June 22, 2013The other three cases are female health care workers aged 29, 39 and 45 from Taif governorate who cared for two previously confirmed MERS-CoV cases and were detected as part of the outbreak investigation and contact tracing. Two of these three cases were asymptomatic and all three tested weakly positive by PCR.
The above comments from the June 22 WHO update represents the first reported PCR confirmed MERS-CoV infections in asymptomatic contacts. The reporting of “weak positives” as confirmed MERS-CoV represents a sea change in MERS-CoV surveillance.
This report is likely due to a series of recent reports which highlighted serious MERS-CoV detection failures using prior approaches, and the finding of weak positives in mild or asymptomatic cases. These developments should help end media myths which overweight negatives generated by highly suspect assays and discount positives on asymptomatic contacts such as one report that assumed the positives in Italy were false and the negatives were true, as well as another report that called the antibody positive data in asymptomatic or mild contacts inJordan “anomalies”.
The sea change began with testing of asymptomatic contacts of the MERS-CoV index case in Italy. 8-10 contacts, including at least five health care workers gave weak PCR positives. Re-testing by a second lab, using different primers failed to confirm the positive results, so the cases remained suspect (while at least one media report called the weak positives false.
The weak positives in Italy were followed by antibody testing of contacts linked to an ICU outbreak in Jordan in the spring of 2012. Retrospective testing confirmed MERS-CoV in the two fatal cases (one by antibody and the other by PCR and sequencing). Testing in 2012 (for SARS coronavirus and other known human respiratory viruses) had exhausted swab samples, but serum sample were collected in 124 contacts and tested with two antibody targets. This testing re-confirmed the two fatal cases as well as 8 contacts. 6 were from the testing of 9 contacts which had been classified as probable cases based on clinical presentation and contact with the two fatal cases. However two cases were confirmedwho had not been previously classified as suspect because one had mild symptoms and was not hospitalized, while the other was asymptomatic. The confirmation of the asymptomatic case was the first confirmation of MERS-CoV in an asymptomatic case. Moreover, 7 additional cases tested positive with one of the two antibody test. Further refinements will likely confirm the 7 additional cases. CIDRAP called the positive antibody tests anomalies, since the cases were mild or asymptomatic.
In addition to the above positive data on mild and asymptomatic contacts, the recent New England Journal of Medicine report on the significant nosocomial outbreak in four hospitals in th eastern region of the Kingdom of Saudi Arabia highlighted detection failures in serious and fatal caseswhich were classified as probable based on clinical presentation and linkage to one or more confirmed cases.
The reporting of mild PCR cases as confirmed cases may reflect a lowering of the cut-off level, or confirmation of weak positives through sequencing of inserts (both of which are long overdue). However, the PCR detection of MERS-CoV in asymptomatic contacts suggest confirmed cases will increase significantly, which will be accompanied by a drop in the case fatality rate.
These weak positives will also impact the monitoring of pilgrims coming to KSA to perform Umrah during Ramadan and demonstrate the sustain transmission of MERS-CoV in humans.