G Model
ARTICLE IN PRESS
JVAC-15867; No. of Pages 6
Vaccine xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006 Joseph Y. Abrams a,∗ , Eric S. Weintraub b , James M. Baggs b , Natalie L. McCarthy b , Lawrence B. Schonberger a , Grace M. Lee c , Nicola P. Klein d , Edward A. Belongia e , Michael L. Jackson f , Allison L. Naleway g , James D. Nordin h , Simon J. Hambidge i , Ermias D. Belay a a
Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, United States Immunization Safety Office, Division of Healthcare Quality and Promotion, Centers for Disease Control and Prevention, Atlanta, GA, United States c Harvard Pilgrim Health Care Institute, Boston, MA, United States d Kaiser Permanente Vaccine Study Center, Oakland, CA, United States e Marshfield Clinic Research Foundation, Marshfield, WI, United States f Group Health Research Institute, Seattle, WA, United States g Kaiser Permanente Northwest, Portland, OR, United States h HealthPartners Research Foundation, Minneapolis, MN, United States i Kaiser Permanente Colorado, Denver, CO, United States b
a r t i c l e
i n f o
Article history: Received 5 August 2014 Received in revised form 21 October 2014 Accepted 24 October 2014 Available online xxx Keywords: Kawasaki disease Vaccine Safety Datalink Adverse events Vasculitis
a b s t r a c t Background: Kawasaki disease is a childhood vascular disorder of unknown etiology. Concerns have been raised about vaccinations being a potential risk factor for Kawasaki disease. Methods: Data from the Vaccine Safety Datalink were collected on children aged 0–6 years at seven managed care organizations across the United States. Defining exposure as one of several time periods up to 42 days after vaccination, we conducted Poisson regressions controlling for age, sex, season, and managed care organization to determine if rates of physician-diagnosed and verified Kawasaki disease were elevated following vaccination compared to rates during all unexposed periods. We also performed case-crossover analyses to control for unmeasured confounding. Results: A total of 1,721,186 children aged 0–6 years from seven managed care organizations were followed for a combined 4,417,766 person-years. The rate of verified Kawasaki disease was significantly lower during the 1–42 days after vaccination (rate ratio = 0.50, 95% CL = 0.27–0.92) and 8–42 days after vaccination (rate ratio = 0.45, 95% CL = 0.22–0.90) compared to rates during unexposed periods. Breaking down the analysis by vaccination category did not identify a subset of vaccines which was solely responsible for this association. The case-crossover analyses revealed that children with Kawasaki disease had lower rates of vaccination in the 42 days prior to symptom onset for both physician-diagnosed Kawasaki disease (rate ratio = 0.79, 95% CL = 0.64–0.97) and verified Kawasaki disease (rate ratio = 0.38, 95% CL = 0.20–0.75). Conclusions: Childhood vaccinations’ studied did not increase the risk of Kawasaki disease; conversely, vaccination was associated with a transient decrease in Kawasaki disease incidence. Verifying and understanding this potential protective effect could yield clues to the underlying etiology of Kawasaki disease. © 2014 Published by Elsevier Ltd.
1. Introduction
∗ Corresponding author. Tel.: +1 404 639 5121; fax: +1 404 235 0299. E-mail address: [email protected] (J.Y. Abrams).
Kawasaki disease (KD) is a self-limited febrile vasculitis which primarily affects young children. Typical clinical presentation for KD includes high-grade fever often lasting longer than 5 days, bilateral conjunctival injection, rash, swelling of the hands and feet, swollen cervical lymph nodes, and inflammation of the lips and
http://dx.doi.org/10.1016/j.vaccine.2014.10.044 0264-410X/© 2014 Published by Elsevier Ltd.
Please cite this article in press as: Abrams JY, et al. Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006. Vaccine (2014), http://dx.doi.org/10.1016/j.vaccine.2014.10.044
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ARTICLE IN PRESS J.Y. Abrams et al. / Vaccine xxx (2014) xxx–xxx
2
tongue. If left untreated, KD can cause coronary artery aneurysms in 20–25% of patients, as well as other serious cardiac complications. Treatment with intravenous immunoglobulin within 10 days of illness onset markedly reduces the risk of these complications [1]. In the United States, hospitalizations attributed to KD occur at a rate of approximately 20 cases per 100,000 children aged
ARTICLE IN PRESS
JVAC-15867; No. of Pages 6
Vaccine xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006 Joseph Y. Abrams a,∗ , Eric S. Weintraub b , James M. Baggs b , Natalie L. McCarthy b , Lawrence B. Schonberger a , Grace M. Lee c , Nicola P. Klein d , Edward A. Belongia e , Michael L. Jackson f , Allison L. Naleway g , James D. Nordin h , Simon J. Hambidge i , Ermias D. Belay a a
Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, United States Immunization Safety Office, Division of Healthcare Quality and Promotion, Centers for Disease Control and Prevention, Atlanta, GA, United States c Harvard Pilgrim Health Care Institute, Boston, MA, United States d Kaiser Permanente Vaccine Study Center, Oakland, CA, United States e Marshfield Clinic Research Foundation, Marshfield, WI, United States f Group Health Research Institute, Seattle, WA, United States g Kaiser Permanente Northwest, Portland, OR, United States h HealthPartners Research Foundation, Minneapolis, MN, United States i Kaiser Permanente Colorado, Denver, CO, United States b
a r t i c l e
i n f o
Article history: Received 5 August 2014 Received in revised form 21 October 2014 Accepted 24 October 2014 Available online xxx Keywords: Kawasaki disease Vaccine Safety Datalink Adverse events Vasculitis
a b s t r a c t Background: Kawasaki disease is a childhood vascular disorder of unknown etiology. Concerns have been raised about vaccinations being a potential risk factor for Kawasaki disease. Methods: Data from the Vaccine Safety Datalink were collected on children aged 0–6 years at seven managed care organizations across the United States. Defining exposure as one of several time periods up to 42 days after vaccination, we conducted Poisson regressions controlling for age, sex, season, and managed care organization to determine if rates of physician-diagnosed and verified Kawasaki disease were elevated following vaccination compared to rates during all unexposed periods. We also performed case-crossover analyses to control for unmeasured confounding. Results: A total of 1,721,186 children aged 0–6 years from seven managed care organizations were followed for a combined 4,417,766 person-years. The rate of verified Kawasaki disease was significantly lower during the 1–42 days after vaccination (rate ratio = 0.50, 95% CL = 0.27–0.92) and 8–42 days after vaccination (rate ratio = 0.45, 95% CL = 0.22–0.90) compared to rates during unexposed periods. Breaking down the analysis by vaccination category did not identify a subset of vaccines which was solely responsible for this association. The case-crossover analyses revealed that children with Kawasaki disease had lower rates of vaccination in the 42 days prior to symptom onset for both physician-diagnosed Kawasaki disease (rate ratio = 0.79, 95% CL = 0.64–0.97) and verified Kawasaki disease (rate ratio = 0.38, 95% CL = 0.20–0.75). Conclusions: Childhood vaccinations’ studied did not increase the risk of Kawasaki disease; conversely, vaccination was associated with a transient decrease in Kawasaki disease incidence. Verifying and understanding this potential protective effect could yield clues to the underlying etiology of Kawasaki disease. © 2014 Published by Elsevier Ltd.
1. Introduction
∗ Corresponding author. Tel.: +1 404 639 5121; fax: +1 404 235 0299. E-mail address: [email protected] (J.Y. Abrams).
Kawasaki disease (KD) is a self-limited febrile vasculitis which primarily affects young children. Typical clinical presentation for KD includes high-grade fever often lasting longer than 5 days, bilateral conjunctival injection, rash, swelling of the hands and feet, swollen cervical lymph nodes, and inflammation of the lips and
http://dx.doi.org/10.1016/j.vaccine.2014.10.044 0264-410X/© 2014 Published by Elsevier Ltd.
Please cite this article in press as: Abrams JY, et al. Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006. Vaccine (2014), http://dx.doi.org/10.1016/j.vaccine.2014.10.044
G Model JVAC-15867; No. of Pages 6
ARTICLE IN PRESS J.Y. Abrams et al. / Vaccine xxx (2014) xxx–xxx
2
tongue. If left untreated, KD can cause coronary artery aneurysms in 20–25% of patients, as well as other serious cardiac complications. Treatment with intravenous immunoglobulin within 10 days of illness onset markedly reduces the risk of these complications [1]. In the United States, hospitalizations attributed to KD occur at a rate of approximately 20 cases per 100,000 children aged
