Annette M. Boyle
SILVER SPRING, MD – While no cases of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in the United States or among U.S. servicemembers, DoD is taking no chances on missing any cases – and can take credit for identifying the earliest known patients.
MERS, a viral respiratory illness first reported in Saudi Arabia in 2012, is caused by a coronavirus called MERS-CoV. Characterized by severe acute respiratory illness in most cases, about half of the victims have died, according to the Centers for Disease Control and Prevention (CDC) in Atlanta.
In the strictest guidelines established thus far, the Armed Forces Health Surveillance Center (AFHSC) recommends that any patient who meets the following criteria should be evaluated for MERS-CoV infection:
- Acute respiratory infection, which may include fever above 38oC or 100.4 F and cough, and
- History of travel to the Arabian Peninsula or neighboring countries within 14 days before onset of illness, and
- Symptoms not already explained by any other infection or etiology.
CDC takes a less stringent screening approach and recommends testing for MERS-CoV only in patients who meet the three DoD requirements and have evidence of pneumonia or Acute Respiratory Distress Syndrome (ARDS). WHO revised its case definition in early July to include cases without evidence of pulmonary parenchymal disease, but only if a direct epidemiologic link with a confirmed case of MERS-CoV exists.1
“We have established more aggressive guidelines, though the CDC and WHO are moving closer to our recommendations. Our population is usually younger and healthier, and we’re looking for sentinels that may tell us what’s happening in civilian populations as well,” said Rohit Chitale, MPH, PhD, director, division of integrated biosurveillance, AFHSC.
Globally, 82 laboratory-confirmed cases of MERS-CoV in eight countries have been reported to the World Health Organization since September 2012. Of those, 45 patients have died.
“We look at sources across the world – WHO, Institut Pasteur, the European CDC, CDC, provincial data and others — to monitor outside U.S. forces and inside forces. The DoD lives in a civilian world and we support our civilian partners,” Chitale told U.S. Medicine.
Identifying First Cases
That support and cooperation with civilian agencies resulted in the identification of the first known cases of MERS-CoV, according to Public Health Service Capt. Michael J. Cooper, PhD, head of respiratory disease for AFHSC’s Global Emerging Infections Surveillance and Response Systems.
The Naval Medical Research Unit-3 (NAMRU-3) in Cairo, working with Jordan’s National Influenza Center, came across 12 Severe Acute Respiratory Syndrome (SARS)-like cases in April 2012.
“They took samples but didn’t know what they were seeing,” Cooper explained. “Then cases in England and Saudi Arabia appeared in November 2012. When the lab went back and sequenced the earlier samples, they found two cases of MERS.”
Cooper noted that, in the early stages of disease identification, success depends on many organizations working together.
“Obviously, there was no ready-made test for this emerging pathogen. Jordan’s influenza center flagged the cases, NAMRU-3 had samples of the virus and CDC created the test,” he said.
With a better sense of the disease’s progression and testing available, GEIS is in constant contact with seven overseas Army and Navy labs, geographic combatant commands and surgeon offices in all commands to disseminate case definitions and how to enhance survival in affected patients.
“We’ve had a respiratory disease surveillance infrastructure in place for 15 years,” said Cooper. “We’ve just tweaked it to provide the additional information and resources clinicians need.”
“We’re fielding a lot of questions about getting testing kits, sending samples, finding a laboratory,” Chitale added.
Currently, clinical diagnostic and surveillance testing can be done at the LRMC Infectious Disease Laboratory, Landstuhl, Germany; Wright-Patterson AFB, OH; Naval Health Research Center, San Diego; and NAMRU-3, Cairo. Four other laboratories can conduct surveillance testing: Army Medical Research Unit, Nairobi, Kenya; Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; NAMRU-2, Phnom Penh, Cambodia; and NAMRU-6, Lima, Peru.
To limit spread of disease, AFHSC recommends that cases of MERS-CoV infection be reported within four hours of confirmation to a service-specific public health chain of command and that AFHSC get the report as an “outbreak or disease cluster.”Healthcare Acquired
A recent article in the New England Journal of Medicine drives home the importance of prompt reporting and response to limit spread of the disease, particularly in a hospital setting. Johns Hopkins researchers found that, in an outbreak this spring in Saudi Arabia, 21 of the 23 cases acquired MERS-CoV through person-to-person transmission in four healthcare facilities. Fifteen of the 23 total cases died, a 65% fatality rate.2
According to the researchers, “person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.”
Early testing of suspected cases has shown significant benefit. The survival rate of patients identified by active surveillance during the outbreak was much higher (75%) than the survival rate of those identified clinically (16%), likely because “enhanced surveillance was more effective at detecting less severe disease than was identification of clinical features,” the authors wrote.
Clinical testing poses challenges, however. Validated serologic assays are not yet available, and throat swabs among patients in this cluster were occasionally negative.
“It is not clear whether sputum or nasopharyngeal samples might be superior to throat samples or whether virus is shed more abundantly later in the course of the illness or in more severe illness,” as it is in severe acute respiratory syndrome (SARS), according to the NEJM report.
AFHSC and WHO strongly recommend obtaining lower respiratory specimens for testing. If lower track specimens are not available or clinically indicated, clinicians should obtain both nasopharyngeal and oropharyngeal swab specimens. If patients strongly suspected to have MERS-CoV have an initial negative result, they should be retested.
The researchers noted that MERS-CoV had many similarities to SARS, including initial symptoms of nonspecific fever and mild, nonproductive cough that progresses to pneumonia and gastrointestinal symptoms in some patients. As with SARS, some MERS-CoV infected patients do not appear to transmit the disease at all, and some seem to be highly contagious.
The median incubation period for SARS is about four days with a serial interval of 8.4 days; for MERS-CoV, the researchers estimated median incubation of 5.2 days and a serial interval of 7.6 days.
MERS-CoV has a much higher fatality rate, however, at 55%, compared with an 8% to 10% fatality rate for SARS. So far, MERS-CoV has not had the rapid spread seen with SARS, which infected more than 8,000 people in nine months.
French researchers recently published a study in Lancet that concluded that MERS-CoV is unlikely to have pandemic potential, partly because it is so lethal.3
1. “Revised interim case definition for reporting to WHO — Middle East respiratory syndrome-coronovirus.” Global Alert and Response (GAR). WHO. July 3, 2013.
2. Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 2013. Epub June 19, 2013.
3. Breban R, Riou J, Fontanet A. “Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk.” The Lancet. Epub ahead of print. July 5, 2013.
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