One of the world’s most baffling diseases may be spread by the wind. A new study has found that Kawasaki disease, which sickens 12,000 children a year in Japan and occurs in other countries including the United States and South Korea, is at its deadliest when the wind blows from northeastern China. The findings suggest that the illness may be caused by an airborne toxin from that region, but just which one remains unclear. 
 
 Kawasaki disease typically strikes children between 6 months and 5 years old. Common symptoms include fever, a blotchy red rash, and redness and sometimes peeling of the hands and feet. It can be treated with antibodies; untreated, it often leads to inflammation of the coronary arteries, sometimes causing aneurysms that can lead to internal bleeding or heart attacks. Some researchers believe Kawasaki to be an infection, but they have never identified the microbe responsible; others suggest it's an immune response to an unidentified toxin. 
 
 In previous research, mathematical ecologist Xavier Rodó and colleagues at the Catalan Institute for Climate Sciences in Barcelona, Spain, had suggested that seasons with large numbers of Kawasaki cases in both Japan and the United States coincide with times when the prevailing winds come from Central Asia. In the new work, they investigated that idea further. 
 
 The researchers examined health records from 1970 to 2010 in each of Japan's 47 administrative divisions. They looked at the days on which the most cases were identified in Tokyo and other major cities, and used computer models of airflow to find out where the air had come from in the previous few days. Because the incubation period for Kawasaki disease is unknown, the team looked at various lag times. 
 
 On the days most children became ill, the air blowing into the cities had spent large amounts of time in the same region in northeastern China, usually about 2 days before reaching Japan and 2.5 days before the children came down with symptoms, the team reports online today in the Proceedings of the National Academy of Sciences. This suggests, the researchers say, that the disease is borne on the wind and that it has an incubation period of only about a half-day. 
 
 They also looked at the possibility that the disease could be an infection spreading between children. However, in all the major cities, most children fell ill on the same days, and the infection peak in all cities died away as soon as the wind changed direction, which would be hard to explain if the children were infecting each other. “It must be in the form of a toxin or some other environmental agent,” Rodó says. His team also found no relationship with days of high levels of pollen or common pollutants such as sulfur and nitrogen oxides. 
 
 The region implicated, the Northeast China Plain, is highly agricultural, so the researchers suggest that a toxin produced by a fungus living on the crops is a likely culprit. They conducted several flights from Japan to northeastern China—the opposite direction of the prevailing winds—and filtered the air they collected. They found many species of Candida, a fungus genus responsible for common human infections and also for symptoms similar to Kawasaki disease in some strains of mice. However, the researchers do not claim to have identified the exact cause of Kawasaki disease, and they are hoping to conduct more flights. They also plan to look in more detail at the cause of the disease in the United States. 
 
 “I think these authors have presented a dataset that is pretty conclusive that this is most likely a microbial toxin of some type,” says environmental microbiologist Dale Griffin of the U.S. Geological Survey in St. Petersburg, Florida. He notes that the techniques of tracking airflow back to a common origin are well established in environmental sciences. 
 
 Anne Rowley, a pediatric infectious disease specialist at Northwestern University’s Feinberg School of Medicine in Chicago, Illinois, says the work is “very interesting” but she remains skeptical about the windborne toxin hypothesis, which, she says, would be unprecedented for a human disease. She notes that a number of diseases, including AIDS and polio, were attributed to unidentified toxins shortly before infectious agents were identified. ||||| Kawasaki disease (KD), the leading cause of acquired heart disease in children worldwide, has remained a mystery for more than 40 y. No etiological agent has yet been identified. By using simulations with the flexible particle dispersion model from different Japanese cities from each single high (low) KD incidence day, the source region KD is retrieved in cereal croplands in northeastern China. We infer the incubation time for KD ranges from 6 h to 2 d, thus favoring an antigenic or toxic exposure as the trigger. Candida sp. is reported as the dominant fungal species collected aloft (54% of all fungal DNA clones) demonstrating the potential for human disease in aerosols transported by wind currents traveling long distances. 
 
 Abstract 
 
 Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987–2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD. ||||| The pathogens responsible for the disease enter through mucous membranes and work their way into the arteries of young children. After the initial symptoms—including fever, rash, bloodshot eyes, and swollen hands and feet—subside, the disease leaves behind cardiac effects that can lead to heart disease and even death years later.(Related: "The Disease, My Friend, Is Blowing in the Wind.") 
 
 More than 40 years after KD was discovered, there is still no diagnostic test for the disease, and the pathogen that causes it—whether toxin, fungus, or other agent—remains a mystery. 
 
 But the discovery that the disease-causing agent travels on the wind "will lead us to the cause of Kawasaki disease," said study co-author Jane Burns, director of the Kawasaki Disease Research Program at the University of California, San Diego. 
 
 Kawasaki disease is the most common cause of acquired heart disease in children in developed countries. Japan, the country with the highest incidence of KD, reports more than 12,000 new cases each year. In the United States, some 5,000 to 6,000 cases are reported annually. 
 
 "We know that KD occurs on every continent and in every race," noted study co-author Daniel Cayan, a climate researcher at the Scripps Institution of Oceanography in La Jolla, California. This research presents a model that scientists can use to search for other regions harboring the Kawasaki agent, he said. 
 
 About ten years ago, after noticing a distinct seasonality in cases of KD, Burns, Cayan, and an international group of researchers began examining Japan's extensive database on the disease as well as wind patterns over that country. They traced outbreaks of KD in Japan to northeastern China, an area of intense agriculture. 
 
 KD was first described in the 1960s, around the time farming practices in that region, and around the world, were dramatically changing. "A more focused investigation should center in this area to precisely determine whether pesticides or fertilizers used have had a role in the generation of these particles," said the study's lead author, Xavier Rodó, a climate scientist at the Catalan Institute of Climate Sciences in Barcelona. There is "no doubt that agricultural practices do have an important implication in this story," he said. 
 
 What makes KD particularly sinister is that many of its early symptoms mimic those of other common childhood diseases. "Disease recognition is really a problem," said Burns. "Over the course of a week to several weeks, the fever subsides and the child feels better." 
 
 Treatment, which includes high doses of intravenous gamma globulin, an immunizing agent that boosts a patient's resistance to disease, can help reduce the risk of future health complications. But that treatment must begin early. 
 
 With this new research, Burns said, "we should be able to come up with an early warning system for pediatric emergency rooms, letting them know when they should have a heightened awareness for cases of KD." ||||| The probable cause of Kawasaki disease — a mysterious and sometimes deadly childhood heart disease that has stumped generations of doctors and that predominantly affects people in Japan, Hawaii and Southern California — may have been found. 
 
 The answer, it seems, is quite literally blowing in the wind — a wind originating in the farmlands of northeastern China carrying a fungus known as Candida, a type of yeast. 
 
 When inhaled, Candida can trigger a severe immune response in some children, inflaming blood vessels and causing permanent heart damage. 
 
 In 2011, an international team of scientists determined that outbreaks of Kawasaki disease in Japan were tied to seasonal winds from China. Now, this same multidisciplinary team has identified Candida in extensive air sampling along the path of the outbreaks. Their study appears today (May 19) in the journal Proceedings of the National Academy of Sciences. [7 Devastating Infectious Diseases] 
 
 "God only knows" 
 
 Kawasaki disease was first identified in 1961 by a Japanese doctor named Tomisaku Kawasaki, who, for a decade, called the illness GOK, short for "God only knows." Telltale signs of the disease include a strawberry-colored tongue and high, prolonged fever. 
 
 Kawasaki disease can now be treated effectively with an injection of immunoglobulin, a blood product containing antibodies. Without treatment, about 25 percent of children infected with Kawasaki disease will develop arterial aneurysms (balloonlike bulges in the arteries) and permanent heart disease; about 1 percent of untreated infections are fatal. 
 
 Kawasaki disease is most prevalent in Japan, where about one in 150 children contracts it, and the number of cases there is on the rise, Kawasaki wrote in a journal article published earlier this year about the history of the disease that now bears his name. In the United States, there are 2,000 to 4,000 cases reported annually, according to the Centers for Disease Control and Prevention. 
 
 The new findings that Candida could cause Kawasaki disease may be a surprise — most scientists have thought the cause is most likely a virus, not fungus, said Dr. Jane Burns, who was part of the discovery team and is the director of the Kawasaki Disease Research Center at the University of California, San Diego School of Medicine. 
 
 "Candida could be making a toxin or a protein or other antigen that triggers Kawasaki disease," Burns told Live Science. 
 
 Burns added that other scientists have found that Candida can trigger Kawasaki-like symptoms in mice. But her team, led by climate scientist Xavier Rodó of the Catalan Institution for Research and Advanced Studies in Barcelona, did not set out looking specifically for Candida. 
 
 Burns called the team's finding "unexpected." 
 
 Blowing in the wind 
 
 The study provides "strong evidence for an atmospheric route of dispersion" of a disease-causing agent, said Dale Griffin of the U.S. Geological Survey in St. Petersburg, Florida, who is a public health microbiologist and an expert on dust storms. Griffin, who wasn't part of the new study, added that microbes, including fungi, can travel vast distances in the stratosphere, often hitching a ride on dust and other fine particles. 
 
 Griffin said that although windborne disease transmission isn't very common, it is not unprecedented. The Coccidioides fungus — which causes valley fever, a disease seen in the southwestern United States — is carried by the wind, albeit over shorter distances than Kawasaki disease fungus travels. 
 
 Some researchers are worried that climate change and warming temperatures will increase the types and incidences of fungal diseases affecting humans, according to Dr. Arturo Casadevall, an immunologist at Albert Einstein College of Medicine in New York. 
 
 Climate changes could foster the growth of fungi that the human immune system has a difficult time combating, according to Casadevall. 
 
 Why the incidence of Kawasaki disease is rising, however, remains a mystery. The disease is increasingly being reported in Southeast Asia, and Australia. 
 
 Rodó said the apparent low rates of Kawasaki disease in the agricultural regions of northeastern China may be due to the low population density there compared with Japanese cities. Burns added that genetics might play a role in susceptibility to the disease, and that the Candida-related agent might somehow become more virulent while airborne. 
 
 "The data suggest that people are doing something new [since World War II] in northeastern China," Burns said. "Could they be burning a biomass fuel in winter that carries the agent on aerosolized ash to Japan? Could there be some agricultural practice or crop or activity that is new since the 1960s? We need to figure out what the activity or condition is that creates these aerosols carried by the winds." 
 
 Acknowledging that many theories about the cause of Kawasaki disease have been proffered (such as carpet cleaners), the authors also said that more studies are needed to directly test the capacity of the microbes and toxins in their air samples to elicit a severe immune response seen in Kawasaki patients. 
 
 Copyright 2014 LiveScience, a TechMediaNetwork company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
– A potential big step forward in discovering the cause of a childhood heart disease so mysterious that it was referred to as GOK—short for "God only knows"—for the decade after its 1961 identification: Scientists now believe that the agent that causes Kawasaki disease, eventually named for the Japanese doctor behind its discovery, is spread from northeastern China by the wind. National Geographic reports that researchers began studying the disease records and wind patterns of Japan about a decade ago; that country sees the highest incidence of the disease, with roughly one out of 150 youngsters contracting it. What they found: The disease struck the most children about 2.5 days after wind from the heavily-agricultural Northeast China Plain reached them, and the infection peak subsided once the wind shifted direction, Science reports. Hawaii and Southern California see instances of the disease, too; as many as 4,000 cases occur annually in the US. But the disease—which causes young children's arteries to become inflamed and, if left untreated, can cause permanent heart disease or even death—is on the rise, with more cases being reported in Australia and Southeast Asia, Scientific American reports. What's still unknown is which airborne agent causes it, though the researchers did note in the Proceedings of the National Academy of Sciences "the unexpected finding of the Candida species," a type of fungus, "as the dominant fungus from aloft samples (54% of all fungal strains)." Study co-author Jane Burns says, "The data suggest that people are doing something new [since World War II] in northeastern China. Could there be some agricultural practice or crop or activity that is new since the 1960s? We need to figure out what the activity or condition is that creates these aerosols carried by the winds." (Click to read about a mystery disease that strikes one family on the planet.)