Diagnostic Accuracy of Eight Commercial Assays
Rubella and congenital rubella syndrome are caused by the rubella virus and can be prevented by vaccination, making eradication of the disease possible. Monitoring progress toward global eradication and local elimination requires sensitive, high-quality surveillance of the disease, including laboratory confirmation of cases. Previous evaluations of rubella IgM detection methods resulted in the wide adoption of Enzygnost enzyme-linked immunosorbent assay (ELISA) kits (most recently manufactured by Siemens) within the global network of measles and rubella laboratories. WHO, but have been discontinued.
This study evaluated seven comparable ELISAs from six manufacturers (Trinity Biotech, Euroimmun, Clin-Tech, NovaTec, and Virion\Serion), as well as an automated chemiluminescent assay (CLIA) from DiaSorin. These assays include three IgM capture assays and five indirect ELISAs. A panel of 238 sera was used for evaluation that included 38 archival rubella-positive IgM sera and 200 sera collected from patients with symptomatically similar diseases, including measles, dengue, parvovirus B19 infection, and roseola.
With this panel of sera, the sensitivity of the methods ranged from 63.2% to 100% and the specificity from 80.0% to 99.5%. No single method had both a sensitivity and specificity >90%, unless sera with equivocal results were considered presumptive positive.
Some assays, notably the Serion ELISA, yielded a large number of false positives with sera positive for parvovirus B19 IgM, as well as sera from confirmed cases of measles. The performance characteristics identified in this evaluation serve as a reminder not to rely solely on rubella IgM results for case confirmation in elimination settings.
Rubella and congenital rubella syndrome are caused by the rubella virus and can be prevented by vaccination. Eradication of the disease is possible through sustained high vaccination coverage, and elimination of the virus that circulates endemically in many countries of the world, including Canada, has been achieved (1, 2). Monitoring progress toward global eradication and local elimination requires sensitive, high-quality disease surveillance that includes laboratory confirmation of cases (1, 3, 4).
Historically, this was often achieved through the detection of rubella-specific IgM antibodies, although this has been augmented or replaced by detection of the virus by reverse transcription PCR (RT-PCR), particularly in countries approaching or have achieved elimination (3–6).
Nonetheless, IgM serology remains an important tool in many countries where it can be used for case confirmation (endemicity settings) and active disease surveillance (case-finding in elimination settings) through reflex testing or pooled testing of sera collected through other surveillance systems, such as those for measles and arboviruses (7, 8).
It is essential that validated methods with high specificity and sensitivity are used. Previous evaluations of rubella virus IgM detection methods resulted in the wide adoption of Enzygnost enzyme-linked immunosorbent assay (ELISA) kits (most recently manufactured by Siemens) within the worldwide network of laboratories. WHO measles and rubella (8, 9). These kits have been discontinued; therefore, there is a need to identify replacement methods (10)
This study evaluated seven comparable ELISA methods from six manufacturers (Trinity Biotech, Euroimmun, Clin-Tech, NovaTec, and Virion\Serion), as well as an automated chemiluminescent immunoassay (CLIA) from DiaSorin. A panel of 238 sera was assembled including, in the non-rubella panel, IgM sera positive for chikungunya virus, dengue virus, measles virus, parvovirus B19, roseola virus, and Zika virus.
These viruses were chosen because they cause illnesses that can also present with fever and rash symptoms and therefore can be captured in rubella testing algorithms during differential diagnosis or active case finding (7, 8, 11–15 ). Some, such as parvovirus B19, have previously been noted as a source of cross-reactivity in methods for the detection of IgM antibodies against rubella virus.