Pathogenesis and Risk Factors for Nontuberculous Mycobacterial Lung Disease

Honda, Jennifer R.; Knight, Vijaya; Chan, Edward D.

doi:10.1016/j.ccm.2014.10.001

Cited by 123 publications

(96 citation statements)

References 64 publications

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“…Pathogenic NTM comprise of many species and strains found in the environment such as in the water and the soil. NTM disease have been increasingly diagnosed worldwide [1]. NTM diseases manifest as pneumonia, lymphadenitis, skin, soft tissue, bone and disseminated infection.…”

Section: Introductionmentioning

confidence: 99%

Factors associated with acquired Anti IFN- γ autoantibody in patients with nontuberculous mycobacterial infection

et al. 2017

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BackgroundThe clinical syndrome of disseminated nontuberculous mycobacterial (NTM) infection in patients who were previously healthy is now well recognized to be associated with an acquired autoantibody to Interferon gamma (Anti IFN- γ autoantibody). However, the risk factors of this syndrome remain unknown.MethodWe performed an unmatched case control study among patients with NTM diseases who were diagnosed and treated at Siriraj Hospital, Bangkok, Thailand. Anti-IFN autoantibody was detected by enzyme-linked immunosorbent assay (ELISA) method. Cases were patients with NTM diseases and detectable anti IFN- γ autoantibody. Controls were randomly selected from those with undetectable anti IFN- γ autoantibody. Data from both groups including demographic data, clinical presentation, laboratory results, other risk factors and HLA genotypes were collected. Univariate and multivariate analyses were performed to identify independent risk factors for this syndrome.Results70 cases (mean age 50 ± 11 years) and 70 controls (mean age 58 ± 18 years) were enrolled into the study. Mycobacterial abscessus was the most common NTM pathogen found in both groups (72.9% in cases and 41.4% in controls respectively). However, disseminated NTM disease was significantly more common in cases (92.9%) than in the controls (14.3%, p<0.001). Binary logistic regression analysis showed that previous OIs (adjusted OR14.87, 95% CI 2.36–93.86), birthplace outside Central region (adjusted OR 19.19, 95% CI 3.86–95.35), lack of comorbidities lead to immunosuppression, such as HIV infection or diabetes mellitus (adjusted OR 23.68, 95% CI 4.01–139.94), and presence of HLA DRB1*15/16 (adjusted OR 153.28, 95% CI 16.87–139.88) were independent factors associated with this syndrome.ConclusionPatients with NTM disease associated with anti IFN- γ autoantibody are almost always previously healthy and HIV negative. Most of these patients presented with disseminated NTM disease with generalized lymphadenitis and often with reactive skin lesions. Factors associated with detectable anti IFN- γ autoantibody are HLA-DRB1 and DQB1 alleles, and history of previous OIs in patients without comorbidity that leads to immunosuppression. Further studies are needed to better understand these associations and to improve the treatment outcome.

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Section: Introductionmentioning

confidence: 99%

Factors associated with acquired Anti IFN- γ autoantibody in patients with nontuberculous mycobacterial infection

et al. 2017

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“…Though M. avium subsp. hominissuis infects individuals with immunosuppression through the gastrointestinal route and such infections often lead to disseminated disease, infections in immunocompetent patients are typically localized to the respiratory tract (1, 6). Underlying respiratory conditions such as cystic fibrosis, chronic obstructive pulmonary disease, and bronchiectasis do increase susceptibility for infection, but individuals who are otherwise healthy can also develop disease (5, 6).…”

Section: Introductionmentioning

confidence: 99%

Identification of Bicarbonate as a Trigger and Genes Involved with Extracellular DNA Export in Mycobacterial Biofilms

Rose

Bermudez

2016

mBio

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Extracellular DNA (eDNA) is an integral biofilm matrix component of numerous pathogens, including nontuberculous mycobacteria (NTM). Cell lysis is the source of eDNA in certain bacteria, but the source of eDNA remains unidentified for NTM, as well as for other eDNA-containing bacterial species. In this study, conditions affecting eDNA export were examined, and genes involved with the eDNA export mechanism were identified. After a method for monitoring eDNA in real time in undisturbed biofilms was established, different conditions affecting eDNA were investigated. Bicarbonate positively influenced eDNA export in a pH-independent manner in Mycobacterium avium, M. abscessus, and M. chelonae. The surface-exposed proteome of M. avium in eDNA-containing biofilms revealed abundant carbonic anhydrases. Chemical inhibition of carbonic anhydrases with ethoxzolamide significantly reduced eDNA export. An unbiased transposon mutant library screen for eDNA export in M. avium identified many severely eDNA-attenuated mutants, including one not expressing a unique FtsK/SpoIIIE-like DNA-transporting pore, two with inactivation of carbonic anhydrases, and nine with inactivation of genes belonging to a unique genomic region, as well as numerous mutants involved in metabolism and energy production. Complementation of nine mutants that included the FtsK/SpoIIIE and carbonic anhydrase significantly restored eDNA export. Interestingly, several attenuated eDNA mutants have mutations in genes encoding proteins that were found with the surface proteomics, and many more mutations are localized in operons potentially encoding surface proteins. Collectively, our data strengthen the evidence of eDNA export being an active mechanism that is activated by the bacterium responding to bicarbonate.

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“…Pre-existing chronic lung diseases, especially COPD, asthma, and bronchiectasis, are the main risk factors for NTM-PD in Europe [39,47,48,49,50]. In contrast to the USA, fibrocavitary disease or consolidating infiltrates are more common than nodular bronchiectatic NTM-PD in Europe [47,51].…”

Section: Population Structurementioning

confidence: 99%

Pulmonary Disease Caused by Non-Tuberculous Mycobacteria

Wassilew¹,

Hoffmann²,

Andréjak³

et al. 2016

Respiration

127

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Non-tuberculous mycobacteria (NTM) include more than 160 ubiquitous, environmental, acid-fast-staining bacterial species, some of which may cause disease in humans. Chronic pulmonary infection is the most common clinical manifestation. Although patients suffering from chronic lung diseases are particularly susceptible to NTM pulmonary disease, many affected patients have no apparent risk factors. Host and pathogen factors leading to NTM pulmonary disease are not well understood and preventive therapies are lacking. NTM isolation and pulmonary disease are reported to rise in frequency in Europe as well as in other parts of the world. Differentiation between contamination, infection, and disease remains challenging. Treatment of NTM pulmonary disease is arduous, lengthy, and costly. Correlations between results of in vitro antibiotic susceptibility testing and clinical treatment outcomes are only evident for the Mycobacterium avium complex, M. kansasii, and some rapidly growing mycobacteria. We describe the epidemiology of NTM pulmonary disease as well as emerging NTM pathogens and their geographical distribution in non-cystic fibrosis patients in Europe. We also review recent innovations for the diagnosis of NTM pulmonary disease, summarize treatment recommendations, and identify future research priorities to improve the management of patients affected by NTM pulmonary disease.

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Pathogenesis and Risk Factors for Nontuberculous Mycobacterial Lung Disease

Cited by 123 publications

References 64 publications

Factors associated with acquired Anti IFN- γ autoantibody in patients with nontuberculous mycobacterial infection

Factors associated with acquired Anti IFN- γ autoantibody in patients with nontuberculous mycobacterial infection

Identification of Bicarbonate as a Trigger and Genes Involved with Extracellular DNA Export in Mycobacterial Biofilms

Pulmonary Disease Caused by Non-Tuberculous Mycobacteria

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