scholarly journals Diagnostic accuracy of combinations of serological biomarkers for identifying clinical tuberculosis

2018 ◽  
Vol 12 (06) ◽  
pp. 429-441 ◽  
Author(s):  
Zaida Araujo ◽  
Noe Macias-Segura ◽  
Juan Ernesto Lopez-Ramos ◽  
Jacobus Henry De Waard ◽  
Magnolia Vanegas ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Roc Analysis ◽  
Target Population ◽  
Diagnostic Tools ◽  
Receiver Operator Curve ◽  
Discriminative Ability ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Serological Biomarkers ◽  
Operator Curve

Introduction: Confirmation of tuberculosis (TB) cases in endemic TB settings is a challenge; obtaining fast and cheap, though accurate, diagnostic tools such as biomarkers is thus urgently needed to enable the early detection of TB. This paper evaluates the diagnostic accuracy of combinations of host serological biomarkers for identifying TB. Methodology: Enzyme-linked immunosorbent assays (ELISA) were used on 70 Venezuelan Creole individuals for evaluating host biomarkers (i.e. CXCL9, sCD14, MMP9 and uPAR proteins) and anti-synthetic peptides covering certain Mycobacterium tuberculosis (Mtb) ESAT-6 (P-12033, P-12034 and P-12037) and Ag85A (P-29878) antigen sequences. The target population consisted of adults having active TB (ATB, n = 28), the tuberculin skin test positive (TST+) or individuals with latent TB infection (LTB, n = 28) and TST- or control subjects (CTRL, n = 14). Results: Receiver operator curve (ROC) analysis revealed good biosignature discriminative ability for 5 serological biomarkers; the accuracy of 3 combinations had a good discriminative ability for diagnosing TB. Anti-P-12034/uPAR detected TB with 96.7% sensitivity and 86.0% specificity, followed by anti-P-12033/uPAR having 96.7% sensitivity and 81.4% specificity. Anti-P-29878/MMP9 had the highest sensitivity (100%), but low specificity (52.17%). Biomarker combinations did not prove efficacious for identifying incipient subclinical TST+TB− subjects at high-risk for TB. Conclusions: The anti-P-12034/uPAR combination could be useful for identifying clinical TB patients. Such an approach holds promise for further validation.

scholarly journals Heme Oxygenase-1 and Neopterin Plasma/Serum Levels and their role in Diagnosing Active and Latent TB among HIV/TB Co-Infected Patients

2019 ◽  
Author(s):  
Uwimaana Esther ◽  
Bernard S Bagaya ◽  
Barbara Castelnuovo ◽  
David P Kateete ◽  
Anguzu Godwin ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Heme Oxygenase ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Heme Oxygenase 1 ◽  
Hiv Patients ◽  
Receiver Operating Characteristic Curves ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background: Tuberculosis(TB) diagnosis in the presence of HIV co-infection remains challenging. Heme oxygenase 1(HO-1) and neopterin have been validated as potential biomarkers for TB diagnosis. Infection of macrophages with Mycobacterium tuberculosis (M .tb ) causes the production of HO-1 and neopterin and previous studies have shown these to be markers of immune activation. This study was conducted to determine the levels of HO-1 and neopterin and their utility in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis(COHSONET) study and the Kampala TB Drug Resistance Survey(KDRS). Methods: A total of 210 participants were enrolled in a study of a diagnostic method aimed at determining the levels of HO-1 and neopterin and determine their diagnostic accuracy as biomarkers in TB diagnosis from March to May 2019. M. tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection(LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using Kruskal Wallis and Receiver Operating Characteristic curves to determine the diagnostic accuracy. Results: HO-1 levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 10.7ng/ml (IQR: 7.3-12.7ng/ml), 7.5ng/ml (IQR: 5.4-14.1ng/ml), 3.3ng/ml (IQR: 2.0-7.1ng/ml) respectively. Neopterin levels among ATB/HIV patients, LTBI/HIV patients and TB negative individuals were 11.7ng/ml (IQR: 5.219.4ng/ml), 8.8ng/ml (IQR: 2.4-19.8ng/ml), and 5.9ng/ml (IQR: 3.410.2ng/ml) respectively. HO-1 showed a sensitivity of 78.57% and a specificity of 71.43% with area under the curve(AUC) of 0.839 when used to diagnose ATB. HO-1 showed AUC of 0.79, sensitivity of 70% and specificity 70% when used to diagnose LTB. Neopterin showed a sensitivity of 61.43% and a specificity of 74.29% with AUC 0.71 when used to diagnose ATB. Neopterin as a biomarker in LTB diagnosis showed AUC of 0.56 which was not significant. Conclusion: HO-1 and neopterin are valuable diagnostic biomarkers for ATB and LTB which could be further utilized to develop less costly rapid diagnostic tools to overcome current TB diagnostic challenges.

scholarly journals Comparison of the Diagnostic Accuracy of theMSLNGene Products, Mesothelin and Megakaryocyte Potentiating Factor, as Biomarkers for Mesothelioma in Pleural Effusions and Serum

2013 ◽  
Vol 35 ◽  
pp. 119-127 ◽  
Author(s):  
Jenette Creaney ◽  
Sophie Sneddon ◽  
Ian M. Dick ◽  
Hanne Dare ◽  
Neil Boudville ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Serum Levels ◽  
Gene Products ◽  
Serum Concentrations ◽  
Receiver Operator Curve ◽  
Healthy Individuals ◽  
Pleural Effusions ◽  
Significant Difference ◽  
Highly Correlated ◽  
Operator Curve

TheMSLNgene products, soluble mesothelin and megakaryocyte potentiating factor (MPF), are being investigated as biomarkers for the asbestos-related cancer malignant mesothelioma (MM). Pleural fluid biomarkers of MM can be elevated when serum levels remain normal. The aim of this study was to determine if this was true for MPF and to compare levels of mesothelin. Biomarker concentrations were compared in 66 MM patients, 39 patients with other malignancies, 37 with benign disease, 18 asbestos-exposed healthy individuals, and 53 patients with chronic kidney disease. In pleural effusions, MPF and soluble mesothelin concentrations were both significantly elevated in MM patients relative to controls. No significant difference between the area under the receiver operator curve (AUC) for MPF (0.945±0.02) and mesothelin (0.928±0.03) when distinguishing MM from all other causes of effusion was observed. MPF and mesothelin serum concentrations were highly correlated and of equivalent diagnostic accuracy with AUCs of0.813±0.04and0.829±0.03, respectively. Serum levels of both markers increased with decreasing kidney function. In conclusion, MPF is elevated in the pleural effusions of MM patients similar to that of mesothelin. Mesothelin and MPF convey equivalent diagnostic information for distinguishing MM from other diseases in pleural effusions as well as serum.

Quantitative morphometrics reveals glomerular changes in patients with infrequent segmentally sclerosed glomeruli

2021 ◽  
pp. jclinpath-2020-207149
Author(s):  
Jennifer A Schaub ◽  
Christopher L O'Connor ◽  
Jian Shi ◽  
Roger C Wiggins ◽  
Kerby Shedden ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Kidney Biopsy ◽  
Geometric Distribution ◽  
Kidney Tissue ◽  
Area Under The Curve ◽  
Clinical Markers ◽  
Receiver Operator Curve ◽  
Multivariate Modelling ◽  
Operator Curve ◽  
Total Nephrectomy

AimsDetection of one segmentally sclerosed glomerulus (SSG) identifies patients with focal segmental glomerulosclerosis (FSGS) but rare SSGs may be missed in kidney biopsies. It is unknown whether alterations of unaffected glomeruli in patients with infrequent SSG can be detected by quantitative morphometrics.MethodsWe determined SSG frequency and obtained quantitative morphometrics in glomeruli without a pathologic phenotype in large kidney sections of non-involved kidney tissue from 137 patients undergoing total nephrectomy. We used multivariate modelling to identify morphometrics independently associated with increasing frequency of SSG and Receiver Operator Curve (ROC) analysis to determine the ability of quantitative morphometrics to identify patients with FSGS. We used the geometric distribution to estimate the sensitivity and specificity of a needle biopsy to identify patients with FSGS.ResultsIn seventy-one patients (51.8%), at least one SSG was observed, and of those, 39 (54.9%) had an SSG lesion in less than 2% of all glomeruli (mean of 249 glomeruli per specimen). Increasing percent of SSG was independently associated with decreasing podocyte density and increasing mesangial index in multivariate modelling. For infrequent SSG lesions (<1% of glomeruli), kidney biopsy could miss FSGS diagnosis more than 74% of the time, and podocyte density had an area under the curve (AUC) of 0.77, and mesangial index, an AUC of 0.79 to identify patients with FSGS.ConclusionsMore than half of patients had FSGS, although 30% had infrequent SSG. Quantitative morphometrics in glomeruli without pathology, such as podocyte density and mesangial index, identified patients with infrequent SSG and may serve as clinical markers to identify patients with FSGS.

scholarly journals Prevalence of latent tuberculosis infection and feasibility of TB preventive therapy among Thai prisoners: a cross-sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sivaporn Gatechompol ◽  
Weerakit Harnpariphan ◽  
Ruamthip Supanan ◽  
Gompol Suwanpimolkul ◽  
Jiratchaya Sophonphan ◽  
...  
Keyword(s):  
Latent Tuberculosis ◽  
Cross Sectional Study ◽  
Preventive Therapy ◽  
Sectional Study ◽  
Cross Sectional ◽  
Ltbi Prevalence ◽  
History Of ◽  
Chest X Ray ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT). Methods A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT. Results From August 2018–November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32–50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16–2.01, p = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74–5.24, p < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24–2.79, p = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH. Conclusion This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components.

scholarly journals Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 517
Author(s):  
Magdalena Druszczynska ◽  
Michal Seweryn ◽  
Sebastian Wawrocki ◽  
Magdalena Kowalewska-Pietrzak ◽  
Anna Pankowska ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Mediators ◽  
Latent Tuberculosis ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Mycobacterium Tuberculosis Infection ◽  
Only Children ◽  
Latent Tb ◽  
Ifn Γ ◽  
Multiplex Bead

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

scholarly journals Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Birhan Alemnew ◽  
Soren T. Hoff ◽  
Tamrat Abebe ◽  
Markos Abebe ◽  
Abraham Aseffa ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Patterns ◽  
Fold Change ◽  
Mrna Levels ◽  
Healthy Children ◽  
Toll Like Receptors ◽  
Relative Expression ◽  
Latently Infected ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers. Methods Messenger RNA (mRNA) levels were analysed in a total of 64 samples collected from apparently healthy children and adolescents latently infected with tuberculosis (n = 32) or non-infected (n = 32). Relative expression in peripheral blood of selected genes encoding TLRs (TLR-1, TLR-2, TLR-4, TLR-6 and TLR-9) was determined with a quantitative real-time polymerase chain reaction (qRT-PCR) using specific primers and florescent labelled probes and a comparative threshold cycle method to define fold change. Data were analysed using Graph-Pad Prism 7.01 for Windows and a p-value less than 0.05 was considered statistically significant. Results An increased mean fold change in the relative expression of TLR-2 and TLR-6 mRNA was observed in LTBI groups relative to non-LTBI groups (p < 0.05), whereas a slight fold decrease was observed for TLR-1 gene. Conclusions An increased mRNA expression of TLR-2 and TLR-6 was observed in latently infected individuals relative to those non-infected, possibly indicating the roles these biomarkers play in sustenance of the steady state interaction between the dormant TB bacilli and host immunity.

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