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

Abstract

The World Health Organization (WHO) has targeted measles for global eradication through mass immunization. For effective monitoring of eradication targets, high quality surveillance is needed. The detection of IgM antibodies, specific to the measles virus, with the use of commercial enzyme-linked immunosorbent assays (ELISA or EIA) is broadly used within the WHO global measles and rubella laboratory network for laboratory confirmation, and in particular ELISA kits manufactured by Siemens (Enzygnost® kits) have been primarily used. Spurred by the discontinuation of these kits, this study aims to report on the clinical sensitivity and specificity of comparable commercial ELISA kits and one automated chemiluminescent immunoassay (CLIA) method. A panel of 239 serum samples was assembled that included sera from confirmed measles cases (n=50) and probable post-MMR vaccine response (n=2). Measles negative sera (n=187) were collected from individuals presenting with other fever and rash illnesses. A total of 7 ELISA kits were evaluated (Euroimmun native antigens and recombinant nucleoprotein, IBL, Clin-Tech Microimmune, NovaTec NovaLisa®, Serion and Siemens Enzygnost®) and one CLIA method (DiaSorin LIAISON® XL). The ELISA kits included two IgM capture methods and five indirect methods. Calculated sensitivities and specificities ranged from 75.0% to 98.1% and 86.6% to 99.5% respectively. The parvovirus B19 IgM positive sera were noted to cause false positive results particularly for the ELISA kits from Serion and NovaLisa®; specificities for this subset of samples ranged from 51.4% to 100.0%. The capture IgM ELISA methods provided the best combination of sensitivity and specificity.

Measles incidence in South Africa: a six-year review, 2015 - 2020

“…Cross-reactive serology occurs reasonably uncommonly using the ELISA methodology, however, the influence of false-positive serology can form a large proportion of cases when overall measles numbers are low and rubella numbers high. Of note, cross-reactive measles and rubella serology has been reported with most commercial assays (16) (20)(21) and likely represents biological increases in polyclonal antibody titres in patients in vivo , rather than in vitro flaws of the diagnostic kits. Such challenges indicate the need for improved molecular diagnostics for routine measles surveillance in South Africa, necessitating future collection of throat swabs, urine samples or other suitable samples for confirmatory measles molecular testing.…”

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

“…A total of 166 residual clinical sera that were confirmed to be IgM positive or equivocal for other fever- and rash-causing viruses were included in the panel ( Table 1 ). Sera from 68 laboratory-confirmed cases that met the national case definition for measles by local public health authorities and collected during measles outbreaks were included ( 17 ). However, the residual volume of all specimens was insufficient for use in the Liaison method, which requires at least 170 μL.…”

Measles incidence in South Africa: a six-year review, 2015—2020

“…A frequent cause of febrile morbilliform rash in our setting is therefore rubella. Cross-reactive measles serology is well described, where measles IgM may be falsely elevated during intercurrent infection with rubella [18][19][20]. Due to overlapping clinical symptoms, such cases are usually classified as both "confirmed measles" and "confirmed rubella" cases due to the difficulty of excluding a measles diagnosis and the need to err on the side of caution regarding early measles outbreak response.…”

“…Factors associated with measles diagnosis among children 1-4 years oldNB: Of 4411 males and 3716 females, only 4079 and 3393 females had data for measles respectively; Of 3575 vaccinees and 70 non-vaccinees, 3321 and 68 had data for measles respectively; 303/329 and 2146/2334 recipients of 1 or two measles doses had measles data; 1774/1814 and 1547/1761 had measles data for the period < 2016 and ≥ 2016; Under age, the table shows the median (IQR) age of 56 measles cases; Of note, cross-reactive measles and rubella serology has been reported with most commercial assays[18][19][20] and likely represents biological increases in polyclonal antibody titres in patients in vivo, rather than in vitro flaws of the diagnostic kits.. Such challenges indicate the need for improved molecular diagnostics for routine measles surveillance in South Africa, necessitating future collection of throat swabs, urine samples or other suitable samples for confirmatory measles molecular testing.…”