Wednesday, May 07, 2014

The explosion in cases of Middle East coronavirus (MERS) in recent weeks raises a simple question: Why? Or more precisely, why now?

After ticking along for nearly 2 years with about 15 cases of the respiratory disease a month, the number of cases started to climb dramatically in late March and early April.

More than 250 cases have been reported by the Kingdom of Saudi Arabia since March 22 -- more than half of the 421 cases reported to date by the Middle East nation.

Saudi Arabia is the center of the outbreak; depending on whose numbers are used, there are about 500 cases reported globally with at least some level of confirmation. But only Saudi Arabia has more than 50 cases, and most other countries have only a handful.

The recent jump was "certainly unexpected on my part," says Daniel Lucey, MD, an infectious diseases specialist at Georgetown University Medical Center in Washington, D.C.

Lucey, who joined the battle against the SARS coronavirus more than a decade ago, has been following MERS closely and has visited the Middle East several times during the outbreak.

He, like other experts, is highly conscious of the risk that the virus could go global and very aware of several important gaps in scientific understanding of MERS.


What Do We Know?

Much is known, of course. The virus is a distant cousin of the SARS coronavirus. Its genes have been sequenced and tests for infection created. It is not really efficiently transmitted from person to person.

But much is also unknown. There is, for instance, no specific treatment or vaccine. And the natural history of the disease remains unclear. In the early months of the outbreak, the virus had a very high case-fatality rate and it is still hovering around 30%, despite an increased number of confirmed cases without symptoms.

Among the open questions:

  • Do asymptomatic people whose infection is only detected by sensitive tests remain without symptoms? Or do some go on to have disease? If so, how many?
  • Are asymptomatic people infectious? Or does contagion require respiratory symptoms to get MERS virus into the surrounding environment?
  • How is transmission occurring -- droplet and airborne infection alone, or can surfaces serve as transmission routes?
  • What's the original source of the infection? And what's the route from the original host to humans?

The answers will undoubtedly become known over time. But for now, the key question -- which bears on many of the others -- remains: Why are we seeing such a dramatic explosion of cases?

There are "a couple" of possible explanations for the recent explosion in cases but none of them is definitive and it's likely none stands alone, Lucey said.

RELATED: 1st MERS Patient Improving, Officials Say

Why the Uptick?

The first thing that jumps to mind is that the virus has changed, mutated so that it transmits more efficiently. But recent work by German virologist Christian Drosten, MD, of the University of Bonn Medical Centre seems to show that's not the case.

Drosten and colleagues sequenced virus isolated from some of the cases early in the recent surge and found the genes were almost identical to those seen earlier in the outbreak.

In particular, the gene for the part of the so-called spike protein that binds to human cells was unchanged. Indeed, Drosten told Science magazine: "You really have to look quite hard to find any changes at all."

Lucey told MedPage Today that work suggests the virus hasn't mutated, but doesn't rule such changes out.

"It's preliminary in my view," he said. "It's possible that the part of the virus they sequenced is not the part that has mutated."

It's also possible that the virus has a seasonal variation, much like influenza, Lucey said, although less marked.

Indeed, the earliest cases, discovered retrospectively after the virus was recognized in September 2012, occurred in April of that year. And last year, there was also a spike in cases in April.

Finally, there's increased testing. Until recently, Saudi Arabia and other countries in the region tested only people who came in with unexplained respiratory illness, following the World Health Organization's case definition.

Now they are testing contacts of confirmed cases, which might expand the number of people with confirmed -- but asymptomatic -- infection. Indeed, over the recent weeks Saudi Arabia's status reports have routinely included one or two cases a day without symptoms.

"There are a lot more people being tested," Lucey says, "so I think that's true."

But they would not be tested if there were not an underlying groundswell of confirmed cases, he says, so that increased testing is just part of the explanation.

Parenthetically, the increased testing, which is often followed by hospital admission and isolation, is imposing an immense burden on hospitals in Jeddah, the center of a large cluster of cases, Drosten said.

RELATED: What Happened to SARS?

The Healthcare Connection

Also puzzling is that the April clusters have tended to have their basis in hospitals among healthcare workers. In the earliest cases, that was natural -- healthcare workers didn't know what they were dealing with and several were infected.

Since then, though, the protocols for dealing with possible MERS cases have been clear -- full barrier precautions, isolation, the whole nine yards.

"There is no more important question in my view" than why healthcare workers are getting infected, Lucey said. In his trips to the region, he said, he has been impressed by how knowledgeable healthcare workers there are about infection control.

"And now we have this striking and concerning increase in the number of healthcare workers affected," he said.

Indeed, the single American so far affected by MERS was a healthcare worker in his 60s who had been working in Riyadh, the capital of Saudi Arabia.

Lucey said either personnel are not adhering strictly enough to infection control guidelines or the virus is finding a way around them. Either scenario is a worry.

But again, he asked, "why only now?"

If there's a bright spot, it's that the virus has affected only a relative handful of people -- perhaps 500 cases in a region with a population of 40 or 50 million -- and it doesn't seem to spread very efficiently.

While there has been some human-to-human transmission, there is no documented case of a longer chain, according to William Schaffner, MD, of Vanderbilt University in Nashville.


"The risk of acquiring MERS is much, much lower than the risk of acquiring influenza," he told MedPage Today. "There has not yet been documented person-to-person-to-person transmission."

Without some connection to the Middle East, he said, an individual's risk of catching MERS is "little."

At the moment, it's true that the risk is "very, very low," Lucey said. But that could change quickly and there is currently no treatment and no vaccine.

"We have to remain vigilant," he said. "This is a potentially very serious new international infectious disease."

But so far, he argued, "there's no cause for panic or excessive fear."