In March 2011, a small research aircraft took off from Japan, and flew into winds blowing in from northeast China. It carried a set of special filters, designed to strain small particles from the air. Among these particles, hopefully, would be the culprit behind Kawasaki disease—an illness whose cause has eluded detection for decades and could, quite literally, be blowing in the wind.
Kawasaki disease was first described by Japanese paediatrician Tomisaku Kawasaki in 1967. It largely affects children under the age of 5. Blood vessels throughout a child’s body become inflamed, leading to a weird constellation of symptoms including swollen hands and feet, red lips, strawberry tongue, irritated eyes, and rashes. If the inflammation affects the arteries of the heart, it can lead to fatal aneurysms. Around one percent of children with Kawasaki disease die from heart problems.
But almost 50 years after its discovery, no one knows what causes the disease. It has all the hallmarks of an autoimmune condition, where the immune system turns on the rest of the body, after overreacting to some trigger. But what’s the trigger? A fungus? A bacterium? A virus? Seasoned scientists have thrown state-of-the-art techniques at the problem and failed to find a culprit. They have, however, found important clues.
The trigger is probably something that you can inhale, since it first affects the airways before causing symptoms elsewhere in the body. It’s probably something seasonal, since Kawasaki cases peak twice a year—once in January and again in June and July. And it might be carried on gusts of wind.
in 2011, a team led by climatologist Xavier Rodó from the Catalan Institute of Climate Sciences compared records of Kawasaki disease against climate patterns, and found that cases in Japan spike whenever strong winds blow from central Asia. If the winds are strong enough to reach Hawaii and California, the disease appears there too.
It was an astonishing result. If true, it would mean that Kawasaki disease is a wind-borne, ocean-spanning illness, caused by something that cross thousands of miles on wisps of air rather than human vehicles. (Jennifer Frazer explores the story of this discovery in her excellent Nature feature.)
Now, Rodó’s team is back with lots of new evidence to support their wind hypothesis. For example, they found that the number of Kawasaki cases in Tokyo and Yokohama— two Japanese cities 28 kilometres apart—were perfectly synchronised during recent epidemics. The disease hit its peak in both cities, on exactly the same days. That’s the pattern you’d expect if something was blowing into Japan and quickly hitting different parts of the nation at once, rather than slowly spreading within it.
Where is this mysterious agent coming from? To find out, Rodó’s team looked at records of KD in Japan between 1970 and 2010. For every time and place with a spike of cases, the team backtracked the path of local winds using software that maps the spread of atmospheric particles. The results consistently pointed to an area of north-east China, on the border with Russia and Mongolia. That’s the source. The area is rife with farmland, and crops like rice, corn and wheat. Maybe Kawasaki disease is caused by something associated with these crops?
The team’s simulations provided another clue about Kawasaki disease: it has a very short incubation time. It typically takes less than a day (and no more than two) for winds from China to start triggering fevers after they reach Japan. That’s too short for even the fastest of viruses to start causing symptoms. “The incubation time makes it absolutely impossible for [the cause] to be an infectious agent unless it’s the fastest one ever found,” says Rodó.
Even then—even if a hypothetical virus reproduced 10 times faster than the speediest ones we know about—it would still take at least a week to spread through the Greater Tokyo area. And that’s not what happens—records show that when Kawasaki disease hits Tokyo, it hits the whole area simultaneously. It’s not caused by something growing in a host, but by something that triggers a fast immune reaction, like an allergen or an inhaled toxin.
An industrial pollutant? The team thinks that’s unlikely: the source region in northeast China has very little industry, and the incidence of Kawasaki disease in Japan doesn’t track with the levels of any atmospheric pollutants.
Pollen? Again, unlikely. The team couldn’t find a link between pollen counts and Kawasaki cases.
The team tried to find the culprit by sending a plane into the skies above Japan, flying against the winds that blow in from China. When they analysed the filters, they found a smorgasbord of fungal spores. And half of these belonged to Candida—a group whose members can cause thrush and other infections.
Their presence is unusual. The team collected samples from the ground and Candida was nowhere to be seen. Other scientists have collected microbes from the skies above the Caribbean, Mediterranean, and other parts of Asia, none of them have ever detected Candida.
There’s not enough evidence to implicate these particular fungi as the cause of Kawasaki disease, but Candida certainly makes for good candidates. Fungal spores are great at riding air currents and their hardy shells allow them to survive tough environmental conditions. Many fungi grow on crop plants, and produce toxins that can cause disease in humans without any need for the spores to actually grow. In mice, molecules on the surface of Candida fungi can trigger immune reactions that inflame the arteries of the heart.
“This only proves that potential human pathogens can be found aloft, can be transported across large distances,” says Rodó. “It might be Candida or it might be something else, but we now need to look along those lines.”
The team now wants to run more sampling flights over Japan, over other parts of the world where Kawasaki disease appears, and over the hypothetical source region in China. They also want to study the people who have the disease, to see if they have antibodies that react to any potential culprits.
Even if the team identifies the cause of Kawasaki disease, there will be more mysteries to solve. For a start, why had no one noticed any cases before 1967, and why is the disease becoming more common? Are farmers in China doing something different? Are changing weather patterns to blame? And does the same region explain Kawasaki cases in India and the Philippines, or are there other source regions.
“It’s the most fascinating scientific problem I’ve been faced with,” says Rodó, who is a climatologist by training. “I would never have imagined that I’d be working on a cardiovascular disease that affects children.”
Reference: Rodó, Curcoll, Robinson, Ballester, Burns, Cayan, Lipkin, Williams, Couto-Rodriguez, Nakamura, Uehara, Tanimoto & Morguí. 2014. Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source o Japan. PNAS http://dx.doi.org/pnas.org/cgi/doi/10.1073/pnas.1400380111 (Link not working? Here’s why.)