Kawasaki Disease In Taiwan Research Articles

Public Health Interventions for COVID-19 Reduce Kawasaki Disease in Taiwan.

Background: Kawasaki disease (KD) is a syndrome of unknown cause that results in high fever and coronary vasculitis in children. The incidence of KD increased in Taiwan over the past few decades. Taiwanese government executed domains of early screening, effective methods for isolation or quarantine, and digital technologies for identifying potential cases for the early elimination strategy for coronavirus disease 2019 (COVID-19) and public health interventions for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 pandemic, leading to an effective reduction of the risk of airway infections in children. The purpose of this study is to analyze whether those public health interventions reduce the incidence of KD in 2020. Methods: Patients with KD who visited Chang Gung Memorial Hospital (CGMH) between 1 January, 2018, and 31 December, 2020 were included for trend analysis. This is a retrospective case series study conducted at the CGMH, which consists of a network of seven hospital branches equipped with more than 10,000 beds in different areas of Taiwan. Results: Compared with the 2018 and 2019 databases, the incidence of KD decreased significantly by 30% and 31%, respectively (p < 0.05) in 2020, when public health interventions were comprehensively implemented in Taiwan. This result shows that the incidence of KD decreased during the COVID-19 pandemic in Taiwan without change of the presentation KD (typical or incomplete) and percentage of IVIG resistance in 2020. Conclusion: As public health interventions were carried out for the SARS-CoV-2 pandemic, the incidence of KD was significantly reduced in Taiwan. Is KD a preventable disease?

Public Health Interventions for COVID-19 Reduce Kawasaki Disease in Taiwan

Background: Kawasaki disease (KD) is a syndrome of unknown cause that results in high fever and coronary vasculitis on the affected children. The incidence of KD increased in Taiwan over the past few decades but seemed to have significantly decreased in 2020, when the Taiwanese government executed public health interventions for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or (coronavirus disease 2019, COVID-19) pandemic, leading to an effective reduction of the risk of airway infections in children. The purpose of this study is to analyze whether those public health interventions reduce the incidence of KD in 2020.Methods: Patients with KD who visited Chang Gung Memorial Hospital (CGMH) between January 1, 2018 and December 31, 2020 were included for trend analysis. This is a retrospective case series study conducted at the CGMH, which consists of a network of 7 hospital branches equipped with more than 10,000 beds in different area of Taiwan.Results: Compared with the 2018 and 2019 databases, the incidence of KD decreased significantly by 30% and 31%, respectively (p Conclusion: As public health interventions were carried out for the SARS-CoV-2 pandemic, the incidence of KD was significantly reduced. Is KD a preventable disease?Funding Statement: This study received funding from the following grants: MOST 108-2314-B-182 -037 -MY3 from the Ministry of Science and Technology of Taiwan and 8E0212, CMRPG8L0021 and CORPG8L0321 from Chang Gung Memorial Hospital, Taiwan. Although these institutes provided financial support, they had no influence on the way in which we collected, analyzed, or interpreted the data or wrote this manuscript.Declaration of Interests: All the authors hereby declare to have no financial interests todisclose with regard to this article.Ethics Approval Statement: This study was approved by the Institutional Review Board of the Chang Gung Medical Foundation (IRB number: 201801163B0 and 20210084B0).

Increased Incidence of Kawasaki Disease in Taiwan in Recent Years: A 15 Years Nationwide Population-Based Cohort Study.

Background: Kawasaki disease (KD) is diagnosed in children suffering from fever for more than five days and five clinical characteristic symptoms. The aim of this article was to research the clinical characteristics among KD children in Taiwan in recent years through a population-based cohort study.Materials and Methods: We carried out a nationwide retrospective cohort study by analyzing the data of KD patients (ICD-9-CM code 4461) from Taiwan's National Health Insurance Research Database (NHIRD) during the period of 1996-2011.Results: Among all the insured children in the NHIRD, insurance claims data were reported for 13,260 patients diagnosed with KD, with 8394 (63.30%) subjects being administered IVIG for treatment. Of the patients diagnosed with KD, 94% were under the age of 5 years old, and the majority of cases occurred in May. Furthermore, the incidence of KD more than doubled (28.58–60.08 per 100,000) during this period in Taiwan.Conclusion: We developed a five-based mnemonic device for parents and first-line clinicians to easily use in order to diagnose KD. We also observed an increased incidence of KD in Taiwan during the study period. In addition, we develop a five-based mnemonic device for parents and first-line clinicians in clinical diagnosis of KD can easily remember: Fever> 5 days, 5 clinical criteria, predominantly in children <5 years of age, and peak seasonal clustering in the 5th month, May (April–June) in Taiwan.

Ambient Air Pollutant Exposures and Hospitalization for Kawasaki Disease in Taiwan: A Case-Crossover Study (2000-2010).

Background:Kawasaki disease (KD) is an acute and multi-systemic vasculitis that occurs predominantly in infants and young children. Although the etiological agent of KD remains unclear, limited studies have reported that windborne environmental factors may trigger KD.Objectives:We conducted a time-stratified case-crossover study to assess the associations between air pollutants and KD in Taiwan.Methods:We identified children < 5 years old with a diagnosis of KD from the Longitudinal Health Insurance Database 2000 (LHID2000) between 2000 and 2010. We obtained data regarding carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), particulate matter with aerodynamic diameter < 10 μm (PM10), and sulfate dioxide (SO2) from 70 monitoring stations and used inverse distance weighting to calculate average daily exposures for the residential postal code of each case. We performed conditional logistic regression to estimate associations between KD and each air pollutant according to interquartile range (IQR) increases and quartiles of exposure on the day of hospitalization versus 3–4 reference days during the same month for each case. Additionally, we estimated associations with single-day exposures lagged 1–2 days.Results:We identified 695 KD hospital admissions during the study period. An IQR increase (28.73 ppb) of O3 was positively associated with KD after adjusting for temperature, humidity, northward wind, and eastward wind [adjusted odds ratio = 1.21; 95% confidence interval (CI): 1.01, 1.44]. There were no significant associations between KD and CO, NO2, PM10, or SO2. The association with O3 was limited to exposure on the day of hospitalization and to exposure during the summer months (June–August).Conclusions:Our results provide new evidence that exposure to O3 may increase the risk of KD in children. However, further investigation is needed to confirm the association and identify a potential biological mechanism.Citation:Jung CR, Chen WT, Lin YT, Hwang BF. 2017. Ambient air pollutant exposures and hospitalization for Kawasaki disease in Taiwan: a case-crossover study (2000–2010). Environ Health Perspect 125:670–676; http://dx.doi.org/10.1289/EHP137

Epidemiological Features of Kawasaki Disease in Taiwan, 1976–2007: Results of Five Nationwide Questionnaire Hospital Surveys

Kawasaki disease (KD) affects mainly children younger than 5 years of age, leading to coronary artery lesions, and even to life-threatening myocardial infarction. In Taiwan, KD was encountered for the first time in 1976; then, it continued to occur in increasing numbers. For the survey of epidemiological features of KD in Taiwan, we conducted five nationwide questionnaire hospital surveys in 1987, 1992, 1994, 2001, and 2008, respectively. In each survey, a special questionnaire form, together with a request letter and diagnostic guidelines for KD, was sent to the chairman of the Department of Pediatrics of all hospitals with 100 or more beds in Taiwan. KD patients increased to a total of 14,399 patients by 2007, with the highest number of 1018 in 2001, and the highest incidence of 66.24 per 100,000 children<5 years of age in 2006. Of the 14,399 patients, the male-to-female ratio ranged from 1.5 to 1.7. Of these patients, 57.6-65.2% were<2 years of age, 23.3-26.6% were 2-4 years of age, and 11.4-15.8% were ≥ 5 years of age. Coronary artery lesions were noted in 20.2-31.5% of patients. Fourteen cases expired, documenting that the fatality rate decreased from 0.4% to 0.03% during the 31 years from 1976 to 2007. In Taiwan, KD was encountered for the first time in 1976, and it continued to occur, reaching the highest annual incidence of 66.24 per 100,000 children<5 years of age in 2006. In Taiwan, the first emergence of KD came in 1976; the annual increment of the incidence rate was lower (2.41 in Taiwan vs. 4.17 Japan), and no significant KD outbreak was observed in Taiwan.

Estimation of the Incidence of Kawasaki Disease in Taiwan. A Comparison of Two Data Sources: Nationwide Hospital Survey and National Health Insurance Claims

Kawasaki disease (KD), first described by Dr. Tomisaku Kawasaki in 1967, was found for the first time in Taiwan in 1976. It continued to occur in increased numbers. For the study of incidence rates and epidemiological features of KD, we conducted five nationwide hospital surveys (NHS) in 1987, 1992, 1994, 2001 and 2008, respectively. We estimated also the annual incidence rates of KD during 1996-2007, based on the National Health Insurance (NHI) database, which had been implemented since 1995, covering 98% of the population in Taiwan. The annual incidence rates of KD during the twelve years, from1996 to 2007, estimated by the NHS and the NHI claims were compared, analyzed and discussed. During 1996-2007, a total of 9,938 cases of KD were reported by the Departments of Pediatrics of all hospitals surveyed, and a total of 11,849 cases of KD were claimed in the NHI database. The annual number of cases and incidence rates of KD based on NHI claims constantly surpassed those by the NHS. The ratio of the two incidence rates varied from 1.10 to 1.33. They were well correlated (r=0.902, p<0.001) with a linear equation, NHI=16.07+0.93*NHS. The changes in annual incidence rate by the NHI were mean 1.149, p=0.07, 95% CI -0.082 - 2.382, and those by the NHS were mean 1.562, p<0.001, CI 0.656 - 2.468. The annual incidence rates of KD can be estimated by the NHI claims and by the classic NHS. The values estimated by the NHI claims constantly outnumbered those by the NHS. Some pitfalls involved in the NHI claims are discussed.

Systems dynamics for estimation of future resource needs

In this issue of The Journal, Huang et al report on future trends for Kawasaki disease in Taiwan and in the US. In order to make these projections, they took data from national data bases and previous studies, as well as birth and mortality rates. In their analysis, they used a statistical modeling technique called systems dynamics modeling, which incorporates the population at risk, the expected incidence of Kawasaki disease, and the risk of coronary complications. The model for the US indicates an annual average of 6200 new patients with Kawasaki disease, with 5664 patients having coronary artery disease by 2030. This approach to modeling can be useful for planning and determination of future health care resource needs. The methods employed by Huang et al could be applied to a number of chronic pediatric diseases. Article page 126▶ Epidemiology of Kawasaki Disease: Prevalence from National Database and Future Trends Projection by System Dynamics ModelingThe Journal of PediatricsVol. 163Issue 1PreviewTo update the epidemiologic trend in Kawasaki disease (KD) and develop models for projection. Full-Text PDF

Kawasaki disease and subsequent risk of allergic diseases: a population-based matched cohort study

BackgroundThe risk of allergic diseases among Kawasaki disease (KD) patients relative to the general population is not known. The aim of this study was to perform a population-based cohort study to investigate the risk of allergic diseases among children after KD in Taiwan- a country with the third highest incidence of KD in the world.MethodsData were obtained from the Taiwan National Health Insurance Research Database. In total, 253 patients who were 5 years of age or younger and had a first-time hospitalization with a diagnosis of KD between 1997 and 2005 were included as the study cohort and 1,012 non-KD patients matched for age and sex were included as comparison cohort. Multivariate Cox proportional hazard regression model was used to adjust for confounding and to compare the 6-year allergic-free survival rate between these two cohorts.ResultsThe incidence rate of allergic diseases (184.66 per 1000 person-year) was significantly higher in the KD cohort than in the control cohort (124.99 per 1000 person-years). After adjusting for potential confounders, the adjusted hazard ratios of asthma and allergic rhinitis were 1.51 (95% confidence interval = 1.17-1.95) and 1.30 (95% confidence interval = 1.04-1.62), respectively.ConclusionWe conclude that KD patients were at an increased risk for allergic diseases compared with the comparison cohort.

Population-Based Study of the Association between Urbanization and Kawasaki Disease in Taiwan

Background. It is unclear if the prevalence of Kawasaki disease (KD) correlates with the degree of urbanization. We hypothesized that the prevalence of KD is more pronounced in urban versus rural environments. Methods. The National Health Insurance (NHI) program was implemented in Taiwan in 1995 and covers most of the population (>99%). We used the NHI database to investigate the epidemiological features of KD. A total of 115 diagnosed patients with KD from 1997 to 2010 were included, together with 1,150 matched controls without KD. Chi-square analyses were performed to investigate the difference between modern city and rural environments. Results. Of the 1265 sampled subjects (claims data from 1,000,000 random subjects), the mean age of the KD study group and control group was 2.08 ± 1.66 and 2.08 ± 1.64 years, respectively. After matching for age, sex, and same index date, no statistically significant differences in urbanization level and geographical location of the patients' residence were observed. Conclusion. Urbanization did not appear to be an important effect modifier of Kawasaki disease in Taiwan.

Role of Anti-neutrophil Cytoplasmic Antibodies in Kawasaki Disease

Background: Kawasaki disease (KD) is characterized by systemic vasculitis and may lead to coronary artery ectasia and aneurysm. Autoantibodies, in particular anti-neutrophil cytoplasmic antibodies (ANCAs), have been identified in association with the vasculitis. The relationship between ANCAs and KD is unclear. The purpose of this study is to investigate the role of ANCAs in KD in Taiwan. Methods: We assessed ANCAs in 10 KD patients (6 male and 4 female; age range, 4 months to 3 years) between January and December 2003. Results: Cytoplasmic (c)-ANCA staining was absent in all patients, but 5 patients showed perinuclear (p)-ANCA staining. C-reactive protein levels were significantly higher in p- ANCA-positive than p-ANCA-negative KD patients (12.672±3.05 vs. 4.186±2.60 mg．dL^-1, respectively; P ＜ 0.01); there was no significant difference in age, white blood cell count, or clinical presentation. Conclusions: Our data showed that CRP levels were significantly higher in p-ANCA-positive patients and c-ANCA was negative in all KD patients. Neither c-ANCA nor p-ANCA was linked to coronary artery abnormalities in KD patients, suggesting that ANCAs may play only a minor role in the pathogenesis of KD.

IL-10 Promoter Genetic Polymorphisms and Risk of Kawasaki Disease in Taiwan

Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (−1082, −819, and −592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci −819 T &gt; C and −592 A &gt; C for KD cases was observed (Ppermutation= 0.029 and Ppermutation= 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p= 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090–2.443; Ppermutation= 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. {The haplotype CC (−819, −592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987–1.797;p= 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant,p= 0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T &gt; C and −592A &gt; C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.

IL-10 promoter genetic polymorphisms and risk of Kawasaki disease in Taiwan.

Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (−1082, −819, and −592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci −819 T > C and −592 A > C for KD cases was observed (Ppermutation = 0.029 and Ppermutation = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090–2.443; Ppermutation = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. {The haplotype CC (−819, −592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987–1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p = 0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and −592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.

Epidemiologic Features of Kawasaki Disease in Taiwan, 2003–2006

Kawasaki disease is the leading cause of acquired heart disease in children worldwide. This study characterizes the epidemiology of Kawasaki disease in Taiwan between 2003 and 2006. Using Taiwan's 2003-2006 national health insurance claims, we investigated the epidemiologic features of Kawasaki disease (ICD-9-CM code 446.1) and coronary artery aneurysm formation (International Classification of Diseases, Ninth Revision, Clinical Modification code 414.11) and compared the incidences of these diseases with those occurring between 1996 and 2002 in Taiwan and those reported by other countries. During our 4-year study period, 3877 children and adolescents <20 years of age were hospitalized for Kawasaki disease. Ninety percent of these children were <5 years of age, and the male/female ratio was 1.62:1. The annual incidence of Kawasaki disease was 153 in 100000 children <1 year of age, 111 in children 1 year of age, 58 in children 2 years of age, 30 in children 3 years of age, 19 in children 4 years of age, and 5.2 in children 5 to 9 years of age. The overall incidence was 69 cases per 100000 for children <5 years of age. Kawasaki disease recurred in 1.5% of all cases. Kawasaki disease occurred most frequently in the summer and least frequently in the winter. Coronary artery aneurysm occurred in 7.2% (279 of 3877) of all Kawasaki disease cases. The overall incidence of Kawasaki disease was 69 in 100000 children <5 years of age between 2003 and 2006 in Taiwan, comparable with the incidence of 66 in 100000 children between 1996 and 2002. Taiwan has the third highest incidence of Kawasaki disease in the world, after Japan and Korea. In Taiwan, it occurs more frequently during the summer.

Lack of Association between Infection with a Novel Human Coronavirus (HCoV), HCoV‐NH, and Kawasaki Disease in Taiwan

We investigated whether infection with a novel human coronavirus (HCoV), called “New Haven coronavirus” (HCoV-NH)—which is similar to and likely represents the same species as another novel HCoV, HCoV-NL63—is associated with Kawasaki disease (KD) in Taiwan. Fifty-three patients with KD were enrolled in our study. Serum, peripheral-blood mononuclear cells, nasopharyngeal aspirates, throat swabs, and rectal swabs from these patients were assayed for HCoV-NL63 by real-time reverse-transcriptase (RT) polymerase chain reaction (PCR), and the throat swabs, nasopharyngeal aspirates, and rectal swabs were also assayed for HCoV-NH by RT-PCR. All PCR results were negative for both HCoV-NL63 and HCoV-NH; therefore, we did not find any association between HCoV-NH infection and KD in Taiwan

Epidemiologic Features of Kawasaki Disease in Taiwan, 1996–2002

Kawasaki disease (KD) is the most common acquired heart disease in children worldwide. The incidence of KD varies among different countries, with Asian countries supposedly having higher incidences than Western countries. However, the incidence of KD in Taiwan has not been well investigated. Since the implementation of Taiwan's National Health Insurance (NHI) in 1995, NHI has covered health care for >96% its population. Using the NHI database from 1996 to 2002, we investigated epidemiologic features of KD (International Classification of Diseases, Ninth Revision, code 446.1), the rate of coronary artery aneurysm formation (International Classification of Diseases, Ninth Revision, code 414.11), and the change in incidence during the recent 7 years. We also compared the annual incidences in Taiwan with those reported by other countries. During the 7-year study period, KD occurred most frequently in the summer and least frequently in winter. It is interesting that the highest peak occurred in the summer of 1998 at the same time that Taiwan's enterovirus 71 epidemic was occurring. Ninety-one percent of KD cases occurred in children who were <5 years old, and the male-to-female ratio was 1.70:1. Recurrence of KD was found in 1.3% (94 of 7305) of these children, and coronary artery aneurysm was found in 7.3% (536 of 7305). The annual incidence per 100,000 children was 146 in children <1 year old, 98 in 1-year-old children, 51 in 2-year-old children, 28 in 3-year-old children, 19 in 4-year-old children, and 5.3 in 5- to 9-year-old children; the incidence of KD decreased with increased age. The overall incidence was 66 cases per 100,000 children <5 years old from 1996 to 2002 with the annual incidence not differing significantly during the 7-year study period. KD in Taiwan occurs more frequently in boys and in the summer months. During the 7-year study period, the annual KD incidence in Taiwan of 66/100000 in children <5 years old was the second highest in the world after Japan.

Kawasaki Disease in Taiwan: A 4th Nationwide Survey, 1994-2000

A Kawasaki disease (KD) survey, 4th nationwide survey was performed retrospectively to evaluate the morbidity and mortality of KD during 1994-2000 in Taiwan. This study was the continuation of past three surveillances since 1976, when the first case appeared. A specially designed questionnaire was sent to all the major hospitals, with 100 or more beds, to collect the number of patients encountered in each hospital, data with identification numbers (ID), sex, age, coronary lesions. The total number of KD cases (1994-2000; n=4892) and incidents were also increased in this survey (year 2000 = 53.33) with two out breaks in 1996 and 1998. Annual incidence were calculated on mid year population of less than 5 years of age. Male to female ratio was 1.7:1 and still showed constant male (n = 3079) dominant ratio. The patients below 2, 2 to 4 and above 4 years were 57%, 27% and 16% respectively. 84% cases (n = 4118) were below 4 years of age. Highest number of cases were reported by northern provinces (n=2142) then followed by south (n=1401) which was same as the previous survey. Early coronary artery dilatation was noted in 1329 cases (27.18%). Fatality rate has come down to 0.06% (n=3) when compared to 0.4 and 0.2% in the previous surveillance. Increasing numbers of patients with peaks, every 2-3 years suggested the possibility of unknown infectious agents playing the role in etiology. The present day advances could not decrease the prevalence rate but improved long-term outcomes significantly.