scholarly journals Anti-HEV IgG Avidity Testing: Utility for Diagnosing Acute and Resolved Genotype 3 Infections

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 236
Author(s):  
Claudia Minosse ◽  
Daniele Lapa ◽  
Antonio Coppola ◽  
Federica Rapagna ◽  
Gianpiero D’Offizi ◽  
...  

European Association of the Study of the Liver (EASL) guidelines specify HEV RNA, as well as anti-HEV IgG and IgM as positive markers for acute HEV infection. HEV RNA assay sensitivity limitations may lead to false negative test results in patients with low levels of viremia. Moreover, anti-HEV IgM positivity is not a reliable indicator for distinguishing between acute and resolved infections given the ability of this antibody to persist several months after a resolved infection. Our study aims were to assess HEV IgG avidity for diagnosing acute and resolved infections, regardless of the anti-HEV IgM serostatus, and examine assay reliability when evaluating different genotype 3 (GT3) HEV subtypes. Patient serum samples (n = 104) were tested for HEV IgG avidity by utilizing the DIA.PRO kit on a DSX automated instrument. Among patients identified with acute HEV infections, 32 were infected with GT3: GT3c (n = 5), GT3e (n = 8), 3f (n = 17) and GT3-unsubtyped (n = 2). Avidity sensitivity was 91.2% and specificity was 100%. For patients with long-lasting anti-HEV IgM persistence, an Avidity Index >70% was observed. Thus, the DIA.PRO avidity assay may be utilized to distinguish between recently acquired and resolved HEV GT3 infections. However, for equivocal results (Avidity Index > 40–70%), HEV RNA molecular testing will be required to confirm a recent infection.

2012 ◽  
Vol 19 (11) ◽  
pp. 1838-1843 ◽  
Author(s):  
Jean-Benjamin Murat ◽  
Coralie L'Ollivier ◽  
Hélène Fricker Hidalgo ◽  
Jacqueline Franck ◽  
Hervé Pelloux ◽  
...  

ABSTRACTDetection and treatment of acute toxoplasmosis during pregnancy can avoid severe disease of the fetus. In this context, assessment of anti-ToxoplasmaIgG avidity has been shown to exclude recent infection. The Elecsys Toxo IgG and IgM assays (Roche Diagnostics) have been validated for screening pregnant women and a new assay, Elecsys Toxo IgG Avidity, was recently developed. Our aims were to investigate the performance characteristics of this new avidity assay and explore whether additional information can be provided by avidity assays. The Elecsys assay was compared with the Vidas (bioMérieux) and Architect (Abbott) Avidity assays using two sets of serum samples (n= 291 andn= 255). The rate of general agreement between the Elecsys and Vidas assays was 74%, and that between the Elecsys and Architect assays was 83%. For 11% of the serum samples, avidity was high with the Vidas assay and within the gray zone with the Elecsys assay. None of the assays detected high-avidity antibodies in serum taken <4 months after infection. Avidity values of >90% were exclusively reported in sera taken >9 months after infection by the Elecsys and Architect assays. Almost all avidities of <19% with the Elecsys assay and <17% with the Architect assay corresponded to sera taken <3 and <2 months after infection, respectively. The Elecsys IgG Avidity assay can be used to exclude recent infection. New ways of interpreting the avidity result are also suggested: very high or low values could exclude infections within the last 9 months or help to confirm a recent infection, respectively. However, these potential interpretations require further investigation.


2016 ◽  
Vol 21 (30) ◽  
Author(s):  
Claudia Lucarelli ◽  
Enea Spada ◽  
Gloria Taliani ◽  
Paola Chionne ◽  
Elisabetta Madonna ◽  
...  

Prevalence of anti-hepatitis E virus (HEV) antibodies is highly variable in developed countries, which seems partly due to differences in assay sensitivity. Using validated sensitive assays, we tested 313 blood donors attending a hospital transfusion unit in central Italy in January and February 2014 for anti-HEV IgG and IgM and HEV RNA. Data on HEV exposure were collected from all donors. Overall anti-HEV IgG prevalence was 49% (153/313). Eating raw dried pig-liver sausage was the only independent predictor of HEV infection (adjusted prevalence rate ratio = 2.14; 95% confidence interval: 1.23–3.74). Three donors were positive for either anti-HEV IgM (n = 2; 0.6%) or HEV RNA (n = 2; 0.6%); they were completely asymptomatic, without alanine aminotransferase (ALT) abnormalities. Of the two HEV RNA-positive donors (both harbouring genotype 3), one was anti-HEV IgG- and IgM-positive, the other was anti-HEV IgG- and IgM-negative. The third donor was positive for anti-HEV IgG and IgM but HEV RNA-negative. HEV infection is therefore hyperendemic among blood donors (80% men 18–64 years-old) from central Italy and associated with local dietary habits. Nearly 1% of donors have acute or recent infection, implying potential transmission to blood recipients. Neither ALT nor anti-HEV IgM testing seems useful to prevent transfusion-transmitted HEV infection.


2020 ◽  
Author(s):  
Manohar B. Mutnal ◽  
Amin A. Mohammad ◽  
Alejandro C. Arroliga ◽  
Yinan Hua ◽  
Liping Wang ◽  
...  

AbstractThe emergence of coronavirus disease 2019 (COVID-19) has become a major global health crisis. Currently, diagnosis is based on molecular techniques, which detect the viral nucleic acids when present at detectable levels. The serum IgG response against SARS-CoV-2 was examined by using an ELISA-based assay. Serum samples, along with nasopharyngeal specimens were collected from various cohorts and analyzed by ELISA and rRT-PCR, respectively. A total of 167 serum samples were tested for serum IgG antibodies against SARS-CoV-2 in outpatient cohorts, 15 (8.9%) were positive by rRT-PCR and the remaining 152 (91%) were negative. We used these data to generate two different assay cutoffs for serum IgG assay and investigated percent concordance with rRT-PCR test results. The emergency department data revealed, out of 151 nasopharyngeal swabs, 4 (2.6%) were positive by rRT-PCR and 18 (11.9%) were positive for serum IgG assay. Among the 18 patients that were positive for serum IgG, 13 (72.2%) exhibited 1-3 symptoms of COVID-19 and 5 (27.7%) patients did not present with any COVID-19 related symptoms, per CDC criteria. All 4 (100%) patients that were positive by rRT-PCR had symptoms of COVID-19 disease. A longitudinal study from the inpatient population suggested there was a sharp increase in the serum IgG titers in 5 patients, a moderate increase in 1 patient and a plateau in 3 patients. Sero-prevalence of COVID-19 disease in pre-procedure patients was 5.5%. Our findings suggest serological tests can be used for appropriate patient triaging when performed as an adjunct to existing molecular testing.


Author(s):  
Catherine Y Zhu ◽  
Ines Donangelo ◽  
Deepashree Gupta ◽  
Dalena T Nguyen ◽  
Joana E Ochoa ◽  
...  

Abstract Context Molecular testing to refine the diagnosis of cytologically indeterminate thyroid nodules has become increasingly popular, but data on long-term durability of test results and the rate of delayed operation are limited. Objective Determine the delayed rate of surgical resection in indeterminate nodules with benign/negative molecular testing and the risk of false-negative molecular test results. Design Prospective follow-up of the Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules randomized controlled trial comparing the diagnostic test performance of Afirma Gene Expression Classifier and ThyroSeq v2. Setting University of California, Los Angeles. Participants Patients who underwent thyroid biopsy with indeterminate (Bethesda III/IV) cytology (April 2016 to July 2017). Intervention Ultrasound surveillance. Main Outcome Measure False-negative rate of molecular testing. Results Of 95 indeterminate nodules with negative/benign molecular test results, 12 nodules underwent immediate resection (11 benign nodules, 1 noninvasive follicular thyroid neoplasm nodule with papillary-like nuclear features). Nonoperative management was pursued for 83 (87.4%) nodules. The median surveillance was 26.7 months. Ten nodules were resected during surveillance and malignancy was identified in 4 nodules (overall false-negative rate of 5.8%). In the 4 malignant nodules that underwent delayed operation, surgery was prompted by sonographic changes during surveillance. Conclusions The majority of indeterminate nodules with negative molecular testing have a stable clinical course over 3 years of follow-up, but our finding of a 6% false-negative rate highlights the importance of continuing sonographic surveillance. Long-term studies are needed to determine the optimal length of follow-up.


2012 ◽  
Vol 6 (12) ◽  
pp. 854-859 ◽  
Author(s):  
Joseph C Forbi ◽  
Mathew D Esona ◽  
Hellen O Iperepolu ◽  
Moses P Adoga ◽  
Simon M Agwale

Introduction: Investigating the incidence and dynamics of HIV-2 and false-negative HIV test results in a highly sexually active population where frequent opportunities exist for acquiring and transmitting infections provides additional understanding of the epidemiology of the virus in Africa. Methodology: The HIV status of 900 active female sex workers (FSWs) was determined using two lateral flow rapid assays in series. The second rapid test device incorporates type-specific recombinant peptides that discriminate between HIV-1 and HIV-2 infection. HIV sero-negative samples were re-tested for HIV infection and their viral loads determined using the NucliSENS real-time nucleic acid sequence-based amplification (NASBA) platform. Results: In total, 335 FSWs were determined to be HIV positive, the majority (227; 67.8%) of whom were between the ages of 20 and 30 years. Eighteen (5.4%) were found to have evidence of HIV-2 infection, 17 of whom were co-infected with HIV-1. Only one HIV-2 mono-infection was observed. Out of 565 HIV-negative individuals determined by serology, 11(1.9%; p>0.05) were found to be HIV-1 positive when tested via the NASBA platform. Conclusion: False negative test results, HIV-2 infection, and complex transmission networks among FSWs may aid in fueling the HIV epidemic in the Nigerian population. These findings demonstrate the need to reevaluate the quality of HIV serological diagnostics, control services, and stress the need for widespread introduction of molecular testing among high-risk populations in the country.


2020 ◽  
Vol 58 (6) ◽  
Author(s):  
Donald R. Latner ◽  
Sun B. Sowers ◽  
Kiana Anthony ◽  
Heather Colley ◽  
Christine Badeau ◽  
...  

ABSTRACT Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary revaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well-characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization, the gold standard method, and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there was good agreement across platforms for IgG-negative sera and for samples with intermediate to high levels of IgG. False-negative test results occurred in approximately 11% of sera, which had low levels of neutralizing antibody.


2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Aref Teimouri ◽  
Sina Mohtasebi ◽  
Elham Kazemirad ◽  
Hossein Keshavarz

ABSTRACT Risk of mother-to-child transmission of Toxoplasma gondii during pregnancy is much greater in women who are exposed to primary T. gondii infection (toxoplasmosis) after conception compared to those who were exposed to the infection before conception. Therefore, laboratory tests that help classify recent primary toxoplasmosis are important tools for the management of pregnant women suspected to have T. gondii exposure. Detection of Toxoplasma IgM (Toxo IgM) is a sensitive indicator of primary toxoplasmosis, but the indicator specificity is low because sometimes natural IgM antibodies react with Toxoplasma antigens in the absence of the infection. Furthermore, Toxo IgM sometimes persists in blood serum for several months or years following the primary infection. In recent decades, Toxo IgG avidity assay has been used as a standard diagnostic technique for a better estimation of the infection acquisition time and identification of the primary T. gondii infection during pregnancy. Avidity is described as the aggregate strength; by which, a mixture of polyclonal IgG molecules reacts with multiple epitopes of the proteins. This parameter matures gradually within 6 months of the primary infection. A high Toxo IgG avidity index allows a recent infection (less than 4 months) to be excluded, whereas a low Toxo IgG avidity index indicates a probable recent infection with no exclusions of the older infections. This minireview is based on various aspects of T. gondii IgG avidity testing, including (i) description of avidity and basic methods used in primary studies on T. gondii IgG avidity and primary infections; (ii) importance of IgG avidity testing in pregnancy; (iii) result summary of the major studies on the use of T. gondii IgG avidity assay in pregnancy; (iv) brief explanation of the T. gondii IgG avidity values in newborns; (v) result summary of the major studies on T. gondii IgG avidity and PCR; (vi) discussion of commercially available T. gondii IgG avidity assays, including newer automated assays; and (vii) current issues and controversies in diagnosis of primary T. gondii infections in pregnancy.


2019 ◽  
pp. 43-50
Author(s):  
Waldemar Rastawicki ◽  
Karolina Śmietańska ◽  
Natalia Rokosz-Chudziak ◽  
Urszula Roguska

Introduction: Tularemia is a highly infectious zoonotic disease caused by Gram-negative bacterium Francisella tularensis. The microbiological diagnosis of tularemia is based mainly on serological investigations. The present study was undertaken to determine the avidity of IgG class antibodies to Francisella tularensis in the course of tularemia in humans and to evaluate its value for estimation of the phase of diseases. Methods: Fifty two serum samples obtained from 40 patients with tularemia were tested by in-house ELISA in duplicate in the same plate, without and after the 0.5 h incubation with 8M urea. The age of the subjects was between 6 and 77 years. From one patient, a 9-years-old girl with oculoglandular form of tularemia, five serum samples were taken, respectively after 0.5, 1.5, 3, 6 and 12 months from the beginning of the first clinical symptoms. Results: The results of the study showed higher values of the avidity index (AI) of IgG antibodies for F. tularensis, often exceeding the value of 0.9, in children and adolescents than in adults. The examination of serum samples obtained 2-3 times in the course of tularemia from few patients did not show significant differences in the level of avidity index depending on the period of the disease. However, in five serum samples obtained from a 9-years-old girl in the different phases of tularemia the avidity index showed increasing values (0.51, 0.80, 0.92, 0.90 and 0.94, respectively). Conclusions: The avidity index of IgG may be helpful in excluding recent infection, but its usefulness in detecting an active phase of invasion requires further research.


2010 ◽  
Vol 17 (9) ◽  
pp. 1349-1355 ◽  
Author(s):  
Hossein Elyasi ◽  
Jalal Babaie ◽  
Hélène Fricker-Hidalgo ◽  
Marie-Pierre Brenier-Pinchart ◽  
Mehrak Zare ◽  
...  

ABSTRACT The usefulness of a specific immunoglobulin G (IgG) avidity enzyme-linked immunosorbent assay (ELISA) based on recombinant GRA6 antigen for distinguishing between acute and chronic Toxoplasma infection was investigated. Two sets of serum samples obtained from pregnant women with acute, chronic, or no Toxoplasma infection collected in France and Iran were used. Among the French subjects, 19 of 20 (95%) women who experienced seroconversion during the past 4 months before sampling displayed low-avidity IgG antibodies against GRA6, while all 17 (100%) women with chronic infection had high-avidity antibodies. When the Euroimmun IgG avidity ELISA was used, 15 of 19 (78.9%) recently infected women had low-avidity antibodies, and 20 of 22 (90.9%) women with chronic infection displayed high-avidity antibodies. The results suggested better performance of the GRA6 avidity ELISA than the Euroimmun avidity ELISA for exclusion of a recent infection occurring less than 4 months previously. Similarly, all 35 Iranian women with acute Toxoplasma infection had low-avidity antibodies against GRA6, whereas all 34 women with chronic infection displayed IgG antibodies of high avidity, indicating the value of GRA6 avidity testing for ruling out a recent infection. Avidity tests based on lysed whole-cell Toxoplasma gondii antigen are currently used to exclude recently acquired infections; however, the use of recombinant antigen(s) might improve the diagnostic performance of avidity tests and facilitate the development of more standardized assays.


2003 ◽  
Vol 42 (02) ◽  
pp. 71-77 ◽  
Author(s):  
I. Schreivogel ◽  
C. Angerstein ◽  
U. Siefker ◽  
K. Lehmann ◽  
G. Altenvoerde ◽  
...  

SummaryAim: Formal and clinical comparison of a new 3rd-gene-ration-Tg-IRMA (3-G-IRMA; Dynotest®Tg-plus) with a conventional Tg-IRMA (3-G-IRMA; SELco®Tg-assay) for patients with differentiated thyroid carcinoma. In addition we evaluated, if thyroglobulin (Tg) levels above a specific threshold concentration indicate the need for further investigations for residual disease. Patients, methods: Tg concentration of 105 sera of 93 consecutive patients with a differentiated thyroid cancer was determined with both assays and compared at different cut-off values (Dynotest®Tg-plus: 0.2, 1, 2 ng/ml; SELco®Tg-assay: 0.5, 1, 2 ng/ml) with the clinical results in respect to the corresponding TSH concentration. Results: Tg concentration did not show any significant difference (SELco®Tg-assay 0.5 ng/ml, Dynotest® Tg-plus 0.2 ng/ml). The Tg-values of both assays correlated with 97%. However, correlation of recovery in both assays was small (40%). The sensitivities and specificities of both assays at different cut-offs and TSH values did not reveal significant differences. In patients with TSH concentration >30 µU/ml the functional assay sensitivity was superior to arbitrary cut-offs in the decision to start further evaluations. Conclusions: In our study neither formal nor clinical significant differences between two Tg-assays were found. In a hypothyroid patient (TSH >30 µU/ml, Tg concentration exceeding the functional assay sensitivity) further investigations for residual disease are warranted. Higher thresholds are of limited value, due to a inacceptable high rate of false negative results.


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