May 22 2014
Kawasaki disease in Japan linked to an environmental trigger in winds from agricultural regions in northeast China

Kawasaki disease, the leading cause of acquired heart disease in children worldwide, may be caused by fungal particles or toxins carried on wind currents from dense croplands in northeastern China to Japan, according to a study by an international team, including researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health. Results appear in the Proceedings of the National Academy of Sciences.

japan.jpgThe causative agent of Kawasaki disease, first observed in Japan in the 1960s and that has since then been recognized in other countries in the world, is yet unknown. Noting that the timing of disease outbreaks coincided with certain wind patterns from Asia, researchers used computer models to simulate air currents and airborne particle transport on days with high Kawasaki disease incidence in Japan using records dating to 1977. The model results suggested that the disease peaked in many locations around Japan, in and out of epidemic years, only when winds originated from a densely cultivated region in northeastern China characterized by vast extensions of cereal croplands.

Further analysis pointed to a very short incubation time of less than 24 hours between exposure and fever onset. This, combined with the evidence of widespread simultaneous occurrence of the disease in many cities around Japan, led the scientists to reason that the source of the disease is unlikely to be an infectious agent requiring replication inside the human host, and suggests instead exposure to an antigenic or toxic trigger.

In an attempt to further characterize the trigger, the authors developed an air filter and performed atmospheric monitoring by aircraft over Japan on days during Kawasaki disease season when air currents originated only from the same region in northeastern China. Detailed genetic analysis of the samples by Brent Williams, PhD, associate research scientist, and W. Ian Lipkin, MD, director, the Center for Infection and Immunity at the Mailman School, detected Candida species as the dominant fungus aloft, demonstrating the potential for human disease in aerosols transported by wind currents. Candida are the most common cause of fungal infections worldwide. Prior studies in the laboratory had confirmed Kawasaki-like symptoms in mice exposed to Candida. This result suggests a new paradigm in which toxins such as those in the fungus or any others linked to those agricultural lands, carried by the wind, may trigger Kawasaki disease, according to the authors.

The researchers now plan to conduct more flights over Japan and northeast China during the high season for Kawasaki disease, as well as future studies in which the capacity for those microbes, antigens or toxins contained in the aerosol samples are tested to see if they elicit a similar immune response as that seen in Kawasaki disease patients.

The authors have recently launched a fund-raising initiative to gather funds to perform these aircraft monitoring campaigns this year and the next. For more information, visit www.kawasaki-disease.com.

Xavier Rodó, the lead author of the study, is an ICREA Professor at the Institut Català de Ciències del Clima, IC3, in Barcelona, Spain. Additional co-authors include senior author Josep-Anton Morgui and Roger Curcoll and Marguerite Robinson, also at IC3; Joan Ballester, at both IC3 and the California Institute of Technology; Jane C. Burns from the KD Research Center at the University of California, San Diego School of Medicine’s and the Rady Children’s Hospital San Diego, Dan Cayan from the Scripps Institution of Oceanography/UCSD and the US Geological Survey in La Jolla; W. Ian Lipkin, Brent L. Williams, and Mara Couto-Rodriguez at Center for Infection and Immunity at the Mailman School; Yoshikazu Nakamura and Ritei Uehara from the Jichi Medical Hospital, Togichi, Japan; and Hiroshi Tanimoto, from the National Institute for Environmental Studies, Tsukuba, Japan.

About Columbia University’s Mailman School of Public Health

Founded in 1922, Columbia University’s Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master’s and doctoral degree programs. The Mailman School is also home to numerous world-renowned research centers including ICAP (formerly the International Center for AIDS Care and Treatment Programs) and the Center for Infection and Immunity. For more information, please visit www.mailman.columbia.edu.