Clues gleaned from the most recent infections with the new coronavirus are behind the World Health Organization's decision to warn countries to broaden their surveillance for cases, an expert with the agency says.
The Geneva-based global health body now believes the risk of exposure to the new virus may exist beyond Saudi Arabia and Qatar, so telling countries they need only look for sick people with travel or residency links to those countries may be misleading and counterproductive.
It's not that the WHO has proof of infections from elsewhere. The issue is rather that its disease experts can think of no reason why a virus that has popped up in different parts of Saudi Arabia and in Qatar would be limited to those two countries.
"It's impossible to know at this point because of the limited amount of testing just how widespread this problem is," says Dr. Anthony Mounts, the WHO's technical point person for the outbreak.
"But it just seems inappropriate to continue to focus on two countries in the region when there's really not much that would lead you to suppose that those were the only two countries affected. ... We have to widen the net a little bit to try and find out how big a problem this is."
On Friday the WHO reported that four additional infections with the new virus a cousin of the coronavirus that caused SARS had been found in Saudi Arabia and Qatar. They bring to six the total of confirmed cases since this virus was first spotted in June.
In that time, four cases have been reported by Saudia Arabia. As well, two relatives of two of the Saudi infections are considered probable cases; they all lived in the same household and were sick with similar symptoms at about the same time.
While one of the probable cases tested negative, not even the Saudi government is confident that is a true negative, Mounts says.
To date there is no validated blood test to confirm infection, so diagnosis relies on PCR short for polymerase chain reaction tests that look for pieces of virus in sputum specimens or on swabs poked into nasal cavities. The reliability of testing in such cases depending on when and how well those samples were taken.
"With PCR especially, a negative isn't as revealing as a positive," Mounts says. "With a negative, you just always have to question whether you just didn't get a good enough swab."
The WHO's Friday statement said countries should consider testing people with unexplained pneumonia for the virus, even if the patients don't have links to the two countries.
It also said countries should investigate clusters of severe respiratory infections especially in health-care workers regardless of where they happen in the world. Health-care workers can be sentinels in disease outbreaks because they get exposed by caring for sick people.
The WHO is in the process of further revising its guidance to countries; it may post the new advice on its website as early as today. Mounts suggests the goal is to try to strike an balance between looking hard enough to see what's really going on and not swamping health-care systems.
"We don't want to overburden everybody," he says. "We don't think that it's necessary at this point for every unexplained pneumonia case in the world to be tested for this virus."
There have already been concerns raised that the agency missed the mark with the advice issued Friday.
In a statement posted on its website Monday, the European Centre for Disease Control said testing all patients with unexplained pneumonias would place a heavy burden on hospitals in the European Union.
The ECDC estimated EU hospitals treat about 750,000 patients a year with pneumonias for which a cause is not identified. It said it may come up with more targeted advice on testing for EU countries.
In the meantime, the ECDC said health-care workers should be on the lookout for patients with severe respiratory illnesses who have travelled to or are residents of the Middle East.
Mounts says when the first two infections with this virus were spotted, in June and then September, both men had been in Mecca, Saudia Arabia, before they got sick. As such the chance existed that the source of infection which is currently unknown was only found there.
But the newest infections show that isn't possible. Some of the Saudi cases had not been to Mecca before they got sick. They live in and fell ill in Riyadh, the capital. And the most recent case from Qatar lives in Doha and had not recently travelled outside the country.
With people falling ill in different places, it seems unlikely that the risk of infection exists only in Saudi Arabia and Qatar, WHO experts believe.
As well, two of the more recent cases were not as sick as the first cases, Mounts notes. They were seriously sick they needed mechanical help breathing for a time but they didn't experience the kidney failure seen in the first two cases.
"So that indicates to us that there is a milder form of the disease. It doesn't always involve multi-organ failure and so on," Mounts says.
"But how mild it could be is unknown. And you know, that's basically because where we look for this is in hospitals. And people have not yet started to test milder cases in the area."
Bats have been named as a possible source of the virus, because its genetic sequence is most like that of other coronaviruses that come from bats. Mounts cautions, though, that at this point the evidence is only suggestive.
But even if that's true, it's not clear how the virus got from bats to people and there are a number of possible routes. Bats could pass the virus to other animals, which in turn somehow infect humans. People could come in contact with bat guano, or dust from it, or bat urine.
Another possible source is contaminated fruit, Mounts notes. It's known that in Nipah virus outbreaks in Asia, date palm sap and fruit contaminated with bat saliva have been the source of disease. (In some countries date palms are tapped like maple trees. The sap that flows is a popular drink. But bats like it too.)
Saudi Arabia and Qatar import a lot of food and animals from other countries, both within the region and beyond. Mounts says the WHO is trying to figure out what connections might be important so it can better advise countries on how to remain alert for infected people.
The two cases from Qatar illustrate one possible route by which the virus might move from wherever it is to further afield.
After they fell ill, both Qatari men flew out of the country to Europe for treatment one went to London, the other to Germany. In both cases the European facilities did not know their new patients were infected with the new virus when they admitted them.
Wealthy Middle Easterners often seek care in Europe. That is factored in to the ECDC guidance, which urges hospitals to test patients with acute respiratory infections who are transferring in from the Middle East.
Mounts says the WHO guidance will also instruct hospitals accepting patients like these to take the type of precautions they would take for other respiratory infections to protect their staff and other patients.