Kawasaki Disease and Tropospheric Wind Patterns

The cause of Kawasaki disease (KD), the most common cause of acquired heart disease in children in the United States, Asia, and Western Europe, has eluded researchers for four decades. The seasonal occurrence of the disease, the self-limited nature of the illness, and the clinical similarity to other rash/fever illnesses in childhood has persuaded investigators that there must be an infectious agent that triggers the destructive immunologic response that we recognize as KD. Genetic susceptibility also plays an important role with children of Asian or African American descent being disproportionately affected. One is every 150 Japanese children will contract KD during the first 10 years of life. In the U.S., there are an estimated 5-6,000 new cases each, although no active surveillance program exists and the true burden of disease is unknown. Without a specific diagnostic test, KD can be confused with other benign rash/fever illnesses and the diagnosis delayed or missed. One in four untreated KD patients will develop permanent, potentially fatal, damage to the coronary arteries and myocardium. Treatment with a high dose of intravenous immunoglobulin downregulates the inflammatory response and prevents coronary artery damage in 90% of patients treated within the first 10 days of fever onset.

Clustering of cases in space and time has been documented and prediction of increased KD activity in a community could heighten physician vigilance and promote timely diagnosis of cases (Kao et al. 2008). Examination of the KD time series from Japan, San Diego and Hawaii show a nearly synchronous peak in KD activity from November through March, which suggested a shared mechanism explaining the seasonality of the disease in the three sites. In Japan, which has the longest and most densely sampled record of any global region, it was found that KD occurred with a seasonal rhythm. In addition to this seasonality, KD in Japan was observed to fluctuate significantly from month to month and season to season, with anomalies often exhibiting a coherent pattern across the entire archipelago (Burns et al 2005). This behavior resembled processes involving weather or climate variations, which lead to an investigation that revealed connections to atmospheric circulation patterns (Rodo et al. 2011).

Two seasonal wind patterns were associated with increases in KD cases: a) a northwesterly flow originating in the mainland of central/eastern Asia that sweeps over Japan and b) a zonal wind pattern that traverses the north Pacific, spanning from Japan to Hawaii and ultimately reaching the mainland of the United States. The window for both of these wind patterns tended to close each year in early spring, which coincided with a decline in KD cases. An enhanced version of these wind patterns also appeared to operate at interannual time scales in association with periods with exceptionally high numbers of KD cases. Seasonality made a prominent contribution to the overall variance in the number of KD cases in Japan, especially when compared to interannual variability of the disease (44% vs.11%, respectively). Similar analyses were performed for other meteorological variables exhibiting seasonality, including minimum and maximum temperature, soil moisture and precipitation, but a similar association with KD did not emerge.

These results suggest that the environmental trigger for KD may be transported through winds, and that bursts of anomalously high numbers of KD cases may be linked via long-range wind transport across oceans. If substantiated, these results suggest that a) tracking of wind patterns could alert clinicians to periods of regional increased KD activity and b) efforts to identify the causative agent of KD should focus on the microbiology of aerosols transported by these regional winds.

An aircraft campaign in March 2011 established the feasibility of aircraft sampling of mid-troposphere aerosol particles over Japan and yielded samples with adequate nucleic acid for analysis. In these experiments an aerosol sampling device was constructed by the IC3 team in Barcelona (Xavier Rodo and colleagues). The air sampler was transported to Tsukuba, Japan, where Hiroshi Tanimoto at the National Institute of Environmental Sciences (NIES) in conjunction with an engineer from IC3 coordinated 3 airplane flights over Japan for the collection of aerosol samples. The flight path was determined by the IC3 and NIES teams and filter samples of approximately 90 m3 (90,000 liters) of air per filter were collected and sent on dry ice to the Lipkin Laboratory at Columbia University. Aerosol samples were also collected at ground level on the same day. Negative control filters handled in the same manner as the experimental filters but without aerosol collection were also sent. Handling of filters was conducted under BSL2 conditions to avoid contamination of the filters with ambient organisms or nucleic acid.

Preliminary analysis of aerosols collected by research aircraft over Japan in March 2011 prior to the earthquake and tsunami and during a period of increased KD activity in Japan revealed a variety of microbial species including bacteria, yeast, and fungi. Whole genome sequencing of amplified nucleic acid from these filters is in progress.

This project brings together an international team of climate scientists, engineers, atmospheric and environmental scientists, infectious disease specialists, and molecular microbiologists to test the hypotheses that changes in large-scale tropospheric wind patterns are reflected in fluctuations in numbers of KD cases, and that tropospheric aerosols contain a rich microbiome that may include the KD agent.

Burns JC, Cayan DR, Tong F, Turner CL, Shike H, Kawasaki T, Nakamura Y, Yashiro M, Yanagawa H. Seasonality and temporal clustering of Kawasaki Syndrome in Japan, 1987-2000. Epidemiology 2005;16:220-225. Kao AS, Getis A, Brodine S, Burns JC. Spatial and temporal clustering of Kawasaki syndrome cases. Ped Inf Dis J. 2008;27(11):981-985. Rodo X, Ballester J, Cayan D, Melish ME, Nakamura Y, Uehara R, Burns JC. Association of Kawasaki disease with tropospheric wind patterns. Science Reports. 2011;1:152.