Evaluation of Diagnostic Accuracy of Eight Commercial Assays for the Detection of Rubella Virus-Specific IgM Antibodies

Hiebert, Joanne; Zubach, Vanessa; Charlton, Carmen; Fenton, Jayne; Fonseca, Kevin; Severini, Alberto

doi:10.1128/jcm.01597-21

Cited by 5 publications

(9 citation statements)

References 16 publications

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“…Confirmation of clinical symptoms and history of exposure to measles using a laboratory-based anti-measles immunoglobulin M (IgM) ELISA is the standard method of diagnosis. Several commercial assays of varying accuracy exist to detect anti-measles IgM, including those against virus lysate and nucleoprotein ( 11 ). To determine whether we could detect anti-measles dIgA, we employed a modified indirect ELISA protocol using Euroimmun kits as well as in-house measles virus lysate-coated plates for the detection of antigen-specific dIgA in the plasma of individuals with acute measles infection and other viral exanthema conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Assays were repeated in a validation panel comprising anonymized residual sera referred to the National Microbiology Lab (Winnipeg, Canada) for serological testing and included sera from laboratory-confirmed measles cases ( n = 50), sera with provisional diagnosis of rubella ( n = 36), roseola ( n = 40), chikungunya/dengue/zika ( n = 41), parvovirus ( n = 35), and other fever and rash illness of unknown etiology ( n = 37). This complete panel was previously used to evaluate the diagnostic accuracy of commercial assays for the detection of measles-specific IgM antibodies ( 11 ).…”

Section: Methodsmentioning

confidence: 99%

“…In outbreak investigations, detection of viral RNA through reverse transcriptase polymerase chain reaction ( 8 ) or IgG avidity assays ( 9 ) to confirm IgM results may be required. IgM “true” positivity may arise following measles, mumps, and rubella (MMR) vaccination ( 10 ), and commercial IgM ELISAs have varied accuracy and low positive predictive values in elimination settings ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Dimeric immunoglobulin A as a novel diagnostic marker of measles infection

Mohd Hanafiah,

Hiebert,

Zubach

et al. 2024

Microbiol Spectr

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Despite tremendous measles incidence reduction through universal vaccination, elimination efforts rely on improved surveillance. The detection of anti-measles immunoglobulin M (IgM) by enzyme-linked immunosorbent assay is the standard laboratory diagnostic method. However, true infection is rare, and seroconversion following measles, mumps, and rubella vaccination also generates IgM, which results in low positive predictive values of assays in elimination settings, thus necessitating confirmatory testing. Improved diagnostic tests for measles infection are a World Health Organization research priority. We investigated whether dimeric immunoglobulin A (dIgA), the predominant antibody produced in mucosal immunity, may be a marker of recent or acute measles infection. We examined a serological panel of confirmed measles infection (anti-measles IgM positives, n = 50) and non-measles infection with rubella ( n = 36), roseola ( n = 40), chikungunya/dengue/zika ( n = 41), parvovirus ( n = 35), and other fever-rash illnesses of unknown cause ( n = 37). Sera were examined on microimmune anti-measles IgM, Euroimmun anti-measles virus lysate (VL), and nucleoprotein (NP) IgM kits. Assays were then modified to detect dIgA using an in-house protocol based on a recombinant chimeric secretory component protein and an anti-secretory component monoclonal antibody. We observed significantly higher levels of anti-measles VL dIgA in measles samples than in non-measles controls ( P < 0.001), and there was a low correlation with IgM (R 2 : 0.01, P value: 0.487). Unlike IgM, dIgA reactive to measles NP was not detected in most samples. The comparable diagnostic potential of anti-measles dIgA (area under the curve, AUC: 0.920–0.945) to anti-measles IgM (AUC: 0.986–0.995) suggests that dIgA may be a new blood-based marker of acute measles, independent of IgM, which merits further investigation and optimization. IMPORTANCE The world is facing a measles resurgence, and improved diagnostic tests for measles infection are an urgent World Health Organization research priority. Detection of measles-specific immunoglobulin M (IgM) as a standard diagnostic test has low positive predictive value in elimination settings, and there is a need for new biomarkers of measles infection to enable enhanced surveillance and response to outbreaks. We demonstrate the detection of measles-specific dimeric immunoglobulin A (dIgA) in patients with confirmed measles infections using a new indirect enzyme-linked immunosorbent assay protocol that selects for the dIgA fraction from total IgA in the blood. The magnitude of measles-specific dIgA responses showed a low correlation with IgM responses, and our results highlight the potential of dIgA for further development as an alternative and/or complementary biomarker to IgM for serological diagnosis of measles infection.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dimeric immunoglobulin A as a novel diagnostic marker of measles infection

Mohd Hanafiah,

Hiebert,

Zubach

et al. 2024

Microbiol Spectr

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“…Heibert and colleagues recently evaluated the test characteristics of eight commercially available measles IgM kits, including the kits from Virion/Serion, Euroimmun, and IBL that are included in our current study (11). This report found that IgM capture assays had the best sensitivity and specificity for detecting measles IgM antibodies.…”

Section: Discussionmentioning

confidence: 99%

Performance Characteristics of Six Immunoglobulin M (IgM) ELISA Assays Used for Laboratory Confirmation of Measles

Sowers

Matthews

Mercader

et al. 2022

Preprint

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Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles specific IgM in serum by enzyme linked immunosorbent assay (ELISA) is the most used method for confirming measles infection. ELISA formats vary as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false negative result, which can delay confirmation of measles cases. Interfering substances can yield a false positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against 5 commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; sensitivity and specificity for the commercial kits ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False positive results occurred in 2.0 to 13.1% of sera while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high quality measles surveillance.

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“…A few studies ( 12 – 16 ) in our analysis contained data for the discontinued Siemens Enzygnost kits. For reader’s interest, we have included these forest plots in the supplementary data showing how the Siemens Enzygnost kits performed compared to the other index tests (Fig.…”

Section: Methodsmentioning

confidence: 99%

Diagnostic accuracy of commercially available serological tests for the detection of measles and rubella viruses: a systematic review and meta-analysis

Zubach,

Beirnes,

Hayes

et al. 2024

J Clin Microbiol

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Measles and rubella serological diagnoses are done by IgM detection. The World Health Organization Global Measles and Rubella Laboratory Network previously endorsed Siemens Enzygnost enzyme-linked immunosorbant assay kits, which have been discontinued. A recommended replacement has not been determined. We aimed to search for suitable replacements by conducting a systematic review and meta-analysis of IgM detection methods that are currently available for measles and rubella. A systematic literature search was performed in Medline, Embase, Global Health, Cochrane Central, and Scopus on March 22 and on 27 September 2023. Studies reporting measles and/or rubella IgM detection with terms around diagnostic accuracy were included. Risk of bias was assessed using QUADAS tools. Meta-DiSc and R were used for statistical analysis. Clinical samples totalling 5,579 from 28 index tests were included in the measles meta-analysis. Sensitivity and specificity of the individual measles studies ranged from 0.50 to 1.00 and 0.53 to 1.00, respectively. Pooled sensitivity and specificity of all measles IgM detection methods were 0.94 (CI: 0.90–0.97) and 0.94 (CI: 0.91–0.97), respectively. Clinical samples totalling 4,983 from 15 index tests were included in the rubella meta-analysis. Sensitivity and specificity of the individual rubella studies ranged from 0.78 to 1.00 and 0.52 to 1.00, respectively. Pooled sensitivity and specificity of all rubella IgM detection methods were 0.97 (CI: 0.93–0.98) and 0.96 (CI: 0.93–0.98), respectively. Although more studies would be ideal, our results may provide valuable information when selecting IgM detection methods for measles and/or rubella.

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Evaluation of Diagnostic Accuracy of Eight Commercial Assays for the Detection of Rubella Virus-Specific IgM Antibodies

Cited by 5 publications

References 16 publications

Dimeric immunoglobulin A as a novel diagnostic marker of measles infection

Dimeric immunoglobulin A as a novel diagnostic marker of measles infection

Performance Characteristics of Six Immunoglobulin M (IgM) ELISA Assays Used for Laboratory Confirmation of Measles

Diagnostic accuracy of commercially available serological tests for the detection of measles and rubella viruses: a systematic review and meta-analysis

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