Paradigm Shift Intervention Monitoring
twitter
Commentary
CDC Battery of MERS Antibody Tests
Recombinomics Commentary 15:50
May 29, 2014
MARK PALLANSCH: …… The most common explanation is that there is some cross-reactivity with a coronavirus and because of the nature of the antigen in the test; this is a possibility that cannot be excluded and in the case of other types of respiratory viruses is known to occur. So that's the most likely explanation in terms of how you get a false-positive signal in an ELISA.
The above comments involve a reporter asking for an explanation on why the ELISA and IFA tests would be positive, and getting an answer that only addresses the ELISA test. This limit explanation is due to the nature of the testing. Individual tests can increase sensitivity at the expense of specificity or increase specificity at the expense of sensitivity. These limitations are addressed by using a combination of tests.
The CDC uses the ELISA test as a highly sensitive assay that has limits on specificity. Thus, it can pick up antibodies that recognize MERS, but also can pick up antibodies directed at other coronavirus. This limited specificity is addressed by two additional tests (IFA and neutralization) that have a lower sensitivity but a high specificity. Two tests are used, in part because the neutralization is more specific but has a lower sensitivity than IFA. Therefore, the CDC definition of a positive requires antibodies that produce a positive ELISA and either a positive on IFA or neutralization.
The Illinois case met that definition because it was positive on ELISA and IFA, so the CDC held on telebriefing on May17. The sample subsequently failed to produce a positive neutralization test, but the Illinois case had limited contact with the PCR confirmed Indiana case, so a negative neutralization test was not unexpected.
Just prior to the US MERS testing, the CDC published a paper on the use of the three tests on serum sample collected from suspect cases, contacts, and other HCWs in Jordan, where an ICU outbreak was reported in April 2012. Only the two fatal cases in that outbreak were MERS PCR confirmed, but the CDC panel of antibody tests identified 7 out of 124 samples which met their definition of a positive (ELISA plus one of the two more specific tests). Six of the seven were positive on all three tests, but one had the same profile as the Illinois case (positive on ELISA and IFA, but negative on neutralization), and was designated as a lab confirmed positive.
The positive result on the Illinois case suggested that additional contacts of the Indiana case would produce similar results because of exposures on April 27 or 28, when the symptoms of the index case were more severe. Neither CDC telebriefing has addressed antibody results on these contacts or the contacts of the Florida case.
Recombinomics
Presentations
Recombinomics
Publications
Recombinomics
Paper
at Nature Precedings