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Published June 3, 2014 | Supplemental Material + Published
Journal Article Open

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

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.

Additional Information

© 2014 National Academy of Sciences. Edited by Mark H. Thiemens, University of California, San Diego, La Jolla, CA, and approved April 4, 2014 (received for review January 9, 2014). Published online before print May 19, 2014. We thank Emiliano Gelati for the data and preliminary maps of cropland areas from MODIS. We especially thank the Institut Català de Ciències del Clima Foundation and its administration for its flexibility in the use of research funds for projects of exceptional interest. Thanks are also given to the anonymous reviewers for their insightful comments. This study was funded by Kawasaki Disease: Disentangling the Role of Climate in the Outbreaks Project 081910 from La Marató de TV3 Foundation 2008 (through a grant to X.R.). Author contributions: X.R., J.C.B., D.R.C., W.I.L., Y.N., H.T., and J.-A.M. designed research; X.R., R.C., M.R., J.B., W.I.L., B.L.W., M.C.-R., Y.N., R.U., H.T., and J.-A.M. performed research; X.R., R.C., B.L.W., M.C.-R., R.U., H.T., and J.-A.M. contributed new reagents/analytic tools; X.R., M.R., J.B., W.I.L., B.L.W., Y.N., and R.U. analyzed data; and X.R., J.C.B., D.R.C., W.I.L., B.L.W., and J.-A.M. wrote the paper. The authors declare no conflict of interest. This Direct Submission article had a prearranged editor. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1400380111/-/DCSupplemental.

Attached Files

Published - PNAS-2014-Rodó-7952-7.pdf

Supplemental Material - pnas.1400380111.sm01.avi

Supplemental Material - pnas.201400380SI.pdf

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August 22, 2023
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