Safety,immunogenicity and shedding of LAIV4 in HIV-infected and uninfected children

ObjectivesHIV-infected children have poor responses to inactivated influenza vaccines. Live vaccines (LAIVs) are highly efficacious in children, but they are not used in HIV-infected children du e to limited information. We investigated the safety, immunogenicity and viral shedding of LAIV4 in HIV-infected compared with uninfected children.DesignForty-six HIV-infected and 56 uninfected children 2 to 25 years old, who had been previously vaccinated against influenza, consented to receive a single dose of LAIV4. All grade adverse events (AEs) were recorded in the first month post-vaccination and serious AEs (SAEs) throughout the influenza season. Nasopharyngeal swabs for influenza PCR and IgA ELISA and blood for hemagglutination inhibition antibody (HAI) measurements were collected at entry, 2–5, 7–10 and 21–28 days post-vaccination.ResultsThe HIV-infected subjects had median CD4+ cells of 649 cells/μL and plasma HIV RNA of 20 copies/mL. AEs were similar in the two groups. There were no vaccine-related SAEs. Shedding of ≥1 vaccine virus was detected in 67% HIV-infected and 50% uninfected participants (p = 0.14). HAI titers did not appreciably change, but mucosal IgA antibodies significantly increased post-vaccination in both groups. High baseline HAI and IgA antibody concentrations were associated with decreased viral shedding in controls, but not in HIV-infected subjects. Similar proportions of HIV-infected vaccinees and controls reported influenza-like illnesses (12% and 6%) throughout the season.ConclusionsLAIV4 was equally safe and immunogenic and caused similar viral shedding in HIV-infected and uninfected children. A correlate of protection against vaccine viral shedding was not identified in HIV-infected participants, although both circulating and mucosal antibodies correlated with protection in controls.     

Self-administration of intranasal influenza vaccine: Immunogenicity and volunteer acceptance

BackgroundIn outbreak settings, mass vaccination strategies could maximize health protection of military personnel. Self-administration of live attenuated influenza vaccine (LAIV) may be a means to vaccinate large numbers of people and achieve deployment readiness while sparing the use of human resources.MethodsA phase IV, open-label, randomized controlled trial evaluating the immunogenicity and acceptance of self-administered (SA) LAIV was conducted from 2012 to 2014. SA subjects were randomized to either individual self-administration or self-administration in a group setting. Control randomized subjects received healthcare worker-administered (HCWA) LAIV. Anti-hemagglutinin (HAI) antibody concentrations were measured pre- and post-vaccination. The primary endpoint was immunogenicity non-inferiority between SA and HCWA groups. Subjects were surveyed on preferred administration method.ResultsA total of 1077 subjects consented and were randomized (529 SA, 548 HCWA). Subject characteristics were very similar between groups, though SA subjects were younger, more likely to be white and on active duty. The per-protocol analysis included 1024 subjects (501 SA, 523 HCWA). Post-vaccination geometric mean titers by vaccine strain and by study group (HCWA vs. SA) were: A/H1N1 (45.8 vs. 48.7, respectively; p = 0.43), A/H3N2 (45.5 vs. 46.4; p = 0.80), B/Yamagata (17.2 vs. 17.8; p = 0.55). Seroresponses to A components were high (∼67%), while seroresponses to B components were lower (∼25%). Seroresponse did not differ by administration method. Baseline preference for administration method was similar between groups, with the majority in each group expressing no preference. At follow-up, the majority (64%) of SA subjects preferred SA vaccine.ConclusionsLAIV immunogenicity was similar for HCWA and SA vaccines. SA was well-tolerated and preferred to HCWA among those who performed SA.     

Many vaginal microbicide trial participants acknowledged they had misreported sensitive sexual behavior in face-to-face interviews

ObjectiveWe investigated whether participants in a phase II randomized clinical trial of a candidate vaginal microbicide ever intentionally misled interviewers.Study Design and SettingWe used audio computer-assisted self-interviews (ACASI) to ask the South African women (n = 132) participating in the trial about the accuracy of self-reported data collected during face-to-face interviews. The trial protocol recommended that women use their assigned gel (active microbicide or placebo) with condoms during each vaginal sex act.ResultsNearly four-fifths of participants (n = 104, 79%) reported that they had misinformed trial interviewers at least once. Motivations included politeness (n = 45, 34% of ACASI participants) to avoid criticism or seek praise (n = 32, 24%), and embarrassment (n = 24, 18%). Participants acknowledged misreporting eligibility characteristics to enroll (11%) and, during follow-up, exaggerating their enthusiasm for the study gel (13%), applicator (13%), and the effect of the gel on sexual pleasure (13%). In general, women who were untruthful had actually used the gel with condoms less and used the gel alone more than they had reported during the trial. Women overwhelmingly found the computer survey easy.ConclusionResearchers cannot assume that participants always tell the truth about sensitive behaviors in face-to-face interviews. ACASI was efficient and acceptable in this population.     

Factors affecting the causality assessment of adverse events following immunisation in paediatric clinical trials: An online survey

BackgroundSerious adverse events (SAEs) in clinical trials require reporting within 24 h, including a judgment of whether the SAE was related to the investigational product(s). Such assessments are an important component of pharmacovigilance, however classification systems for assigning relatedness vary across study protocols. This on-line survey evaluated the consistency of SAE causality assessment among professionals with vaccine clinical trial experience.MethodsMembers of the clinical advisory forum of experts (CAFÉ), a Brighton Collaboration online-forum, were emailed a survey containing SAEs from hypothetical vaccine trials which they were asked to classify. Participants were randomised to either two classification options (related/not related to study immunisation) or three options (possibly/probably/unrelated). The clinical scenarios, were (i) leukaemia diagnosed 5 months post-immunisation with a live RSV vaccine, (ii) juvenile idiopathic arthritis (JIA) 3 months post-immunisation with a group A streptococcal vaccine, (iii) developmental delay diagnosed at age 10 months after infant capsular group B meningococcal vaccine, (iv) developmental delay diagnosed at age 10 months after maternal immunisation with a group B streptococcal vaccine.ResultsThere were 140 respondents (72 two options, 68 three options). Across all respondents, SAEs were considered related to study immunisation by 28% (leukaemia), 74% (JIA), 29% (developmental delay after infant immunisation) and 42% (developmental delay after maternal immunisation). Having only two options made respondents significantly less likely to classify the SAE as immunisation-related for two scenarios (JIA p = 0.0075; and maternal immunisation p = 0.045). Amongst study investigators (n = 43) this phenomenon was observed for three of the four scenarios: (JIA p = 0.0236; developmental delay following infant immunisation p = 0.0266; and developmental delay after maternal immunisation p = 0.0495).ConclusionsSAE causality assessment is inconsistent amongst study investigators and can be influenced by the classification systems available to them. There is a pressing need for SAE classification systems to be standardised across study protocols.     

Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2–49 years

BackgroundQuadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013–2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2–49 years.MethodsThis was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell’s palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients.ResultsA total of 62,040 eligible Q/LAIV recipients were identified during the 2013–2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2–4, 5–8, 9–17, and 18–49 years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV.ConclusionIn this large population study of individuals aged 2–49 years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person-years.Trial registration: ClinicalTrials.gov NCT01985997     

Hospitalizations within 14 days of vaccination among pediatric recipients of the live attenuated influenza vaccine,United States 2010–2012

BackgroundLive attenuated influenza vaccine (LAIV) is safe in healthy children ⩾2 years. The original clinical trials excluded individuals with underlying conditions; however, post-marketing data suggest LAIV may be safe for these populations.MethodsWe analyzed MarketScan Commercial Claims Databases from 2010 to 2012 to describe hospitalizations within 14 days of vaccination among LAIV recipients. We evaluated LAIV recipients aged 2–18 years and defined underlying conditions by presence of inpatient or outpatient ICD-9 code during the previous calendar year. We excluded asthma and immunocompromising conditions. We defined risk windows as 1–7 days and 8–14 days after vaccination; the control period was 12–4 days prior to and 15–23 days after vaccination. We conducted a self-controlled case series analysis using a conditional Poisson regression model to estimate incidence-rate ratios (IRR).Results1,216,123 children aged 2–18 years received LAIV from 2010 to 2012. 634 children met our inclusion criteria and were hospitalized during the observation period (12 days prior to vaccination to 23 days after vaccination). Of those hospitalized, 72 (11.4%) had non-asthma, non-immunocompromising underlying conditions. Children with non-asthma, non-immunocompromising underlying conditions had an all-cause hospitalization IRR of 1.1 (95% CI 0.6–2.0, p = 0.83) in the 1–7 day risk period and 0.9 (95% CI 0.4–1.7, p = 0.67) in the 8–14 day risk period. Children with no underlying conditions had an all-cause hospitalization IRR of 0.9 (0.8–1.2, p = 0.60) in the 1–7 day risk period and 1.1 (95% CI 0.9–1.3, p = 0.53) in the 8–14 day risk period. There were no differences in all-cause hospitalization risk in individuals with non-asthma, non-immunocompromising underlying conditions compared to those without underlying conditions in the 1–7 day (p = 0.88) or 8–14 day (p = 0.24) risk period.ConclusionsWe found no evidence of differences in post-LAIV hospitalization risk among children with non-asthma, non-immunocompromising underlying conditions compared to healthy children.     

Physical activity outcomes in afterschool programs: A group randomized controlled trial

IntroductionAfterschool programs (ASPs) across the US are working towards achieving the standard of all children accumulating 30 min of moderate-to-vigorous physical activity (MVPA) during program time. This study describes the two-year impact of an intervention designed to assist ASPs meeting the 30 min/day MVPA standard.MethodsUsing a two-year delayed treatment, group randomized controlled trial, 20 ASPs serving ~ 1700 children/year (6–12 yrs) were randomized to either an immediate (n = 10, baseline-2013 and 2 yrs intervention fall-2013-to-spring-2015) or delayed group (n = 10, baseline 2013–2014 and 1 yr intervention fall-2014-to-spring-2015). The intervention, Strategies-To-Enhance-Practice (STEPs), focused on programming MVPA in the daily schedule, training of staff and leaders, and ongoing technical support/assistance. Accelerometry-derived proportion of children meeting the 30 min/day MVPA standard was measured in the spring of each year. Mixed model logistic regressions were used to examine the change in the odds of achieving the MVPA standard. Analyses were conducted in 2015. Data were collected in one southeastern US state.ResultsImmediate boys (n = 677) and delayed girls (n = 658) increased the percent achieving 30 min MVPA/day from 35.9% to 47.0% (odds ratio [OR] = 1.88, 95% CI 1.18–3.00) and 13.1% to 19.1% (OR = 1.42, 95% CI 1.03–1.96). Immediate girls (n = 613) and delayed boys (n = 687) exhibited a nonsignificant increase from 19.1% to 21.6% (OR = 1.20, 95% CI 0.84–1.72) and 29.0% to 31.3% (OR = 1.13, 95%CI 0.80–1.58).ConclusionsSTEPs can have an impact on children's MVPA and time spent sedentary, yet was unable to fully achieve the goal of all children accumulating 30 min MVPA/day. Additional efforts are need to identify strategies ASPs can use to meet this important public health standard.     

Safety,tolerability, and immunogenicity of 7-valent pneumococcal conjugate vaccine in older infants and young children in China who are naive to pneumococcal vaccination: Results of a phase 4 open-label trial

BackgroundThis postlicensure study was conducted to assess immunogenicity and safety of PCV7 catch-up regimens in previously unvaccinated older infants and young children in China.MethodsHealthy children 121 days to <72 months were grouped by age and immunized with 1 of 4 PCV7 dosing regimens. Serotype-specific IgG geometric mean concentrations (GMCs) and percentage of subjects with IgG ≥ 0.35 μg/mL were assessed before vaccination and 1 and 12 months postvaccination. The incidence of clinically important adverse events (AEs) and serious AEs (SAEs), AEs leading to study withdrawal, and protocol-related AEs were assessed throughout the study.ResultsPrevaccination serotype-specific GMCs were generally low in subjects <24 months; the majority of children 24 to <72 months had IgG concentrations ≥0.35 μg/mL. One month postvaccination, GMCs were similar across groups for the 7 PCV serotypes, ranging from 3.95 to 13.02 μg/mL; the highest antibody levels were observed for serotype 14. Regardless of dosing regimen, >90% of subjects had IgG ≥ 0.35 μg/mL for each PCV serotype. At 12-month follow-up, IgG GMCs ranged from 0.65 to 5.19, and all remained above prevaccination IgG GMC; >70% of subjects had IgG ≥ 0.35 μg/mL. Older children generally had the most robust immune response both at 1 month postvaccination and during 12-month follow-up. PCV7 was well tolerated. Pyrexia, which was mild to moderate in severity, was the most common AE. Two subjects reported SAEs (n = 4), and there was 1 study withdrawal; none of these were considered treatment related.ConclusionIn China, PCV7 catch-up vaccinations given to older infants and young children naive to pneumococcal vaccines resulted in a robust immune response to all serotypes; this response persisted after 1 year. PCV7 was well tolerated in Chinese infants and children.     

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized,double-blind,placebo-controlled trial

BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE).Methods4040 participants aged 6–12 weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n = 2020) or placebo (n = 2020), administered ∼4 weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14 days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14 days after the third dose. All adverse events (AEs) were collected for 30 days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385).ResultsVE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30 days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related.ConclusionsIn Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.     

The ‘Healthy Dads,Healthy Kids’ community randomized controlled trial: A community-based healthy lifestyle program for fathers and their children

ObjectiveTo evaluate the effectiveness of the ‘Healthy Dads, Healthy Kids (HDHK)’ program when delivered by trained facilitators in community settings.MethodA two-arm randomized controlled trial of 93 overweight/obese fathers (mean [SD] age = 40.3 [5.3] years; BMI = 32.5 [3.8] kg/m²) and their primary school-aged children (n = 132) from the Hunter Region, Australia. In 2010–2011, families were randomized to either: (i) HDHK intervention (n = 48 fathers, n = 72 children) or (ii) wait-list control group. The 7-week intervention included seven sessions and resources (booklets, pedometers). Assessments were held at baseline and 14-weeks with fathers' weight (kg) as the primary outcome. Secondary outcomes for fathers and children included waist, BMI, blood pressure, resting heart rate, physical activity (pedometry), and self-reported dietary intake and sedentary behaviors.ResultsLinear mixed models (intention-to-treat) revealed significant between-group differences for fathers' weight (P < .001, d = 0.24), with HDHK fathers losing more weight (− 3.3 kg; 95%CI, − 4.3, − 2.4) than control fathers (0.1 kg; 95%CI, − 0.9,1.0). Significant treatment effects (P < .05) were also found for fathers' waist (d = 0.41), BMI (d = 0.26), resting heart rate (d = 0.59), energy intake (d = 0.49) and physical activity (d = 0.46) and for children's physical activity (d = 0.50) and adiposity (d = 0.07).DiscussionHDHK significantly improved health outcomes and behaviors in fathers and children, providing evidence for program effectiveness when delivered in a community setting.     

Picky eating in preschool children: The predictive role of the child's temperament and mother's negative affectivity

ObjectiveThe objective of this study is to describe the development and examine predictors of picky eating from 1.5 to 4.5 years of age in a community sample of children.MethodsMothers completed a questionnaire, assessing picky eating and a range of child and maternal factors, when their children were aged 1.5 (n = 913), 2.5 (n = 777), and 4.5 (n = 727) years.ResultsPicky eating increased significantly from 1.5 to 4.5 years. Lower maternal age, higher levels of child emotionality, and maternal negative affectivity at the child's age 1.5 predicted an increase in picky eating from 1.5 years to 2.5 and 4.5 years. Having siblings protected against the development of picky eating.ConclusionChild and maternal temperament at a very early stage in the child's life increase the risk for picky eating later on.     

Vaccine-associated reduction in symptom severity among patients with influenza A/H3N2 disease

BackgroundThe moderate level of protection conferred by influenza vaccines is well-known, but the vaccine's ability to attenuate symptom severity among vaccinated individuals (i.e., vaccine failures) has not been established.MethodsWe enrolled otherwise healthy adults who presented with influenza-like illness (ILI) at five US military hospitals between 2009 and 2014. Influenza was diagnosed and subtyped by PCR. Individual and composite severity scores were compared between those who had vs. had not received the seasonal influenza vaccine >14 days prior to enrollment.ResultsA total of 155 cases of influenza (A/H1N1, n = 69; A/H3N2, n = 66; A/untyped, n = 3; B, n = 17) were identified, of whom 111 (72%; A/H1N1, n = 44; A/H3N2, n = 52; A/untyped, n = 3; B, n = 12) had been vaccinated. Women were significantly less likely to be vaccinated than men (49% vs. 89%; p < 0.01). In multivariate analysis, vaccinated individuals were significantly less likely to report a fever >101 °F (OR 0.24; 95% CI [0.10, 0.62]) and more likely to report myalgias (OR 3.31; 95% CI [1.22, 8.97]) than vaccinated individuals. Among patients with A/H3N2 infection, upper respiratory and total symptom severity scores were significantly lower for vaccinated patients during the first 2 days of illness, and differences in total symptom severity persisted over 7 days (p < 0.05 for all comparisons). Differences across additional symptom categories (lower respiratory and systemic) were also observed throughout 7 days of illness in bivariate analyses. Differences in symptom severity were not observed between vaccinated and unvaccinated participants with A/H1N1 infection.ConclusionsAmong patients with A/H3N2 infection, receipt of seasonal influenza vaccine was associated with reduced symptom severity. Patient-centered discussion about the benefits of influenza vaccination should be expanded to include the possibility that the vaccine could attenuate symptoms.     

Safety of live attenuated influenza vaccine in mild to moderately immunocompromised children with cancer

Background

The safety of intranasal live-attenuated influenza vaccine (LAIV) in immunocompromised children with cancer is unknown. The objective of this study was to describe the safety and immunogenicity of LAIV in mild to moderately immunocompromised children with cancer.

Methods

We conducted a multicenter, randomized, double-blind study of LAIV versus placebo in children aged 5-17 years with cancer. LAIV (frozen formulation) or allantoic fluid/buffer was administered intranasally. Reactogenicity, adverse events, blood for immune assays, and nasal swabs for viral shedding were obtained during 5 visits over the first 42 days postvaccination; information concerning serious adverse events (SAEs) was collected for 180 days.

Results

20 subjects were enrolled (LAIV, n = 10; placebo, n = 10) with a mean age of 12.2 years. Ten subjects had hematologic malignancy (LAIV, n = 4; placebo, n = 6); 10 subjects had solid tumors (LAIV, n = 6; placebo, n = 4). One subject was excluded from immunogenicity analysis for not receiving a full dose of LAIV. LAIV resulted in an increased incidence of runny nose/nasal congestion occurring in all LAIV recipients; no related SAEs were observed. Four of 10 LAIV recipients shed vaccine virus, with none exceeding 7-10 days duration. LAIV demonstrated modest immunogenicity by hemagglutination inhibition (≥4 fold rise for any strain, 33%) and microneutralization assays (≥4 fold rise for any strain, 44%).

Conclusion

In this small pilot study conducted in mild to moderately immunocompromised children with cancer, runny nose/nasal congestion was increased in LAIV recipients, no related SAEs occurred, and prolonged viral shedding was not detected. Moderate immunogenicity was demonstrated in this small group of individuals. (ClinTrials.gov: NCT00112112).     

Safety and immunogenicity of a trivalent recombinant PcpA,PhtD, and PlyD1 pneumococcal protein vaccine in adults,toddlers, and infants: A phase I randomized controlled study

BackgroundPneumococcal protein vaccines (PPrVs) may provide improved protection over currently available polysaccharide and conjugated polysaccharide vaccines. Here, we examined the safety and immunogenicity of a trivalent recombinant PPrV containing PcpA, PhtD, and PlyD1.MethodsThis was a phase I, single-center, randomized, observer-blind study with safety review between cohorts. Adults (18–50 years; n = 30) and then toddlers (12–13 months; n = 30) were randomized 2:1 to receive aluminum-adjuvanted trivalent PPrV (PPrV + adj) containing 50 μg per antigen or placebo. Infants (42–49 days; n = 220) were next randomized to be injected at 6, 10, and 14 weeks of age with 10 μg PPrV + adj or placebo (n = 60; 2:1); 25 μg PPrV + adj, 25 μg unadjuvanted PPrV, or placebo (n = 100; 2:2:1); and 50 μg PPrV + adj or placebo (n = 60; 2:1). Solicited reactions were recorded for 7 days and unsolicited adverse events for 30 days after each vaccination. Concentrations of antibodies to the three vaccine antigens were measured by enzyme-linked immunosorbent assay.ResultsTenderness/pain was the most frequent injection-site reaction. Abnormal crying and irritability (infants), loss of appetite (toddlers), and headache, malaise, and myalgia (adults) were the most frequent systemic reactions. Reactions were mostly mild or moderate, resolved within 3 days, were not adjuvant- or dose-dependent, and were not increased by repeated vaccination. No immediate adverse events, hypersensitivity reactions, or treatment-related serious adverse events were reported. In all PPrV + adj cohorts, at least 75% of subjects had a ≥2-fold increase in all three antibody concentrations. In infants, antibody concentrations were higher with PPrV + adj than with unadjuvanted PPrV, higher with three than two vaccinations, and similar at the different vaccine doses.ConclusionsThe candidate trivalent PPrV was safe and immunogenic in adults, toddlers, and infants. Addition of aluminum adjuvant improved immunogenicity in infants without changing the safety profile.     

Self-assessment of immediate post-vaccination pain after two different MMR vaccines administered as a second dose in 4- to 6-year-old children

The aim of this study was to compare self-reported immediate post-vaccination pain and safety of Priorix^® versus RORVax^® in 4- to 6-year-old children receiving their second dose of MMR vaccine, using the Faces Pain Scale-Revised (FPS-R), a validated self-report pain scale recommended by the French National Accreditation Agency and Health Evaluation.A total of 620 children from 28 French pediatricians completed all study procedures. Immediate post-vaccination pain was reported by 17.8% of the subjects in Priorix^® group (N = 309) and by 44.7% of the subjects in RORVax^® group (N = 311) [OR = 3.7; P < 0.001]. Parents’ pain scores correlated significantly with children's scores. The reduction of immediate pain incidence in Priorix^® group persisted over the 4 post-vaccination days.This study, using a validated self-assessment pain scale, confirmed previous data showing a significantly lower incidence of immediate post-vaccination pain with Priorix^® as compared to RORVax^®.     

Influenza vaccines effectiveness 2013–14 through 2015–16, a test-negative study in children

BackgroundTrivalent inactivated and live attenuated influenza vaccines (IIV3 and LAIV3) have been reformulated with an extra B strain (IIV4 and LAIV4). They were licensed based on immunogenicity and their effectiveness (VE) still must be empirically tested.MethodsChildren 1–17 years tested for influenza during 2013–16 were included and their immunization status verified. They were considered vaccinated if received ≥1 dose of an influenza vaccine ≥10 days before evaluated for a respiratory episode. Age-groups were classified as 1–4 years or 5–17 years. VE was estimated by comparing vaccination status of influenza-positive versus influenza-negative cases.Results6779 children were enrolled in the three seasons. Overall, 27.2% received an influenza vaccine (87.1% IIV3 or IIV4 and 12.9% LAIV4), and 15.6% tested positive for influenza (77.9% A). IIV3 was predominantly used in 2013–14 and IIV4 in 2014–15 and 2015–16. IIV3 and IIV4 had comparable VE over the three seasons (60%, 57% and 53%) and performed similarly against influenza A and B and both age-groups. LAIV4 performed poorly for influenza A (15%, 37% and 48%) but better for influenza B (100%, 56% and 100%), especially among children 5–17 years of age with VE = 100% (95%CI: 55, 100).ConclusionsInfluenza vaccination showed modest but consistent effectiveness over the years. The switch from IIV3 to IIV4 did not affect VE. LAIV4 did not perform as well as IIVs, yet it improved over the years and was particularly good protecting older children against influenza B. These results emphasize the regional nature of influenza and the need for local surveillance.     

Association between unmet dental needs and school absenteeism because of illness or injury among U.S. school children and adolescents aged 6–17 years, 2011–2012

BackgroundWe assessed the prevalence of dental disease among U.S. children and adolescents aged 6–17 years, as well as the impact of unmet dental needs on school absenteeism because of illness/injury within the past 12 months.MethodsData were from the 2011/2012 National Survey of Children's Health (n = 65,680). Unmet dental need was defined as lack of access to appropriate and timely preventive or therapeutic dental healthcare when needed within the past 12 months. The impact of unmet dental needs on school absenteeism was measured using a multivariate generalized linear model with Poisson probability distribution (p < 0.05).ResultsWithin the past 12 months, 21.8% (10.8 million) of all U.S. children and adolescents aged 6–17 years had “a toothache, decayed teeth, or unfilled cavities.” Of all U.S. children and adolescents aged 6–17 years, 15.8% (7.8 million) reported any unmet dental need (i.e., preventive and/or therapeutic dental need) within the past 12 months. The mean number of days of school absence because of illness/injury was higher among students with an unmet therapeutic dental need in the presence of a dental condition compared to those reporting no unmet dental need (β = 0.25; p < 0.001).ConclusionsEnhanced and sustained efforts are needed to increase access to dental services among underserved U.S. children and adolescents.     

Comparative analysis of influenza A(H3N2) virus hemagglutinin specific IgG subclass and IgA responses in children and adults after influenza vaccination

Two different influenza vaccines are generally used in many countries; trivalent live attenuated influenza vaccine (LAIV3) and trivalent inactivated influenza vaccine (IIV3). Studies comparing the antibody response to IIV3 and LAIV3 commonly investigate the seroprotective response by hemagglutination-inhibition (HI) assay. However, there is limited data regarding comparative analysis of IgG subclass and IgA responses induced by LAIV3 and IIV3.Fifteen children <5 years received 2 doses of LAIV3 while 14 children aged 10–17 years received one dose. In addition, 15 adults were vaccinated with either intranasal LAIV3 or intramuscular IIV3. We analyzed the H3N2 humoral responses by HI assay and the hemagglutinin (HA) specific IgG1, IgG2, IgG3, IgG4 and IgA1 responses by ELISA. Furthermore, we investigated the avidity of induced IgG antibodies.Pre-existing seroprotective HI antibodies were present in adults (73%) previously vaccinated with IIV3. Vaccination resulted in a significant increase in HI titers in all groups, except LAIV3 vaccinated adults. Furthermore, a negative correlation between age and HI titers in LAIV3 vaccinated subjects was observed post-vaccination. LAIV3 in children and IIV3 in adults induced HA-specific IgG1, low IgG3 but no IgG2 or IgG4. Moreover, significant IgA1 responses were only induced in children. Interestingly, IIV3 and LAIV3 induced IgG antibodies with comparable and significantly augmented avidity post-vaccination in children and adults.Our results suggest that age and/or exposure history play a significant role in determining the antibody response.Clinical trial registry: ClinicalTrials.gov NCT01003288 and NCT01866540     

Long-term follow-up of Japanese encephalitis chimeric virus vaccine: Immune responses in children

BackgroundA single dose of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) was shown to be immunogenic and well tolerated when given either as a booster to formalin-inactivated Japanese encephalitis (JE)-vaccine (mouse brain-derived vaccine [MBDV])-primed 2–5-year-olds, or as a primary vaccination to JE-vaccine-naïve 12–24-month-old toddlers in Thailand. A 5-year follow-up assessment of immune response persistence over time was conducted.MethodsFour additional visits (at 2, 3, 4, and 5 years) for immunologic assessments were added to the original 12-month open-label crossover study, in which 100 healthy children aged 2–5 years with a history of two-dose primary vaccination with MBDV (according to the Thai Expanded Program for Immunization schedule), and 200 healthy JE-vaccine-naïve 12–24-month-old toddlers, were randomized 1:1 to receive JE-CV, containing ⩾4 log₁₀ plaque forming units, 1 month before or after hepatitis A control vaccine.ResultsIn MBDV-primed 2–5-year-olds (n = 78), the immune response to the JE-CV vaccine persisted up to at least 5 years after vaccination with a single dose of JE-CV, with all (n = 78) children seroprotected at the year 5 visit (geometric mean titers [GMT]: 252 1/dil). There was no decrease of seroprotection rate over time (100% at 6 months post-vaccination and 96.8% (90.3–98.9) at 5 years post-vaccination). In JE-vaccine-naïve toddlers, a protective immune response persisted up to at least 5 years in 58.8% (50.9–66.4) after a single-dose administration of JE-CV (GMT 26.7 1/dil; sensitivity analysis).ConclusionsA single-dose of JE-CV as a booster following MBDV administration provided long-lasting immunity. In JE-vaccine-naïve toddlers, despite relatively high seroprotection rates persisting over time, a subsequent booster dose is recommended following a JE-CV primary vaccination for long-term protection.This study was registered on www.clinicaltrials.gov (NCT00621764).     

Influenza vaccination rates in children decline when the live attenuated influenza vaccine is not recommended

BackgroundIn 2016 the Centers for Disease Control and Prevention (CDC) recommended against using the live attenuated influenza vaccine (LAIV) for the 2016–2017 influenza season. This recommendation is potentially important for vaccination rates because perceived effectiveness and ease of administration are among the primary determinants of families decisions to vaccinate their children. This investigation sought to determine whether rates of pediatric influenza vaccination changed in a season when the LAIV was not recommended.MethodsThis study used cohort and cross sectional data from an academic primary care pediatric center in central Pennsylvania that serves approximately 12,500 patients. Early season (prior to November 1) and end-of-season (prior to March 1) vaccination rates in the 2015–16 and 2016–17 influenza seasons were recorded for individuals 2–17 years old. Repeat vaccination rates (percentage of children receiving influenza vaccination in one season who were also vaccinated in the next season) were recorded for the 2015–16 into 2016–17 seasons. A logistic regression model adjusting for race, ethnicity, age, insurance type and type of vaccination received was employed to identify predictors of repeat vaccination.ResultsIn the absence of LAIV (2016–17) early vaccination rates were significantly higher (24.7% vs 22.8%, p = 0.004), but end-of-season rates were lower (50.4% vs 52.0%, p = 0.03) than when LAIV was offered (2015–16). After adjusting for covariates, those who had received IIV in the 2015–16 season had higher odds (OR 1.32, 95% CI, 1.15–1.52) of getting a repeat vaccination in the 2016–17 season, compared with those who had received LAIV in the 2015–16 season.ConclusionsEnd-of-season vaccination rates were lower in 2016–17 when LAIV was not recommended, particularly among children who received LAIV in the preceding year. Unavailability of LAIV in the 2016–17 season may have impacted influenza vaccination convenience and perceived effectiveness, two factors which could influence vaccine uptake in pediatric populations.