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      Epidemiology and Clinical Features of Pulmonary Nontuberculous Mycobacteriosis in Nagasaki, Japan

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          Abstract

          Background and Objectives

          Recent reports indicate that the incidence of nontuberculous mycobacterial-lung disease (NTM-LD) is increasing. This study aimed to investigate the epidemiology and clinical features of NTM-LD patients in Nagasaki prefecture, Japan to identify the negative prognostic factors for NTM-LD in Japan.

          Methods

          The medical records of patients newly diagnosed with NTM-LD in eleven hospitals in Nagasaki prefecture between January 2001 and February 2010 were reviewed. Data regarding the annual population of each region and the incidence of all forms of tuberculosis were collected to assess geographic variations in NTM-LD incidence, isolates, and radiological features.

          Results

          A total 975 patients were diagnosed with NTM-LD. The incidence increased over the study period and reached 11.0 and 10.1 per 100,000 population in 2008 and 2009, respectively. M. intracellulare was the most common pathogen in the southern region, and M. avium most common in other regions. The most common radiographic pattern was the nodular-bronchiectatic pattern. Age >60 years, body mass index <18.5 kg/m 2, underlying lung disease, and cavitary pattern were the negative prognostic factors at the 1-year follow-up.

          Conclusions

          The incidence of NTM-LD has been increasing in Nagasaki prefecture. The isolates and radiographic features of patients vary markedly by region.

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          Most cited references22

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          Surrounded by mycobacteria: nontuberculous mycobacteria in the human environment.

          A majority of the Mycobacterium species, called the nontuberculous mycobacteria (NTM), are natural inhabitants of natural waters, engineered water systems, and soils. As a consequence of their ubiquitous distribution, humans are surrounded by these opportunistic pathogens. A cardinal feature of mycobacterial cells is the presence of a hydrophobic, lipid-rich outer membrane. The hydrophobicity of NTM is a major determinant of aerosolization, surface adherence, biofilm-formation, and disinfectant- and antibiotic resistance. The NTM are oligotrophs, able to grow at low carbon levels [>50 microg assimilable organic carbon (AOC) l(-1)], making them effective competitors in low nutrient, and disinfected environments (drinking water). Biofilm formation and oligotrophy lead to survival, persistence, and growth in drinking water distribution systems. In addition to their role as human and animal pathogens, the widespread distribution of NTM in the environment, coupled with their ability to degrade and metabolize a variety of complex hydrocarbons including pollutants, suggests that NTM may be agents of nutrient cycling.
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            Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology.

            Nontuberculous mycobacteria (NTM) are important human pathogens, yet little is known about disease prevalence in the United States. Reports suggest prevalence has increased, particularly in women, but population-based data to substantiate this are lacking. We sought to estimate NTM disease prevalence in Oregon, and describe disease by site, species, and patient demographic characteristics. We contacted laboratories that performed mycobacterial cultures on Oregon residents in 2005-2006. For each isolate, we obtained source, collection date, species, and patient demographics. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease. We identified 933 patients with > or =1 NTM isolate. Of these, 527 (56%) met the case definition (annualized prevalence, 7.2 cases per 100,000 persons). Pulmonary cases predominated (5.6 cases per 100,000 persons), followed by skin/soft-tissue cases (0.9 cases per 100,000 persons). Mycobacterium avium complex was the most common species identified in pulmonary cases (4.7 cases per 100,000 persons). Pulmonary disease prevalence was significantly higher in women (6.4 cases per 100,000 persons) than men (4.7 cases per 100,000 persons) and was highest in persons aged >50 years (15.5 cases per 100,000 persons). NTM are frequently isolated from Oregon residents; more than one-half of all isolates likely represent true disease. Pulmonary NTM is most common among elderly women, and M. avium causes most disease. Future efforts to monitor disease trends should be undertaken, and efforts made to validate the use of the ATS/IDSA microbiologic criteria alone to predict pulmonary NTM disease.
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              Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease.

              Respiratory specimens with nontuberculous mycobacteria (NTM) are increasingly common; however, pulmonary disease prevalence is unknown. To determine the disease prevalence, clinical features, and risk factors for NTM disease, and to examine the predictive value of the microbiologic criteria of the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) pulmonary NTM case definition for true NTM disease. We identified all Oregon residents during 2005-2006 with at least one respiratory mycobacterial isolate. From a population-based subset of these patients, we collected clinical and radiologic information and used the ATS/IDSA pulmonary NTM disease criteria to define disease. In the 2-year time period, 807 Oregonians had one or more respiratory NTM isolates. Four hundred and seven (50%) resided within the Portland metropolitan region, among which 283 (70%) had evaluable clinical records. For those with records, 134 (47%) met ATS/IDSA pulmonary NTM disease criteria for a minimum overall 2-year period prevalence of 8.6/100,000 persons, and 20.4/100,000 in those at least 50 years of age within the Portland region. Case subjects were 66 years of age (median; range, 12-92 yr), frequently female (59%), and most with disease caused by Mycobacterium avium complex (88%). Cavitation (24.5%), bronchiectasis (16%), chronic obstructive pulmonary disease (28%), and immunosuppressive therapy (25.5%) were common. Eighty-six percent of patients meeting the ATS/IDSA microbiologic criteria for disease also met the full ATS/IDSA disease criteria. Respiratory NTM isolates frequently represent disease. Pulmonary NTM disease is not uncommon, particularly among elderly females. The ATS/IDSA microbiologic criteria are highly predictive of disease and could be useful for laboratory-based NTM disease surveillance.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 May 2015
                2015
                : 10
                : 5
                : e0128304
                Affiliations
                [1 ]Department of Respiratory Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
                [2 ]Unit of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
                [3 ]Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
                [4 ]Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
                [5 ]Nagasaki Municipal Hospital, Nagasaki, Japan
                [6 ]Isahaya Health Insurance General Hospital, Isahaya, Japan
                [7 ]Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, Isahaya, Japan
                [8 ]Sasebo City General Hospital, Sasebo, Japan
                [9 ]Hokusho Central Hospital, Sasebo, Japan
                [10 ]National Hospital Organization Nagasaki Medical Center, Omura, Japan
                [11 ]Izumikawa Hospital, Minami-Shimabara, Japan
                [12 ]Nagasaki Goto Central Hospital, Goto, Japan
                [13 ]Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan
                [14 ]Department of Clinical Infectious Diseases, Toyama University Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
                Cambridge University, UNITED KINGDOM
                Author notes

                Competing Interests: Shigeru Kohno received an honorarium, lecture fees, and research funds from Taisho Toyama Pharmaceutical Co. Ltd. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: SI SN YY. Performed the experiments: SI. Analyzed the data: SI SN YY YK Y. Fukuda HI ES KY YH KH Y. Futsuki YI KF NS SK. Contributed reagents/materials/analysis tools: SI SN YY. Wrote the paper: SI SN.

                Article
                PONE-D-14-19351
                10.1371/journal.pone.0128304
                4447365
                26020948
                55de310d-b882-482d-9c61-ab52e03fd97a
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 17 May 2014
                : 27 April 2015
                Page count
                Figures: 5, Tables: 4, Pages: 12
                Funding
                This study was partially supported by a grant from the Global Centers of Excellence Program (S.I., S.N., and S.K.). Funding source: Japan Society for the Promotion of Science. Website: https://www.jsps.go.jp/english/index.html. Funding source: Taisho Toyama Pharmaceutical Co. Ltd. Website: http://www.taishotoyama.co.jp. These funders paid for analysis and interpretation of data, but had no involvement in the study.
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                All relevant data are within the paper and its Supporting Information files.

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