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Clinical Microbiology and Infection :... Sep 2021Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological...
BACKGROUND
Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological tests detecting viral antigen or virus-specific antibodies.
OBJECTIVES
We provide an overview of the challenges towards serological testing for the most important emerging arboviruses, including Zika, dengue and chikungunya viruses.
SOURCES
We retrieved a data set on performance of commercially available antibody- and antigen-detecting tests from 89 peer-reviewed articles conducting a systematic literature research in PubMed.
CONTENT
We identified commonly used antibody- and antigen-detecting tests and analysed their overall performance. We discuss how timing of serological testing and the use of paired samples from acute and convalescent phases of infection are crucial to optimize diagnostic sensitivity and specificity. We then exemplify how serological diagnostics are challenged by the patient's infection history through the 'original antigenic sin' and cross-reactive antibodies in the context of global co-circulation of antigenically related viruses. We highlight how individual infection histories with different arboviruses and with other pathogens such as herpes viruses and Plasmodia can produce inaccurate test results. We show that rapid tests for antibody and antigen detection in point-of-care settings have a significantly lower sensitivity compared with laboratory-based tests such as ELISA. We show that the performance of antibody- and antigen-detecting tests varies greatly between tropical regions of endemic transmission and non-endemic regions. Finally, we highlight that test sensitivity and specificity have to be equilibrated carefully and frequently either of them must be prioritized over the other, depending on disease prevalence and intended use of tests.
IMPLICATIONS
For reliable serological diagnostics, it is essential to be aware of inherent test limitations. Although multiplexed testing and testing of convalescence samples can improve diagnostic performance, global spread of (re-)emerging viruses requires careful implementation and evaluation of serological testing and unambiguous results may not always be achievable.
Topics: Antibodies, Viral; Antigens, Viral; Arbovirus Infections; Arboviruses; Humans; Sensitivity and Specificity; Serologic Tests
PubMed: 34111589
DOI: 10.1016/j.cmi.2021.05.047 -
Frontiers in Neuroscience 2021To review the available evidence on sensitivity and specificity of anti-NF155 antibody detection in diagnosing a specific subset of patients with chronic inflammatory...
To review the available evidence on sensitivity and specificity of anti-NF155 antibody detection in diagnosing a specific subset of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to calculate the frequencies of different autoantibodies to paranodal proteins. Diagnosis of CIDP relies on clinical and neurophysiologic criteria and lacks useful diagnostic biomarkers. A subset of CIDP patients exhibit atypical clinical phenotypes and impaired response to conventional treatments. These patients were reported as having autoantibodies targeting paranodal protein neurofascin isoform 155 (NF155), contactin-1 (CNTN1), and contactin-associated protein-1 (CASPR1). Here, we conducted a meta-analysis to summarize evidence on the diagnostic and prognostic value of these autoantibodies, especially for anti-NF155 antibody. We searched the following electronic bibliographic databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Eligible studies provided information to calculate the frequencies of anti-NF155 antibody and anti-CNTN1 antibody, the sensitivity and specificity of anti-NF155 antibody, and the incidence of improvement and deterioration among anti-NF155 antibody seropositive CIDP patients. Heterogeneity was assessed using Q and statistics. The pooled frequency of anti-NF155 autoantibody across 14 studies was 7% [95% confidence interval (CI): 0.05-0.10] with high heterogeneity; the overall pooled sensitivity and specificity of anti-NF155 antibody for the diagnosis of a specific subgroup of CIDP patients were 0.45 (95% CI: 0.29-0.63) and 0.93 (95% CI: 0.86-0.97), respectively. For diagnosing of a specific subset of CIDP characterized by poor response to intravenous immunoglobulin (IVIg), we found a moderate sensitivity and a high specificity. The anti-NF155 antibody test should be used as a confirmatory test rather than a screening test. PROSPERO, identifier: CRD42020203385 and CRD42020190789.
PubMed: 34108854
DOI: 10.3389/fnins.2021.637336 -
Pathogens (Basel, Switzerland) May 2021is the zoonotic parasite responsible for toxoplasmosis in warm-blooded vertebrates. This systematic review compares and evaluates the available knowledge on... (Review)
Review
is the zoonotic parasite responsible for toxoplasmosis in warm-blooded vertebrates. This systematic review compares and evaluates the available knowledge on enzyme-linked immunosorbent assays (ELISAs), their components, and performance in detecting antibodies in animals. Four databases were searched for published scientific studies on and ELISA, and 57 articles were included. Overall, indirect (95%) and in-house (67%) ELISAs were the most used types of test among the studies examined, but the 'ID Screen Toxoplasmosis Indirect Multi-species' was common among commercially available tests. Varying diagnostic performance (sensitivity and specificity) and Kappa agreements were observed depending on the type of sample (serum, meat juice, milk), antigen (native, recombinant, chimeric) and antibody-binding reagents used. Combinations of recombinant and chimeric antigens resulted in better performance than native or single recombinant antigens. Protein A/G appeared to be useful in detecting IgG antibodies in a wide range of animal species due to its non-species-specific binding. One study reported cross-reactivity, with and spp. This is the first systematic review to descriptively compare ELISAs for the detection of antibodies across different animal species.
PubMed: 34063342
DOI: 10.3390/pathogens10050605 -
Frontiers in Immunology 2021Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical...
Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established. More than 30 mature commercial technology platforms have been used to create and develop BsAbs based on the heterologous recombination of heavy chains and matching of light chains. The detailed mechanisms of clinical/therapeutic action have been demonstrated with these different types of BsAbs. Three kinds of BsAbs have received market approval, and more than 110 types of BsAbs are at various stages of clinical trials. In this paper, we elaborate on the classic platforms, mechanisms, and applications of BsAbs. We hope that this review can stimulate new ideas for the development of BsAbs and improve current clinical strategies.
Topics: Animals; Antibodies, Bispecific; Antibody Specificity; Binding Sites, Antibody; Biotechnology; Drug Design; Epitopes; Humans; Immunotherapy; Protein Engineering; Recombinant Proteins; Translational Research, Biomedical
PubMed: 34025638
DOI: 10.3389/fimmu.2021.626616 -
F1000Research 2021Mass testing and adequate management are essential to terminate the spread of coronavirus disease 2019 (COVID-19). This testing is due to the possibility of...
Mass testing and adequate management are essential to terminate the spread of coronavirus disease 2019 (COVID-19). This testing is due to the possibility of unidentified cases, especially ones without COVID-19 related symptoms. This review aimed to examine the outcome of the existing studies on the ways of identifying COVID-19 cases, and determine the populations at risk, symptom and diagnostic test management of COVID-19. The articles reviewed were scientific publications on the PubMed, Science Direct, ProQuest, and Scopus databases. The keywords used to obtain the data were COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and case detection, case management or diagnostic test. We applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Population, Intervention, Control and Outcomes (PICO) approaches. A total of 21 articles from 13 countries met the inclusion criteria and were further analyzed qualitatively. However, 62% of the articles used a rapid antibody test for screening rather than a rapid antigen test. According to the rapid antigen test, 51.3% were positive, with men aged above 50 years recording the highest number of cases. Furthermore, 57.1% of patients were symptomatic, while diagnostic tests' sensitivity and specificity increased to 100% in 14 days after the onset. : Real-time polymerase chain reaction (RT-PCR) is recommended by the World Health Organization for detection of COVID-19. Suppose it is unavailable, the rapid antigen test is used as an alternative rather than the rapid antibody test. Diagnosis is expected to be confirmed using the PCR and serological assay to achieve an early diagnosis of COVID-19, according to disease progression, gradual rapid tests can be used, such as rapid antigen in an earlier week and antibody tests confirmed by RT-PCR and serological assay in the second week of COVID-19.
Topics: COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Humans; Male; SARS-CoV-2; Sensitivity and Specificity
PubMed: 35719313
DOI: 10.12688/f1000research.50929.3 -
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 -
PLoS Neglected Tropical Diseases Mar 2021Most of national schistosomiasis elimination programmes in Asia are relying on stool examination, particularly Kato Katz stool examination technique for regular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most of national schistosomiasis elimination programmes in Asia are relying on stool examination, particularly Kato Katz stool examination technique for regular transmission monitoring. However, the Kato-Katz technique has shown low sensitivity for the detection of light-intensity infections, and therefore highly sensitive diagnostic tools are urgently required to monitor prevalence of infection in low transmission settings. The objective of this systematic review was to evaluate and synthesize the performance of diagnostic tests for detecting Schistosoma japonicum and S. mekongi infection in people living in endemic areas.
METHODOLOGY/PRINCIPAL FINDINGS
We comprehensively searched these nine electronic databases and other resources until July 2019, with no language or publication limits: PubMed, EMBASE, MEDLINE, Web of Science, BIOSIS Citation Index, HTA, CINAHL PLUS, The Cochrane Library, and PsycINFO. We included original studies that assessed diagnostic performance using antibody, antigen, and molecular tests with stool examination test as a reference standard. Two reviewers independently extracted a standard set of data and assessed study quality. We estimated the pooled estimates of sensitivity and specificity for each index test. We used diagnostic odds ratio to determine the overall accuracy and hierarchical summary receiver operating characteristics (HSROC) curve to assess the index tests performance. Fifteen studies (S. japonicum [n = 13] and S. mekongi [n = 2]) testing 15,303 participants were included in the review. Five studies reported performance of enzyme-linked immunosorbent assay (ELISA), seven studies reported indirect hemagglutination assay (IHA), and four studies reported polymerase chain reaction (PCR) for detecting S. japonicum. The pooled sensitivity and specificity were 0.93 (95% CI: 0.84-0.98) and 0.40 (95% CI: 0.29-0.53) for ELISA, 0.97 (95% CI: 0.90-0.99) and 0.66 (95% CI: 0.58-0.73) for IHA, and 0.89 (95% CI: 0.71-0.96) and 0.49 (95% CI: 0.29-0.69) for PCR respectively. A global summary indicated the best performance for IHA, closely followed by ELISA. We were unable to perform meta-analysis for S. mekongi due to insufficient number of studies.
CONCLUSIONS/SIGNIFICANCE
IHA showed the highest detection accuracy for S. japonicum. Further studies are needed to determine the suitable diagnostic methods to verify the absence of transmission of S. mekongi and also to compare detection accuracy against more sensitive reference standards such as PCR.
Topics: Animals; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Polymerase Chain Reaction; Schistosoma; Schistosoma japonicum
PubMed: 33730048
DOI: 10.1371/journal.pntd.0009244 -
PloS One 2021Increasingly, vaccine efficacy studies are being recommended in low-and-middle-income countries (LMIC), yet often facilities are unavailable to take and store infant...
BACKGROUND
Increasingly, vaccine efficacy studies are being recommended in low-and-middle-income countries (LMIC), yet often facilities are unavailable to take and store infant blood samples correctly. Dried blood spots (DBS), are useful for collecting blood from infants for diagnostic purposes, especially in low-income settings, as the amount of blood required is miniscule and no refrigeration is required. Little is known about their utility for antibody studies in children. This systematic review aims to investigate the correlation of antibody concentrations against infectious diseases in DBS in comparison to serum or plasma samples that might inform their use in vaccine clinical trials.
METHODS AND FINDINGS
We searched MEDLINE, Embase and the Cochrane library for relevant studies between January 1990 to October 2020 with no language restriction, using PRISMA guidelines, investigating the correlation between antibody concentrations in DBS and serum or plasma samples, and the effect of storage temperature on DBS diagnostic performance. We included 40 studies in this systematic review. The antibody concentration in DBS and serum/plasma samples reported a good pooled correlation, (r2 = 0.86 (ranged 0.43 to 1.00)). Ten studies described a decline of antibody after 28 days at room temperature compared to optimal storage at -20°C, where antibodies were stable for up to 200 days. There were only five studies of anti-bacterial antibodies.
CONCLUSIONS
There is a good correlation between antibody concentrations in DBS and serum/plasma samples, supporting the wider use of DBS in vaccine and sero-epidemiological studies, but there is limited data on anti-bacterial antibodies. The correct storage of DBS is critical and may be a consideration for longer term storage.
Topics: Antibodies; Antibodies, Bacterial; Communicable Diseases; Dried Blood Spot Testing; Humans; Protein Stability; Sensitivity and Specificity; Temperature
PubMed: 33720928
DOI: 10.1371/journal.pone.0248218 -
International Journal of Rheumatic... May 2021To evaluate the diagnostic value of anti-citrullinated α-enolase peptide 1 (anti-CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic... (Meta-Analysis)
Meta-Analysis
AIM
To evaluate the diagnostic value of anti-citrullinated α-enolase peptide 1 (anti-CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic review and meta-analysis.
METHODS
The PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases were searched for relevant studies published until September 23, 2020. A bivariate mixed-effects model was used to calculate the diagnostic indices from primary data of eligible studies. We performed meta-regression and subgroup analysis to explore the sources of heterogeneity.
RESULTS
Twenty-four articles, with a total of 17 380 patients with RA and 7505 control participants, met the criteria for inclusion in the meta-analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratios for the anti-CEP 1 antibody were 44% (95% CI: 38%-51%), 97% (95% CI: 96%-98%), and 14.81 (95% CI: 10.66-20.57) and 0.57 (95% CI: 0.52-0.64), respectively. The pooled positive and negative predictive values were 0.96 (95% CI: 0.95-0.97) and 0.53 (95% CI: 0.43-0.63), respectively. The area under the summary receiver operating characteristic curve was 0.86. Meta-regression indicated that the anti-CEP 1 antibody detection method may be a source of heterogeneity. The subgroup analysis of the group in which the anti-CEP 1 antibody was detected by using a commercial enzyme-linked immunosorbent assay (ELISA) kit had a sensitivity of 59% (95% CI: 50%-68%) and a specificity of 93% (95% CI: 85%-97%).
CONCLUSIONS
The anti-CEP 1 antibody had moderate RA diagnostic value with relatively low sensitivity and high specificity. An ELISA may increase the RA diagnostic sensitivity.
Topics: Anti-Citrullinated Protein Antibodies; Antibodies; Arthritis, Rheumatoid; Biomarkers, Tumor; DNA-Binding Proteins; Enzyme-Linked Immunosorbent Assay; Genetic Predisposition to Disease; Humans; Peptides, Cyclic; Phosphopyruvate Hydratase; Sensitivity and Specificity; Tumor Suppressor Proteins
PubMed: 33713557
DOI: 10.1111/1756-185X.14093 -
Medical Journal (Fort Sam Houston, Tex.) 2021Coronavirus Disease-19 (COVID-19), a disease caused by infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a global pandemic. Diagnosis...
BACKGROUND
Coronavirus Disease-19 (COVID-19), a disease caused by infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a global pandemic. Diagnosis is critical and diagnostic techniques include reverse transcriptase polymerase chain reaction (RT-PCR), serologic antibody testing, and chest computed tomography (CT). Despite rigorous meta-analyses looking into these techniques, there is no summary and additionally no algorithm to help guide diagnostic testing. Our objective is to perform a systematic review of the literature and to provide evidence-based algorithms for diagnosing or ruling out COVID-19.
METHODS
Data were gathered using PubMed and Ovid research databases using a predefined medical subject heading (MeSH) based search, and sources that were included in the study had their references reviewed to screen for more sources for this study. Sources were collected up to 23 August 2020. Two researchers searched through the databases for articles and data/articles meeting inclusion criteria were extracted.
RESULTS
395 articles were identified, and 10 studies were included. Meta-analyses of diagnostic tests were included in our systematic review. An overview was then provided for each diagnostic test. Sensitivities and specificities for RT-PCR, serologic antibody tests and chest CT were collected, and the data was stratified by categorical variables. Two evidence-based algorithms were developed for symptomatic and asymptomatic patients in the hospitalized and ambulatory settings.
CONCLUSIONS
This article provides a summary of the up-to-date efficacy of the most utilized diagnostic tests currently available for COVID-19. Additionally, this article provides evidence-based COVID-19 diagnostic algorithms for symptomatic and asymptomatic patients in the hospitalized and ambulatory settings.
Topics: Algorithms; COVID-19; COVID-19 Nucleic Acid Testing; COVID-19 Serological Testing; Humans; Radiography, Thoracic; Sensitivity and Specificity
PubMed: 33666912
DOI: No ID Found