Health officials keep close watch over MERS as potential pandemic

It has been more than 1 year since the first case of the Middle East respiratory syndrome, or MERS, coronavirus was reported in Saudi Arabia. As of Aug. 27, there have been 104 reported cases, including 49 deaths, since September 2012, according to the CDC.

Although the incidence of new cases appears to have leveled off for now, and most cases have been confined to the Arabian Peninsula, a perfect storm of events is brewing that could potentially lead to the spread of the disease globally.

“There are a number of reasons to be concerned, but not necessarily alarmed,” Martin Cetron, MD, director of the Division of Global Migration and Quarantine at the CDC, told Infectious Disease News. “We do have a novel coronavirus that causes dramatic respiratory infections and has a high case-fatality rate. The good news is that MERS doesn’t seem to be easily transmitted from person to person, and we’re not seeing a high reproductive rate like we typically see with the influenza virus. However, coronaviruses are highly mutable, and as a consequence, we need to be able to anticipate that this could become very transmissible.”

In July, WHO convened an International Health Regulations Emergency Committee to evaluate the threat of MERS. Although the committee did not declare MERS a public health emergency of international concern at the time, it will continue to monitor the situation.

Martin Cetron, MD, said that MERS is not yet cause for alarm; however, coronaviruses are highly mutable so it is necessary to prepare for potential widespread transmission.

Martin Cetron, MD, said that
MERS is not yet cause for alarm;
however, coronaviruses are highly
mutable so it is necessary to
prepare for potential widespread
transmission.

Photo courtesy of Cetron M

“The committee said that the situation is serious and requires close monitoring,” Keiji Fukuda, MD, MPH, WHO assistant director-general, said during a press conference. “They highlighted several countries that WHO should pay attention to, taking steps to strengthen the preparation in those countries.”

Infectious Disease News spoke with several experts to discuss MERS, why it is so concerning, and what is being done globally to prepare for a potential pandemic.

Comparison to SARS

The last coronavirus that plagued the world was the severe acute respiratory syndrome (SARS) coronavirus, which resulted in approximately 8,000 cases and 800 deaths, Cetron said. Both MERS and SARS have a similar clinical presentation as acute respiratory distress syndrome and often cause organ failure.

Although not identical, the two share some genetic similarities as both are animal-derived coronaviruses and are highly mutable, able to change their genome, their symptom profile, target organs and route of transmission. However, SARS was more communicable — there were several generations of spread compared with what has been seen so far with MERS, Cetron said, in which there has not been significant person-to-person spread outside of health care workers and close family. SARS and MERS seem to have similar incubation periods, but SARS appears to have spread around the globe more efficiently from the time of its detected emergence in humans.

“SARS was much more explosive in terms of quick international spread from the epicenter in China to many different places,” Kamran Khan, MD, MPH, scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute, and associate professor in the division of infectious diseases at the University of Toronto, told Infectious Disease News. “MERS has been around now since at least April 2012, and there has been limited international spread that we’re aware of. The cases outside of the Arabian Peninsula have all been linked to travel within the peninsula.”

Of the 103 cases, 82 were in Saudi Arabia, six were in the United Arab Emirates, two were in Jordan and three were in Qatar. The remaining 10 cases were among travelers from the United Kingdom, Italy, France and Tunisia.

According to Khan, MERS appears to be more virulent and cause more severe disease among individuals who are older and have underlying comorbidities. However, only a small number of children aged 7 to 15 years have been affected by the virus. The same was true for SARS, according to a 2007 CDC report published in the Pediatric Infectious Disease Journal.

“There have been a small number of pediatric cases who were close contacts of the documented cases, but the majority had mild disease or were asymptomatic,” Roberta DeBiasi, MD, division chief of infectious diseases at Children’s National Medical Center in Washington, D.C., said in an interview. “A 16-year-old boy was hospitalized with more severe disease, but recovered. With any new virus, it’s impossible to predict what will happen. It could be a concern for pediatrics, but we don’t know yet. In the big picture, so far, it has primarily affected adults, and the kids who were affected so far had a lower severity of illness. But this is based on very small numbers.”

Unknown virus origin

Currently, it is unknown where the MERS virus originated, which is a concern because it hinders the ability of health officials to prevent its dissemination, Khan said.

Most recently, researchers from the Saudi Arabia Ministry of Health reported in Emerging Infectious Diseases that they found one bat with a coronavirus that was 100% identical to the MERS coronavirus found in the human index patient. The researchers collected samples from bats that were within 12 km of the home of the index patient. Among the 96 bats tested, there were several coronaviruses circulating, but MERS coronavirus was found in only one.

Other researchers have identified camels in the Middle East that had antibodies against the MERS coronavirus, suggesting that they may be a reservoir of the virus, according to a report in The Lancet Infectious Diseases. The antibodies were found in 50 serum samples taken from dromedary camels throughout Oman, and also from samples taken from two herds of dromedary camels in the Canary Islands.

In an accompanying editorial, 
Emmie de Wit, PhD, and Vincent Munster, PhD, both with the National Institute of Allergy and Infectious Diseases, said these data provide some insight into a potential animal reservoir for this virus, the first since its discovery 1 year ago.

Roberta DeBiasi

Roberta DeBiasi

“In the absence of prophylactic or therapeutic treatment options for MERS coronavirus, blocking zoonotic and human-to-human transmission could be the most promising and cost-effective method to prevent further human fatalities,” they wrote. “However, doing so requires knowledge of the virus’ hosts. Although this study … leaves many questions unanswered, it is an important step to a more comprehensive understanding of the emergence of MERS coronavirus.”

Infectious Disease News Editorial Board member Paul A. Volberding, MD, said this study supports the One Health movement to always consider infectious disease relationships between humans and animals, including domestic ones.

Transmission in health care settings

Researchers from Saudi Arabia have documented person-to-person transmission of MERS coronavirus in health care settings, according to findings in a report in The New England Journal of Medicine.

In September 2012, the Ministry of Health in Saudi Arabia requested that patients admitted to the ICU with pneumonia be tested for MERS coronavirus. From April 1 to May 23, 2013, there were 23 confirmed cases of MERS coronavirus. All of these cases and 11 probable cases were part of one outbreak among four health care facilities. Twenty-one of the cases were linked to person-to-person transmission that took place in hemodialysis units, ICUs or inpatient units.

According to DeBiasi, the researchers also looked at 217 household contacts of the cases, including 120 adults and 97 children. Among this group, five people also developed MERS infection, but none of them were children.

“The message from this report is that even among people with early exposure to a patient with MERS, the rate of transmission seems relatively low, and it’s primarily in adults so far,” she said.

Cetron said during the SARS epidemic, there were super-spreading events in health care settings. For example, people may have received breathing treatments that could spread the virus quickly and farther through the air.

“Good infection control measures should be able to prevent secondary spread to patients,” Cetron said. “This is very important. I can’t emphasize enough that in the health care setting, all practitioners need to be aware of and practice good infection control.”

Although MERS has not been identified in the United States, many are taking precautions based on what they learned during the SARS epidemic. According to Thomas Talbot, MD, MPH, associate professor of medicine and chief hospital epidemiologist at Vanderbilt University Medical Center, MERS is an issue that many, if not all, hospital epidemiologists are keeping a close watch on.

“We have implemented guidelines for providers to carefully investigate patients who arrive with severe respiratory disease, to make sure that they have not recently traveled to concerning areas like the Arabian Peninsula,” Talbot told Infectious Disease News. “It is OK if individuals raise the concern, and it turns out to be a false alarm. If someone comes in with MERS, and we expose health care workers and other patients to the virus, it could be a serious event.”

Upcoming gathering

According to the CDC, the annual Hajj pilgrimage to Mecca, Saudi Arabia, which takes place in October this year, draws nearly 3 million Muslims from around the world, including approximately 11,000 Americans. A similar pilgrimage, Umrah, takes place at any time of the year, but is especially crowded during the month of Ramadan, which just ended.

The spread of respiratory diseases is inevitable at large gatherings such as the Hajj and Umrah. This year is no different, but there is heightened concern about the potential spread of MERS.

“It’s really anybody’s guess if we’re going to see a spike in cases in association with the Hajj,” Khan said. “With pilgrims coming in from around the Kingdom of Saudi Arabia, foreign pilgrims could conceivably acquire infections and take them back home. It’s possible, but no one really knows at this point in time how likely that scenario is, and to what extent it might take place.”

In a study published in PLOS Currents: Outbreaks, Khan and colleagues evaluated 2012 worldwide flight data and historical Hajj data to predict movement through the Middle East, to help countries assess their risk for MERS importation. From June to November 2012, 16.8 million travelers departed on commercial flights from Saudi Arabia, Jordan, Qatar and United Arab Emirates, of which 51.6% were heading to India, Egypt, Pakistan, the United Kingdom, Kuwait, Bangladesh, Iran and Bahrain.

Travel concerns

According to Khan, Saudi Arabia has discussed decreasing the number of domestic pilgrims who perform the Hajj, by as much as 50%. Close to 1.5 million pilgrims from Saudi Arabia perform the Hajj each year.

In the United States, Hajj is on the radar of many travel medicine specialists, but neither the CDC nor WHO has implemented any travel restrictions. CDC has recommended that travelers to the Arabian Peninsula pay attention to their health during and after their trips and see a health care provider if they develop symptoms of a respiratory infection.

According to the CDC, the Saudi Arabia Ministry of Health has made recommendations for travelers to Hajj and Umrah. The following groups are advised to postpone their pilgrimage: adults older than 65 years; children younger than 12 years; pregnant women; those with chronic diseases, including diabetes, heart disease, kidney disease and respiratory disease; those with weakened immune systems; and those with cancer or terminal illness.

Aside from these groups, there are no official travel recommendations or restrictions. For many patients traveling, MERS is not currently a cause for concern.

“I see a lot of global medicine patients, but have not yet had any who are concerned about MERS,” Stephen Gluckman, MD, professor of medicine at the Hospital of the University of Pennsylvania, told Infectious Disease News. “There is mostly a theoretical concern among my travel medicine colleagues. It is contagious and has the potential to cause a significant outbreak. In addition, of the diagnosed cases, it has a very high mortality. ”

With many diseases, Gluckman said, the most severe cases are identified first, and it may turn out that there are many more people who have mild or subclinical disease.

“If someone comes to me and they’re interested in a trip to the Arabian Peninsula, I would ask ‘why now?’” Gluckman said. “If it’s a necessary trip that can’t be postponed, the best thing I can tell them is to wash their hands. The advice would be the same for preventing influenza.”

Potential directions

Fukuda said during the press conference that a lot is unknown about MERS. It is unclear what has caused the sporadic cases not linked to person-to-person contact. Possibilities include an animal reservoir or a contaminated environment. Another key piece of missing information is whether there are people with mild infections and no symptoms.

However, some of the features of the virus are relatively clear, Fukuda said. For example, most infections are occurring in older people, particularly men, and among those with comorbidities. Sporadic infections in the community have been reported, and there has been limited person-to-person transmission, primarily in families and in health care facilities.

Khan said there are three potential scenarios that could play out regarding MERS. First, the virus could fizzle out and disappear. The second scenario is what clinicians are seeing now: The disease simply just trickles along.

“MERS has not been growing by leaps and bounds, but rather it’s just simmering in the background,” Khan said. “There are new cases, but there hasn’t been a large spike in terms of major regional or international epidemics.”

The third scenario is that it becomes much more evolved and amplified within the Middle East, perhaps in association with Hajj and Umrah, and then it spreads internationally. If this happens, Khan said it will likely be to mostly low- or lower-middle income countries. According to the PLOS Currents: Outbreaks paper, 65.1% of the 1.74 million foreign pilgrims who performed Hajj last year originated from low- and lower-middle income countries. Khan also said South Asia is an important area to watch after Hajj, as well as Indonesia, as it is the world’s largest, most populated Muslim country. In addition, Khan said 25% of the travelers leaving from the Middle East goes to India, Pakistan and Bangladesh, which are low- and lower-middle income countries.

US on alert

Although CDC always works to raise awareness of travel health among all travelers, it is especially emphasizing that travelers to Saudi Arabia practice basic protection measures, including covering a cough, proper hand hygiene, not traveling if sick and not being around those who are sick, Cetron said.

Health care professionals also must be sure to ask patients with respiratory illnesses about their travel history. If they have recent travel to the Arabian Peninsula, or close contact with a recent traveler, testing for MERS is prudent. Cetron also said health care workers must be aware that lower respiratory tract specimens are much more likely to be positive for MERS than upper respiratory tract specimens.

DeBiasi and Gluckman said the disease should especially be on the radars of physicians practicing in metropolitan areas, where there are large international populations and direct flights to the Arabian Peninsula.

CDC has guidance for health care providers and encourages them to be aware of MERS. Cetron reiterated the importance of infection control practices and making sure that health care workers take proper precautions to prevent air and contact spread. Talbot said many hospitals are taking this potential threat seriously.

“There is increasing awareness of the clusters related to health care that are raising red flags similar to what we saw with SARS,” Talbot said. “This is something that my colleagues and I are taking very seriously. We hope that we won’t need to do anything, but we are prepared.” – by Emily Shafer

References:

Assiri A. N Engl J Med. 2013;369:407-416.
de Wit E. Lancet Infect Dis. 2013;doi:10.1016/S1473-3099(13)70193-2.
Khan K. PLoS Curr. 2013;doi:10.1371/currents.outbreaks.a7b70897ac2fa4f79b59f90d24c860b8.
Reusken C. Lancet Infect Dis. 2013;doi:10.1016/S1473-3099(13)70164-6.
Stockman L. Pediatr Infect Dis J. 2007;26:68-74.

For more information:

Martin Cetron, MD, can be reached at mcetron@cdc.gov.
Roberta DeBiasi, MD, can be reached at rdebiasi@childrensnational.org.
Stephen Gluckman, MD, can be reached at Stephen.gluckman@uphs.upenn.edu.
Kamran Khan, MD, MPH, can be reached via the website for Bio.Diaspora at www.biodiaspora.com/contact.html.
Thomas Talbot, MD, can be reached at tom.talbot@vanderbilt.edu.

Disclosure: Khan is the founder of Bio.Diaspora, a social benefit corporation confronting issues of globalization and infectious disease risk. Cetron, DeBiasi, Gluckman and Talbot report no relevant financial disclosures.

Is there any benefit to exit screening for MERS at airports in Saudi Arabia?

POINT

In theory, it’s an excellent tool, but it has a lot of challenges.

That’s a tricky question. How do you screen? Do you screen for fever? Cough? Fever and cough? It is something that has been tried before, and there are machines that try to screen large numbers of people who are passing through airports for fever or elevated body temperature. I don’t know how effective they are. If you’re screening for cough or other respiratory symptoms, there will be many people who have a simple cold or maybe influenza. What do you do with these people when you identify them? Do you quarantine them? And who’s going to pay for that? There would be hundreds of thousands of travelers stuck in Saudi Arabia, and the government would have to decide to quarantine for a specific time and who’s being isolated. If you screen people when they’re in the local home airport, coming into the country, what do you if you start recognizing or identifying lots of people who are positive? Screening, theoretically, would be an excellent tool, but the actual implementation has a lot of challenges.

David Hamer

This year, I would advise people wanting to travel to Saudi Arabia, for Hajj or other reasons, to defer their trip until the outbreak is better clarified and we have a better feel for what the risk factors are. With the Hajj, millions of people are crammed into very small spaces and the risk for transmission of respiratory pathogens is greatly increased. The second piece of advice is to limit exposure to crowds, which is somewhat impossible during the Hajj, or especially exposure in areas that are poorly ventilated. In outdoor areas, maintain space between you and other people and avoid people who are coughing and sneezing. Good hand hygiene after touching local surfaces, in case the virus can be spread by droplets onto a surface and then spread by touching your membranes, will also help to reduce the risk of transmission. The last step is more theoretical, and has little data, but one possibility is to counsel people to wear a light mask over the face, like the Chinese did during the SARS outbreak. These masks are not perfect, but they may help prevent respiratory droplet-type virus transmission.

David Hamer, MD, is a professor at Boston University Schools of Public Health and Medicine. He is also director of the Travel Medicine Clinic at Boston Medical Center. Disclosure: Hamer reports no relevant financial disclosures.

COUNTER

There is no proven benefit to exit screening in outbreak settings.

Exit screening has never been shown to be of any benefit. We’ve had the experience with SARS in 2003, and also with H5N1 and swine flu. There is considerable literature out that says that there is no benefit. First of all, many people with the disease may be missed, even if they have the perfect screening tools. People may be in the incubation phase, which we know is about 5 days, on average, for MERS. People may not be sick at all, but are still carriers. When this was studied, of all the people that were taken from the line because they had fever, the yield of finding that someone had SARS or something similar is so low that it is almost immeasurable. In Singapore, during SARS, they pulled hundreds of people from line for a complete medical investigation and I don’t think they were attribute more than one case to SARS. It’s really not shown to be an effective technique. On the other hand, de facto screening is already in place by all international airlines. In general, airlines do not let very obviously sick or feverish people on the plane. It’s not just a matter of the airport authorities. Flight crew members and airport ticket agents are trained to identify people who are ill. The chances of the sickest and most contagious ending up on the flight are small.

David O. Freedman

There are no travel restrictions right now. The most serious thing right now is that we don’t know where it’s coming from. We are telling travelers to the Middle East to avoid close contact with animals and with sick people, but not restrict their activities in any way. One of the most obvious ways that MERS spreads is through health care settings. If people are hospitalized in the Middle East, they should make every effort to stay away from those with respiratory illness. I’m not in favor of any travel restrictions right now. There is guidance in place for the Hajj. The Saudi Arabian government is discouraging people who have underlying medical illness from traveling for the Hajj. Most of the people who have had MERS so far have been older people, with an average age of 60 years, who have some type of underlying disease. There may be younger people who have acquired the disease, but are not symptomatic. The risk seems to be highest in Saudi Arabia, and there have been a few cases in Jordan and United Arab Emirates. The CDC lists the risk countries as all of the countries on the Arabian peninsula.

David O. Freedman, MD, is a professor of medicine and epidemiology at the University of Alabama at Birmingham. He is also director of the UAB Travelers Health Clinic. Disclosure: Freedman reports no relevant financial disclosures.