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The aim of this study was to evaluate the diagnostic accuracy of the IGRA, TST, and TBST by combining diagnostic test accuracy (DTA) analysis and network meta-analysis (NMA) to increase the reliability and accuracy of diagnostic methods and promote the eradication of TB. An electronic search of the PubMed, Embase, and Cochrane databases was conducted, from the date of establishment to September 30, 2024. Data were synthesized with frequentist random-effects network meta-analyses, a single-group rate meta-analysis algorithm, and a bivariate mixed-effects logistic regression model. Summarized receiver operating characteristic curves and Fagan nomograms were used to assess diagnostic accuracy and clinical utility. Deeks' funnel plots and the Quality Assessment of Diagnostic Accuracy Studies 2 tools were used to assess publication bias and risk of bias. Sources of heterogeneity were investigated using subgroup analyses. Forty-nine studies were identified. The diagnostic performance of the three diagnostic methods for TB infection is summarized as follows: the pooled sensitivity was 77.9% (95% confidence interval [CI], 0.69–0.856), and the pooled specificity was 80.3% (95% CI, 0.75–0.86). The sensitivity and specificity of the IGRA were 82.1% (95% CI, 0.78–0.86) and 81.1% (95% CI, 0.75–0.86), respectively, both higher than the TST. However, the TBST exhibited the highest specificity, at 98.5% (95% CI, 0.96–1.00), with a sensitivity of 78.7% (95% CI, 0.68–0.88), which was between that of the IGRA and TST. Subgroup analysis found that population categories and reference standards, among other factors, may be attributed to heterogeneity. In addition, the TST and IGRA add-on TBST can significantly improve diagnostic accuracy. In our study, the IGRA showed higher sensitivity, whereas the TBST showed higher specificity. Interestingly, under certain conditions, TST add-on TBST and IGRA add-on TBST showed better accuracy than TST and IGRA alone and could provide more effective guidance for clinical practice (PROSPERO CRD42023420136). [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a global infectious threat, and the emergence of multidrug-resistant TB has become a major challenge in eradicating the disease that requires the discovery of new treatment strategies. This study aimed to elucidate the immune infiltration and molecular regulatory network of T cell-interacting activating receptors on myeloid cell 1 (TARM1)-related genes based on a bioinformatics analysis. The GSE114911 dataset was obtained from the Gene Expression Omnibus (GEO) and screened to identify 17 TARM1-related differentially expressed genes (TRDEGs). Genes interacting with the TRDEGs were analyzed using a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A gene set enrichment analysis (GSEA) was used to identify the biological pathways significantly associated with a Mycobacterium tuberculosis (Mtb) infection. The key genes were obtained based on Cytoscape's cytoHubba plug-in. Furthermore, protein–protein interaction (PPI) networks were analyzed through STRING, while mRNA–RNA-binding protein (RBP) and mRNA–transcription factor (TF) interaction networks were developed utilizing the StarBase v3.0 and ChIPBase databases. In addition, the diagnostic significance of key genes was evaluated via receiver operating characteristic (ROC) curves, and the immune infiltration was analyzed using an ssGSEA and MCPCounter. The key genes identified in the GSE114911 dataset were confirmed in an independent GSE139825 dataset. A total of seventeen TRDEGs and eight key genes were obtained in a differential expression analysis using the cytoHubba plug-in. Through the GO and KEGG analysis, it was found that these were involved in the NF-κB, PI3K/Akt, MAPK, and other pathways related to inflammation and energy metabolism. Furthermore, the ssGSEA and MCPCounter analysis revealed a significant rise in activated T cells and T helper cells within the Mtb infection group, which were markedly associated with these key genes. This implies their potential significance in the anti-Mtb response. In summary, our results show that TRDEGs are linked to inflammation, energy metabolism, and immune cells, offering fresh insights into the mechanisms underlying TB pathogenesis and supporting further investigation into the possible molecular roles of TARM1 in TB, as well as assisting in the identification of prospective diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4+ Effective Memory T Cell (CD4+ TEM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4+ TEM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10−15) and LAG3 (rs67706382, p = 6.16× 10−16). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4+ TEM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4+ TEM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find. [ABSTRACT FROM AUTHOR]

Anaplasma phagocytophilum—the causative agent of human granulocytic anaplasmosis (HGA)—is a tick-borne pathogen transmitted by Ixodid ticks infecting wild and domestic mammals as well as humans. Despite the availability of evidence regarding this emerging infection among vectors, host animals, and individuals in China, there is limited knowledge on the prevalence and distribution of A. phagocytophilum in the Yunnan Province. The aim of this study was to assess the seroprevalence of A. phagocytophilum in healthy adults and patients with acute undifferentiated fever from four regions in the Yunnan Province. The enzyme-linked immunosorbent assay and indirect immunofluorescence assay were used to detect immunoglobulin (Ig) G and IgM antibodies against A. phagocytophilum in sera obtained from 1185 healthy blood donors and 245 patients with acute undifferentiated fever, respectively. Demographic variables were assessed as potential risk factors using the chi-squared test. The rates of seropositivity rates were 7.59% and 4.49% in healthy donors and fever patients, respectively. Analysis of risk factors such as gender, age groups, and place of residence showed statistically significant differences. Infections with A. phagocytophilum occur widely among individuals residing in southwestern China. Our results indicate that there is serological evidence of HGA in this population and presence of acute A. phagocytophilum infections in patients with undifferentiated fever in the Yunnan Province. [ABSTRACT FROM AUTHOR]

A liquid chromatographic method with tandem mass spectrometric detection (LC-MS/MS) for the determination of N-methyl-4-isoleucine-cyclosporin (NIM811) was developed and validated over the concentration range 1-2500 ng/mL in human whole blood using a 0.05 mL sample volume. NIM811 and the internal standard, d12-cyclosporin A (d12-CsA), were extracted from blood using MTBE via liquid-liquid extraction. After evaporation of the organic solvent and reconstitution, a 10 µL aliquot of the resulting extract was injected onto the LC-MS/MS system. Chromatographic separation of NIM811 and internal standard was performed using a Waters Symmetry RP-8 (50 × 4.6 mm, 3 µm particle size) column. The mobile phase consists of 10 m m ammonium acetate in water (A) and acetonitrile (B), with 45% B from 0 to 0.2 min, 45 to 85% B from 0.2 to 0.8 min and 85% B from 0.8 to 2.2 min. The total run time was 3.5 min with a flow rate of 0.8 mL/min. The method was validated for sensitivity, linearity, reproducibility, stability, dilution integrity and recovery. The precision and accuracy of quality control samples at low (2.00 ng/mL), medium (20.0 and 400 ng/mL) and high (2000 ng/mL) concentrations were in the range 1.1-4.3% relative standard deviation (RSD) and −2.5-10.0% (bias), respectively, from three validation runs. The method has been used to measure the exposure of NIM811 in human subjects. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Both Borrelia burgdorferi (Bb) and Anaplasma phagocytophilum (Ap) can infect humans and animals through tick-borne transmission, resulting in zoonosis. Under certain conditions, human infection can lead to Lyme disease (LD) and human granulocytosis (HGA), whereas infection in animals can cause various acute and non-specific symptoms. The combination of Bb and Ap has been reported to increase the disease severity in infected animals. In this systematic review and meta-analysis, we investigated the global diversity of Bb and Ap coinfection in animals and their prevalence and distribution regarding spatial and species ecoepidemiology., Methods: We queried PubMed, Web of Science, Embase, and the Cochrane Library for original studies on Bb and Ap coinfection. We assessed the rate of Bb and Ap in all included articles by single-group meta-analysis and subgroup analyses. We evaluated publication bias using a combination of funnel plots, Egger's tests, and Begg's tests, and conducted risk of bias assessment using the SYRCLE tool., Results: Our search retrieved 40 articles, with eight involving 8419 infected animals meeting our inclusion criteria. The SYRCLE bias risk assessment indicated that most of the included studies were of high quality. Forest maps showed that the combined Bb and Ap infection rate in animals worldwide was 5.5% (95% confidence interval (CI) = 2.4-9.6). Subgroup analysis of forest maps showed that the coinfection rates were 8.2% (95% CI = 2.2-17.2) in North American, 0.2% (95% CI = 0.1-0.7) in European, and 1.2% (95% CI = 0.8-1.8) in Asian animals. Coinfection rates were 6.7% (95% CI = 2.7-12.2) in domestic and 0.0% (95% CI = 0.0-0.4) in wild animals. The coinfection rates were 9% (95% CI = 5.7-12.8) in domestic horses and 6% (95% CI = 1.9-12.2) in domestic dogs, whereas 7.5% (95% CI = 3-17.9) in wild squirrels and 0.2% (95% CI = 0.1-0.7) in wild mice. Funnel diagrams, Egger's tests, and Begg's tests showed no significant publication bias in the included studies., Conclusions: Spatial epidemiology showed that coinfection with Bb and Ap in animals worldwide was most prevalent in the southwestern region of North America, whereas species epidemiology showed that coinfection was most prevalent in domesticated horses, followed by wild squirrels and domesticated dogs, but was less common in wild mice. These data on the epidemiological status of Bb and Ap coinfection in animals may help guide the prevention and treatment of zoonosis., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interest., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Introduction: Ixodes ticks are pivotal in transmitting diseases like Lyme disease and human granulocytic anaplasmosis, caused by Borrelia burgdorferi and Anaplasma phagocytophilum , respectively. These pathogens not only affect humans through single or multiple tick bites but also pose risks to animal hosts, leading to potential coinfections. Despite regional studies indicating significant prevalence, their global coinfection data remain sparse. This study aims to bridge this gap through a systematic review and meta-analysis of B. burgdorferi and A. phagocytophilum coinfections in Ixodes ticks worldwide. Addressing data limitations and study variability, it seeks to provide a nuanced understanding of coinfection patterns, their epidemiological implications and inform targeted prevention strategies., Methods and Analysis: Following Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015 guidelines and PROSPERO registration, this study will undertake a thorough database search without constraints on language or publication date, using standardised screening and data extraction protocols. The quality and bias of studies will be evaluated using Joanna Briggs Institute tools. In the statistical analysis phase, conducted in R, we will initially determine the use of fixed or random-effects models based on the assessment of data heterogeneity. This choice will guide the framework for subsequent analyses. Within the selected model's framework, we will perform subgroup analyses and meta-regression to investigate the effects of various factors, ensuring that each step is tailored to the initial model selection to maintain analytical consistency., Ethics and Dissemination: As this study does not involve clinical research or data collection from subjects, ethical approval is not required. We will uphold ethical standards in synthesising and reporting data. Study outcomes will be published in peer-reviewed journals, communicating findings to the scientific community and contributing to the understanding of Ixodes tickborne diseases., Prospero Registration Number: CRD42023449735., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)