Suspected cases of measles or rubella are most frequently confirmed by detection of specific IgM antibody in serum specimens. The most common method of detection used is a commercial enzyme immunoassay (EIA), which has largely replaced the immunofluorescence assay (IFA), which is a much less sensitive and specific method than EIA.
Most commercially available IgM EIA kits for measles and rubella use either an indirect format or a capture format. The indirect format includes an absorbent in the diluent or a pre-treatment step to bind IgG antibodies to reduce non-specific reactions. The IgM assays based on the capture format do not require the removal of IgG antibodies and are generally considered to be more sensitive and specific than indirect EIAs. All assays have an equivocal range and the standard procedure is to repeat the test if an equivocal result is obtained. If the IgM result for the serum specimen after re-testing remains equivocal, a second sample may be required. Refer to ‘Timing of the serum specimen’ in section 4.2.
There are many considerations to guide the selection of an EIA kit for measles and rubella IgM detection in addition to high sensitivity and specificity. The reliability of the manufacturer to produce a sufficient quantity of kits, the cost of kits and required reagents, and required purchase of necessary equipment are among the most important factors to consider. In addition, the type of specimen (serum or OF), the workload, and ease of use will also influence the choice of kits. The assays used for testing IgM in oral fluid (OF) must be evaluated for testing OF, as discussed in section 4.4 below.
Eleven different kits were used by the GMRLN to test the WHO proficiency panels for measles IgM in 2016. The Enzygnost® Anti-Measles Virus EIA kit, most recently produced by Siemens (Marburg, Germany,) has been utilized by many network laboratories for many years. However, as these kits are no longer available in some markets, other commercial kits are being utilized, including the Serion kit (Institut Virion/Serion, Wurzburg, Germany), and Euroimmun (Luebeck, Germany).
There was less concordance in the results obtained for rubella IgM among the 18 different kits used for the 2016 proficiency panel. However, there is a greater choice of mu-capture rubella IgM kits on the market, which are generally less likely to produce false positive IgM results. Although there is data available from proficiency panel testing that may provide some indication of the relative performance of the various kits, proficiency testing does not provide a true comparison of how the kits perform. The samples included in the panels are selected primarily to test the competence of the laboratory and not to compare kit function. A summary with an analysis of results obtained using different IgM kits for measles and rubella for proficiency testing is available in Annex 4.1. Additional information regarding kit selection will be made available through links on the GMRLN website upon completion of the evaluation of measles and rubella IgM kits.