Nontuberculous Mycobacteria Disease Research Articles

Clinical and microbiological characteristics of non-tuberculous mycobacteria diseases in Singapore with a focus on pulmonary disease, 2012-2016

BackgroundInformation on non-tuberculosis mycobacterial (NTM) diseases remains limited in Singapore and other Southeast Asian countries. This study aimed to delineate epidemiological and clinical features of pulmonary NTM disease.MethodsA retrospective review was performed on all NTM isolates identified in Singapore General Hospital from 2012 to 2016 using the 2007 ATS/IDSA diagnostic criteria.ResultsA total of 2026 NTM isolates from 852 patients were identified. M. abscessus-chelonae group (1010, 49.9%) was the most commonly isolated and implicated in pulmonary NTM disease. Pulmonary cases (352, 76%) had the highest prevalence among patients diagnosed with NTM diseases (465/852, 54.6%) with no gender difference. Male patients were older (68.5 years, P = 0.014) with a higher incidence of chronic obstructive pulmonary disease (COPD) (23.6%, P < 0.001) and recurrent cough with phlegm production (51.6%, P = 0.035). In contrast, more female patients had bronchiectasis (50%, P < 0.001) and haemoptysis (37.6%, P = 0.042). Age and COPD were associated with multiple NTM species isolation per patient.ConclusionsM. abscessus-chelonae group was the commonest NTM species isolated in Singapore. Pulmonary NTM infection has the highest frequency with male and female patients associated with a higher incidence of COPD and bronchiectasis respectively. Age and COPD were associated with multiple NTM species isolation per patient.

Profile of patients with pulmonary non-tuberculous mycobacterial disease mimicking pulmonary tuberculosis

IntroductionWith the introduction of newer molecular diagnostic tools, an increasing number of Non-tuberculous Mycobacteria (NTM) affecting the respiratory system and mimicking symptoms of pulmonary tuberculosis (PTB) are being identified. They may be misdiagnosed and treated as PTB, often categorized as treatment failures if they do not respond to treatment. This manuscript aims to characterize patients with pulmonary NTM disease. MethodsPatient characteristics of bacteriologically confirmed pulmonary NTM disease, attending the ICMR-National Institute for Research in Tuberculosis, Chennai were prospectively compiled over a two-year period (2017–2018). ResultsA total of 122 patients with recurrent chest symptoms and not responding to anti-tuberculosis treatment were screened for NTM. Thirty-nine cases (26 males and 13 females) of symptomatic pulmonary NTM were diagnosed. The mean (SD) patient age and body mass index were 48.6 ± 11 years and 16.3 ± 3. All male participants were smokers, had at least one episode of previous ATT. Mycobacterium kansasii (48.7%) was the most frequently isolated species followed by Mycobacterium intracellulare (20.5%), Mycobacterium abscessus (7.6%) followed by Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium kyorinense, and Mycobacterium simiae. Infection with multiple NTMs was seen in four patients. Isoniazid resistance was identified in 20 patients. Based on species identified, treatment was initiated as per American Thoracic Society guidelines and continued up to 12 months of culture negativity. ConclusionsM. kansasii is the commonest pulmonary NTM isolated in Tamilnadu with a higher prevalence in males and elderly. Sensitization of both patients and providers is essential to avoid misdiagnosis and delay in diagnosis of pulmonary NTM disease as pulmonary TB.

The sporadic nature of Legionella pneumophila, Legionella pneumophila Sg1 and Mycobacterium avium occurrence within residences and office buildings across 36 states in the United States.

AimPremise plumbing may disseminate the bacteria Legionella pneumophila and Mycobacterium avium, the causative agents for legionellosis and pulmonary nontuberculous mycobacterium disease respectively.Methods and ResultsUsing quantitative PCR, the occurrence and persistence of L. pneumophila, L. pneumophila serogroup (Sg)1 and M. avium were evaluated in drinking water samples from 108 cold water taps (residences: n = 43) and (office buildings: n = 65). Mycobacterium avium, L. pneumophila and L. pneumophila Sg1 were detected 45, 41 and 25% of all structures respectively. Two occurrence patterns were evaluated: sporadic (a single detection from the three samplings) and persistent (detections in two or more of the three samples).ConclusionsThe micro‐organism's occurrence was largely sporadic. Office buildings were prone to microbial persistence independent of building age and square footage. Microbial persistence at residences was observed in those older than 40 years for L. pneumophila and was rarely observed for M. avium. The microbial occurrence was evenly distributed between structure types but there were differences in density and persistence.Significance of and Impact of the StudyThe study is important because residences are often suspected to be the source when a case of disease is reported. These data demonstrate that this may not be the case for a sporadic incidence.

Clinical and Laboratory Characteristics of Disseminated Non-tuberculous Mycobacterial Disease

Objective To explore the clinical and laboratory characteristics and the prognosis of disseminated non-tuberculous mycobacteria(NTM)diseases in human immunodeficiency virus(HIV)negative patients. Methods Cases of disseminated NTM disease were retrospectively collected in Peking Union Medical College Hospital from January 2012 to October 2018.Clinical manifestations,laboratory findings,treatment,and prognosis of these cases were retrieved from the electronic medical record system. Results Among the 23 HIV negative patients with disseminated NTM disease,21 had underlying diseases,with rheumatoid immune disease(n=7)as the most common one.The main clinical manifestation was fever(n=23).Laboratory tests showed anemia [hemoglobin(85.78±25.47)g/L],hypoalbuminemia [albumin 29(27-32)g/L],elevated erythrocyte sedimentation rate [(85.73±43.78)mm/h] and hypersensitive C-reactive protein [(112.00±70.90)mg/L],and reduction of lymphocyte count [0.69(0.29-2.10)×10 9/L].Lymphocyte subset analysis indicated reduction in CD4 + T cells [213(113-775)/μl],CD8 + T cells [267(99-457)/μl],B cells [39(4-165)/μl],and NK cells [88(32-279)/μl] and elevation of human leukocyte antigen-D related(HLA-DR),and CD38 expression in CD8 + T cells [HLA-DR +CD8 +/CD8 +,60(40-68)%;CD38 +CD8 +/CD8 +,81(65-90)%].The most common species of NTM was Mycobacterium intracellular(n=6).Lymphocyte,CD8 + T cell,B cell,and NK cell counts were significantly lower in dead patients than surviving patients(P =0.045,P=0.045,P=0.032,and P=0.010,respectively). Conclusions Disseminated NTM disease in HIV negative patients is mainly manifested as fever,anemia,hypoalbuminemia,and elevated inflammatory indicators.It is more likely to occur in immunocompromised patients.Patients with decreased lymphocytes,CD8 + T cells,B cells and NK cells tend to have a poor prognosis.

Nontuberculous Mycobacterial Infections in Children.

1. Jyotsna Bhattacharya, MD* 2. Sindhu Mohandas, MBBS* 3. David L. Goldman, MD† 1. *Department of Pediatric Infectious Diseases and 2. †Department of Pediatrics and Microbiology and Immunology, Children’s Hospital at Montefiore/Albert Einstein College of Medicine, Bronx, NY * Abbreviations: AFB: : acid-fast bacillus CF: : cystic fibrosis HAART: : highly active antiretroviral therapy HIV: : human immunodeficiency virus IFN-γ: : interferon-γ IGRA: : interferon-γ release assay IRIS: : immune reconstitution inflammatory syndrome MAC: : Mycobacterium avium complex MALDI-TOF: : matrix-assisted laser desorption/ionization–time of flight NTM: : nontuberculous mycobacteria RGM: : rapidly growing mycobacteria SGM: : slowly growing mycobacteria SSTI: : skin and soft tissue infection After completing this article, readers should be able to: 1. Recognize the major clinical features associated with nontuberculous mycobacteria (NTM) infections in children. 2. Recognize that NTM infections are a potential risk related to medical tourism for cosmetic surgery. 3. Understand the strengths and weaknesses of currently available diagnostic methods. 4. Plan the appropriate management of NTM infections based on the specific clinical presentation and mycobacterial species. Nontuberculous mycobacteria (NTM) include all mycobacteria other than Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium leprae . Children are constantly exposed to NTM, yet clinical signs of infection are unusual. NTM exist primarily in the environment, causing human disease as opportunistic pathogens in the appropriate clinical context. Lymphadenitis is far and away the most common manifestation of NTM disease in children. Other, less common, manifestations include skin and soft tissue infections (SSTIs), lung infections, and disseminated disease. Since the last review of NTM disease in Pediatrics in Review , (3) several important developments have occurred, including changes in the epidemiology and treatment, which are reviewed herein. Currently there are more than 170 recognized NTM species, although a limited number of species cause human disease. It survives inside amoeba, and the traits that promote this process may also allow for successful macrophage infection. (4 …

Risk of mycobacterial disease among cancer patients: A population-based cohort study in a TB endemic area

ObjectivesTuberculosis (TB) and nontuberculous mycobacteria (NTM) disease have similar symptoms, which makes them difficult to distinguish clinically and leads to the danger of NTM disease being neglected. The aim of this study was to assess the risk of developing mycobacterial disease among cancer patients. MethodsWe conducted a retrospective cohort study using a population-based database. The multivariable Cox proportional hazards model was adjusted to identify independent factors contributing to the development of mycobacterial disease in the cancer cohort. ResultsThe results showed that the increased risk of developing TB and NTM disease was 1.84-fold and 4.43-fold, respectively, in cancer patients compared with the general population. Advanced age (≥65years) and being male were risk factors for developing TB disease. There was a 4.09-fold significantly increased risk of TB disease within six months of a cancer diagnosis. Hematological cancer patients were most likely to develop mycobacterial disease. Younger hematological cancer patients (< 45years) had a higher risk of NTM disease development. ConclusionThere is an increasing risk of mycobacterial disease in cancer patients. We suggest that the possibility of mycobacterial disease in cancer patients should be assessed during the period of cancer therapy, particularly in those who have risk factors.

Treatment of Extrapulmonary Nontuberculous Mycobacterial Diseases.

Nontuberculous mycobacteria (NTM) diseases mainly manifest as pulmonary illnesses, but 20 -30% of NTM isolates originate from extrapulmonary diseases. These diseases cause a variety of clinical syndromes, including skin and soft-tissue infections, musculoskeletal infections, lymphadenitis, and disseminated disease. In skin and soft-tissue infections, musculoskeletal infections, prolonged treatment with combinations of antibiotics is effective in the treatment of NTM diseases, with surgery as an important complementary tool. The recommended duration of therapy for skin and soft-tissue infection is usually 2 – 4 months for mild disease and 6 months for severe disease, while treatment of musculoskeletal NTM disease usually requires at least 6 - 12 months. Management options of NTM lymphadenitis include surgical intervention, medical therapy, or observation. Treatment of disseminated NTM disease generally requires 6 to 12 months after immune restoration. However, despite a considerable increase in knowledge about NTM diseases, determining optimal treatment approaches remains a complex and challenging task.

Assessment of Interferon-Gamma Release Assay in Patients with Non-Tuberculous Mycobacteria Pulmonary Disease.

Interferon-gamma release assay (T-SPOT.TB) has the theoretical possibility of discriminating TB from most non-tuberculous mycobacteria (NTM) infections, but there are limited reports on the use of T-SPOT.TB for diseases due to NTM in high TB burden country. The aim of the present study was to assess the utility of T-SPOT.TB in patients with NTM pulmonary disease. Clinical parameters and laboratory characteristics of patients with NTM pulmonary disease between July 2011 and Jan 2017 were investigated retrospectively and comprehensively reviewed. A total of 127 patients with NTM pulmonary disease were retrospectively reviewed. Seven NTM species were isolated from 115 patients, and the most common species were M. intracellulare (48.7%, 56/115) and M. abscessus (34.8%, 40/115). NTM isolates were mainly prevalent in people aged 50 years or older (73.0%). The overall positive rate of T-SPOT.TB test was 29.6% (24/81). In patients infected with NTM sharing the RD1 region of Mycobacterium tuberculosis (M. TB), 50% (3/6) were positive in the T-SPOT.TB test, whereas 28.0% (21/75) was positive in the group with NTM not sharing the RD1 region of M. TB. No significant difference was detected in the positive rate of T-SPOT.TB between definite (28.3%, 15/53) and probable disease (32.1%, 9/28). Our data indicated a relatively high positive rate of T-SPOT.TB test in patients infected with NTM not sharing the RD1 region of M. TB. Thus, T-SPOT.TB test displays a limited ability in differentiating TB infection from NTM disease in a high TB burden country.

Comprehensive subspecies identification of 175 nontuberculous mycobacteria species based on 7547 genomic profiles

ABSTRACT The prevalence of nontuberculous mycobacteria (NTM) pulmonary diseases has been increasing worldwide. NTM consist of approximately 200 species and distinguishing between them at the subspecies level is critical to treatment. In this study, we sequenced 63 NTM genomes, 27 of which were newly determined, by hybrid assembly using sequencers from Illumina and Oxford Nanopore Technologies (ONT). This analysis expanded the available genomic data to 175 NTM species and redefined their subgenus classification. We also developed a novel multi-locus sequence typing (MLST) database based on 184 genes from 7547 assemblies and an identification software, mlstverse, which can also be used for detecting other bacteria given a suitable MLST database. This method showed the highest sensitivity and specificity amongst conventional methods and demonstrated the capacity for rapid detection of NTM, 10 min of sequencing of the ONT MinION being sufficient. Application of this methodology could improve disease epidemiology and increase the cure rates of NTM diseases.

Host Variability in NTM Disease: Implications for Research Needs.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that may cause opportunistic infections in susceptible hosts. Lung infections in immunocompetent persons with structural lung disease are most common, while disseminated disease occurs primarily in immunocompromised individuals. Human disease caused by certain species, such as Mycobacterium avium complex, Mycobacterium abscessus, and Mycobacterium kansasii, is increasing in incidence and varies by geographic distribution. The spectrum of NTM disease varies widely in presentation and clinical outcome, but certain patterns can be organized into clinical phenotypes. Treatment options are limited, lengthy, and often toxic. The purpose of this case-based review is to provide non-clinician scientists with a better understanding of human NTM disease with an aim to stimulate more research and development.

Surgery in nontuberculous mycobacteria pulmonary disease.

Medical treatment of pulmonary nontuberculous mycobacteria (NTM) disease has highly variable outcomes. Despite the use of multiple antibiotics, sputum clearance is often difficult to achieve, especially in cases with macrolide resistant NTM infection. Immunocompromised patients and those with structural lung disease are at increased risk, although occurrence in immunocompetent patients without structural lung disease is well recognised. Most pulmonary NTM disease involves Mycobacterium avium complex (MAC), but with enhanced identification multiple species have now been recognised as opportunistic pathogens. The observed increase in NTM disease, especially infection with multidrug-resistant Mycobacterium abscessus complex, is probably multifactorial. Surgery has been used as adjuvant treatment in patients with 1) focal disease that can be removed or 2) bothersome symptoms despite medical treatment that can be ameliorated. Early post-surgical mortality is low, but long-term morbidity and mortality are highly dependent on the degree of lung involvement and the residual lung function, the potency of medical treatment and the type of surgical intervention. In conjunction with antibiotic therapy, reported post-surgical sputum clearance was excellent, although publication bias should be considered. Bronchopleural fistulae were problematic, especially in pneumonectomy cases. Study results support the use of minimal resection surgery, in a carefully selected subgroup of patients with focal disease or persistent symptoms.Educational aimsTo critically review the literature describing the use of surgery in the treatment of pulmonary disease caused by nontuberculous mycobacteria (NTM).To assess the outcomes and complications observed with different surgical approaches used in the treatment of pulmonary NTM disease.

Epidemiology of pulmonary disease due to nontuberculous mycobacteria in Southern China, 2013\u20132016

BackgroundPulmonary nontuberculous mycobacteria (NTM) disease is of increasing public health concern in China. Information is limited regarding risk factors associated with this disease in China. The objective of this study was to describe the epidemiology of pulmonary disease due to NTM in Southern China.MethodsWe retrospectively reviewed the medical records of pulmonary NTM patients registered in the Guangzhou Chest Hospital with positive mycobacterial cultures during 2013–2016. We described sex, age, residence, treatment history, laboratory examination results and comorbidities of pulmonary NTM patients.ResultsAmong the 607 NTM cases, the most prevalent species were Mycobacterium avium complex (44.5%), Mycobacterium abscessus complex (40.5%), Mycobacterium kansasii (10.0%) and Mycobacterium fortuitum (2.8%). The male:female ratio was significantly lower among patients infected with rapidly growing mycobacteria (RGM) than among those with slowly growing mycobacteria (SGM). The risk of developing SGM disease significantly increased with advancing age. In addition, pulmonary RGM diseases were more common in migrant population than resident population. Notably, patients with pulmonary RGM diseases were significantly more likely to have bronchiectasis underlying noted than those with SGM diseases. No significant difference was observed in in vitro drug susceptibility among NTM species.ConclusionOur data illustrate that the M. avium complex is the most predominant causative agent of pulmonary NTM disease in Southern China. Female, migrant population, the presence of bronchiectasis are independent risk factors for pulmonary diseases due to RGM. In addition, the prevalence of SGM increases significantly with advancing age.

Clinico-microbiological analysis of 121 patients with pulmonary Mycobacteroides abscessus complex disease in Japan - An NTM-JRC study with RIT.

No comprehensive analysis has previously been performed to evaluate the clinical aspects of and microbiological evidence associated with Mycobacteroides abscessus complex (MABC) infection in a region, such as Japan, with a low MABC incidence. This study aimed to clarify the clinicopathological characteristics of MABC, which included clinical relatedness to erm(41) sequevar, phenotype (as colony morphology and minimum inhibitory concentration), and genotype. A total of 121 MABC patients (68 with M. abscessus subsp. abscessus and 53 with M. abscessus subsp. massiliense) were recruited into this retrospective clinical-biological study from tertiary hospitals in Japan between 2004 and 2014. Approximately 30% of MABC patients had a history of previous nontuberculous mycobacterium (NTM) disease. Furthermore, 24.8% of the patients had another concomitant NTM infection after they were diagnosed with MABC. Fewer than 10% of the patients in the M. abscessus group had T28C in erm(41). While we observed a higher conversion rate for M. massiliense than for M. abscessus (72.4% and 34.8%, respectively, p = 0.002), recurrence remained relatively common for M. massiliense (31.0%). In the M. abscessus patients, the MIC of clarithromycin (CLR) was significantly lower on day 3 in patients with a better treatment response than in refractory patients (The median MIC; 0.75 μg/ml v.s 2.0 μg/ml, p = 0.03). There was no significant relation between clinical manifestations and variable number of tandem repeat genotypes. Because the history and simultaneous isolation of other NTM in MABC infection are relatively common, these information should be carefully translated into clinical actions. The evaluation of early CLR resistance in M. abscessus and the erm(41) functions should be important to improve the treatment strategy.

Recent advances in molecular diagnostics and understanding mechanisms of drug resistance in nontuberculous mycobacterial diseases

Accumulating evidence suggests that human infections caused by nontuberculous mycobacteria (NTM) are increasing worldwide, indicating that NTM disease is no longer uncommon in many countries. As a result of an increasing emphasis on the importance of differential identification of NTM species, several molecular tools have recently been introduced in clinical and experimental settings. These advances have led to a much better understanding of the diversity of NTM species with regard to clinical aspects and the potential factors responsible for drug resistance that influence the different outcomes of NTM disease. In this paper, we review currently available molecular diagnostics for identification and differentiation of NTM species by summarizing data from recently applied methods, including commercially available assays, and their relevant strengths and weaknesses. We also highlight drug resistance-associated genes in clinically important NTM species. Understanding the basis for different treatment outcomes with different causative species and drug-resistance mechanisms will eventually improve current treatment regimens and facilitate the development of better control measures for NTM diseases.

EPIDEMIOLOGY OF NONTUBERCULOUS MYCOBACTERIUM FROM AN INNER-CITY PHILADELPHIA HOSPITAL IN PATIENTS WITHOUT HIV

SESSION TITLE: Chest Infections 2 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Nontuberculous mycobacterium (NTM) are free-living organisms that are ubiquitous in the environment, however the importance of NTM disease in humans is increasingly evident. As NTM is a non-reportable disease and as environmental exposure is dependent on geographical areas, the incidence and risk factors of NTM in our area are ill-defined. This study is to help us determine the incidence of NTM in inner Philadelphia in those without HIV infection, the risk factors which lead to disease and the speciation related to the different diseases. METHODS: We conducted a retrospective study of patients without known HIV infection who had an AFB culture positive from 2016 to 2017. Patients with blood cultures or tissue biopsy positive for NTM were concluded to have disease; respiratory disease was considered if they met ATS guidelines: 1. chest radiograph or, in the absence of cavitations, chest high-resolution computed tomography; 2. Positive cultures from sputum samples or one bronchial wash; and 3. Exclusion of other disorders, such as TB. The data was collected from cultures at Hahnemann University Hospital in Philadelphia. This was an IRB study. RESULTS: From 2016-2017, there were 87 total patients who were identified to have NTM positive cultures, of which 61 were in patients who were not infected with HIV, of those 42 were identified to have an active NTM infection. Demographics include: average age 57, 27 males and 15 females, and 20 White, 14 Black, 5 Asian and 3 Hispanic patients. Out of the 42 infections, there were 36 respiratory infections, 3 positive tissue cultures, 2 positive blood cultures and 1 urinary culture. Species identified included 33 cultures positive for MAC, 4 cultures M. abscessus, 3 cultures M. bolletii, 2 cultures each of M. chelonae and M. kansasii, and 1 culture each for M. xenoxpix and M. szulgai. Coexisting medical illnesses included 24 with underlying lung disease, 6 patients immunocompromised, 4 patients with cancer, 3 transplant patients and 6 with no underlying medical illness. There were 3 patients on immunosuppressants, 2 on steroids, 1 on chemotherapy and 1 on an immunomodulator. There were patients who occasionally had >1 NTM in the AFB culture, more than one source of culture positivity or more than one underlying medical co-illness. CONCLUSIONS: Although MAC was shown to be the most prevalent in the community, 31% of cultures grew disease causing NTM species other than MAC with the next most common being M. abscessus and M. bolletii. It is important to note that in those with underlying lung disease, various species of NTM can be attributed to disease and should be treated. CLINICAL IMPLICATIONS: This small study gives us an insight into the types of infections and the speciation of those with disease that is prevalent in this community. Although MAC being the most common, patients with other infectious NTM species should be considered for treatment also. DISCLOSURES: No relevant relationships by Janpreet Mokha, source=Web Response No relevant relationships by Ekamjeet Randhawa, source=Web Response No relevant relationships by Michael Stephen, source=Web Response

EPIDEMIOLOGY OF NONTUBERCULOUS MYCOBACTERIUM FROM AN INNER-CITY PHILADELPHIA HOSPITAL IN PATIENTS WITH HIV

SESSION TITLE: Chest Infections 2 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: MAC is the most common pathogen of Nontuberculous Mycobacterium (NTM) that is known to cause disease in HIV infected individuals. However, patients with MAC and other NTM species are at greatest risk of developing disease as CD4 cell counts fall below 50 cells/mm3. This study was done to help determine the incidence of NTM in inner Philadelphia in those with known HIV infections and the risk of disease at the CD4 level. METHODS: We conducted a retrospective study of patients with known HIV infection who had a AFB culture positive from 2016 to 2017. Patients with blood cultures or tissue biopsy positive for NTM were concluded to have disease; respiratory disease was considered if they met ATS guidelines: 1. chest radiograph or, in the absence of cavitation, chest high-resolution computed tomography; 2. Positive cultures from sputum samples or one bronchial wash; and 3. Exclusion of other disorders, such as TB. The data was collected from cultures at Hahnemann University Hospital in Philadelphia. This was an IRB study. RESULTS: From 2016-2017, there were 87 total patients who were NTM culture positive of which 26 had HIV/AIDS and 22 were determined to have NTM infections. The average age was 46, out of the 22 patients 14 were males and 8 females, and 20 were black and 2 were white. There were 16 patients who had respiratory disease with the most common NTM being MAC in 14 cultures, and there were 3 other cultures which grew M. chelonae, M. bolletii or M. litoral. 7 patients were found to be bacteremic with 6 being MAC positive and 1 growing M. abscesses; and 4 patients had NTM infection of a GI source with all 4 growing MAC. 5 of the 7 patients with NTM bacteremia also had growth in respiratory or GI cultures. The average CD4 count for those with respiratory infections was 130, not including one patient with a CD4 level of 1362. Those who were or also had bacteremia had an average CD4 count of 36. The average CD4 count of those with a GI source was 6. There were several patients who had multiple sources of NTM culture positivity. CONCLUSIONS: HIV infected patients are at an increased risk of disease from MAC compared to other NTM species in non-HIV infected patients. Patients with CD4 counts <50 cells/mm3 can be at higher risk of disseminated and GI disease; however those with higher CD4 counts are still at risk of respiratory disease. CLINICAL IMPLICATIONS: Based on the demographics of this study, in Philadelphia, black patients are at the greatest risk of NTM disease most likely secondary to . Patients with HIV/AIDS should be assessed for NTM infections even if their CD4 counts are >100 cells/mm3. DISCLOSURES: No relevant relationships by Ekamjeet Randhawa, source=Web Response No relevant relationships by Michael Stephen, source=Web Response

Genome-Wide Association Study in Patients with Pulmonary Mycobacterium Avium Complex Disease

Background Pulmonary nontuberculous mycobacteria (NTM) disease is a chronic progressive lung disease caused by environmental mycobacteria. Although epidemiological data indicate a potential genetic predisposition to NTM disease, the nature of this remains unclear. The present study aimed to identify host genes associated with susceptibility to Mycobacterium avium complex (MAC), the most common NTM pathogen. Methods We conducted a genome-wide association study (GWAS) in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate SNPs in another group of patients and controls. For verification in European populations, we performed imputation to estimate genotypes of a candidate SNP from exome sequencing data. Findings The GWAS discovery set included 475 pulmonary MAC patients and 417 healthy subjects. After quality control filtering of genotyped variants, 622,723 autosomal variants were analysed. Both GWAS and replication analysis of 591 pulmonary MAC patients and 718 controls identified strongest association with chromosome 16p21, and particularly with rs109592 (p = 1.60E-13, odds ratio = 0.54). This SNP is located in an intronic region of the calcineurin like EF-hand protein 2 (CHP2) gene, and expression quantitative trait locus analysis showed association with lung CHP2 expression. Further, patient radiological findings showed that this SNP was associated with the nodular bronchiectasis disease subtype. This SNP is also significantly associated in European populations (p = 5.08E-06, odds ratio = 0.23). Interpretation These findings identify CHP2 as a candidate gene for further investigation of the pathogenesis of pulmonary MAC disease. Funding: JSPS KAKENHI, AMED, Keio Gijuku Academic Development Funds, NIH. Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: This study was reviewed and approved by the research ethics committees of the Keio University School of Medicine (2012-0336), the Graduate School of Medicine, the University of Tokyo (G3579), and other collaborating institutions (UMI21692). Regarding European cohort, the subjects were enrolled in studies under National Institute of Allergy and Infectious Diseases Institutional Review Board-approved protocol (93-I-0119). All adult subjects provided written informed consent and all the experiments were performed in accordance with the relevant guidelines and regulations.

Mycobacterium simiae pulmonary disease in Iran: systematic review and meta-analysis.

Mycobacterium simiae is one of the most common nontuberculous mycobacteria (NTM) microorganisms causing lung disease in many countries in the world. A reliable estimate of the extent of M. simiae pulmonary disease has not been well investigated in Iran. We systematically searched multiple databases to identify relative studies. Studies were excluded if they did not use the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) diagnostic criteria for NTM diseases. Data were extracted independently and in duplicate. We assessed pooled estimate by using a random model effect, and sources of heterogeneity were assessed by using Cochran's Q and the I2 statistic. The potential for publication bias was explored by using Begg's and Egger's tests. All analyses were conducted with Stata 14.0 (StataCorp, College Station, TX, USA). Of 172 articles identified, seven met the inclusion criteria. Of 355 patients who were culture positive for NTM, 82 had M. simiae pulmonary disease according to the ATS/IDSA diagnostic criteria. The pooled frequency of M. simiae pulmonary disease among patients with NTM was 25.0% (95% confidence interval, 16.8–33.2). No evidence of publication bias was observed among the included studies (p >0.05 for Begg's and Egger's tests). Clinical isolates of M. simiae are increasingly being recognized as a cause of pulmonary disease in Iran and need further attention by health authorities.

Extrapulmonary Nontuberculous Mycobacterial Disease Surveillance - Oregon, 2014-2016.

Nontuberculous mycobacteria (NTM), ubiquitous in soil and water, usually infect immunocompromised persons. However, even healthy persons are susceptible to infection through percutaneous inoculation. Although 77% of NTM diseases manifest as primarily pulmonary illnesses (1), NTM also infect skin, bones, joints, the lymphatic system, and soft tissue. NTM infections can have incubation periods that exceed 5 years (2), often require prolonged treatment, and can lead to sepsis and death. Extrapulmonary NTM outbreaks have been reported in association with contaminated surgical gentian violet (3), nail salon pedicures (4), and tattoos received at tattoo parlors (5), although few surveillance data have been available for estimating the public health burden of NTM.* On January 1, 2014, the Oregon Health Authority designated extrapulmonary NTM disease a reportable condition. To characterize extrapulmonary NTM infection, estimate resources required for surveillance, and assess the usefulness of surveillance in outbreak detection and investigation, 2014–2016 extrapulmonary NTM surveillance data were reviewed, and interviews with stakeholders were conducted. During 2014–2016, 134 extrapulmonary NTM cases (11 per 1 million persons per year) were reported in Oregon. The age distribution was bimodal, with highest incidence among persons aged <10 years (20 per 1 million persons per year) and persons aged 60–69 years (18 per 1 million persons per year). The most frequently reported predisposing factors (occurring within 14–70 days of symptom onset) were soil exposure (41/98; 42%), immunocompromised condition (42/124; 34%), and surgery (32/120; 27%). Overall, 43 (33%) patients were hospitalized, 18 (15%) developed sepsis, and one (0.7%) died. Surveillance detected or helped to control two outbreaks at low cost. Jurisdictions interested in implementing extrapulmonary NTM surveillance can use the Council of State and Territorial Epidemiologists (CSTE) standardized case definition (6) for extrapulmonary NTM reporting or investigative guidelines maintained by the Oregon Health Authority (7).

Epidemiology of Pulmonary Nontuberculous Mycobacterial Sputum Positivity in Patients with Cystic Fibrosis in the United States, 2010-2014.

Pulmonary nontuberculous mycobacteria (NTM) disease represents a significant threat to patients with cystic fibrosis (CF), with an estimated annual prevalence of 12%. Prior studies reported an increasing annual NTM prevalence in the general population, though similar trends in persons with CF have not been assessed. In this study we aimed to identify the prevalence, geographic patterns, temporal trends, and risk factors for NTM positivity by mycobacterial species among persons with CF throughout the United States. Using annualized CF Patient Registry (CFFPR) data from 2010 to 2014, we identified patients with mycobacterial culture results to estimate the annual and period prevalence of pathogenic NTM species by demographic and geographic factors. Regression models were used to estimate the annual percent change over time and risk factors for NTM isolation. Geographic patterns were described and mapped. Of 16,153 included persons with CF, 3,211 (20%) had a pathogenic NTM species isolated at least once over the 5-year period; 1,949 (61%) had Mycobacterium avium complex (MAC), and 1,249 (39%) had M. abscessus. The period prevalence was 12% for MAC (confidence interval [CI], 12-13%), 8% for M. abscessus (CI, 7-8%), and 4% for other NTM species (CI, 3.8-4.3%). The period prevalence for MAC was nearly three times greater among patients ≥60 years old with a body mass index < 19 (33% [CI, 16-51%]); this trend was not present for patients with M. abscessus (4% [CI, 0-11%]). NTM prevalence showed a significant relative increase of 5% per year, from 11.0% in 2010 to 13.4% in 2014 (P = 0.0008), although this varied by geographic area. For M. abscessus, the states with the highest prevalence were Hawaii (50%), Florida (17%), and Louisiana (16%), and for MAC they were Nevada (24%), Kansas (21%), and Hawaii and Arizona (both 20%). Study participants with either MAC or M. abscessus were significantly more likely to have been diagnosed with CF at an older age (P < 0.0001), have a lower body mass index (P < 0.0001), higher forced expiratory volume in 1 second % predicted (P < 0.01), and fewer years on chronic macrolide therapy (P < 0.0001). NTM remains highly prevalent among adults and children with CF in the United States, with one in five affected, and appears to be increasing over time. Prevalence varies by geographic region and by patient-level factors, including older age and receiving an initial CF diagnosis later in life. Routine screening for NTM, including mycobacterial speciation, especially in high-risk geographic areas, is critical to increase our understanding of its epidemiology and changes in prevalence over time.