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Frontiers in Immunology 2020Leprosy, a disease caused by the intracellular parasite or , has affected humans for more than 4,000 years and is a stigmatized disease even now. Since clinical... (Review)
Review
Leprosy, a disease caused by the intracellular parasite or , has affected humans for more than 4,000 years and is a stigmatized disease even now. Since clinical manifestations of leprosy patients present as an immune-related spectrum, leprosy is regarded as an ideal model for studying the interaction between host immune response and infection; in fact, the landscape of leprosy immune responses has been extensively investigated. Meanwhile, leprosy is to some extent a genetic disease because the genetic factors of hosts have long been considered major contributors to this disease. Many immune-related genes have been discovered to be associated with leprosy. However, immunological and genetic findings have rarely been studied and discussed together, and as a result, the effects of gene variants on leprosy immune responses and the molecular mechanisms of leprosy pathogenesis are largely unknown. In this context, we summarized advances in both the immunology and genetics of leprosy and discussed the perspective of the combination of immunological and genetic approaches in studying the molecular mechanism of leprosy pathogenesis. In our opinion, the integrating of immunological and genetic approaches in the future may be promising to elucidate the molecular mechanism of leprosy onset and how leprosy develops into different types of leprosy.
Topics: Humans; Leprosy
PubMed: 32373110
DOI: 10.3389/fimmu.2020.00567 -
Neurotherapeutics : the Journal of the... Oct 2021Neuropathy and related disabilities are the major medical consequences of leprosy, which remains a global medical concern. Despite major advances in understanding the... (Review)
Review
Neuropathy and related disabilities are the major medical consequences of leprosy, which remains a global medical concern. Despite major advances in understanding the mechanisms of M. leprae entry into peripheral nerves, most aspects of the pathogenesis of leprosy neuropathy remain poorly understood. Sensory loss is characteristic of leprosy, but neuropathic pain is sometimes observed. Effective anti-microbial therapy is available, but neuropathy remains a problem especially if diagnosis and treatment are delayed. Currently there is intense interest in post-exposure prophylaxis with single-dose rifampin in endemic areas, as well as with enhanced prophylactic regimens in some situations. Some degree of nerve involvement is seen in all cases and neuritis may occur in the absence of leprosy reactions, but acute neuritis commonly accompanies both Type 1 and Type 2 leprosy reactions and may be difficult to manage. A variety of established as well as new methods for the early diagnosis and assessment of leprosy neuropathy are reviewed. Corticosteroids offer the primary treatment for neuritis and for subclinical neuropathy in leprosy, but success is limited if nerve function impairment is present at the time of diagnosis. A candidate vaccine has shown apparent benefit in preventing nerve injury in the armadillo model. The development of new therapeutics for leprosy neuropathy is greatly needed.
Topics: Animals; Armadillos; Leprosy; Mycobacterium leprae; Neuritis; Peripheral Nervous System Diseases
PubMed: 34799845
DOI: 10.1007/s13311-021-01153-z -
Clinical Microbiology Reviews Jan 2015Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the... (Review)
Review
Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the global incidence remains high, and patients often have long-term complications associated with the disease. In this article, we discuss recent findings related to genetics, susceptibility, and disease reservoirs and the implications of these findings for Hansen's disease control and health outcomes for patients. We describe the continued difficulties associated with treatment of inflammatory episodes known as "leprosy reactions," which cause much of the disability associated with the disease and can affect people for many years after MDT is complete. We also discuss some of the contemporary challenges for physicians and patients, including international and internal migration of people affected by the disease. We suggest some important areas of focus for future Hansen's disease research.
Topics: Animals; Armadillos; Disease Reservoirs; Disease Susceptibility; Humans; Incidence; Leprosy; Risk Factors
PubMed: 25567223
DOI: 10.1128/CMR.00079-13 -
BMJ Clinical Evidence Apr 2007The World Health Organization field leprosy classification is based on the number of skin lesions: single-lesion leprosy (1 lesion), paucibacillary leprosy (2-5 skin... (Review)
Review
INTRODUCTION
The World Health Organization field leprosy classification is based on the number of skin lesions: single-lesion leprosy (1 lesion), paucibacillary leprosy (2-5 skin lesions), and multibacillary leprosy (more than 5 skin lesions). Worldwide, about 720,000 new cases of leprosy are reported each year, and about 2 million people have leprosy-related disabilities.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent leprosy? What are the effects of treatments for leprosy? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: Bacillus Calmette Guerin (BCG) plus killed Mycobacterium leprae vaccine; BCG vaccine; ICRC vaccine; multidrug treatment; multiple-dose treatment; mycobacterium w vaccine; single-dose treatment.
Topics: BCG Vaccine; Humans; Leprosy; Leprosy, Lepromatous; Leprosy, Multibacillary; Leprosy, Paucibacillary; Leprosy, Tuberculoid; Mycobacterium leprae; World Health Organization
PubMed: 19454067
DOI: No ID Found -
Frontiers in Immunology 2018Neurotrophins are a family of proteins that regulate different aspects of biological development and neural function and are of great importance in neuroplasticity. This... (Review)
Review
Neurotrophins are a family of proteins that regulate different aspects of biological development and neural function and are of great importance in neuroplasticity. This group of proteins has multiple functions in neuronal cells, as well as in other cellular populations. Nerve growth factor (NGF) is a neurotrophin that is endogenously produced during development and maturation by multiple cell types, including neurons, Schwann cells, oligodendrocytes, lymphocytes, mast cells, macrophages, keratinocytes, and fibroblasts. These cells produce proNGF, which is transformed by proteolytic cleavage into the biologically active NGF in the endoplasmic reticulum. The present review describes the role of NGF in the pathogenesis of leprosy and its correlations with different clinical forms of the disease and with the phenomena of regeneration and neural injury observed during infection. We discuss the involvement of NGF in the induction of neural damage and the pathophysiology of pain associated with peripheral neuropathy in leprosy. We also discuss the roles of immune factors in the evolution of this pathological process. Finally, we highlight avenues of investigation for future research to broaden our understanding of the role of NGF in the pathogenesis of leprosy. Our analysis of the literature indicates that NGF plays an important role in the evolution and outcome of infection. The findings described here highlight an important area of investigation, as leprosy is one of the main causes of infection in the peripheral nervous system.
Topics: Animals; Autoimmunity; Gene Expression Regulation; Humans; Immune System; Immunomodulation; Leprosy; Nerve Growth Factor; Signal Transduction
PubMed: 29867937
DOI: 10.3389/fimmu.2018.00939 -
Arquivos de Neuro-psiquiatria Sep 2013Leprosy is a chronic infectious peripheral neuropathy caused by Mycobacterium leprae. The different clinical presentations of the disease are determined by the quality... (Review)
Review
Leprosy is a chronic infectious peripheral neuropathy caused by Mycobacterium leprae. The different clinical presentations of the disease are determined by the quality of the host immune response. Early detection of leprosy and treatment by multidrug therapy are the most important steps in preventing deformity and disability. Thus the early recognition of the clinical leprosy presentation is essential. Mononeuritis, mononeuritis multiplex (MM), polyneuritis (MM summation) are the most frequent. The frequent anesthetic skin lesions are absent in the pure neuritic leprosy presentation form. Isolated peripheral nerve involvement is common, including the cranial ones. Arthritic presentation is occasionally seen, usually misdiagnosed as rheumatoid arthritis. Attention should be given to autonomic dysfunctions in leprosy. There are clinical presentations with severe neuropathic pain - painful small-fiber neuropathy. Leprous late-onset neuropathy (LLON) clinical presentation should be considered facing a patient who develop an inflammatory neuropathy many years after a previous skin leprosy treatment.
Topics: Diagnosis, Differential; Humans; Leprosy; Peripheral Nerves; Peripheral Nervous System Diseases
PubMed: 24141500
DOI: 10.1590/0004-282X20130146 -
PLoS Neglected Tropical Diseases Aug 2021The number of new leprosy cases is declining globally, but the disability caused by leprosy remains an important disease burden. The chance of disability is increased by...
BACKGROUND
The number of new leprosy cases is declining globally, but the disability caused by leprosy remains an important disease burden. The chance of disability is increased by delayed case detection. This review focusses on the individual and community determinants of delayed leprosy case detection.
METHODS
This study was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The study protocol is registered in PROSPERO (code: CRD42020189274). To identify determinants of delayed detection, data was collected from five electronic databases: Embase.com, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library.
RESULTS
We included 27 papers from 4315 records assessed. They originated in twelve countries, had been published between January 1, 2000, and January 31, 2021, and described the factors related to delayed leprosy case detection, the duration of the delayed case, and the percentage of Grade 2 Disability (G2D). The median delay in detection ranged from 12 to 36 months, the mean delay ranged from 11.5 to 64.1 months, and the percentage of G2D ranged from 5.6 to 43.2%. Health-service-seeking behavior was the most common factor associated with delayed detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge. The most common socioeconomic factors were living in a rural area, performing agricultural labor, and being unemployed. Stigma was the most common social and community factor.
CONCLUSIONS
Delayed leprosy case detection is clearly correlated with increased disability and should therefore be a priority of leprosy programs. Interventions should focus on determinants of delayed case detection such as health-service-seeking behavior, and should consider relevant individual, socioeconomic, and community factors, including stigmatization. Further study is required of the health service-related factors contributing to delay.
Topics: Delayed Diagnosis; Disabled Persons; Humans; Leprosy; Patient Acceptance of Health Care; Risk Factors; Social Stigma; Socioeconomic Factors; Time-to-Treatment
PubMed: 34383768
DOI: 10.1371/journal.pntd.0009651 -
Revista Do Instituto de Medicina... Sep 2019Mycobacterium leprae is the primary causative agent of Hansen's disease or leprosy. Besides human beings, natural infection has been described in animals such as... (Review)
Review
Mycobacterium leprae is the primary causative agent of Hansen's disease or leprosy. Besides human beings, natural infection has been described in animals such as mangabey monkeys and armadillos. Leprosy is considered a global health problem and its complete pathogenesis is still unknown. As M. leprae does not grow in artificial media, armadillos have become the primary experimental model for leprosy, mimicking human disease including involvement of the peripheral nervous system. Leprosy transmission occurs through continuous and close contact of susceptible people with untreated infected people. However, unknown leprosy contact has been reported in leprosy-affected people, and contact with armadillos is a risk factor for leprosy. In the USA, leprosy is considered a zoonosis and this classification has recently been accepted in Brazil. This review presents information regarding the role of wild armadillos as a source of M. leprae for human infections, as well as the pathogenesis of leprosy.
Topics: Animals; Armadillos; Disease Models, Animal; Disease Reservoirs; Humans; Leprosy; Mycobacterium leprae
PubMed: 31531622
DOI: 10.1590/S1678-9946201961044 -
Malawi Medical Journal : the Journal of... Sep 2022
Topics: Humans; Malawi; Leprosy
PubMed: 36406097
DOI: 10.4314/mmj.v34i3.1 -
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