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Recent CDC Evaluation of Commercial MERS MDx Could be Boon in Light of New Outbreak

TEM of MERS-CoV. Credit: National Institute of Allergy and Infectious Diseases.

NEW YORK (GenomeWeb) – In April, at the Clinical Virology Symposium in Daytona Beach, Florida, researchers from the US Centers for Disease Control and Prevention presented a small, preliminary evaluation of three commercial assays for Middle East Respiratory Syndrome coronavirus, also called MERS or MERS-CoV.

The evaluation may be somewhat timely, as MERS — which in April 2013 was deemed by the US Food and Drug Administration to pose a significant enough risk for a public health emergency — is again emerging, with a new outbreak in South Korea causing a public health crisis.  

As part of the recent evaluation the researchers used the CDC's Novel Coronavirus 2012 rRT-PCR, which received US Food and Drug Administration Emergency Use Authorization in June 2014, as the comparator assay.

They then tested the RealStar MERS-CoV RT-PCR Kit from Altona Diagnostics, the FTD hCoV-EMC from Fast-track Diagnostics, and the genesig Novel Coronavirus hCoV-MERS from Primerdesign.

MERS is thought to be zoonotic, and may be transmitted to humans by camels, particularly calves. Since September 2012, the World Health Organization has been notified of 1,218 laboratory-confirmed cases of infection, including at least 449 related deaths, WHO said today in a statement.

PCR is the preferred method to test for MERS, a CDC spokesperson told GenomeWeb in an email this week.

The technique is sensitive enough to detect only a few viral particles, and assays are easy to develop since reagents are commercially available and primers and probes can be quickly synthesized. The technique is also relatively safe, unlike viral culture, and it can be coupled to sequencing to support molecular epidemiology studies, the spokesperson noted. 

CDC evaluated commercial tests because it "has the responsibility to provide diagnostic and surveillance support for current [and] newly emergent respiratory diseases to our domestic and international public health partners," the CDC spokesperson explained.

This support comes in different forms, he said, "from developing CDC's own testing methods and reagents to evaluating commercial products that fulfill the needs … The broad goal of this work is to simply be prepared to support all of our public health partners in ways most beneficial to them and the public they serve."

The three kits were the only ones on the market the researchers considered to be "comprehensive" when the study began.

"There were other kits available, but they only supplied some of the necessary reagents to perform the tests," the spokesperson said.

"In trying to stick to a modest budget as well as a very limited volume of precious clinical specimens, the research team had to pick a subset of commercial offerings in addition to its own developed method," the spokesperson noted.

The evaluation measured analytical sensitivity using 10-fold dilutions of viral isolate, and clinical sensitivity on seven known cases and two cases that had an unrelated infection.

It found all the assays to be 100 percent specific when challenged with concentrated nucleic acid from 12 other respiratory viruses and 10 clinical specimens with a diversity of non-MERS pathogens.

The Altona assay had the same limit of detection as the CDC test, and both correctly identified five out of seven MERS cases. Two samples that had high Ct values were negative, even upon repeat testing.

The other two tests had lower LODs, and while the Fast-track kit detected four of the seven known cases, the PrimerDesign only detected a single case, with a kit from a different lot showing identical results.

The agency concluded that the three commercial kits have all necessary reagents and easy-to-follow instructions. The Altona and Fast-track tests performed "comparably" to the CDC assay, but the PrimerDesign kit lacked sensitivity. Testing was limited by kit costs and lack of clinical specimens, so further kit evaluation is warranted.

Altona's Ebola kit is among the assays on WHO's list of in vitro diagnostics eligible for procurement in affected countries and is distributed by Qiagen. Fast-track Diagnostics also makes an Ebola assay but has not received EUA, and recently partnered with Biocartis to develop assays for the Idylla platform. The Primerdesign MERS test, meanwhile, can run on the genesig q16 qPCR system, which the firm launched last year.

The current outbreak

An outbreak of Middle East Respiratory Syndrome in South Korea has so far infected 95 people, killing eight, and has led to quarantine for more than 2,000 individuals who have potentially been exposed.

The index case — a 68 year-old South Korean man with a history of travel to four countries in the Middle East — was diagnosed on May 20, according to a recent WHO situation assessment. The cases in that country include primarily clinicians who treated this man, as well as other patients and visitors at the four different centers where he sought care.

"Based on current data and WHO’s risk assessment, there is no evidence to suggest sustained human-to-human transmission in communities and no evidence of airborne transmission," WHO said in a statement last week.

"However, MERS-CoV is a relatively new disease and information gaps are considerable."

The CDC has been consulting with the National Institute of Health and Korea Center for Disease Control and Prevention "to offer assistance with viral genomic sequencing, sequence analysis, and serology," the CDC spokesperson said.

"The Korea CDC is currently using PCR assays recommended by the World Health Organization for virus detection," he said. The WHO recommendations refer to assays byBonnUniversity inGermany, but also mention the Altona and Fast-track Diagnostics tests.

"WHO does not endorse any particular product and laboratories are encouraged to make their own enquiries to determine which kit, if any, is appropriate to their particular circumstances," the guidelines state.

Bioneer, a South Korea-based company, also recently began supplying a MERS diagnostic kit, the firm told GenomeWeb in an email last week.

That product uses a dual hot start RT-qPCR method, providing improved sensitivity from a small amount of template RNA.

The assay can run on the company's 96-well qPCR system, called the Exicylcer, or on other qPCR systems, and the firm also makes a sample preparation system that automates pipetting steps, helping to minimize laboratory-acquired infections.

In the US, the current CDC interim guidelines explain that many state health department laboratories are approved for MERS testing using the CDC rRT-PCR assay. Viral culture is not recommended, and "must be performed in a BSL-3 facility using BSL-3 work practices." Differential diagnostic testing for common respiratory pathogens by molecular or antigen detection methods, but not by viral culture, is also strongly recommended.