Pediatrics
September 2014, VOLUME 134 / ISSUE 3
http://pediatrics.aappublications.org/current.shtml

Article
Long-term Study of a Quadrivalent Human Papillomavirus Vaccine
Daron Ferris, MDa, Rudiwilai Samakoses, MDb, Stan L. Block, MDc, Eduardo Lazcano-Ponce, Dd,
Jaime Alberto Restrepo, MDe, Keith S. Reisinger, MD, MPHf, Jesper Mehlsen, MDg, Archana Chatterjee, MD, PhDh, Ole-Erik Iversen, MDi, Heather L. Sings, PhDj, Qiong Shou, PhDj, Timothy A. Sausser, BSj, and Alfred Saah, MDj
Author Affiliations
aDepartment of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia;
bDepartment of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand;
cKentucky Pediatric and Adult Research, Inc, Bardstown, Kentucky;
dCenter for Research in Population Health, National Institute of Public Health, Cuernavaca Morelos, Mexico;
eClinical Research Center, Medellín, Colombia;
fPrimary Physicians Research, Pittsburgh, Pennsylvania;
gCoordinating Research Centre, Frederiksberg Hospital, Frederiksberg, Denmark;
hDepartment of Pediatrics, University of South Dakota Sanford School of Medicine, Sanford Children’s Specialty Clinics, Sioux Falls, South Dakota;
iDepartment of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; and
jMerck & Co., Inc, Whitehouse Station, New Jersey
Abstract
BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine.
METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6. At month 30, the placebo group (n = 482) received HPV4 vaccine following the same regimen and both cohorts were followed through month 96. Subjects ≥16 years were eligible for effectiveness evaluations. The primary objective was to evaluate the long-term anti-HPV6/11/16/18 serological levels. The secondary objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease.
RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti-HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none developed HPV6/11/16/18-related disease or persistent infection of ≥12 months’ duration. Acquisition of new sexual partners (among those ≥16 years) was ∼1 per year. Subjects receiving HPV4 vaccine at month 30 (mean age 15 years) had a similar baseline rate of seropositivity to ≥1 of the 4 HPV types to those vaccinated at day 1 (mean age 12 years; 1.9% [9 of 474] vs 1.7% [20 of 1157]); however, 4 of the 9 subjects vaccinated at the later age were seropositive to 3 vaccine types, indicating previous HPV exposure. No new significant serious adverse events were observed for 8 years postvaccination in both genders.
CONCLUSIONS: When administered to adolescents, the HPV4 vaccine demonstrated durability in clinically effective protection and sustained antibody titers over 8 years.

Article
Missed Opportunities for HPV Vaccination in Adolescent Girls: A Qualitative Study
Rebecca B. Perkins, MD, MSca, Jack A. Clark, PhDb,c, Gauri Apte, MB, BS, MPHc, Jessica L. Vercruysse, MAa, Justen J. Sumner, MD, MPHa, Constance L. Wall-Haas, DNP, PPCNP-BCd,
Anna W. Rosenquist, MDe, and Natalie Pierre-Joseph, MD, MPHa
Author Affiliations
aBoston University School of Medicine, Boston, Massachusetts;
bEdith Nourse Rogers Memorial Veterans Hospital–Bedford, Bedford, Massachusetts;
cBoston University School of Public Health, Boston, Massachusetts;
dHarvard Vanguard Medical Associates, Chelsmford, Massachusetts; and
eHarvard Vanguard Medical Associates, Burlington, Massachusetts
Abstract
OBJECTIVE: The goal of this study was to identify the rationale by parents/guardians and providers for delaying or administering human papillomavirus (HPV) vaccination to girls.
METHODS: Qualitative interviews were conducted with parents/guardians accompanying their vaccine-eligible 11- to 17-year-old daughters to medical visits. Interviews were conducted in 1 public clinic and 3 private practice settings to ascertain why girls did or did not receive HPV vaccination. Questions probed vaccine decision-making from the point of view of parents/guardians and providers.
RESULTS: A total of 124 parents/guardians and 37 providers participated. The most common reasons parents reported for not vaccinating their daughters was the lack of a physician recommendation (44%). Both parents and providers believed that HPV vaccination provided important health benefits, but the timing of vaccination with relation to sexual activity was an important theme related to vaccine delay. Providers with lower self-reported vaccination rates delayed vaccine recommendations in girls perceived to be at low risk for sexual activity, and several parents reported that their providers suggested or supported delaying vaccination until their daughters were older. However, parents/guardians and providers agreed that predicting the timing of sexual debut was extremely difficult. In contrast, providers with high vaccination rates presented HPV vaccination as a routine vaccine with proven safety to prevent cancer, and parents responded positively to these messages.
CONCLUSIONS: Although most parents and providers believe that HPV vaccination is important, missed opportunities result from assumptions about the timing of vaccination relative to sexual activity. Routinely recommending HPV vaccination as cancer prevention to be coadministered with other vaccines at age 11 years can improve vaccination rates

Article
Vaccine Message Framing and Parents’ Intent to Immunize Their Infants for MMR
Kristin S. Hendrix, PhDa,b, S. Maria E. Finnell, MD, MSa,b,c, Gregory D. Zimet, PhDa, Lynne A. Sturm, PhDa, Kathleen A. Lane, MSd, and Stephen M. Downs, MD, MSa,b
Author Affiliations
aDepartments of Pediatrics, and
dBiostatistics, Indiana University School of Medicine, Indianapolis, Indiana;
bRegenstrief Institute, Inc, Indianapolis, Indiana; and
cRyan White Center for Pediatric Infectious Disease, Riley Hospital for Children, Indianapolis, Indiana
Abstract
BACKGROUND AND OBJECTIVE: Emphasizing societal benefits of vaccines has been linked to increased vaccination intentions in adults. It is unclear if this pattern holds for parents deciding whether to vaccinate their children. The objective was to determine whether emphasizing the benefits of measles-mumps-rubella (MMR) vaccination directly to the vaccine recipient or to society differentially impacts parents’ vaccine intentions for their infants.
METHODS: In a national online survey, parents (N = 802) of infants RESULTS: Compared with the VIS-only group (mean intention = 86.3), parents reported increased vaccine intentions for their infants when receiving additional information emphasizing the MMR vaccine’s benefits either directly to the child (mean intention = 91.6, P = .01) or to both the child and society (mean intention = 90.8, P = .03). Emphasizing the MMR vaccine’s benefits only to society did not increase intentions (mean intention = 86.4, P = .97).
CONCLUSIONS: We did not see increases in parents’ MMR vaccine intentions for their infants when societal benefits were emphasized without mention of benefits directly to the child. This finding suggests that providers should emphasize benefits directly to the child. Mentioning societal benefits seems to neither add value to, nor interfere with, information highlighting benefits directly to the child.

Article
Impact of a Pertussis Epidemic on Infant Vaccination in Washington State
Elizabeth R. Wolf, MD, MPHa,b, Douglas Opel, MD, MPHa,b, M. Patricia DeHart, ScDc,
Jodi Warren, BSNd, and Ali Rowhani-Rahbar, MD, MPH, PhDe
Author Affiliations
aSeattle Children’s Research Institute, Seattle, Washington;
Departments of bPediatrics, and
eEpidemiology, University of Washington, Seattle, Washington;
cWashington State Department of Health, Olympia, Washington; and
dWashington State Immunization Information System, Seattle, Washington
Abstract
BACKGROUND AND OBJECTIVES: Washington State experienced a pertussis epidemic from October 2011 to December 2012. There was wide variation in incidence by county. The objectives of this study were to determine how the pertussis epidemic affected infant vaccination in Washington State and whether the incidence in counties modified this effect.
METHODS: We conducted an ecologic before–after study to compare the proportion of infants up to date (UTD) with a pertussis-containing vaccine at time points before (September 30, 2011), during (September 30, 2012), and after (September 30, 2013) the epidemic. Children aged 3 to 8 months enrolled in the Washington State Immunization Information System with documented county of residence were included. UTD status was determined as ≥1, ≥2, or ≥3 doses of a pertussis-containing vaccine at ages 3, 5, and 7 months, respectively. Generalized linear models with extension to the binomial family and clustered robust standard errors were used to examine differences in the proportion of UTD infants between preepidemic and either epidemic or postepidemic points. The potential modifying effect of pertussis incidence by county was examined.
RESULTS: We found no significant difference in statewide UTD status with a pertussis-containing vaccine between preepidemic and either epidemic (absolute difference 2.1%; 95% confidence interval, −1.6 to 5.9) or postepidemic (absolute difference 0.2%; 95% confidence interval, −4.0 to 4.5) time points. There was no significant modification by county pertussis incidence. There was wide variation in the absolute difference in UTD status across counties.
CONCLUSIONS: A statewide pertussis epidemic does not appear to have significantly changed the proportion of infants who were UTD with a pertussis-containing vaccine.

Commentary
Pertussis Resurgence and Vaccine Uptake: Implications for Reducing Vaccine Hesitancy
Jessica E. Atwell, MPHa,b and Daniel A. Salmon, PhD, MPHa,b,c,d
Author Affiliations
aGlobal Disease Epidemiology and Control,
cHealth, Behavior, and Society,
bDepartment of International Health, and
dInstitute for Vaccine Safety, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
Previously controlled vaccine preventable diseases (VPDs) are in resurgence.1,2 To date, there have been 477 confirmed measles cases in the United States in 2014, the most in 18 years.3 In 2013 there were ∼25 000 pertussis cases in the United States. Vaccine refusal has been associated with outbreaks of invasive Haemophilus influenzae type b disease,4 varicella,5 pneumococcal disease,6 measles,7 and pertussis.8–12
Even while national and statewide immunization coverage remain high, rates of parents who refuse vaccines via nonmedical exemptions (NMEs) to school immunization requirements have been increasing.13,14 Furthermore, NMEs cluster geographically,9,10 leading to critical reductions in herd immunity and a perfect storm for sustained transmission, outbreaks, and increased risk of VPDs to both unvaccinated and vaccinated individuals.7,9,10,15,16
Beyond active refusal, many parents are delaying vaccines and using “alternative immunization schedules” to spread out the number of vaccines given per visit or in infancy.17 Seventy-seven percent of parents of young children report concerns about vaccines, such as the number of vaccines or doses given simultaneously or before age two, what ingredients are contained in vaccines, or if there are associations with adverse outcomes such as autism and other chronic diseases.18 Some have gone so far as to identify a “vaccine crisis in confidence…”19–21