI: 10.1007/978-1-0716-1460-0_1 -
International Reviews of Immunology 2022Leprosy is a disease caused by (ML) with diverse clinical manifestations, which are strongly correlated with the host's immune response. Skin lesions may be accompanied...
Leprosy is a disease caused by (ML) with diverse clinical manifestations, which are strongly correlated with the host's immune response. Skin lesions may be accompanied by peripheral neural damage, leading to sensory and motor losses, as well as deformities of the hands and feet. Both innate and acquired immune responses are involved, but the disease has been classically described along a Th1/Th2 spectrum, where the Th1 pole corresponds to the most limited presentations and the Th2 to the most disseminated ones. We discuss this dichotomy in the light of current knowledge of cytokines, Th subpopulations and regulatory T cells taking part in each leprosy presentation. Leprosy reactions are associated with an increase in inflammatory activity both in limited and disseminated presentations, leading to a worsening of previous symptoms or the development of new symptoms. Despite the efforts of many research groups around the world, there is still no adequate serological test for diagnosis in endemic areas, hindering the eradication of leprosy in these regions.
Topics: Adaptive Immunity; Cytokines; Humans; Leprosy; Mycobacterium leprae; T-Lymphocytes, Regulatory
PubMed: 33241709
DOI: 10.1080/08830185.2020.1851370 -
Acta Tropica Sep 2019Leprosy is an ancient disease caused by the acid-fast bacillus Mycobacterium leprae, also known as Hansen's bacillus. M. leprae is an obligate intracellular... (Review)
Review
Leprosy is an ancient disease caused by the acid-fast bacillus Mycobacterium leprae, also known as Hansen's bacillus. M. leprae is an obligate intracellular microorganism with a marked Schwann cell tropism and is the only human pathogen capable of invading the superficial peripheral nerves. The transmission mechanism of M. leprae is not fully understood; however, the nasal mucosa is accepted as main route of M. leprae entry to the human host. The complete sequencing and the comparative genome analysis show that M. leprae underwent a genome reductive evolution process, as result of lifestyle change and adaptation to different environments; some of lost genes are homologous to those of host cells. Thus, M. leprae reduced its genome size to 3.3 Mbp, contributing to obtain the lowest GC content (approximately 58%) among mycobacteria. The M. leprae genome contains 1614 open reading frames coding for functional proteins, and 1310 pseudogenes corresponding to 41% of the genome, approximately. Comparative analyses to different microorganisms showed that M. leprae possesses the highest content of pseudogenes among pathogenic and non-pathogenic bacteria and archaea. The pathogen adaptation into host cells, as the Schwann cells, brought about the reduction of the genome and induced multiple gene inactivation. The present review highlights the characteristics of genome's reductive evolution that M. leprae experiences in the genetic aspects compared with other pathogens. The possible mechanisms of pseudogenes formation are discussed.
Topics: Acclimatization; DNA, Bacterial; Evolution, Molecular; Gene Expression Regulation, Bacterial; Genome, Bacterial; Humans; Leprosy; Mycobacterium leprae
PubMed: 31152726
DOI: 10.1016/j.actatropica.2019.105041 -
Microbiology Spectrum Aug 2016The use of paleomicrobiological techniques in leprosy has the potential to assist paleopathologists in many important aspects of their studies on the bones of victims,... (Review)
Review
The use of paleomicrobiological techniques in leprosy has the potential to assist paleopathologists in many important aspects of their studies on the bones of victims, solving at times diagnostic problems. With Mycobacterium leprae, because of the unique nature of the organism, these techniques can help solve problems of differential diagnosis. In cases of co-infection with Mycobacterium tuberculosis, they can also suggest a cause of death and possibly even trace the migratory patterns of people in antiquity, as well as explain changes in the rates and level of infection within populations in antiquity.
Topics: Bacteriological Techniques; Bone and Bones; Coinfection; Fossils; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; History, Medieval; Humans; Leprosy; Mycobacterium leprae; Mycobacterium tuberculosis; Paleopathology
PubMed: 27726813
DOI: 10.1128/microbiolspec.PoH-0009-2015 -
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