Thursday, May 15, 2014

Serological Testing Of 2012 Jordanian MERS Outbreak

Coronavirus

Photo Credit NIAID

 

 

# 8625

 

Our first indication that a novel coronavirus was circulating in Saudi Arabia came from a September 2012 letter posted in ProMed Mail (NOVEL CORONAVIRUS - SAUDI ARABIA: HUMAN ISOLATE) by Dr. Ali Mohamed Zaki - an Egyptian Virologist working In Saudi Arabia. Retrospective analysis, however, showed the MERS coronavirus to have been involved in a pneumonia outbreak at a hospital in Jordan in April of that year.


That outbreak, which made headlines in the Middle East and was monitored by FluTrackers at the time, appeared to involve at least 11 people, 2 of whom died. 

 

Testing for `the usual pathogenic suspects’  found no identifiable cause for the illness. This happens more often than most people might imagine,  but since the outbreak appeared to be contained, it was temporarily forgotten.

 

After a handful of novel coronavirus cases were identified during the fall of 2012, retrospective testing was done on some of the samples taken from that outbreak, and in December 2012 (see Background and summary of novel coronavirus infection) we learned that at least 2 of those cases tested positive for nCoV (the old name for MERS-CoV).


Making this Jordanian hospital outbreak the earliest identified human infections from this emerging coronavirus.


Serological testing at the time was still in its infancy (in late 2012, only 9 cases had been identified), and so while more cases from this hospital were suspected, verifying that fact wasn’t possible at the time.

 

Fast forward to June of 2013 and Helen Branswell brought us her report on the research by Dr. Mohammad Al-Abdallat &  Dr. Mark Pallansch et al., that found evidence that at least 10 people had been infected during that earliest outbreak (see MERS-CoV: Early Serological Results).

Helen interviewed Dr. Pallansch, Director of the CDC’s division of viral diseases, on the limitations of testing at the time:

 

He explained that there are still questions about the accuracy of blood tests for MERS, because labs like the CDC which have developed tests have been unable to validate them to this point. To do that, a lab needs both samples known to be negative and samples known to be positive to be sure the test finds only true cases. The only country with lots of positive blood samples is Saudi Arabia, and it is still working out an agreement with the CDC to share blood samples.

So the U.S. agency is using three different tests on the samples. They believe the tests are specific, meaning that positive results are likely true positives, Pallansch said. But they haven't been able to assess the sensitivity of the tests, meaning they cannot be sure that a negative result is a true negative.

 

All of which serves as prelude to a new study by these same researchers, which appeared yesterday in the journal Clinical Infectious Diseases, that seeks to further update, describe, and quantify this outbreak.

 

Hospital-associated outbreak of Middle East Respiratory Syndrome Coronavirus: A serologic, epidemiologic, and clinical description

Mohammad Mousa Al-Abdallat*,1, Daniel C. Payne*,2, Sultan Alqasrawi1,  Brian Rha2,3, Rania A. Tohme4, Glen R. Abedi2, Mohannad Al Nsour5,  Ibrahim Iblan6,  Najwa Jarour1, Noha H. Farag7,  Aktham Haddadin8,  Tarek Al-Sanouri8,  Azaibi Tamin2,  Jennifer L. Harcourt2,  David T. Kuhar9,  David L. Swerdlow2,  Dean D. Erdman2, Mark A. Pallansch2, Lia M. Haynes2,  Susan I. Gerber2, the Jordan MERS-CoV Investigation Team

Abstract

Background. In April 2012, the Jordan Ministry of Health (JMoH) investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; two fatal cases were retrospectively confirmed by rRT-PCR to be the first detected cases of Middle East Respiratory Syndrome (MERS-CoV).

Methods. Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical chart reviews and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using three U.S. Centers for Disease Control and Prevention (CDC) serologic tests for detection of anti-MERS-CoV antibodies.

Results. Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti-MERS-CoV antibodies by at least two of three serologic tests, in addition to two fatal cases identified by rRT-PCR. The case fatality rate among the nine total cases was 22%. Six cases were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at two transfer hospitals having acceptable infection control practices.

Conclusion. Novel serological tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts of a Jordan hospital-associated respiratory illness outbreak in April 2012, resulting in a total of nine test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most cases had no major, underlying medical conditions; none were on hemodialysis. Our observed case fatality was lower than has been reported from outbreaks elsewhere.

 

Since people who are infected with a virus only shed that virus at detectable levels for a limited amount of time (usually days, sometimes weeks) there is a narrow window of opportunity to test them using standard rRT-PCR techniques.

 

Creating, and validating serological tests - which can detect antibodies showing that a person has previously been infected - is our best hope for determining just how widespread a viral illness really is in any population.

 

Today’s study reconfirms a good deal of what was previously known, or suspected, about the Jordanian hospital outbreak. If confirms that at least 9 people were infected in this cluster.  It also indicates that the virus did not spread efficiently beyond the environs of the hospital, and suggests an attack rate of 10% among hospital employees. 


While it may seem more important to be able to detect where a virus currently is (detecting active infections via  rRT-PCR testing or viral culture), you really can’t begin to understand a virus’s behavior, or where it might be going, until you can figure out where it’s been.