TORONTO -- Infectious disease watchers were worried in the late summer of 2013. The largest annual mass gathering in the world, the Hajj, was approaching. Meanwhile, infections with the new MERS coronavirus were mounting weekly in Saudi Arabia, where more than two million of the Muslim faithful would soon gather.
The fear was the event would give the new virus wings -- a round-the-world ticket to wherever returning pilgrims might travel. It was easy to imagine MERS taking root in the slums of south Asia or Africa, fuelling outbreaks in overcrowded hospitals in some of the world's mega-cities. In other words, becoming the next SARS.
It didn't happen.
In fact, when experts studying this disease reflect on MERS in 2013 and prognosticate on how the disease's story will play out in 2014, the non-event of the Hajj is a source of marvel -- and relief.
"Probably the biggest surprise in 2013 for me is that the epidemic didn't come from the Northwestern Hemisphere," says Dr. Christian Drosten, a coronavirus expert who runs the University of Bonn's institute of virology.
"I'm really very surprised that it has not left the region."
In fact, the virus has made a few faltering forays beyond the Arabian Peninsula, where all known chains of transmission started and all individual cases occurred.
A few infected people from the region have been transported by air ambulance to hospitals in Europe. A French tourist brought the virus home from the United Arab Emirates. A Tunisian man returning from Qatar infected two of his children. And yes, two residents of Spain who attended the Hajj caught the virus, though it's not clear if they were infected during the pilgrimage.
But the lack of any real post-Hajj outbreaks and the passage of time have lowered alarm levels on MERS, a number of the experts who have been heavily involved in researching the new disease acknowledge.
"I have really the growing feeling that it's not very contagious," says Drosten, whose personal level of concern was considerably higher earlier in 2013.
The World Health Organization's top MERS expert, Dr. Anthony Mounts, also admits to a lessening of tensions about the virus.
"Time has shown us that it's not an explosive outbreak that's going to spread from person to person outside of the region in an explosive way," Mounts says.
"I can't say 'Never,' but it hasn't so far. It hasn't shown that potential. So unless something changes with its behaviour, I think it's going to continue to be a concern and a problem, but it's certainly proving it doesn't have the same capacity as SARS did to transmit."
Still, coronaviruses mutate. And there is no way to know if the virus will continue to behave the way it has, with cases emerging in a steady trickle, or if it will change and become more easily spread from one infected person to the next.
And even if it does not change, the virus could still wreck significant havoc, Mounts suggests. All it would take is for one of the many "guest workers" who toil as nurses or nannies or construction labourers in the Middle East to get infected and bring the virus home to Bangladesh or Pakistan or the Philippines. An undetected case in a crowded hospital in Karachi or New Delhi could take off.
"This virus, even the way it's behaving now, without any mutation or any change at all, could easily cause some very large outbreaks in that type of setting," he says.
With that in mind, the people studying the virus are keen for more answers to the myriad questions that remain about the virus behind Middle East Respiratory Syndrome.
The working hypothesis is that it's a bat virus; that was strengthened in 2013 by the discovery of a small RNA fragment from a bat that was a perfect match for the human virus. But how are people contracting a bat virus?
A cascade of studies in 2013 showed camels have some role in the MERS story, with many carrying antibodies -- a sign they were previously infected. A recent study found virus fragments -- current infection -- in camels on a farm in Qatar where two infected people lived. And last week Drosten and colleagues reported the puzzling finding that MERS or a very similar virus was infecting camels in the United Arab Emirates at least 10 years ago.
But do camels infect people? Do people infect camels? If camels were infected in 2003, why did human cases only start to be noticed in 2012? Can camels be infected multiple times? Is there some other unidentified animal in the chain of transmission? These are the questions Marion Koopmans would like answered.
Koopmans is a virologist with the Dutch National Institute of Public Health and Erasmus Medical Centre in Rotterdam; she has had a major role in MERS research done to date.
"What happened in the camels between 2003 and 2011?" she offers when asked what is the key question she'd like answered in 2014.
"I would want to really see that one. Because it's really the root of the problem. And I think a lot can be derived from that."
Koopmans would also like to see how far afield the virus can be found by looking for antibodies in camels outside the countries where the diseases is currently known to exist.
Dr. Frederick Hayden, a respiratory disease expert at the University of Virginia, hopes a clearer picture will come into focus in 2014 of what MERS does to the body during infection.
Despite the fact there have been at least 177 cases -- and 74 of those people have been killed by the virus -- there have been few detailed reports showing what it does to lungs, kidneys and other organ systems. And to date there have been no published autopsies, which would provide a wealth of this kind of information.
Knowing what the virus does is crucial to figuring out what doctors treating MERS patients should use in their care, explains Hayden, who is chairman of the International Severe Acute Respiratory and Emerging Infection Consortium.
The group, which goes by the acronym ISARIC, co-hosted a meeting late last year with doctors who have treated MERS patients. The goal: to try to co-ordinate data collection on cases, so that a common set of facts about infected people could be studied for clues. As well, the group hopes to foster co-operation and data sharing among affected countries.
"I would say that there was real enthusiasm to try to work together," Hayden says. "(But) the whole issue of data sharing ... across borders is a fraught issue that has not been resolved, certainly, within the region."
Autopsies are not common among Muslims; in fact, they are becoming rarer in general. Hayden hopes there may be a work-around.
"One approach that might be acceptable would be a so-called post-mortem biopsy, where you're just getting limited tissue from key sites, like the lung."
"You need those things" -- tissues and detailed reports of disease progression in cases -- "to really inform therapeutic interventions," he says.
In 2013 there were repeated calls for a case control study to be done. This type of study compares people who contract an infection with similar people who have not, to try to zero in on what exposure led to disease transmission.
Mounts is hopeful a multinational case control study will take place in 2014. A meeting of MERS-affected countries in Cairo late in 2013 led to agreement to proceed with the study.
He also thinks a large study Qatar has undertaken, testing the people and animals on the farm where the infected camels were discovered, will be very informative. Mounts acknowledges, though, that it will take time to generate and analyze those findings.

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