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Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015-2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25-2.60) for the Weng Park plant and 1.39 (1.12-1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission. [ABSTRACT FROM AUTHOR]

Introduction: Few real-world studies have investigated drug-drug interactions (DDIs) involving non-vitamin-K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). The interactions encompass drugs inducing or inhibiting cytochrome P450 3A4 and permeability glycoprotein. These agents potentially modulate the breakdown and elimination of NOACs. This study investigated the impact of DDIs on thromboembolism in this clinical scenario. Method: Patients who had NVAF and were treated with NOACs were selected as the study cohort from the National Health Insurance Research Database of Taiwan. Cases were defined as patients hospitalised for a thromboembolic event and who underwent a relevant imaging study within 7 days before hospitalisation or during hospitalisation. Each case was matched with up to 4 controls by using the incidence density sampling method. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer or inhibitor or both with NOACs was identified. The effects of these interactions on the risk of thromboembolic events were examined with univariate and multivariate conditional logistic regressions. Results: The study cohort comprised 60,726 eligible patients. Among them, 1288 patients with a thromboembolic event and 5144 matched control patients were selected for analysis. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer resulted in a higher risk of thromboembolic events (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.004-1.51). Conclusion: For patients with NVAF receiving NOACs, the concurrent use of cytochrome P450 3A4/permeability glycoprotein inducers increases the risk of thromboembolic events. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is one of the most common infectious diseases worldwide. During active tuberculosis, T helper (Th) 17 cells are decreased, however the association with inhibitory immune regulation is unclear.Methods: We enrolled 27 patients with TB and 20 age- and sex-matched controls and studies their lymphocyte status. Peripheral blood lymphocytes were isolated and programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) were measured on Th17 cells by using flow cytometry after the cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin for 6 h. In addition, Th2 and regulatory T cells were measured and analyzed.Results: The TB group had lower levels of Th17 cells but higher levels of Th2 and Treg cells than the controls. In Th17 cells, the percentage of PD-L1 was higher in the TB group than that in the controls. In Th2 and Treg cells, the percentage of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) was lower in the TB group and PD-1 was higher in Treg cells in the TB group. In the patients with extra-pulmonary TB, levels of Th1, Th2 and T17 cells were lower than those with pulmonary TB. The percentage of PD-1 on Th1 lymphocytes positively correlated with radiographic score.Conclusions: Lower level of Th17 in TB patients may be associated with increased percentage of PD-L1 and increasing levels of Th2 and Treg cells which influenced by CTLA-4. [ABSTRACT FROM AUTHOR]

Objectives We assessed the fluoroquinolone (FQ) susceptibility of clinical isolates of Mycobacterium tuberculosis in an endemic area. The genetic mutations responsible for FQ resistance were also evaluated. Methods A total of 420 M. tuberculosis isolates during January 2004 to December 2005 were randomly selected. Data on the clinical characteristics of the patients were obtained from medical records. The MICs of ofloxacin, ciprofloxacin, levofloxacin and moxifloxacin were determined. Spoligotyping and sequencing of the gyrA and gyrB genes were performed for all isolates resistant to any tested FQ. Results Of the 420 isolates, 52 (12.4%), 26 (6.2%), 26 (6.2%) and 30 (7.1%) were resistant to isoniazid, rifampicin, ethambutol and streptomycin, respectively. Multidrug resistance was found in 5.0% of isolates. For all tested FQs, the susceptibility rate was higher than 97%. Resistance to any first-line drug and isolation from a patient with prior anti-tuberculous treatment were correlated with FQ resistance. Multidrug resistance had the strongest correlation with FQ resistance (19% of isolates). Neither the previous use of FQs nor the duration of FQ exposure was correlated with the FQ susceptibility. Of the 14 FQ-resistant isolates, five (35.7%) had gyrA mutations (four D94G and one A90V) and another one (7.1%) had a gyrB mutation (N538D). Conclusions This study found FQ resistance in 3.3% of all clinical isolates of M. tuberculosis. FQ resistance was correlated with first-line drug resistance and prior anti-tuberculous treatment, suggesting the need for routine FQ susceptibility testing in patients with these characteristics. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) disease can be caused by either recent transmission from infectious patients or reactivation of remote latent infection. Spatial dependency (correlation between nearby geographic areas) in tuberculosis incidence is a signature for chains of recent transmission with geographic diffusion. To understand the contribution of recent transmission in the TB endemic in Taiwan, where reactivation has been assumed to be the predominant mode of pathogenesis, we used spatial regression analysis to examine whether there was spatial dependency between the TB incidence in each township and in its neighbors. A total of 90,661 TB cases from 349 townships in 2003-2008 were included in this analysis. After adjusting for the effects of confounding socioeconomic variables, including the percentages of aboriginals and average household income, the results show that the spatial lag parameter remains positively significant (0.43, p<0.001), which indicates that the TB incidences of neighboring townships had an effect on the TB incidence in each township. Townships with substantial spatial spillover effects were mainly located in the northern, western and eastern parts of Taiwan. Spatial dependency implies that recent transmission plays a significant role in the pathogenesis of TB in Taiwan. Therefore, in addition to the current focus on improving the cure rate under directly observed therapy programs, more resource need to be allocated to active case finding in order to break the chain of transmission. [ABSTRACT FROM AUTHOR]

Objectives: Owing to the high virulence of mycobacterium kansasii and the increasing incidence in Kaohsiung, the present study aimed to analyze the spatial pattern of mycobacterium kansasii infection in Kaohsiung. Methods: We applied the Moran's I to estimate the spatial pattern of incidence risk and to identify the cluster core. The core of the cluster was confirmed by the spatial relative risk function with contouring an infection hotspot that the location of the comparative group were randomly sampled from the address database. Results: The positive and significant spatial autocorrelation based on the incidence risk of the basic statistical area was illustrated by the significance map with the cluster core locating in Xiaogang district. The spatial relative risk function indicated two hotspots, one located across Qianjin district and Yancheng district, and the other mainly sat in Xiaogang district. All the significant spatial relative risk ranged from 1.54 to 2.27. Conclusions: Two hotspots indicated that the mycobacterium kansasii infection not homogeneously distributes in Kaohsiung City. Infection sources may have specific spatial patterns, yet the susceptible host probably has other tendencies too. Therefore, our results should be interpreted as a combination of all factors related to this infection. [ABSTRACT FROM AUTHOR]

Objectives: Aspergillus-specific IgG (Asp-IgG) cut-off level in diagnosing chronic pulmonary aspergillosis (CPA) remains unknown. Methods: We prospectively recruited participants with clinical suspicion of CPA in three centers in Taiwan during 2019 June to 2020 August. Serum Aspergillus fumigatus-specific IgG (Asp-IgG) (Phadia, Uppsala, UPPS, Sweden) was examined. Optimal cut-off level was determined by Youden’s index and validated. Results: A total of 373 participants were recruited. In the derivation cohort (n = 262), Asp-IgG had an area under the receiver-operating-characteristic curve (AUC) of 0.832. The optimal cut-off level was 40.5 mgA/L. While applying this cut-off level to the validation cohort (n = 111), the sensitivity and specificity were 86.7% and 80.2%. Lowering the cut-off level from 40.5 to 27 mgA/L, the sensitivity was steady (30/36, 83.3% to 31/36, 86.1%) while specificity dropped from 81.9% (276/337) to 63.5% (214/337). Restricting CPA diagnosis to only chronic cavitary pulmonary aspergillosis (CCPA) and chronic fibrosing pulmonary aspergillosis (CFPA) yielded a cut-off level of 42.3 mgA/L in the derivation cohort with a sensitivity of 100% and specificity of 84.4% in the validation cohort. Conclusions: Serum Asp-IgG performs well for CPA diagnosis and provides a low false-positive rate when using a higher cut-off level (preferably around 40 mgA/L). [ABSTRACT FROM AUTHOR]

Since Taiwan is an endemic area for tuberculosis (TB), differential diagnosis between the intestinal TB and Crohn's disease is an important issue. The steering committee of Taiwan Society of Inflammatory Bowel Disease (TSIBD) has arranged a seminar accordingly on May 24th, 2014 and the different point of views by gastroenterologist, radiologist, pathologist and infectious disease specialist were suggested to help the proper diagnosis and management of these two diseases. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis is a common infectious disease in long-term dialysis patients. The prevalence of latent tuberculosis infection (LTBI) in this population is unclear, particularly in those receiving peritoneal dialysis (PD). This study investigated the prevalence of LTBI in patients receiving either hemodialysis (HD) or PD to determine predictors of LTBI and indeterminate results of interferon-gamma release assay. Methods: Patients receiving long-term ($3 months) HD or PD from March 2011 to February 2012 in two medical centers were prospectively enrolled. QuantiFERON-Gold in tube (QFT) test was used to determine the status of LTBI after excluding active tuberculosis. The LTBI prevalence was determined in patients receiving different dialysis modes to obtain predictors of LTBI and QFT-indeterminate results. Results: Of 427 patients enrolled (124 PD and 303 HD), 91 (21.3%) were QFT-positive, 316 (74.0%) QFT-negative, and 20 (4.7%) QFT-indeterminate. The prevalence of LTBI was similar in the PD and HD groups. Independent predictors of LTBI were old age (OR: 1.034 [1.013--1.056] per year increment), TB history (OR: 6.467 [1.985-- 21.066]), and current smoker (OR: 2.675 [1.061--6.747]). Factors associated with indeterminate QFT results were HD (OR: 10.535 [1.336--83.093]), dialysis duration (OR: 1.113 [1.015--1.221] per year increment), anemia (OR: 8.760 [1.014--75.651]), and serum albumin level (OR: 0.244 [0.086--0.693] per 1 g/dL increment). Conclusion: More than one-fifth of dialysis patients have LTBI. The LTBI prevalence is similar in PD and HD patients but is higher in the elderly, current smokers, and those with prior TB history. Such patients require closer follow-up. Repeated or alternative test may be required for malnutrition patients who received long length of HD. [ABSTRACT FROM AUTHOR]

Objective: Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD. Design, Setting, and Participants: This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database. Main Outcome Measures: Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment. Results: The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768-2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD. Conclusions: Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients. [ABSTRACT FROM AUTHOR]