Notes

Cytarabine-Induced Encephalitis.
Combined with the microbiological detection in BALF, such as microscopy and culture, the BALMC ELISPOT offers the opportunity for the more accurate diagnosis of PTB, especially those with clinical comorbidities.The local situation with tuberculosis (TB) is shaped by the complex interplay of multiple factors related to both human host and Mycobacterium tuberculosis. We hypothesized that TB epidemiology in the rural regions in the Soviet Union was impacted by construction of the Gulag camps and significant incoming migration. This molecular M. tuberculosis study was conducted in 2017 in the Komi Republic in northern Russia, a region with high rate (26%) of primary multidrug-resistant (MDR) TB. MDR was detected in 30.8% (40/130) isolates; eight were extensively drug resistant. The Beijing genotype was predominant (56.2%). The main Beijing subtypes B0/W148 and 94-32 differed in the MDR rate, 83.3% and 27.2%, respectively. The non-Beijing isolates represented five genotypes (LAM, Ural, Haarlem, X, T). The proportion of Beijing B0/W148 in the "camp" cities (originated from Gulag camps) was twice as large as in other districts of the Komi Republic. To conclude, сirculation of the MDR-associated Beijing B0/W148 cluster critically influences the current situation with MDR-TB in this Russian region. The increased prevalence of B0/W148 in the urban setting on the whole, and in the "camp cities", in particular, indirectly points to the increased transmission capacity of this successful Russian strain of M. tuberculosis.Background Diabetes is associated with increased prevalence of TB infection in the US. We assessed associations between diabetes and interferon-gamma (IFN-γ) TB antigen response among adults with TB infection using US representative data. Methods National Health and Nutrition Examination (NHANES) participants >19 years from 2011 to 2012 with positive QuantiFERON®-TB Gold-In-Tube (QFT) results were eligible. Diabetes was defined by combination of self-report and glycated hemoglobin (HbA1c). Quantitative IFN-γ TB antigen was classified as high (≥10 IU/mL), intermediate (1.01-9.99 IU/mL), or low (0.35-1.00 IU/mL). Analyses accounted for NHANES weighted design. Results Among NHANES participants >19 years, n = 513 had positive QFT (5.9%). Among those with positive QFT, diabetes prevalence was 22.2% and pre-diabetes was 25.9%. Overall, 16.7% of positive QFT participants had high IFN-γ TB antigen levels including 21.7% among those with diabetes, 20.8% among those with pre-diabetes, and 12.6% among euglycemic participants. In adjusted analyses, high IFN-γ TB antigen response was more common among those with pre-diabetes (aOR 1.9, 95%CI 1.0, 3.6) compared to euglycemic participants. Conclusion Higher antigen responses may reflect immunopathy consistent with an exaggerated inflammatory but ineffectual response to TB or a reflection of more Mtb replication in participants with pre-diabetes or diabetes.Background Diagnosing tuberculous pleurisy (TP) remains a clinical challenge and the best method to diagnose it is controversial. Although several studies have investigated the performance of pleural fluid (PF) T-SPOT for pleural tuberculosis (plTB) diagnosis, the heterogeneity of its accuracy exists. Therefore, we performed an updated meta-analysis of the existing evidence on the utility of PF T-SPOT to diagnose TP. Methods PubMed and EmBase were searched for relevant English articles up to July 29, 2019. Statistical analysis was performed using Stata, Revman, and Meta-Disc. SCH527123 Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic (SROC) curves and the area under the curve (AUC) were used to summarize the overall diagnostic performance. Results A total of 13 studies (997 patients with TP and 656 patients without TP) were identified and enrolled to meta-analysis, giving the following pooled values for diagnostic accuracy of PF T-SPOT sensitivity, 0.91 (95% CI, 0.89-0.92, I2 = 80.9%); specificity, 0.88 (95% CI, 0.86-0.91, I2 = 87.3%); PLR, 6.28 (95% CI, 2.88-13.69, I2 = 93.3%); NLR, 0.12 (95% CI, 0.07-0.21, I2 = 84.9%); DOR, 59.74 (95% CI, 24.13-147.93, I2 = 78.3%); and the area under the SROC curve, 0.95 (95% CI, 0.93-0.97). Conclusions Our meta-analysis suggests that PF T-SPOT has important diagnostic value for plTB. However, the standardization of the operating procedure needs to be further promoted, which would make the results more credible.Tuberculous meningitis (TBM) is the most devastating form of TB, resulting in death or neurological disability in up to 50% of patients affected. Treatment is similar to that of pulmonary TB, despite poor cerebrospinal fluid (CSF) penetration of the cornerstone anti-TB drug rifampicin. Considering TBM pathology, it is critical that optimal drug concentrations are reached in the meninges, brain and/or the surrounding CSF. These type of data are difficult to collect in TBM patients. This review aims to identify and describe a preclinical model representative for human TBM which can provide the indispensable data needed for future pharmacological characterization and prioritization of new TBM regimens in the clinical setting. We reviewed existing literature on treatment of TBM in preclinical models only eight articles, all animal studies, could be identified. None of the animal models completely recapitulated human disease and in most of the animal studies key pharmacokinetic data were missing, making the comparison with human exposure and CNS distribution, and the study of pharmacokinetic-pharmacodynamic relationships impossible. Another 18 articles were identified using other bacteria to induce meningitis with treatment including anti-TB drugs (predominantly rifampicin, moxifloxacin and levofloxacin). Of these articles the pharmacokinetics, i.e. plasma exposure and CSFplasma ratios, of TB drugs in meningitis could be evaluated. Exposures (except for levofloxacin) agreed with human exposures and also most CSFplasma ratios agreed with ratios in humans. Considering the lack of an ideal preclinical pharmacological TBM model, we suggest a combination of 1. basic physicochemical drug data combined with 2. in vitro pharmacokinetic and efficacy data, 3. an animal model with adequate pharmacokinetic sampling, microdialysis or imaging of drug distribution, all as a base for 4. physiologically based pharmacokinetic (PBPK) modelling to predict response to TB drugs in treatment of TBM.
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