Seasonality and temporal clustering of Kawasaki syndrome

Abstract

Background: The distribution of a syndrome in space and time may suggest clues to its etiology. The cause of Kawasaki syndrome, a systemic vasculitis of infants and children, is unknown, but an infectious etiology is suspected.

Methods: Seasonality and clustering of Kawasaki syndrome cases were studied in Japanese children with Kawasaki syndrome reported in nationwide surveys in Japan. Excluding the years that contained the 3 major nationwide epidemics, 84,829 cases during a 14-year period (1987-2000) were analyzed. To assess seasonality, we calculated mean monthly incidence during the study period for eastern and western Japan and for each of the 47 prefectures. To assess clustering, we compared the number of cases per day (daily incidence) with a simulated distribution (Monte Carlo analysis).

Results: Marked spatial and temporal patterns were noted in both the seasonality and deviations from the average number of Kawasaki syndrome cases in Japan. Seasonality was bimodal with peaks in January and June/July and a nadir in October. This pattern was consistent throughout Japan and during the entire 14-year period. Some years produced very high or low numbers of cases, but the overall variability was consistent throughout the entire country. Temporal clustering of Kawasaki syndrome cases was detected with nationwide outbreaks.

Conclusions: Kawasaki syndrome has a pronounced seasonality in Japan that is consistent throughout the length of the Japanese archipelago. Temporal clustering of cases combined with marked seasonality suggests an environmental trigger for this clinical syndrome.

FIGURE 1

Incidence of Kawasaki syndrome in Japan, 1979–2000. Incidence (solid line): number of hospitalizations (cases per year). Incidence rate (dashed line): number of Kawasaki syndrome hospitalizations per 100,000 children younger than 5 years of age per year. Note the epidemics in 1982 and 1986 and the rising attack rate during the decade of the 1990s.

FIGURE 2

Geographic patterns of Kawasaki syndrome cases. Average incidence (cases per day) by month, averaged over time period from July 1987 to June 2000, in eastern Japan (solid line) and western Japan (dashed line).

FIGURE 3

Monthly Kawasaki syndrome activity, 1987–2000. The mean hospitalizations per month were calculated for each prefecture during the 14-year period and ranked on a 1–12 scale (see color bar), with red and blue representing the highest and lowest means for each prefecture, respectively. Months of the year are designated by single letter. Note the peaks in January and June/July with a nadir in October. Because of the continuous color algorithm, the color variations do not precisely correspond to prefecture boundaries.

FIGURE 4

Monthly anomalies, 1987–2000. Average number of Kawasaki syndrome hospitalizations per day expressed as a deviation from the mean number of hospitalizations per day for (A) eastern Japan and (B) western Japan after linear regression analysis to eliminate the effect of increasing incidence during the 14-year period. C, Correlation coefficient for detrended monthly anomalies for eastern versus western Japan.

FIGURE 5

Comparison of the observed distribution of daily Kawasaki syndrome incidence (black bars) with the simulated distribution of the same number of synthetic cases created by a random number generator and repeated 10,000 times (Monte Carlo distribution, gray bars) for eastern Japan, January-December. Data are for 1987–2000 (5114 days). The inset shows a detail of the number of days on which there were 16–26 cases per day.