Accuracy Of Serological Tests Research Articles

Diagnosis of celiac disease in Poland – what should thelaboratory diagnostician pay special attention?

Celiac disease (CD) is an autoimmune disorder in which the immune system reactsabnormally when exposed to gluten consumption in genetically predisposed individuals. Thedisease affects about 1% of the population, making it one of the most common autoimmunediseases. Due to the heterogeneous presentation of clinical symptoms, celiac disease oftenremains undiagnosed or diagnosed late, even in elderly patients. According to the EuropeanSociety for Paediatric Gastroenterology and Nutrition (ESPGHAN) guidelines in force since2020, the diagnosis of CD in children is based on: serological tests (evaluation of specificantibodies in peripheral blood serum) and histopathological tests (determination of thepresence of lesions in duodenal sections taken during endoscopic examination). Currently,genetic testing of the HLA-DQ2/DQ8 haplotype does not increase the diagnostic accuracy ofserological tests and can only

Identifying the Optimum Strategy for Identifying Adults and Children With Celiac Disease: A Cost-Effectiveness and Value of Information Analysis

ObjectivesCeliac disease (CD) is thought to affect around 1% of people in the United Kingdom, but only approximately 30% are diagnosed. The aim of this work was to assess the cost-effectiveness of strategies for identifying adults and children with CD in terms of who to test and which tests to use. MethodsA decision tree and Markov model were used to describe testing strategies and model long-term consequences of CD. The analysis compared a selection of pre-test probabilities of CD above which patients should be screened, as well as the use of different serological tests, with or without genetic testing. Value of information analysis was used to prioritize parameters for future research. ResultsUsing serological testing alone in adults, immunoglobulin A (IgA) tissue transglutaminase (tTG) at a 1% pre-test probability (equivalent to population screening) was most cost-effective. If combining serological testing with genetic testing, human leukocyte antigen combined with IgA tTG at a 5% pre-test probability was most cost-effective. In children, the most cost-effective strategy was a 10% pre-test probability with human leukocyte antigen plus IgA tTG. Value of information analysis highlighted the probability of late diagnosis of CD and the accuracy of serological tests as important parameters. The analysis also suggested prioritizing research in adult women over adult men or children. ConclusionsFor adults, these cost-effectiveness results suggest UK National Screening Committee Criteria for population-based screening for CD should be explored. Substantial uncertainty in the results indicate a high value in conducting further research.

Accuracy of Serological Markers, Synovial Fluid, Microbiological Culture, and Histopathological Examination for Diagnosing Periprosthetic Knee Infection.

Objective This study assessed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of serological tests, synovial fluid markers, microbiological tissue culture, and histopathological examination of the periprosthetic membrane in diagnosing periprosthetic knee infection. Methods This study is prospective, and it includes patients undergoing total knee arthroplasty revision surgery from November 2019 to December 2021. The analysis consisted of serological tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and D-dimer), synovial fluid markers (leukocyte and polymorphonuclear cell counts), periprosthetic tissue culture, and histopathological examination of the periprosthetic membrane of all patients. Results Sixty-two patients had periprosthetic joint infection (PJI) according to the 2018 International Consensus Meeting criteria (infection group), while 22 subjects had no infection. ESR sensitivity and specificity were 83.6% and 45.4%, respectively. CRP sensitivity and specificity were 64.5% and 100%, whereas D-dimer sensitivity and specificity were 78.9% and 25%, respectively. Leukocyte count sensitivity and specificity were 75.6% and 100%, polymorphonuclear cell count sensitivity and specificity were 33% and 100%, respectively. Periprosthetic tissue culture sensitivity and specificity culture were, respectively, 77.4% and 100%. Histopathological examination sensitivity and specificity were 43.7% and 100%, respectively. Conclusions In our study, the total blood cell count in synovial fluid and microbiological cultures of periprosthetic tissues were the most accurate tests for PJI diagnosis. In contrast, polymorphonuclear cell percentage was the least accurate test for PJI diagnosis.

Anti-Arbovirus Antibodies Cross-React With Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in regions where dengue (DENV) and chikungunya (CHIKV) viruses are endemic. Any serological cross-reactivity between DENV, CHIKV, and SARS-CoV-2 is significant as it could lead to misdiagnosis, increased severity, or cross-protection. This study examined the potential cross-reactivity of anti-DENV and CHIKV antibodies with SARS-CoV-2 using acute and convalescent-phase samples collected before the SARS-CoV-2 pandemic. These included healthy, normal human (NHS, n = 6), CHIKV-positive (n = 14 pairs acute and convalescent), primary DENV-positive (n = 20 pairs), secondary DENV-positive (n = 20 pairs), and other febrile illnesses sera (n = 23 pairs). Samples were tested using an in-house SARS-CoV-2 and a EUROIMMUN IgA and IgG ELISAs. All NHS samples were negative, whereas 3.6% CHIKV, 21.7% primary DENV, 15.7% secondary DENV, and 10.8% febrile diseases sera resulted as anti-SARS-CoV-2 antibody positive. The EUROIMMUN ELISA using spike 1 as the antigen detected more positives among the primary DENV infections than the in-house ELISA using spike 1-receptor binding domain (RBD) protein. Among ELISA-positive samples, four had detectable neutralizing antibodies against SARS-CoV-2 reporter virus particles yet none had detectable neutralizing antibodies against the live Wuhan strain of SARS-CoV-2. These data demonstrated the SARS-CoV-2 diagnostic cross-reactivity, but not neutralizing antibody cross-reactivity, among dengue seropositive cases. IMPORTANCE SARS-CoV-2 continues to cause significant morbidity globally, including in areas where DENV and CHIKV are endemic. Reports using rapid diagnostic and ELISAs have demonstrated that serological cross-reactivity between DENV and SARS-CoV-2 can occur. Furthermore, it has been observed that convalescent DENV patients are at a lower risk of developing COVID-19. This phenomenon can interfere with the accuracy of serological testing and clinical management of both DENV and COVID-19 patients. In this study, the cross-reactivity of primary/secondary anti-DENV, CHIKV, and other febrile illness antibodies with SARS-CoV-2 using two ELISAs has been shown. Among ELISA-positive samples, four had detectable levels of neutralizing antibodies against SARS-CoV-2 reporter virus particles. However, none had detectable neutralizing antibodies against the live Wuhan strain of SARS-CoV-2. These data demonstrated SARS-CoV-2 diagnostic cross-reactivity, but not neutralizing antibody cross-reactivity, among dengue seropositive cases. The data discussed here provide information regarding diagnosis and may help guide appropriate public health interventions.

Screening for SARS-CoV-2: Health Policy Implications in Low- and Middle-Income Countries

Screening for SARS-CoV-2: Health Policy Implications in Low- and Middle-Income Countries

Seropositivity rate and diagnostic accuracy of serological tests in 2019-nCoV cases: a pooled analysis of individual studies.

Currently, detection of SARS-CoV-2 RNA is standard in the diagnosis of COVID-19 (2019-nCoV). However, reliable and rapid serological diagnostic methods to screen SARS-CoV-2 infected patients, including those who do not have overt symptoms, are urgently needed. Most studies have described serological tests based on the detection of SARS-CoV-2-specific IgM and IgG. Here, we attempted to systematically analyze the positive rates and comprehensive diagnostic efficacy of IgM and IgG in response to SARS-CoV-2 infection. By systematically searching PubMed, medRxiv, bioRxiv and other databases, studies regarding the detection of peripheral blood IgM and/or IgG related to SARS-CoV-2 were collected. The positive rate, sensitivity (SEN), specificity (SPE), area under the curve (AUC) and corresponding 95% CIs were obtained by weighted quantitative mergence, and the source of heterogeneity was explored by performing a subgroup study and sensitivity analysis. A total of 30 studies were included, which were comprised of 3856 confirmed SARS-CoV-2 RNA positive cases, 368 suspected RNA negative cases, 1167 asymptomatic carriers, and 2526 RNA negative controls. The corresponding meta-analysis showed that in confirmed cases with 2019-nCoV, the positive rates of single IgM, single IgG and their joint detection related to SARS-CoV-2 were 61.2% (95% CI: 53.4%-69.0%), 58.8% (95% CI: 49.6%-68.0%) and 62.1% (52.7%-71.4%), respectively. In suspected RNA negative cases, the positive rates of single IgM, single IgG and their joint detection were 29.0% (95% CI: 14.0%-44.0%), 37.0% (95% CI: 20.0%-55.0%) and 55.0% (95% CI: 19.0%-90.0%), respectively. Interestingly, IgM/IgG detection also demonstrated a positive rate of 19% (95% CI: 10.0%-27.0%) in asymptomatic cases. Using RT-PCR test as reference, the AUCs of IgM, IgG and IgM/IgG in the diagnosis of 2019-nCoV infection were 0.9656, 0.9766, and 0.9838, respectively. The stratified analyses showed that among confirmed cases with 2019-nCoV, the positive rates of IgM and IgG were 27.3% (95%CI: 19.8%-34.8%) and 22.3% (95% CI: 11.3%-33.3%), respectively, 0-7days following the onset of symptoms, whereas the positive rate of parallel IgM/IgG testing attained 39.3% (95% CI: 24.2%-54.4%). Moreover, the efficacy of antibody testing based on CLIA (chemiluminescence enzyme immunoassays) in diagnosing 2019-nCoV infection was higher than that of LFIA (lateral flow immunoassays) and ELISA (enzyme linked immunosorbent assay). IgM, IgG and their joint testing exhibited high clinical value in the diagnosis of 2019-nCoV, which may assist in making up for the deficiency of throat swab RNA tests.

The risk of over-diagnosis in serological testing. Implications for communications strategies.

since the beginning of the COVID-19 pandemic, the importance of developing a serological test has emerged and a debate on test accuracy and reliability become an issue widely discussed in the media. The importance of communication during this pandemic has been strongly underlined by public health experts, epidemiologists, media expert, psychologists, sociologists. In the case of serological tests, there are several aspects that have to be considered: why we perform the test, what population is tested, which are the parameters conditioning the results and their interpretation. to show how to quantify the uncertainty related to the validity of the serological test with respect to its predictive value and in particular the positive predictive value. the evaluation of a qualitative diagnostic test includes four distinct assessments: accuracy, empirical evidence, practical importance, and prevalence of the pathology. Accuracy is measured by the sensitivity and specificity of the test; empirical evidence is quantified by the likelihood ratio, respectively for a positive and negative test result; the practical importance of the result of a diagnostic test is assessed by the positive or negative predictive value. Prevalence of COVID-19 is substantial uncertainty and it is possible to estimate the apparent prevalence starting from the results obtained with a diagnostic test. at the moment, the knowledge about the accuracy of serological tests is limited and little attention is paid to confidence interval on point estimates. In terms of practical importance of testing at individual level, while negative predictive values are high whatever the level of sensitivity of the test, the interpretation of a positive results is very cumbersome. Positive predictive values above 90% can be reached only by tests with specificity above 99% at the expected prevalence rate of 5%. There is a linear relationship between apparent - testing positive - prevalence and real prevalence. The apparent prevalence in the context of serological test for COVID-19 is always larger than real prevalence. The level of specificity is crucial. the main applications of the serological test in the epidemic contest are: to study the seroprevalence of the virus antibodies in the general population; to screen the healthcare workers for the early identification of contagious subjects' health care settings and to screen the general population in order to identify new incident cases. In the first two cases, seroprevalence study and screening of a high-risk population, the consequences of the uncertainty associated to the statistics are already accounted for in the first situation, or are overcome by repeating the screening on the healthcare workers, and using the molecular test to verify the presence of the virus in those tested positive. The case of screening of general population is more complex and of major interest for the implication it may have on individual behaviours and on the implementation of public health interventions by the political decision makers. A positive result has, per se, no practical value for individuals since the probability of being really infected by the virus is low. The uncertainty associated with the different estimates (sensitivity, specificity and disease prevalence) play a double role: it is a key factor in defining the informative content of the test result and it might guide the individual actions and the public policy decisions.

Prevalence of celiac disease in children with type 1 diabetes mellitus and the accuracy of serological tests

In children with type 1 diabetes mellitus (DM), prevalence of some autoimmune diseases like celiac disease (CD) has been increased. It is also reported that CD often can be asymptomatic and only serologically evident in patients with type 1 DM. In our study, we aimed to investigate the prevalence of asymptomatic CD and the specificity and sensitivity of anti-gliadin antibodies (AGA), anti-endomysium (EMA) and tissue transglutaminase (tTG) antibodies that used for diagnosis of CD in these patients. Anti-gliadin-IgA, AGA-IgG, EMA, tTG-IgA levels were evaluated. Small-intestine biopsies were applied to the children that parents were positive for at least one of AGA-IgA, AGA IgG, EMA and tTG-IgA. A total of 268 Type 1 DM children were included in the study. Of these sixty-four children who had at least one serological positive underwent small intestine biopsies and in five children (1.9%) CD was diagnosed. Anti-endomysium and tTG-IgA positivity were detected in all cases with Celiac disease, and sensitivity was 100% for both and 95% and 86% for specificity, respectively. The sensitivity and specificity of anti-endomysium and tTG-IgA antibodies were considered to be the most reliable indicator because of their higher specificity than other serological tests. Our results, which support current guidelines, suggest that children with Type 1 DM can be screened with tTG-IgA and EMA, which are the most sensitive and specific tests to detect asymptomatic CD in these patients.

Comparison of the serum and salivary antibodies to detect gastric Helicobacter pylori infection in Kashan (Iran)

Background and aimHelicobacter pylori (H. pylori) is an important and common contagious human pathogen which may cause peptic ulcer and also gastric cancer. The definite diagnosis of it is made through invasive tests. Recently, non-invasive tests including serologic tests of serum and saliva have been conducted for diagnosis of H. pylori infection. In this research, the diagnostic values of serum and salivary serology were compared together to use salivary anti-H. pylori test as an alternative method in the future.MethodsDuring this prospective case-control study on patients who were candidates for endoscopy and gastric biopsy from March 2015 to April 2016 in Shahid Beheshti hospital, Kashan, Iran, serum and salivary samples were obtained for measurement of Immunoglobulin G (IgG) antibody levels against H. pylori by enzyme-linked immunosorbent assay (ELISA). Histopathology was the gold standard test. Statistical analysis was performed by SPSS software version 16. Statistical tests included Kolmogorov-Smirnov, independent-samples t-test, Chi-square, Mann-Whitney U, Kruskal-Wallis, McNemar and correlation.ResultsOf 123 patients, sixty-one patients (49.6%) were H. pylori-positive according to histology. The median levels of anti-H. pylori antibodies in serum (p<0.001) and saliva (p<0.001) of H. pylori-positive cases were significantly higher than H. pylori-negative cases. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and accuracy of serologic tests in serum were 75%, 79%, 3.5, 0.3, 77% and for saliva were 85%, 82%, 4.7, 0.18, 84% respectively.ConclusionDiagnostic values of salivary ELISA are comparable to serum ELISA and can be used as an alternative modality for diagnosis of H. pylori infection.

Accuracy of serological testing in the city, country and beyond!

<h3>Aims</h3> External quality assurance programs provide samples on a regular basis, for which the expected or target result is unknown to the participants enrolled in the scheme. This enables participants to evaluate their performance compared to their peers in the pre-analytical, analytical and post-analytical phases of sample analysis. The Royal College of Pathologist of Australasia (RCPA) Serology Quality Assurance Program (QAP) evaluated how a laboratory can assess their accuracy simply by reviewing their individualised Participant Assessment Report. <h3>Methods</h3> The RCPA Serology QAP uses the consensus of qualitative results, as the assigned value to which participant performance is evaluated, whilst robust statistics are used to evaluate (not score) quantitative serological results returned by participants. <h3>Results</h3> An analysis of 2011 survey results highlighted issues with participant accuracy when compared with their peers. <h3>Conclusion</h3> Quality assurance is a means of evaluating overall laboratory performance. A laboratory can record reproducible daily quality control, indicating that their assays are precise, but QA gives an indicator of accuracy. The RCPA Serology QAP individualised Participant Assessment Reports provide a ‘score' for the qualitative data but apply robust statistics to evaluate quantitative data to provide participants with an indication of a bias in their operating system and an overall assessment of their accuracy compared with their peers.

Comparison of the value of measurement of serum galactomannan and Aspergillus-specific antibodies in the diagnosis of canine sino-nasal aspergillosis

Serology is currently used for the diagnosis of canine sino-nasal aspergillosis (SNA). However, the accuracy of serological testing using commercially available, standardized purified antigen preparations of Aspergillus (CAPur AspAg) has only been poorly documented. The aim of the present study was to assess the diagnostic value of an agar-gel double immunodiffusion (AGDD) test and an anti- Aspergillus IgG ELISA, using CAPur AspAg and the commercially available Platelia™ test for the detection of serum galactomannan. Sera from 17 dogs with SNA, 18 dogs with a nasal tumour (NT), 11 dogs with lymphoplasmacytic rhinitis (LPR) and 33 control dogs were tested with the 3 methods. AGDD result was positive in 76.5% of dogs with SNA, whereas all sera from dogs with non-fungal nasal disease and control dogs were negative. A positive IgG ELISA result was obtained in 88% of dogs with SNA and in 18% of dogs with LPR. All patients with NT and control dogs had a negative IgG ELISA result. The Platelia™ test was positive in 24% of dogs with SNA, 11% of dogs with NT, 9% of dogs with LPR and 24% of control dogs. The results of this study suggest that (1) the detection of serum Aspergillus-specific antibodies with AGDD or ELISA, using CAPur AspAg, provides excellent specificity and good sensitivity, (2) the specificity is higher for AGDD (100%) than for ELISA (96.8%) while sensitivity is higher for ELISA (88.2%) than for AGDD (76.5%) and (3) serum galactomannan quantification with the Platelia™ test is unreliable for the diagnosis of canine SNA.

Molecular Diagnosis of a Bilateral Panuveitis due to &lt;i&gt;Borrelia burgdorferi&lt;/i&gt; Sensu Lato by Cerebral Spinal Fluid Analysis

The present paper describes a case of bilateral panuveitis due to Borrelia burgdorferi sensu lato diagnosed by a PCR approach using cerebral spinal fluid. Since the culture of B. burgdorferi takes a long time to grow and the accuracy of serological tests is doubtful in patients, the PCR method of amplifying a B. burgdorferi flagellin could be suitable to make a positive diagnosis in a case of atypical clinical history of Lyme disease.

Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing Celiac Disease

Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing Celiac Disease

Investigation and management of coeliac disease

Coeliac disease (CD) is common in children with an estimated prevalence of approximately 1:100. The clinical presentation has altered over the last decade, with most children manifesting non-specific or mild...

Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing Celiac Disease

Estimates of the diagnostic performance of serologic testing and HLA-DQ typing for detecting celiac disease have mainly come from case-control studies. To define the performance of serologic testing and HLA-DQ typing prospectively. Prospective cohort study. University hospital. Patients referred for small-bowel biopsy for the diagnosis of celiac disease. Celiac serologic testing (antigliadin antibodies [AGA], antitransglutaminase antibodies [TGA], and antiendomysium antibodies [EMA]) and HLA-DQ typing. Diagnostic performance of serologic testing and HLA-DQ typing compared with a reference standard of abnormal histologic findings and clinical resolution after a gluten-free diet. Sixteen of 463 participants had celiac disease (prevalence, 3.46% [95% CI, 1.99% to 5.55%]). A positive result on both TGA and EMA testing had a sensitivity of 81% (CI, 54% to 95.9%), specificity of 99.3% (CI, 98.0% to 99.9%), and negative predictive value of 99.3% (CI, 98.0% to 99.9%). Testing positive for either HLA-DQ type maximized sensitivity (100% [CI, 79% to 100%]) and negative predictive value (100% [CI, 98.6% to 100%]), whereas testing negative for both minimized the negative likelihood ratio (0.00 [CI, 0.00 to 0.40]) and posttest probability (0% [CI, 0% to 1.4%]). The addition of HLA-DQ typing to TGA and EMA testing, and the addition of serologic testing to HLA-DQ typing, did not change test performance compared with either testing strategy alone. Few cases of celiac disease precluded meaningful comparisons of testing strategies. In a patient population referred for symptoms and signs of celiac disease with a prevalence of celiac disease of 3.46%, TGA and EMA testing were the most sensitive serum antibody tests and a negative HLA-DQ type excluded the diagnosis. However, the addition of HLA-DQ typing to TGA and EMA testing, and the addition of serologic testing to HLA-DQ typing, provided the same measures of test performance as either testing strategy alone.

Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing Celiac Disease

Accuracy of Serologic Tests and HLA-DQ Typing for Diagnosing Celiac Disease