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Life (Basel, Switzerland) Apr 2022With the progression of the COVID-19 pandemic, new technologies are being implemented for more rapid, scalable, and sensitive diagnostics. The implementation of... (Review)
Review
With the progression of the COVID-19 pandemic, new technologies are being implemented for more rapid, scalable, and sensitive diagnostics. The implementation of microfluidic techniques and their amalgamation with different detection techniques has led to innovative diagnostics kits to detect SARS-CoV-2 antibodies, antigens, and nucleic acids. In this review, we explore the different microfluidic-based diagnostics kits and how their amalgamation with the various detection techniques has spearheaded their availability throughout the world. Three other online databases, PubMed, ScienceDirect, and Google Scholar, were referred for articles. One thousand one hundred sixty-four articles were determined with the search algorithm of microfluidics followed by diagnostics and SARS-CoV-2. We found that most of the materials used to produce microfluidics devices were the polymer materials such as PDMS, PMMA, and others. Centrifugal force is the most commonly used fluid manipulation technique, followed by electrochemical pumping, capillary action, and isotachophoresis. The implementation of the detection technique varied. In the case of antibody detection, spectrometer-based detection was most common, followed by fluorescence-based as well as colorimetry-based. In contrast, antigen detection implemented electrochemical-based detection followed by fluorescence-based detection, and spectrometer-based detection were most common. Finally, nucleic acid detection exclusively implements fluorescence-based detection with a few colorimetry-based detections. It has been further observed that the sensitivity and specificity of most devices varied with implementing the detection-based technique alongside the fluid manipulation technique. Most microfluidics devices are simple and incorporate the detection-based system within the device. This simplifies the deployment of such devices in a wide range of environments. They can play a significant role in increasing the rate of infection detection and facilitating better health services.
PubMed: 35629317
DOI: 10.3390/life12050649 -
Archives of Medical Science : AMS 2022The rapid transmission of coronavirus disease 2019 (COVID-19) requires a fast, accurate, and affordable detection method. Despite doubts of their diagnostic accuracy,... (Review)
Review
INTRODUCTION
The rapid transmission of coronavirus disease 2019 (COVID-19) requires a fast, accurate, and affordable detection method. Despite doubts of their diagnostic accuracy, rapid diagnostic tests (RDTs) are used worldwide due to their practicality. This systematic review aims to determine the diagnostic accuracy of antibody-based RDTs in detecting COVID-19.
MATERIAL AND METHODS
A literature search was carried out on five journal databases using the PRISMA-P 2015 method. We included all studies published up to February 2021. The risk of bias was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Diagnostic Test Accuracy Studies. Data regarding peer-review status, study design, test kit information, immunoglobulin class, target antigen, and the number of samples were extracted and tabulated. We estimated the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with a 95% confidence interval.
RESULTS
Thirty-three studies met the eligibility criteria. The pooled data results showed that the combined detection method of IgM or IgG had the highest sensitivity and NPV, which were 73.41% (95% CI: 72.22-74.57) and 75.34% (95% CI: 74.51-76.16), respectively. The single IgG detection method had the highest specificity and PPV of 96.68% (95% CI: 96.25-97.07) and 95.97% (95% CI: 95.47-96.42%), respectively.
CONCLUSIONS
Antibody-based RDTs are not satisfactory as primary diagnostic tests but have utility as a screening tool.
PubMed: 35832707
DOI: 10.5114/aoms/135910 -
Blood Feb 2016Immunoassays are essential in the workup of patients with suspected heparin-induced thrombocytopenia. However, the diagnostic accuracy is uncertain with regard to... (Meta-Analysis)
Meta-Analysis Review
Immunoassays are essential in the workup of patients with suspected heparin-induced thrombocytopenia. However, the diagnostic accuracy is uncertain with regard to different classes of assays, antibody specificities, thresholds, test variations, and manufacturers. We aimed to assess diagnostic accuracy measures of available immunoassays and to explore sources of heterogeneity. We performed comprehensive literature searches and applied strict inclusion criteria. Finally, 49 publications comprising 128 test evaluations in 15 199 patients were included in the analysis. Methodological quality according to the revised tool for quality assessment of diagnostic accuracy studies was moderate. Diagnostic accuracy measures were calculated with the unified model (comprising a bivariate random-effects model and a hierarchical summary receiver operating characteristics model). Important differences were observed between classes of immunoassays, type of antibody specificity, thresholds, application of confirmation step, and manufacturers. Combination of high sensitivity (>95%) and high specificity (>90%) was found in 5 tests only: polyspecific enzyme-linked immunosorbent assay (ELISA) with intermediate threshold (Genetic Testing Institute, Asserachrom), particle gel immunoassay, lateral flow immunoassay, polyspecific chemiluminescent immunoassay (CLIA) with a high threshold, and immunoglobulin G (IgG)-specific CLIA with low threshold. Borderline results (sensitivity, 99.6%; specificity, 89.9%) were observed for IgG-specific Genetic Testing Institute-ELISA with low threshold. Diagnostic accuracy appears to be inadequate in tests with high thresholds (ELISA; IgG-specific CLIA), combination of IgG specificity and intermediate thresholds (ELISA, CLIA), high-dose heparin confirmation step (ELISA), and particle immunofiltration assay. When making treatment decisions, clinicians should be a aware of diagnostic characteristics of the tests used and it is recommended they estimate posttest probabilities according to likelihood ratios as well as pretest probabilities using clinical scoring tools.
Topics: Anticoagulants; Enzyme-Linked Immunosorbent Assay; Heparin; Humans; Immunoassay; Sensitivity and Specificity; Thrombocytopenia
PubMed: 26518436
DOI: 10.1182/blood-2015-07-661215 -
Frontiers in Immunology 2022The diversity of three hypervariable loops in antibody heavy chain and light chain, termed the complementarity-determining regions (CDRs), defines antibody's binding...
The diversity of three hypervariable loops in antibody heavy chain and light chain, termed the complementarity-determining regions (CDRs), defines antibody's binding affinity and specificity owing to the direct contact between the CDRs and antigens. These CDR regions typically contain tyrosine (Tyr) residues that are known to engage in both nonpolar and pi stacking interaction with antigens through their complementary aromatic ring side chains. Nearly two decades ago, sulfotyrosine residue (sTyr), a negatively charged Tyr formed by Golgi-localized membrane-bound tyrosylprotein sulfotransferases during protein trafficking, were also found in the CDR regions and shown to play an important role in modulating antibody-antigen interaction. This breakthrough finding demonstrated that antibody repertoire could be further diversified through post-translational modifications, in addition to the conventional genetic recombination. This review article summarizes the current advances in the understanding of the Tyr-sulfation modification mechanism and its application in potentiating protein-protein interaction for antibody engineering and production. Challenges and opportunities are also discussed.
Topics: Complementarity Determining Regions; Immunoglobulin Heavy Chains; Antigens; Golgi Apparatus; Tyrosine
PubMed: 36569848
DOI: 10.3389/fimmu.2022.1072702 -
Journal of Medical Virology Jan 2023We reviewed the literature on the importance of selected anti-high-risk human papillomavirus (HR-HPV) antibodies (namely, 16/18 and early oncoproteins E6 and E7) as... (Meta-Analysis)
Meta-Analysis Review
We reviewed the literature on the importance of selected anti-high-risk human papillomavirus (HR-HPV) antibodies (namely, 16/18 and early oncoproteins E6 and E7) as potential serological markers for early detection of individuals at high risk of cervical cancer. We searched for studies in PubMed and Embase databases published from 2010 to 2020 on antibodies against HR-HPV E6 and E7 early proteins and cervical cancer. Pooled sensitivity and specificity for HPV16 and HPV18 antibodies were calculated using a bivariate hierarchical random-effects model. A total of 69 articles were identified; we included three studies with 1550 participants. For the three HPV16/18 E6 and E7 antibody tests, enzyme-linked immunosorbent assay-based assays had a sensitivity of 18% for detecting CIN2+ (95% confidence interval [CI]: 15-21) and a specificity of 96% (95% CI: 92-98), for slot-blot, sensitivity was 28.9% (95% CI: 23.3-35.1) and specificity was 72% (95% CI: 66.6-77.0) for detecting CIN2+, and for multiplex HPV serology assay based on a glutathione S-transferase, sensitivity was 16% (95% CI: 8.45-28.6) and specificity was 98% (95% CI: 97-99) for detecting invasive cervical cancer. HR-HPV16/18 E6 and E7 serological markers showed high specificity, but sensitivity was suboptimal for the detection of cervical cancer in either population screening settings or as point-of-care screening tests.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Human papillomavirus 16; Human papillomavirus 18; Oncogene Proteins, Viral; Enzyme-Linked Immunosorbent Assay; Papillomavirus E7 Proteins; Papillomaviridae
PubMed: 35641882
DOI: 10.1002/jmv.27900 -
The Cochrane Database of Systematic... Jun 2020Plague is a severe disease associated with high mortality. Late diagnosis leads to advance stage of the disease with worse outcomes and higher risk of spread of the...
BACKGROUND
Plague is a severe disease associated with high mortality. Late diagnosis leads to advance stage of the disease with worse outcomes and higher risk of spread of the disease. A rapid diagnostic test (RDT) could help in establishing a prompt diagnosis of plague. This would improve patient care and help appropriate public health response.
OBJECTIVES
To determine the diagnostic accuracy of the RDT based on the antigen F1 (F1RDT) for detecting plague in people with suspected disease.
SEARCH METHODS
We searched the CENTRAL, Embase, Science Citation Index, Google Scholar, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov up to 15 May 2019, and PubMed (MEDLINE) up to 27 August 2019, regardless of language, publication status, or publication date. We handsearched the reference lists of relevant papers and contacted researchers working in the field.
SELECTION CRITERIA
We included cross-sectional studies that assessed the accuracy of the F1RDT for diagnosing plague, where participants were tested with both the F1RDT and at least one reference standard. The reference standards were bacterial isolation by culture, polymerase chain reaction (PCR), and paired serology (this is a four-fold difference in F1 antibody titres between two samples from acute and convalescent phases).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. We appraised the methodological quality of each selected studies and applicability by using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. When meta-analysis was appropriate, we used the bivariate model to obtain pooled estimates of sensitivity and specificity. We stratified all analyses by the reference standard used and presented disaggregated data for forms of plague. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included eight manuscripts reporting seven studies. Studies were conducted in three countries in Africa among adults and children with any form of plague. All studies except one assessed the F1RDT produced at the Institut Pasteur of Madagascar (F1RDT-IPM) and one study assessed a F1RDT produced by New Horizons (F1RDT-NH), utilized by the US Centers for Disease Control and Prevention. We could not pool the findings from the F1RDT-NH in meta-analyses due to a lack of raw data and a threshold of the test for positivity different from the F1RDT-IPM. Risk of bias was high for participant selection (retrospective studies, recruitment of participants not consecutive or random, unclear exclusion criteria), low or unclear for index test (blinding of F1RDT interpretation unknown), low for reference standards, and high or unclear for flow and timing (time of sample transportation was longer than seven days, which can lead to decreased viability of the pathogen and overgrowth of contaminating bacteria, with subsequent false-negative results and misclassification of the target condition). F1RDT for diagnosing all forms of plague F1RDT-IPM pooled sensitivity against culture was 100% (95% confidence interval (CI) 82 to 100; 4 studies, 1692 participants; very low certainty evidence) and pooled specificity was 70.3% (95% CI 65 to 75; 4 studies, 2004 participants; very low-certainty evidence). The performance of F1RDT-IPM against PCR was calculated from a single study in participants with bubonic plague (see below). There were limited data on the performance of F1RDT against paired serology. F1RDT for diagnosing pneumonic plague Performed in sputum, F1RDT-IPM pooled sensitivity against culture was 100% (95% CI 0 to 100; 2 studies, 56 participants; very low-certainty evidence) and pooled specificity was 71% (95% CI 59 to 80; 2 studies, 297 participants; very low-certainty evidence). There were limited data on the performance of F1RDT against PCR or against paired serology for diagnosing pneumonic plague. F1RDT for diagnosing bubonic plague Performed in bubo aspirate, F1RDT-IPM pooled sensitivity against culture was 100% (95% CI not calculable; 2 studies, 1454 participants; low-certainty evidence) and pooled specificity was 67% (95% CI 65 to 70; 2 studies, 1198 participants; very low-certainty evidence). Performed in bubo aspirate, F1RDT-IPM pooled sensitivity against PCR for the caf1 gene was 95% (95% CI 89 to 99; 1 study, 88 participants; very low-certainty evidence) and pooled specificity was 93% (95% CI 84 to 98; 1 study, 61 participants; very low-certainty evidence). There were no data providing data on both F1RDT and paired serology for diagnosing bubonic plague.
AUTHORS' CONCLUSIONS
Against culture, the F1RDT appeared highly sensitive for diagnosing either pneumonic or bubonic plague, and can help detect plague in remote areas to assure management and enable a public health response. False positive results mean culture or PCR confirmation may be needed. F1RDT does not replace culture, which provides additional information on resistance to antibiotics and bacterial strains.
Topics: Adult; Antigens, Bacterial; Child; Confidence Intervals; Cross-Sectional Studies; False Negative Reactions; False Positive Reactions; Humans; Plague; Sensitivity and Specificity; Time Factors; Yersinia pestis
PubMed: 32597510
DOI: 10.1002/14651858.CD013459.pub2 -
Journal of Medical Microbiology Apr 2017Rapid and effective diagnosis of Legionnaires' disease (LD) cases is extremely important so that timely and appropriate therapy can be provided, thereby lowering the... (Review)
Review
PURPOSE
Rapid and effective diagnosis of Legionnaires' disease (LD) cases is extremely important so that timely and appropriate therapy can be provided, thereby lowering the morbidity and mortality rates and reducing the health and economic costs associated with this disease.
METHODOLOGY
Diagnosis is established solely by microbiological tests. There are several methods available, each with different performance, sensitivity and specificity characteristics, and further understanding is required. Our objective was to assess the accuracy of urinary antigen detection, direct fluorescent antibody (DFA) staining, serological testing and the polymerase chain reaction (PCR) method versus culture analysis (the reference standard) in patients suspected of being infected with Legionella or patients with laboratory-confirmed LD. We performed a MEDLINE search in November 2014. Two authors independently assessed the trials and extracted data. Pooled analysis was performed through Meta-DiSc version 1.4.
RESULT
The inclusion criteria were met by 11 studies. All the studies evaluated PCR and DFA tests to detect Legionella in clinical specimens, comparing them to culture techniques, and were included in the meta-analysis. The pooled sensitivity and specificity for PCR were 83 % [95 % confidence interval (CI): 79-87 %] and 90 % (95 % CI: 88-92 %), respectively. DFA was evaluated in one study and the sensitivity and specificity of this test were 67 % (95 % CI: 30-93 %) and 100 % (95 % CI: 91-100 %), respectively. PCR had high sensitivity and specificity for early diagnosis of LD.
CONCLUSION
Culture analysis is deemed necessary for epidemiological studies, molecular strain typing and antibiotic sensibility evaluations; however, the performance of PCR in recent studies calls for additional, well-designed studies in order to achieve the best standard test, which will enable optimization of the Legionella infection diagnostic.
Topics: Antigens, Bacterial; Diagnostic Tests, Routine; Fluorescent Antibody Technique, Direct; Humans; Legionnaires' Disease; Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 28463665
DOI: 10.1099/jmm.0.000454 -
Diagnostic Microbiology and Infectious... Apr 2019Candida albicans germ tube antibody (CAGTA) may be helpful as a marker for the diagnosis of invasive candidiasis (IC). However, the performance has been variable. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Candida albicans germ tube antibody (CAGTA) may be helpful as a marker for the diagnosis of invasive candidiasis (IC). However, the performance has been variable. We conducted a meta-analysis to assess the diagnostic accuracy of this assay for diagnosing IC.
METHOD
We searched MEDLINE, EMBASE, Cochrane Collaboration databases, reference lists of retrieved studies, and review articles. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and a summary receiver-operating characteristic curve of CAGTA for diagnosing IC were pooled using meta-analysis.
RESULTS
A total of 976 patients (262 with proven or probable IC), included in 7 studies, were analyzed. The pooled sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios and area under the curve were 66% (95% confidence interval [95% CI], 59% to 73%), 76% (95% CI, 58% to 88%), 2.8 (95% CI, 1.5 to 5.8), 0.44 (95% CI, 0.34 to 0.57), 6 (95% CI, 3 to 5), and 0.68 (95% CI, 0.64 to 0.72), respectively. Heterogeneity of specificity was significant.
CONCLUSION
The diagnostic accuracy of the CAGTA assay is moderate for IC. Since the CAGTA assay is not absolutely sensitive and specific for IC, the CAGTA results should be interpreted in parallel with other biomarkers and clinical findings.
Topics: Antibodies, Fungal; Antigens, Fungal; Candida albicans; Candidiasis, Invasive; Humans; Immunoassay; Predictive Value of Tests; Sensitivity and Specificity; Serologic Tests
PubMed: 30552034
DOI: 10.1016/j.diagmicrobio.2018.10.017 -
PLoS Neglected Tropical Diseases Aug 2016Dengue fever is a ubiquitous arboviral infection in tropical and sub-tropical regions, whose incidence has increased over recent decades. In the absence of a rapid point... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dengue fever is a ubiquitous arboviral infection in tropical and sub-tropical regions, whose incidence has increased over recent decades. In the absence of a rapid point of care test, the clinical diagnosis of dengue is complex. The World Health Organisation has outlined diagnostic criteria for making the diagnosis of dengue infection, which includes the use of the tourniquet test (TT).
PURPOSE
To assess the quality of the evidence supporting the use of the TT and perform a diagnostic accuracy meta-analysis comparing the TT to antibody response measured by ELISA.
DATA SOURCES
A comprehensive literature search was conducted in the following databases to April, 2016: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, BIOSIS, Web of Science, SCOPUS.
STUDY SELECTION
Studies comparing the diagnostic accuracy of the tourniquet test with ELISA for the diagnosis of dengue were included.
DATA EXTRACTION
Two independent authors extracted data using a standardized form.
DATA SYNTHESIS
A total of 16 studies with 28,739 participants were included in the meta-analysis. Pooled sensitivity for dengue diagnosis by TT was 58% (95% Confidence Interval (CI), 43%-71%) and the specificity was 71% (95% CI, 60%-80%). In the subgroup analysis sensitivity for non-severe dengue diagnosis was 55% (95% CI, 52%-59%) and the specificity was 63% (95% CI, 60%-66%), whilst sensitivity for dengue hemorrhagic fever diagnosis was 62% (95% CI, 53%-71%) and the specificity was 60% (95% CI, 48%-70%). Receiver-operator characteristics demonstrated a test accuracy (AUC) of 0.70 (95% CI, 0.66-0.74).
CONCLUSION
The tourniquet test is widely used in resource poor settings despite currently available evidence demonstrating only a marginal benefit in making a diagnosis of dengue infection alone.
REGISTRATION
The protocol for this systematic review was registered at
PROSPERO
CRD42015020323.
Topics: Dengue; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Humans; Sensitivity and Specificity; Tourniquets
PubMed: 27486661
DOI: 10.1371/journal.pntd.0004888 -
Nephrology, Dialysis, Transplantation :... Jun 2016Studies in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) have revealed promising biomarkers. The aim of our study was to validate the most... (Review)
Review
BACKGROUND
Studies in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) have revealed promising biomarkers. The aim of our study was to validate the most encouraging markers of granulomatosis with polyangiitis and microscopic polyangiitis identified by literature search and to create biomarker panels.
METHODS
A systematic literature review was performed and we identified 161 marker molecules that were ranked by their quantitative differential expression between active and inactive disease. Enzyme-linked immunosorbent assays were used to validate the results in a cross-sectional cohort of patients with renal involvement. Active vasculitis as assessed by the Birmingham Vasculitis Score version 3 (BVAS v3) was defined as BVAS v3 ≥1 and inactive disease as BVAS v3 = 0. Statistical analysis was performed with SPSS version 21 and the Salford Predictive Modeler 7.0 was used to generate a predictive biomarker panel.
RESULTS
The review indicated abundant expression of sC5bC9, C3a, C5a and monocyte chemotactic protein (MCP)-1 in urine, whereas granulocyte macrophage colony-stimulating factor, C-reactive protein (CRP), soluble fms-like tyrosine kinase-1, interleukin-17A (IL-17A), C5a, hyaluronan, C3a and interleukin-18 binding protein (IL-18BP) were identified to be highly diverse in active and inactive disease in blood samples. Our cross-sectional analysis revealed significant up-regulation of CRP, C5a, C3a, IL-18BP in blood and C5a and MCP-1 in urine samples during active AAV (all P < 0.05). Creation of a biomarker panel comprising CRP and urinary MCP-1 yielded a sensitivity and specificity of 76% (area under the curve 0.89).
CONCLUSIONS
We identified promising biomarkers in a literature-based review that were in part corroborated as has been shown for CRP, C3a, C5a, IL-18BP in blood and MCP-1 and C5a in urine samples. Moreover, we propose a biomarker panel comprising CRP and urinary MCP-1 in patients with AAV and renal involvement. Further investigations to confirm our preliminary results are clearly warranted, including the reliability to predict disease relapses.
Topics: Biomarkers; Enzyme-Linked Immunosorbent Assay; Granulomatosis with Polyangiitis; Humans; Interleukin-17; Kidney; Microscopic Polyangiitis
PubMed: 26410887
DOI: 10.1093/ndt/gfv336