Pediatrics
July 2015, VOLUME 136 / ISSUE 1
http://pediatrics.aappublications.org/current.shtml

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Article
Pneumococcal Conjugate Vaccine and Clinically Suspected Invasive Pneumococcal Disease
Arto A. Palmu, MD, PhDa, Terhi M. Kilpi, MD, PhDb, Hanna Rinta-Kokko, MScb, Hanna Nohynek, MD, PhDb, Maija Toropainen, PhDc, J. Pekka Nuorti, MD, PhDc,d, and Jukka Jokinen, PhDb
Author Affiliations
aDepartment of Health Protection, National Institute for Health and Welfare, Tampere, Finland;
bDepartment of Health Protection, National Institute for Health and Welfare, Helsinki, Finland;
cDepartment of Infectious Diseases, National Institute for Health and Welfare, Helsinki, Finland; and
dDepartment of Epidemiology, School of Health Sciences, University of Tampere, Finland
Abstract
OBJECTIVE: Ten-valent pneumococcal conjugate vaccine (PCV10) was earlier shown to reduce clinically suspected, non–laboratory-confirmed invasive pneumococcal disease (IPD) in a cluster-randomized trial (the Finnish Invasive Pneumococcal disease trial). PCV10 was introduced into the Finnish national vaccination program in September 2010 using a 3-dose schedule. We evaluated the impact of PCV10 on clinically suspected IPD among vaccine-eligible children in a population-based nationwide study.
METHODS: The target cohort eligible for vaccination program (children born June 2010–September 2013) was compared with 2 season- and age-matched (ages 3–42 months) reference cohorts before PCV10 introduction. The trial period (January 2009–August 2010) was excluded. Hospitals’ inpatient and outpatient discharge notifications with International Classification of Diseases, 10th Revision, diagnoses compatible with IPD (A40.3/B95.3/G00.1/M00.1) and unspecified sepsis (A40.9/A41.9/A49.9/G00/G00.9/I30.1/M00/M00.9/B95.5) were collected from the national Care Register. Laboratory-confirmed IPD cases were excluded. Rates of register-based non–laboratory-confirmed IPD (or unspecified sepsis) before and after PCV10 implementation were calculated.
RESULTS: The rate of register-based non–laboratory-confirmed IPD episodes was 32 in 100 000 person-years in the vaccine-eligible target cohort and 94 in the combined reference cohorts. Relative rate reduction was 66% (95% confidence interval: 59–73) and absolute rate reduction 62 in 100 000 person-years. For the more sensitive case definition of register-based non–laboratory-confirmed IPD or unspecified sepsis, the relative rate reduction was 34% (95% confidence interval 29–39), but the absolute reduction was as high as 122 in 100 000 person-years.
CONCLUSIONS: This is the first report demonstrating nationwide PCV impact on clinically suspected IPD during routine vaccination program. The large absolute rate reductions observed have major implications for cost-effectiveness of PCVs.

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Article
Immunogenicity and Safety of a 9-Valent HPV Vaccine
Pierre Van Damme, MD, PhDa, Sven Eric Olsson, MDb, Stanley Block, MDc, Xavier Castellsague, MDd, Glenda E. Gray, MDe, Teobaldo Herrera, MDf, Li-Min Huang, MDg, Dong Soo Kim, MDh,
Punnee Pitisuttithum, MDi, Joshua Chen, PhDj, Susan Christiano, MSj, Roger Maansson, MSj, Erin Moeller, MPHj, Xiao Sun, PhDj, Scott Vuocolo, PhDj, and Alain Luxembourg, MD, PhDj
Author Affiliations
aCenter for the Evaluation of Vaccination, University of Antwerp, Antwerp, Belgium;
bKarolinska Institute at Danderyd Hospital, Uppsala, Sweden;
cKentucky Pediatric/Adult Research, Inc, Bardstown, Kentucky;
dInstitut Català d’Oncologia, IDIBELL, CIBERESP, L’Hospitalet De Llobregat, Catalonia, Spain;
eDepartment of Pediatrics, University of the Witwatersrand, Johannesburg, South Africa;
fInstituto de Investigation Nutricional, Lima, Peru;
gDivision of Infectious Diseases, Children’s Hospital, National Taiwan University College of Medicine, Taipei, Taiwan;
hDivision of Infectious Disease and Immunology, Department of Pediatrics, Yonsei University College of Medicine, Severance Children’s Hospital, Seoul, Korea;
iFaculty of Tropical Medicine, Mahidol University, Nakhon Pathom, Thailand; and
jMerck and Company, Inc, Whitehouse Station, New Jersey
Abstract
OBJECTIVES: Prophylactic vaccination of youngwomen aged 16 to 26 years with the 9-valent (6/11/16/18/31/33/45/52/58) human papillomavirus (HPV) virus-like particle (9vHPV) vaccine prevents infection and disease. We conducted a noninferiority immunogenicity study to bridge the findings in young women to girls and boys aged 9 to 15 years.
METHODS: Subjects (N = 3066) received a 3-dose regimen of 9vHPV vaccine administered at day 1, month 2, and month 6. Anti-HPV serologic assays were performed at day 1 and month 7. Noninferiority required that the lower bound of 2-sided 95% confidence intervals of geometric mean titer ratios (boys:young women or girls:young women) be >0.67 for each HPV type. Systemic and injection-site adverse experiences (AEs) and serious AEs were monitored.
RESULTS: At 4 weeks after dose 3, >99% of girls, boys, and young women seroconverted for each vaccine HPV type. Increases in geometric mean titers to HPV types 6/11/16/18/31/33/45/52/58 were elicited in all vaccine groups. Responses in girls and boys were noninferior to those of young women. Persistence of anti-HPV responses was demonstrated through 2.5 years after dose 3. Administration of the 9vHPV vaccine was generally well tolerated. A lower proportion of girls (81.9%) and boys (72.8%) than young women (85.4%) reported injection-site AEs, most of which were mild to moderate in intensity.
CONCLUSIONS: These data support bridging the efficacy findings with 9vHPV vaccine in young women 16 to 26 years of age to girls and boys 9 to 15 years of age and implementing gender-neutral HPV vaccination programs in preadolescents and adolescents.

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Article
Personal Belief Exemptions to Vaccination in California: A Spatial Analysis
Margaret Carrel, PhDa,b and Patrick Bitterman, BSa
Author Affiliations
Departments of aGeographical and Sustainability Sciences, and
bEpidemiology, University of Iowa, Iowa City, Iowa
Abstract
BACKGROUND: School vaccination rates in California have fallen as more parents opt for personal belief exemptions (PBEs) for their children. Our goals were to (1) spatially analyze PBE patterns over time, (2) determine correlates of PBEs, and (3) examine their spatial overlap with personal medical exemptions (PMEs).
METHODS: PBE and PME data for California kindergarten classes from the 2001/2002 to 2013/2014 school years were matched to the locations of schools. Nonspatial clustering algorithms were implemented to group 5147 schools according to their trends in PBE percentages among kindergartners. Cluster assignments were mapped and hotspot analysis was performed to find areas in California where schools sharing trends in PBEs over time were colocated. Schools were further associated both with school-level data on minority enrollment and free and reduced price lunch participation and with charter/private and rural/urban status. Spatial regression was implemented to determine which school-level variables were correlated with PBE rates in the 2013/2014 school year.
RESULTS: Distinct spatial patterns are observed in California when PBE cluster assignments are mapped. Results indicate that schools belonging to the “high PBE” cluster are spatially buffered from those in “low PBE” areas by “medium PBE” schools. Further, PBE rates are positively associated with the percentage of white students, charter status, and private schools.
CONCLUSIONS: Hotspots of high PBE schools are in some cases colocated with schools that have elevated PME rates, prompting concern that herd immunity is diminished for school populations where students have no choice but to remain unvaccinated.

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Commentary
Physician Communication With Vaccine-Hesitant Parents: The Start, Not the End, of the Story
Julie Leask, PhD, MPH, Dip App Scia and Paul Kinnersley, MB ChB, MD, FRCGPb
Author Affiliations
aSchool of Public Health, University of Sydney, New South Wales, Australia; and
bInstitute of Medical Education, Cardiff University, Cardiff, Wales, United Kingdom
Extract
In this month’s issue of Pediatrics, Henrikson et al1 report a trial of the impact of communication training for physicians on the vaccine hesitancy of parents. The authors found that a physician-targeted communication intervention did not reduce vaccine hesitancy in mothers nor improve physician confidence compared with standard care. However, the study requires careful interpretation and should be seen as the start, not the end, of the story in finding effective approaches to vaccine hesitancy.
There is a clear need to develop new approaches to vaccine consultation. Although only 0.7% of children in the United States are completely unvaccinated, an estimated 13% of parents delay or select out of certain vaccines,2,3 and the risk of this choice is enhanced by geographic clustering, creating a critical mass for disease outbreaks.4 Even parents who fully vaccinate have some concerns (eg, the number of vaccines, the vaccine ingredients, whether they potentially “damage” the immune system).5,6
To address vaccination concerns, hesitancy, and refusal, some advocate a tougher line with strong physician recommendation, little room for expression of concern, and even …