Pediatrics
February 2015, VOLUME 135 / ISSUE 2
http://pediatrics.aappublications.org/current.shtml

Article
Safety of Measles-Containing Vaccines in 1-Year-Old Children
Nicola P. Klein, MD, PhDa, Edwin Lewis, MPHa, Bruce Fireman, MAa, Simon J. Hambidge, MD, hDb, Allison Naleway, PhDc, Jennifer C. Nelson, PhDd, Edward A. Belongia, MDe, W. Katherine Yih, PhD, MPHf, James D. Nordin, MD, MPHg, Rulin C. Hechter, MD, PhDh, Eric Weintraub, MPHi, and Roger Baxter, MDa
Author Affiliations
aKaiser Permanente Vaccine Study Center, Oakland, California;
bKaiser Permanente Colorado Institute for Health Research, Denver and Department of Ambulatory Care Services, Denver Health, Denver, Colorado;
cThe Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon;
dGroup Health Cooperative and the University of Washington, Seattle, Washington;
eCenter for Clinical Epidemiology & Population Health, Marshfield Clinic Research Foundation, Marshfield, Wisconsin;
fHarvard Pilgrim Health Care Institute, Boston, Massachusetts;
gHealthPartners Research Foundation, Minneapolis, Minnesota;
hResearch and Evaluation, Kaiser Permanente Southern California, Pasadena, California; and
iImmunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia
Abstract
BACKGROUND AND OBJECTIVES: All measles-containing vaccines are associated with several types of adverse events, including seizure, fever, and immune thrombocytopenia purpura (ITP). Because the measles-mumps-rubella-varicella (MMRV) vaccine compared with the separate measles-mumps-rubella (MMR) and varicella (MMR + V) vaccine increases a toddler’s risk for febrile seizures, we investigated whether MMRV is riskier than MMR + V and whether either vaccine elevates the risk for additional safety outcomes.
METHODS: Study children were aged 12 to 23 months in the Vaccine Safety Datalink from 2000 to 2012. Nine study outcomes were investigated: 7 main outcomes (anaphylaxis, ITP, ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease), seizure, and fever. Comparing MMRV with MMR + V, relative risk was estimated by using stratified exact binomial tests. Secondary analyses examined post-MMRV or MMR + V risk versus comparison intervals; risk and comparison intervals were then contrasted for MMRV versus MMR+V.
RESULTS: We evaluated 123 200 MMRV and 584 987 MMR + V doses. Comparing MMRV with MMR + V, risks for the 7 main outcomes were not significantly different. Several outcomes had few or zero postvaccination events. Comparing risk versus comparison intervals, ITP risk was higher after MMRV (odds ratio [OR]: 11.3 [95% confidence interval (CI): 1.9 to 68.2]) and MMR + V (OR: 10 [95% CI: 4.5 to 22.5]) and ataxia risk was lower after both vaccines (MMRV OR: 0.8 [95% CI: 0.5 to 1]; MMR + V OR: 0.8 [95% CI: 0.7 to 0.9]). Compared with MMR + V, MMRV increased risk of seizure and fever 7 to 10 days after vaccination.
CONCLUSIONS: This study did not identify any new safety concerns comparing MMRV with MMR + V or after either the MMRV or the MMR + V vaccine. This study provides reassurance that these outcomes are unlikely after either vaccine.

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Article
Variation in Rotavirus Vaccine Coverage by Provider Location and Subsequent Disease Burden
Leila C. Sahni, MPHa, Jacqueline E. Tate, PhDb, Daniel C. Payne, PhD, MSPHb, Umesh D. Parashar, MBBS, MPHb, and Julie A. Boom, MDa,c
Author Affiliations
aImmunization Project, Texas Children’s Hospital, Houston, Texas;
bDivision of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and
cDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas
Abstract
BACKGROUND: Rotavirus vaccines were introduced in the United States in 2006. Full-series coverage is lower than for other vaccines, and disease continues to occur. We examined variation in vaccine coverage among provider locations and correlated coverage with the detection of rotavirus in children who sought treatment of severe acute gastroenteritis (AGE).
METHODS: Vaccine records of children enrolled in an AGE surveillance program were obtained and children were grouped by the location that administered each child’s 2-month vaccines. Cases were children with laboratory-confirmed rotavirus AGE; controls were children with rotavirus-negative AGE or acute respiratory infection. Location-level coverage was calculated using ≥1 dose rotavirus vaccine coverage among controls and classified as low (<40%), medium (≥40% to <80%), or high (≥80%). Rotavirus detection rates among patients with AGE were calculated by vaccine coverage category.
RESULTS: Of controls, 80.4% (n = 1123 of 1396) received ≥1 dose of rotavirus vaccine from 68 locations. Four (5.9%) locations, including a NICU, were low coverage, 22 (32.3%) were medium coverage, and 42 (61.8%) were high coverage. In low-coverage locations, 31.4% of patients with AGE were rotavirus-positive compared with 13.1% and 9.6% in medium- and high-coverage locations, respectively. Patients with AGE from low-coverage locations had 3.3 (95% confidence interval 2.4–4.4) times the detection rate of rotavirus than patients with AGE from high vaccine coverage locations.
CONCLUSIONS: We observed the highest detection of rotavirus disease among locations with low rotavirus vaccine coverage, suggesting that ongoing disease transmission is related to failure to vaccinate. Educational efforts focusing on timely rotavirus vaccine administration to age-eligible infants are needed.

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Article
Geographic Clusters in Underimmunization and Vaccine Refusal
Tracy A. Lieu, MD, MPHa, G. Thomas Ray, MBAa, Nicola P. Klein, MD, PhDa,b, Cindy Chung, MDc, and Martin Kulldorff, PhDd
Author Affiliations
aDivision of Research, Kaiser Permanente Northern California, Oakland, California;
bVaccine Study Center, Kaiser Permanente, Oakland, California;
cDepartment of Pediatrics, San Rafael Medical Center, Kaiser Permanente Northern California, San Rafael, California; and
dDepartment of Population Medicine, Harvard Pilgrim Health Care and Harvard Medical School, Boston, Massachusetts
Abstract
BACKGROUND AND OBJECTIVE: Parental refusal and delay of childhood vaccines has increased in recent years and is believed to cluster in some communities. Such clusters could pose public health risks and barriers to achieving immunization quality benchmarks. Our aims were to (1) describe geographic clusters of underimmunization and vaccine refusal, (2) compare clusters of underimmunization with different vaccines, and (3) evaluate whether vaccine refusal clusters may pose barriers to achieving high immunization rates.
METHODS: We analyzed electronic health records among children born between 2000 and 2011 with membership in Kaiser Permanente Northern California. The study population included 154 424 children in 13 counties with continuous membership from birth to 36 months of age. We used spatial scan statistics to identify clusters of underimmunization (having missed 1 or more vaccines by 36 months of age) and vaccine refusal (based on International Classification of Diseases, Ninth Revision, Clinical Modification codes).
RESULTS: We identified 5 statistically significant clusters of underimmunization among children who turned 36 months old during 2010–2012. The underimmunization rate within clusters ranged from 18% to 23%, and the rate outside them was 11%. Children in the most statistically significant cluster had 1.58 (P < .001) times the rate of underimmunization as others. Underimmunization with measles, mumps, rubella vaccine and varicella vaccines clustered in similar geographic areas. Vaccine refusal also clustered, with rates of 5.5% to 13.5% within clusters, compared with 2.6% outside them.
CONCLUSIONS: Underimmunization and vaccine refusal cluster geographically. Spatial scan statistics may be a useful tool to identify locations with challenges to achieving high immunization rates, which deserve focused intervention.

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Review Article
Duration of Pertussis Immunity After DTaP Immunization: A Meta-analysis
Ashleigh McGirr, MPH and David N. Fisman, MD, MPH, FRCPC
Author Affiliations
Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
Abstract
BACKGROUND AND OBJECTIVES: Pertussis incidence is increasing, possibly due to the introduction of acellular vaccines, which may have decreased the durability of immune response. We sought to evaluate and compare the duration of protective immunity conferred by a childhood immunization series with 3 or 5 doses of diphtheria-tetanus-acellular pertussis (DTaP).
METHODS: We searched Medline and Embase for articles published before October 10, 2013. Included studies contained a measure of long-term immunity to pertussis after 3 or 5 doses of DTaP. Twelve articles were eligible for inclusion; 11 of these were included in the meta-analysis. We assessed study quality and used meta-regression models to evaluate the relationship between the odds of pertussis and time since last dose of DTaP and to estimate the probability of vaccine failure through time.
RESULTS: We found no significant difference between the annual odds of pertussis for the 3- versus 5-dose DTaP regimens. For every additional year after the last dose of DTaP, the odds of pertussis increased by 1.33 times (95% confidence interval: 1.23–1.43). Assuming 85% vaccine efficacy, we estimated that 10% of children vaccinated with DTaP would be immune to pertussis 8.5 years after the last dose. Limitations included the statistical model extrapolated from data and the different study designs included, most of which were observational study designs.
CONCLUSIONS: Although acellular pertussis vaccines are considered safer, the adoption of these vaccines may necessitate earlier booster vaccination and repeated boosting strategies to achieve necessary “herd effects” to control the spread of pertussis.

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Quality Report
Quality Improvement Initiative to Increase Influenza Vaccination in Pediatric Cancer Patients
Jason L. Freedman, MD, MSCEa, Anne F. Reilly, MD, MPHa,b, Stephanie C. Powell, MSNc, and
L. Charles Bailey, MD, PhDa,b
Author Affiliations
aDivision of Oncology, and
cDepartment of Nursing, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and
bDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Abstract
BACKGROUND: Pediatric patients with cancer face more severe complications of influenza than healthy children. Although Centers for Disease Control and Prevention guidelines recommend yearly vaccination in these patients, in our large academic center, <60% of oncology patients receiving chemotherapy were immunized at baseline. Our objective was to increase this rate through a multifaceted quality improvement initiative.
METHODS: Eligible patients were >6 months old, within 1 year of receiving chemotherapy, >100 days from stem cell transplant, and had ≥1 outpatient oncology visit between September 1, 2012, and March 31, 2013. Five interventions were instituted concomitantly: (1) family education: influenza/vaccine handouts were provided to families in clinic waiting rooms; (2) health informatics: daily lists of outpatients due for immunization were generated from the electronic medical record and sent automatically to triage staff and nurses; (3) outpatient clinic: patients due for vaccination were given colored wristbands during triage to alert providers; (4) inpatient: vaccine order was built into admission order set; and (5) provider education: staff education was provided at conferences on screening of patients, vaccine ordering, and documentation of refusals/contraindications.
RESULTS: The complete influenza immunization rate increased by 20.1% to 64.5%, and the proportion of patients receiving ≥1 dose of vaccination increased by 22.9% to 77.7%. Similar changes were noted across all cancer types, with highest rates of immunization in leukemia/lymphoma patients (86.8%) and lowest in patients after stem cell transplant (66.7%).
CONCLUSIONS: Technology, education, and multidisciplinary clinical process changes increased influenza vaccination rates. Ongoing efforts are targeting subgroups with lowest rates of immunization.