Eastern Ontario, Ottawa and 5Division of Cardiology, Department of Pediatrics, Queen's University, .... Hospital for Sick Children (HSC) Research Ethics Board.
Pediatrics International (2010) 52, 699–706
Original Article
ped_3092
doi: 10.1111/j.1442-200X.2010.03092.x
699..706
Repeated systematic surveillance of Kawasaki disease in Ontario from 1995 to 2006 Yahui T. Lin,1 Cedric Manlhiot,1 Joyce C.Y. Ching,1 Ra K. Han,1 Lynne E. Nield,1 Rejane Dillenburg,2 Dion Pepelassis,3 Lillian S. Lai,4 John F. Smythe,5 Nita Chahal,1 Rae S.M. Yeung6 and Brian W. McCrindle1 1 Labatt Family Heart Centre and 6Division of Rheumatology, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, 2Division of Cardiology, Department of Pediatrics, McMaster University, McMaster Children’s Hospital, Hamilton, 3Division of Cardiology, Department of Pediatrics, University of Western Ontario, Children Hospital of Western Ontario, London, 4Division of Cardiology, Department of Pediatrics, University of Ottawa, Children Hospital of Eastern Ontario, Ottawa and 5Division of Cardiology, Department of Pediatrics, Queen’s University, Kingston General Hospital, Kingston, Ontario, Canada Abstract
Background: Rising incidences of Kawasaki disease (KD) have been reported worldwide. Reported herein are the results of 4 triennial KD surveillances conducted in Ontario. Methods: Between 1995 and 2006 all hospitals in Ontario were asked on 4 occasions to identify all patients with discharge diagnoses of KD and report incident cases. Results: The latest surveillance identified 697 new KD patients (100% response rate) for a total of 2378 KD patients through all 4 surveillances. Yearly incidence was 26.2/100 000 for 8 mm were classified as having giant aneurysms.16 Highcaseload hospitals were defined as those hospitals reporting at least 20 patients during a 3 year surveillance period. Estimates of nationwide and Ontario KD incidence
Estimates of the population at risk (denominator) for 4 age groups (0–4 years, 5–9 years, 10–14 years and 15–24 years) in Ontario were obtained from Statistics Canada censuses conducted in 1996, 2001 and 2006. Nationwide estimates of KD incidence in children 0–4 years old, from 1979 to 2004, were obtained from the national hospital discharge database maintained by the Canadian Institute for Health Information (CIHI), with the population at risk obtained from Statistics Canada. Cases were identified from this database using ICD9 and ICD10 codes. Data analysis
Data are presented as mean 1 SD, medians with minimum and maximum values and frequencies as appropriate. Annual incidence per 100 000 children was calculated by dividing the number of valid cases diagnosed in any given year by the at-risk population. Trends over time were estimated using univariable linear regression models using year of diagnosis as the independent variable. Reported are estimates of change per year and their standard error. Seasonal trends were estimated by calculating the binomial probability of the number of cases observed in each calendar month assuming equal distribution of cases throughout the year. Differences between patients initially admitted at highcaseload hospitals versus low-caseload hospitals were assessed using Fisher’s exact test and Student’s t-test. All statistical analyses were performed using SAS Statistical Software v9.1 (SAS Institute, Cary, NC, USA).
Results Incidence, age and gender distribution
A total of 2378 patients were reported over the 4 surveillances, with a significant increase in the number of patients reported
Kawasaki disease in Ontario, Canada
Fig. 1 Incidence of Kawasaki disease in Ontario and throughout ) CIHI–Canada, 0–4 years; Canada from 1979 to 2006. ( ( ) CIHI–Ontario, 0–4 years; ( ) Ontario surveillance 0–4 ) Ontario surveillance 5–9 years; ( ) Ontario surveilyears; ( lance 10–14 years. CIHI, Canadian Institute of Health Information.
during each consecutive surveillance. We observed an important year-to-year variation in the number of patients reported. The overall annual KD incidence for children 0–4 years of age significantly increased over time from 14.4/100 000 in 1995–1997 to 26.2/100 000 in 2004–2006 (P < 0.001; Fig. 1). Incidence data from the nationwide CIHI hospital discharge database was found to closely correlate the Ontario surveillance for years for which both estimates were available, and showed an increase in annual
701
Fig. 2 Age and gender distribution of Kawasaki disease patients ) cumulative percentage. 1995–2006. ( ) Male; (䊐) female; (
KD incidence in children 0–4 years old from 2.8/100 000 in 1979 to 24.1/100 000 in 2004. As expected, the incidence was highest in children 0–4 years of age (73% of cases) and significantly decreased thereafter (Table 1). The incidence of both complete and incomplete KD was found to increase over time, but the incidence of incomplete KD had a faster increase than that of complete KD (+0.35 cases/100 000 per year incomplete KD more than complete KD, P < 0.001). The 1.62 : 1 male : female ratio was consistent across all age groups (Fig. 2). There were no differences in the demographic characteristics of patients reported in each of the 4 surveillances.
Table 1 Kawasaki disease incidence from 1995–2006 vs age and gender for Ontario
1995–1997 Total 0–4 years 5–9 years 10–14 years 15–24 years 1998–2000 Total 0–4 years 5–9 years 10–14 years 15–24 years 2001–2003 Total 0–4 years 5–9 years 10–14 years 15–24 years 2004–2006 Total 0–4 years 5–9 years 10–14 years 15–24 years
KD male, n
KD female, n
KD total, n
274 200 57 13 4
155 117 36 2 0
429 317 93 15 4
381 268 99 12 2
208 143 57 6 2
391 285 86 19 1 426 323 86 16 1
Census†
Population male
Population female
Population total
Incidence male†
Incidence female†
Incidence total‡
1996 1996 1996 1996
. 376 730 383 890 375 755 754 565
. 357 440 364 175 356 225 733 275
. 734 170 748 065 731 980 1 487 840
. 17.70 4.95 1.15 0.18
. 10.91 3.30 0.19 0.00
. 14.39 4.14 0.68 0.09
589 411 156 18 4
. 2001 2001 2001 2001
. 343 340 396 385 404 970 754 565
. 327 910 376 265 383 800 733 275
. 671 250 772 650 788 770 1 487 840
. 26.02 8.33 0.99 0.09
. 14.54 5.05 0.52 0.09
. 20.41 6.73 0.76 0.09
272 201 64 7 0
663 486 150 26 1
. 2001 2001 2001 2001
. 343 340 396 385 404 970 754 565
. 327 910 376 265 383 800 733 275
. 671 250 772 650 788 770 1 487 840
. 27.67 7.23 1.56 0.04
. 20.43 5.67 0.61 0.00
. 24.13 6.47 1.10 0.02
271 205 59 5 2
697 528 145 21 3
. 2006 2006 2006 2006
. 343 475 369 675 420 705 827 630
. 327 290 351 920 397 740 802 740
. 670 765 721 595 818 445 1 630 370
. 31.35 7.75 1.27 0.04
. 20.88 5.59 0.42 0.08
. 26.24 6.70 0.86 0.06
.
†Census used to obtain population figures. ‡Yearly incidence per 100 000. KD, Kawasaki disease.
© 2010 The Authors Pediatrics International © 2010 Japan Pediatric Society
702
YT Lin et al. portion of patients with non-giant or giant aneurysms remained constant over all 4 surveillances, although a non-statistical reduction was observed in the proportion of patients with nongiant aneurysms, from 7% to 3% (P = 0.11). Incomplete versus complete presentation was not found to be associated with changes in risk of either coronary artery ectasia/dilation (odds ratio [OR], 0.80; P = 0.13), non-giant coronary artery aneurysm (OR, 1.03; P = 0.93) or giant coronary artery aneurysms (OR, 1.26; P = 0.67). A total of 15 patients (0.6%) had a myocardial infarction as a result of KD and 1 fatal case (0.04%) was reported. High- versus low-caseload hospitals
Fig. 3 Seasonal distribution of Kawasaki disease in Ontario 1995– 2006. (—) April–October; (- - -) November–March.
Seasonal distribution
We observed a prominent seasonal distribution of cases (Fig. 3), with the highest caseload reported from November to March (14–31% higher than average, P < 0.001) and the lowest caseload reported from May to July (12–13% lower than average, P = 0.04) and from August to October (20–25% lower than average, P < 0.001). A total of 8 months between 1995 and 2001, demonstrated a caseload of more than twice the number of patients for an average month in their respective surveillances; 4 of these months were between November 2004 and May 2005. Other periods of high caseload were February 1996, January 1998 and November–January 2001–2002. These 4 periods would qualify as KD epidemics by the criteria set forth in the Japanese biennial nationwide surveys (statistically significant increase from previous period and statistically significant decrease in the following period). Clinical signs at presentation and treatment
Although the age and gender distribution did not change across the 4 surveillances, the proportion of cases involving incomplete clinical presentation did increase over time. Over time, the proportion of patients diagnosed in high-caseload hospitals, other than HSC, increased (from 20% to 31%, P < 0.001), while the proportion of patients diagnosed at HSC decreased over time (from 45% to 42%, P = 0.005). There were no changes over time in the proportion of patients diagnosed in low-caseload hospitals (P = 0.45). The proportion of patients with incomplete KD presentation significantly increased from 19% in 1995–1998 to 41% in 2004–2006 (P < 0.001; Table 2). A higher proportion of patients received appropriate treatment in the first and last surveillances. Disease outcomes
Total duration of fever from disease onset to defervescence and duration of hospitalization remained constant over the 4 surveillances. The proportion of patients with coronary artery ectasia/dilation decreased from 23% in the first surveillance to 12% in the most recent surveillance (P < 0.001). The pro© 2010 The Authors Pediatrics International © 2010 Japan Pediatric Society
In comparing hospitals with high versus low caseloads, many important differences emerged. The demographic (gender and age at diagnosis) characteristics between the 2 groups were similar, but a higher proportion of patients diagnosed in lowcaseload hospitals had an incomplete presentation (37% vs 25%, P < 0.001). Patients diagnosed in low-caseload hospitals were less likely to receive aspirin, i.v. immunoglobulin or steroids than those diagnosed in high-caseload hospitals, but were more likely to receive antibiotics. In terms of disease outcomes, coronary artery ectasia/dilation was more frequently seen in high-caseload hospitals. There were no differences between groups regarding total number of days of fever, duration of hospitalization, frequency of non-giant aneurysms and frequency of giant coronary artery aneurysms (Table 3).
Discussion KD epidemiology
The epidemiological information gathered in these 4 surveillances provides an important basis for the comparison of KD epidemiology in Ontario and Canada with other nations. By far, Asian nations have the highest annual KD incidence in children 0–4 years old reported worldwide, starting with Japan (184.6/ 100 000)4 (197.7/100 000 in Japanese–US children living in Hawaii26), and followed in order by Korea (105.0/100 000),27 Taiwan (69.0/100 000),28 China (55.1/100 000)29 and Hong Kong (39.0/100 000).30 Presumably other Asian countries have similarly high levels of KD, but the infrastructure for diagnosis and/or reporting of these cases is absent.2 Outside of Asia, rates of 17.1/100 000 have been reported in the USA,15 followed by 15.2/ 100 000 in Ireland,31 8.6/100 000 in New Zealand,32 8.1/100 000 in England,33 3.7/100 000 in Australia34 and 3.6/100 000 in Denmark.35 With 26.2 cases per 100 000 children reported in the present study, Ontario ranks as one of the regions outside of Asia with the highest reported incidence of KD, although other regions of Canada such as British Columbia could have higher rates. The population of East Asian descent (defined as Japanese, Korean, Chinese or Taiwanese) in Ontario is comparatively large at 5.7% for Ontario alone compared to 4.7% for all of Canada, 12.6% for British Columbia (2006 Canada Census), 1.9% for the USA (2000 US Census) and 0.7% for the European Union (2009 Eurostat). As such, high rates of KD might be somewhat expected
Kawasaki disease in Ontario, Canada
703
Table 2 Kawasaki disease clinical characteristics, treatment and trends over time
No. KD cases Age at diagnosis (years), median (range) Gender (male) Clinical Diagnosed at HSC Diagnosed in high-caseload hospital Diagnosed in low-caseload hospital Incomplete KD (
