On the interpretation of the atmospheric mechanism transporting the environmental trigger of Kawasaki Disease.

Recent advances on the environmental determinants of Kawasaki Disease have pointed to the important role of the atmospheric transport of a still unknown agent potentially triggering the disease. The hypothesis arose from an innovative methodology combining expertise in climate dynamics, the analysis of ocean and atmosphere data, the use of dispersion models and the search for biological agents in air samples. The approach offered a new perspective to reveal the identity of the potential trigger, but at the same time, it increased the level of complexity, which could potentially lead to the misinterpretation of the mechanisms. Some years after it was originally formulated, we here provide a brief clarification on the approach and limits of the methodology in order to prevent an eventual misuse of our research ideas and theory, so that further research can better focus on the knowledge gaps that still remain open.

Revisiting the role of environmental and climate factors on the epidemiology of Kawasaki disease.

Can environmental factors, such as air-transported preformed toxins, be of key relevance to the health outcomes of poorly understood human ailments (e.g., rheumatic diseases such as vasculitides, some inflammatory diseases, or even severe childhood acquired heart diseases)? Can the physical, chemical, or biological features of air masses be linked to the emergence of diseases such as Kawasaki disease (KD), Henoch-Schönlein purpura, Takayasu's aortitis, and ANCA-associated vasculitis? These diseases surprisingly share some common epidemiological features. For example, they tend to appear as clusters of cases grouped geographically and temporarily progress in nonrandom sequences that repeat every year in a similar way. They also show concurrent trend changes within regions in countries and among different world regions. In this paper, we revisit transdisciplinary research on the role of environmental and climate factors in the epidemiology of KD as a paradigmatic example of this group of diseases. Early-warning systems based on environmental alerts, if successful, could be implemented as a way to better inform patients who are predisposed to, or at risk for, developing KD. Further research on the etiology of KD could facilitate the development of vaccines and specific medical therapies.

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

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.