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PLoS Neglected Tropical Diseases Feb 2019Seemingly innocuous nontuberculous mycobacteria (NTM) species, classified by their slow or rapid growth rates, can cause a wide range of illnesses, from skin ulceration... (Review)
Review
Seemingly innocuous nontuberculous mycobacteria (NTM) species, classified by their slow or rapid growth rates, can cause a wide range of illnesses, from skin ulceration to severe pulmonary and disseminated disease. Despite their worldwide prevalence and significant disease burden, NTM do not garner the same financial or research focus as Mycobacterium tuberculosis. In this review, we outline the most abundant of over 170 NTM species and inadequacies of diagnostics and treatments and weigh the advantages and disadvantages of currently available in vivo animal models of NTM. In order to effectively combat this group of mycobacteria, more research focused on appropriate animal models of infection, screening of chemotherapeutic compounds, and development of anti-NTM vaccines and diagnostics is urgently needed.
Topics: Anti-Bacterial Agents; Humans; Mycobacterium Infections, Nontuberculous
PubMed: 30763316
DOI: 10.1371/journal.pntd.0007083 -
Immunology Dec 2014Interferon-γ (IFN-γ) is an integral and critical molecule of the immune system, with multiple functions, mostly related to the T helper type 1 (Th1) response to... (Review)
Review
Interferon-γ (IFN-γ) is an integral and critical molecule of the immune system, with multiple functions, mostly related to the T helper type 1 (Th1) response to infection. It is critical for defence against mycobacterial infection and is of increasing interest in defence against fungi. In this article, we review the genetic and epigenetic variants affecting IFN-γ expression and investigate its role in disease, with an emphasis on fungal diseases such as invasive and chronic pulmonary aspergillosis. Over 347 IFN-γ gene variants have been described, in multiple ethnic populations. Many appear to confer a susceptibility to disease, especially tuberculosis (TB) and hepatitis, but also some non-infectious conditions such as aplastic anaemia, cervical cancer and psoriasis. Several epigenetic modifications are also described, increasing IFN-γ expression in Th1 lymphocytes and reducing IFN-γ expression in Th2 lymphocytes. Recombinant IFN-γ administration is licensed for the prophylaxis of infection (bacterial and fungal) in patients with the phagocyte functional deficiency syndrome chronic granulomatous disease, although the benefits appear limited. Interferon-γ therapy is given to patients with profound defects in IFN-γ and interleukin-12 production and appears to be beneficial for patients with invasive aspergillosis and cryptococcal meningitis, but the studies are not definitive. A high proportion of patients with chronic pulmonary aspergillosis are poor producers of IFN-γ in response to multiple stimuli and could also benefit from IFN-γ administration. The investigation and management of patients with possible or demonstrated IFN-γ deficiency in adulthood is poorly studied and could be greatly enhanced with the integration of genetic data.
Topics: Antibodies; Clinical Trials as Topic; Epigenesis, Genetic; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Immunity; Interferon-gamma; Mycobacterium Infections; Mycoses
PubMed: 25052001
DOI: 10.1111/imm.12362 -
Pediatric Pulmonology Feb 2020This review summarizes the discussion of a session held during the 2018 North American Cystic Fibrosis (CF) Conference titled "Challenging Cases in Nontuberculous... (Review)
Review
This review summarizes the discussion of a session held during the 2018 North American Cystic Fibrosis (CF) Conference titled "Challenging Cases in Nontuberculous Mycobacterial (NTM) Management." In this session, a multidisciplinary panel of NTM experts discussed clinical challenges related to the management of NTM infection in people with CF in which decision-making falls outside of the Cystic Fibrosis Foundation/European Cystic Fibrosis Society NTM guidelines. Topics discussed included managing newly acquired NTM infection, selecting and monitoring treatment regimens, determining treatment endpoints, and caring for patients after NTM treatment.
Topics: Cystic Fibrosis; Decision Making; Diagnostic Tests, Routine; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 31821718
DOI: 10.1002/ppul.24604 -
Tuberculosis (Edinburgh, Scotland) Mar 2020Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria... (Review)
Review
Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and 'omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts.
Topics: Animals; Bacteriology; Biomedical Research; Congresses as Topic; Diffusion of Innovation; Disease Models, Animal; Host-Pathogen Interactions; Humans; Infectious Disease Medicine; Mycobacterium; Mycobacterium Infections, Nontuberculous; Tuberculosis
PubMed: 32279870
DOI: 10.1016/j.tube.2020.101914 -
Frontiers in Immunology 2021
Topics: Cytokines; Immunotherapy; Mycobacterium Infections; Tuberculosis, Pulmonary
PubMed: 33968090
DOI: 10.3389/fimmu.2021.684200 -
International Journal of Infectious... Apr 2016Non-tuberculous mycobacteria (NTM) are emerging worldwide as significant causes of chronic pulmonary infection, posing a number of challenges for both clinicians and... (Review)
Review
Non-tuberculous mycobacteria (NTM) are emerging worldwide as significant causes of chronic pulmonary infection, posing a number of challenges for both clinicians and researchers. While a number of studies worldwide have described an increasing prevalence of NTM pulmonary disease over time, population-based data are relatively sparse and subject to ascertainment bias. Furthermore, the disease is geographically heterogeneous. While some species are commonly implicated worldwide (Mycobacterium avium complex, Mycobacterium abscessus), others (e.g., Mycobacterium malmoense, Mycobacterium xenopi) are regionally important. Thoracic computed tomography, microbiological testing with identification to the species level, and local epidemiology must all be taken into account to accurately diagnose NTM pulmonary disease. A diagnosis of NTM pulmonary disease does not necessarily imply that treatment is required; a patient-centered approach is essential. When treatment is required, multidrug therapy based on appropriate susceptibility testing for the species in question should be used. New diagnostic and therapeutic modalities are needed to optimize the management of these complicated infections.
Topics: Disease Susceptibility; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Respiratory Tract Infections
PubMed: 26976549
DOI: 10.1016/j.ijid.2016.03.006 -
Frontiers in Immunology 2021Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial... (Review)
Review
Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial infection may present different clinical presentations and it is associated with stigma, deformity, and disability. The understanding of the immunopathogenic mechanisms related to mycobacterial infection in human skin is of pivotal importance to identify targets for new therapeutic strategies. The occurrence of reactional episodes and relapse in leprosy patients, the emergence of resistant mycobacteria strains, and the absence of effective drugs to treat mycobacterial cutaneous infection increased the interest in the development of therapies based on repurposed drugs against mycobacteria. The mechanism of action of many of these therapies evaluated is linked to the activation of autophagy. Autophagy is an evolutionary conserved lysosomal degradation pathway that has been associated with the control of the mycobacterial bacillary load. Here, we review the role of autophagy in the pathogenesis of cutaneous mycobacterial infection and discuss the perspectives of autophagy as a target for drug development and repurposing against cutaneous mycobacterial infection.
Topics: Autophagy; Drug Discovery; Humans; Mycobacterium; Mycobacterium Infections; Skin Diseases, Bacterial
PubMed: 34113346
DOI: 10.3389/fimmu.2021.674241 -
Thorax May 1994
Topics: Anti-Bacterial Agents; Diagnosis, Differential; Drug Therapy, Combination; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Tuberculosis, Pulmonary
PubMed: 8016760
DOI: 10.1136/thx.49.5.435 -
Minerva Medica Aug 2022
Topics: Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Mycobacterium Infections, Nontuberculous; Tomography, X-Ray Computed
PubMed: 33576200
DOI: 10.23736/S0026-4806.21.07351-1 -
Experimental and Clinical... Oct 2021Data are limited regarding the clinical significance of nontuberculous mycobacteria pulmonary infections among lung transplant recipients. We investigated the incidence...
OBJECTIVES
Data are limited regarding the clinical significance of nontuberculous mycobacteria pulmonary infections among lung transplant recipients. We investigated the incidence and characteristics of pulmonary nontuberculous mycobacteria infection in ourlung transplant patient population.
MATERIALS AND METHODS
We obtaineddata of the patients who underwent lung transplant in our center from January 1997 to March 2019.
RESULTS
Of 690 patients, nontuberculous mycobacteria were identified in 58 patients (8.4%) over a median follow-up of 3 years. Types of species were as follows: Mycobacterium simiae (n = 24), avium complex (n = 12), abscessus (n = 9), fortuitum (n = 6), chelonae (n = 2), szulgai (n = 1), kansasii (n = 1), lentiflavum (n = 1), and undefined mycobacteria (n = 2). When we compared infections in the early versus late period posttransplant (before and after 6 months), infections with Mycobacterium simiae (16 vs 8 incidents) and Mycobacterium fortuitum (5 vs 1 incident) were more often observed within the early period, whereas most Mycobacterium abscessus (7 vs 1 incident) and Mycobacterium avium complex (9 vs 3 incidents) were observed in the later period. The median forced expiratory volume in 1 second overtime did not differ significantly between patients with and without nontuberculous mycobacteria infection (P = .29). Nontuberculous mycobacteria acquisition was significantly associated with decreased survival (relative risk of 2.41, 95% CI, 1.70-3.43; P ⟨ .001).
CONCLUSIONS
The nontuberculous mycobacteria species isolated varied according to the time elapsed since transplant. Among lung transplant recipients, nontuberculous mycobacteria infection was associated with increased mortality but not with lung dysfunction.
Topics: Humans; Lung; Mycobacterium; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Opportunistic Infections; Transplant Recipients; Treatment Outcome
PubMed: 34641777
DOI: 10.6002/ect.2021.0177