A new analysis of MERS case data suggests a large number of infections are going undetected, with the researchers estimating that for each case that has been found, five to 10 may have been missed.
The scientific paper, from European researchers, further suggests that transmission of the MERS virus is occurring at a rate close to the threshold where it would be considered able to pass from person to person in a sustained manner.
In fact, the authors say based on the available evidence they cannot rule out the possibility that person-to-person spread is the main mode of transmission of the virus at this point. The other option, they say, is that the virus is spreading via a combination of animal-to-person and then person-to-person transfer.
"We conclude that a slow growing epidemic is underway, but current epidemiological data do not allow us to determine whether transmission is self-sustaining in man," they write in the article, published Wednesday in the journal Lancet Infectious Diseases.
The scientists are from Imperial College London, the University of Edinburgh and the Institut Pasteur in Paris. The work was done with funding from Britain's Medical Research Council, the Bill and Melinda Gates Foundation and other agencies.
To date there have been roughly 155 confirmed MERS cases and at least 65 of those infections have ended in death. All the cases trace back to infections in a handful of countries on the Arabian Peninsula: Jordan, Saudi Arabia, Qatar, the United Arab Emirates and Oman.
Neil Ferguson, from Imperial College's MRC Centre for Outbreak Analysis and Modelling, said that while publicly available data are spotty, calculations based on what is known support the argument that only a small proportion of cases are coming to light.
"At the very least there probably have been double that number of infections," Ferguson said in an interview.
"But it's considerably more likely in my view that we've had maybe five to 10 times more human infections than that. And symptomatic human infections, I would say."
He stressed that he and his co-authors are not suggesting that the MERS-affected countries are hiding cases, just that the way they are looking for them is not capturing the full scope of the outbreak.
Experts have previously expressed concern that surveillance systems that look only for MERS among people who seek hospital care will only catch the sickest of cases. And in at least one affected country, Saudi Arabia, the criteria for who gets tested for MERS may be less inclusive still.
Dr. Anthony Mounts, the World Health Organization's leading expert on MERS, said the agency has been told Saudi health officials are focusing their testing on people with MERS-like symptoms who are gravely ill.
"I know that their surveillance strategy is focused on intensive care patients," Mounts said in an interview. "That's the focus of their surveillance strategy."
Mounts agrees that many MERS cases are probably being missed. But he noted that some other affected countries are taking a different testing approach. For instance, Qatar has tested over 3,000 specimens over the past six months, looking for MERS in people who seek medical help for influenza-like illness, and all people diagnosed with pneumonia.
"They really are testing a lot of people and they're not seeing this," he said.
Eight Qataris have been diagnosed with MERS since the virus hit the global public health radar in September 2012. As well a man from Tunisia who contracted the virus is believed to have been infected on a visit to Qatar.
Because of the scarcity of publicly available data, Ferguson and his colleagues used some different approaches to try to estimate the state of the outbreak. He acknowledged that their calculations are estimates, and said of the analysis "it's not definitive ... but I still think it's informative at least."
"I would say we're doing the best we can with the data available to try and address a couple of key questions," he said. "We would certainly be in a better position if there was fuller (case) reporting."
A commentary by Canadian epidemiologists lauded the team for the techniques they used to reach their conclusions. Dr. David Fisman and Ashleigh Tuite, who are with the University of Toronto's Dalla Lana Faculty of Public Health, also hinted that the often-seen instinct to withhold information during infectious disease outbreaks may be futile in the era of computational biology.
"The ability to draw inferences about diseases from non-traditional data sources will hopefully both provide alternate means of characterizing epidemics and diminish the temptation towards non-transparency in traditional public health authorities," they wrote.
One of the questions Ferguson and his co-authors tried to answer relates to whether the virus is spreading person to person at this point or whether what is being seen are infections from an animal source that is igniting limited spread in people.
To do that, they tried to calculate what is known as the virus's reproductive number — the number of people, on average, an infected person would pass the virus on to. For a virus to sustain itself in people, each person needs to infect at least one other person, a reproductive number of 1.0 or greater.
They could not come to a definitive conclusion, saying with what is known, either scenario is possible. But they said the evidence suggests the reproductive number is near 1.0.
Mounts said he believes animals — perhaps camels, but possibly others as well — are still playing a role in spreading MERS.
But coronavirus expert Dr. Christian Drosten disagreed, saying if at this point MERS was mainly an animal virus occasionally jumping into people, there would be widespread reports of sick animals.
Studies have found camels in several Middle Eastern countries have antibodies to MERS or a MERS-like virus, but antibodies signal prior, not current, infection.
"Our previous results from dromedaries rather suggest a steady, long-standing presence of the virus in dromedaries, which is not pointing toward an epidemic (in camels)," Drosten said in an email.
"So my interpretation of the situation remains unchanged: we have a human-to-human epidemic ... with limited efficiency of transmission compared to flu, and mild presentation in most or many cases (which is) similar to flu."
Ferguson said that whichever argument is correct, MERS bears watching.
"A virus which is capable of causing a large outbreak, even if it hasn't yet been conclusively demonstrated to be causing a sustained regional epidemic, is something we need to be concerned about," he said.