Herve Caspard

Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2–17 years of age in 2013–2014 in the United States

BACKGROUND A postmarketing observational study was initiated to evaluate quadrivalent live attenuated influenza vaccine (LAIV) effectiveness in children aged 2-17 years in the United States. METHODS Children and adolescents aged 2-17 years seeking outpatient care for febrile acute respiratory illness <5 days duration were enrolled at 4 geographically diverse sites during the 2013-2014 influenza season. Nasal swabs were tested for influenza using reverse transcription polymerase chain reaction. Vaccination status was documented from medical records or immunization registries. Children who received ≥1 dose of influenza vaccine ≥14 days before study visit were considered vaccinated. Vaccine effectiveness (VE) was estimated as 100×(1-adjusted odds ratio), where the odds of interest are the odds of vaccine exposure among influenza cases and test-negative controls. RESULTS In total, 1033 children and adolescents were included in the analysis. Influenza was detected in 14% (145/1033) of all children, with 74% (108/145) of the influenza cases due to A/H1N1pdm09 strains, 21% (31) to influenza B, and 4% (6) to influenza H3N2. LAIV did not show significant effectiveness against A/H1N1pdm09 (VE 13% [95% CI: -55 to 51]) but was effective against B/Yamagata strains (82% [95% CI: 12-96]). Inactivated influenza vaccine was effective against A/H1N1pdm09 (74% [95% CI: 50-86]) and B/Yamagata (70% [95% CI: 18-89]). CONCLUSIONS LAIV provided significant protection against B/Yamagata influenza but not against A/H1N1pdm09 in children aged 2-17 years in 2013-2014, resulting in a proposed change of the 2015-2016 formulation with a new and more heat-stable A/H1N1pdm09 LAIV strain.

Live-Attenuated Influenza Vaccine Effectiveness in Children From 2009 to 2015–2016: A Systematic Review and Meta-Analysis

Abstract Background This systematic review and meta-analysis describes and consolidates findings from all studies that assessed the effectiveness of live-attenuated influenza vaccine (LAIV) against laboratory-confirmed influenza since the 2009 pandemic in children and young adults. Methods A MEDLINE search was conducted for articles published from January 1, 2010 to November 30, 2016. All original publications reporting an effectiveness estimate of LAIV against cases of influenza confirmed by reverse-transcription polymerase chain reaction or culture were retained for analysis. Effectiveness estimates were categorized by LAIV formulation (monovalent, trivalent, and quadrivalent) and strain (any influenza strain, A(H1N1)pdm09, A(H3N2), and B strains). Consolidated estimates were obtained with a random-effects model. Results A total of 24 publications presenting 29 observational studies were retained for meta-analysis. Live-attenuated influenza vaccine was not shown to be effective against A(H1N1)pdm09 strains as a monovalent formulation in 2009–2010 or as a trivalent formulation from 2010–2011 to 2013–2014, but consolidated sample sizes were small. It was effective as a quadrivalent formulation but less effective than inactivated influenza vaccine (IIV). Live-attenuated influenza vaccine was consistently effective against B strains and matched A(H3N2) strains but was not shown to provide significant protection against mismatched A(H3N2) strains in 2014–2015. Conclusions These findings confirm that effectiveness of LAIV against A(H1N1)pdm09 strains has been lower than IIV. A systematic investigation has been initiated to determine the root cause of the difference in effectiveness between pre- and postpandemic A(H1N1) vaccine strains and to identify a more consistently effective A(H1N1)pdm09 vaccine strain.

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

BACKGROUND Quadrivalent 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 2-49years. METHODS This 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, Bells 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. RESULTS A 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 18-49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV. CONCLUSION In this large population study of individuals aged 2-49years, 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.

Recent trends in the prevalence of type 2 diabetes and the association with abdominal obesity lead to growing health disparities in the USA: An analysis of the NHANES surveys from 1999 to 2014

To assess whether the secular trends in type 2 diabetes prevalence differ between abdominally obese and non‐obese individuals.

Efficacy of live attenuated influenza vaccine against influenza illness in children as a function of illness severity.

A recent study of inactivated influenza vaccine (IIV) in children aged 3-8 years demonstrated higher efficacy against moderate/severe influenza. A meta-analysis of all previous published randomized clinical trials of live attenuated influenza vaccine (LAIV) that collected information on illness severity in children aged 24-71 months was conducted. Moderate/severe influenza was defined as fever >39°C, acute otitis media, or lower respiratory tract illness; other cases were classified as milder influenza. LAIV efficacy versus placebo was 95.4% [95% confidence interval: 88.5, 98.1] (year 1) and 88.5% [77.4, 94.9] (year 2) against moderate/severe influenza and 91.4% [77.9, 96.7] (year 1) and 84.2% [56.7, 94.3] (year 2) against milder influenza. The relative efficacy of LAIV versus IIV was 52.2% [31.6, 66.6] for moderate/severe influenza and 45.0% [28.6, 57.5] for milder influenza. Efficacy against all influenza illnesses, regardless of severity, is critical to prevent influenza illness and transmission in the community.

2015–2016 Vaccine Effectiveness of Live Attenuated and Inactivated Influenza Vaccines in Children in the United States

This test-negative case-control study showed live attenuated influenza vaccine and inactivated influenza vaccine were effective against any influenza in 2015–2016.

Uptake of childhood influenza vaccine from 2012–2013 to 2014–2015 in the UK and the implications for high-risk children: a retrospective observational cohort study

Objectives To evaluate changes in influenza vaccination rates in healthy and at-risk children following the implementation of the UKs childhood influenza immunisation programme. Design Observational cohort study before and after initiation of the UKs childhood influenza immunisation programme over three influenza seasons (2012–2013, 2013–2014 and 2014–2015) using data from the Clinical Practice Research Datalink (CPRD). Setting More than 500 primary care practices in the UK. Population All individuals aged 2–17 years on 1 September, with at least 12 months of medical history documented in CPRD were retained in the analysis. Intervention Starting in 2013–2014, all children aged 2 and 3 years were offered influenza vaccination through general practice, and primary school-aged children were offered influenza vaccination in selected counties in England (described as pilot regions). The vaccination programme was extended to all children aged 4 years in England in 2014–2015. Main outcome measure Cumulative vaccination rate from 1 September to 28 February of the next calendar year as assessed by a time-to-event statistical model (vaccination uptake). Age group, sex, region and type of high-risk medical condition were assessed as predictors. Results Vaccination uptake increased considerably from 2012–2013 to 2013–2014 in targeted children aged 2–3 years, both in children with a high-risk medical condition (from 40.7% to 61.1%) and those without (from 1.0% to 43.0%). Vaccination rates increased also, though less markedly, in older children. In 2014–2015, vaccination rates remained higher than 40% in healthy children aged 2–3 years, although they decreased slightly from 2013–2014 (from 43.0% to 41.8%). Vaccination rates in older healthy children continued to increase, driven primarily by an increase in children aged 4 years to 31.3% in 2014–2015. Conclusions The introduction of a universal childhood vaccination policy in the UK increased vaccination rates for targeted children, including those with high-risk conditions.

Standard methods based on last menstrual period dates misclassify and overestimate US preterm births.

Objective:To compare number of US preterm births based on obstetric versus last menstrual period (LMP) estimates and evaluate their correlations with clinical risk indicators associated with prematurityStudy Design:Preterm births were assessed from LMP, per standard practice, and, separately, from obstetric estimates using the 2012 Natality Public Use File. Percentages of infants with neonatal intensive care unit (NICU) admission and low birth weight (LBW) were calculated.Result:More births were <37 weeks gestational age (GA) by reported LMP (11.4%) versus obstetric estimates (9.5%). Among infants preterm by LMP, but born at 37–41 weeks by obstetric estimates, there were 5.7% NICU admission and 7.7% LBW rates versus 25.2% and 35.4%, respectively, of those preterm by obstetric estimates but born 37–41 weeks by LMP assessments.Conclusion:Obstetric estimates provide the most clinically relevant estimates of US preterm births. Assessments calculated from LMP alone may overestimate prematurity incidence by ~20%.

Seasonal influenza vaccination trends from 2007-2011 in privately insured children and adults in the United States

BACKGROUND To ensure adequate protection from seasonal influenza in the US, the Advisory Committee on Immunization Practices recommends vaccination of all persons aged 6 months or older, with rare exceptions. It also advises starting vaccination as soon as available and continuing throughout the influenza season. This study examined US seasonal vaccination trends during five consecutive influenza seasons in privately-insured children and adults. METHODS This retrospective, observational cohort study examined trends in influenza vaccination during the 2007-2008 through 2011-2012 influenza seasons using administrative claims data from a large national insurer. RESULTS The size of analysis population ranged from 1144,098 to 1245,487 (children, ≥6 months-17 years of age) and from 3931,622 to 4158,223 (adults, 18-64 years of age). Vaccination frequency increased through 2010-2011, was most frequent in young children, and decreased with age. Vaccination rates were highest in the Northeast and lowest in the West and were higher in individuals with frequent outpatient office visits than in those with no or rare visits, with larger differences seen in children. Between 2007 and 2011, the use of preservative-free inactivated vaccine increased, the use of multidose vaccines containing preservatives decreased, and the use of live attenuated influenza vaccines increased among children 2-17 years of age. From 2007-2008 through 2009-2010, the timing of vaccination each year began earlier than the previous one; it remained stable from 2009-2010 through 2011-2012. CONCLUSION Annual influenza vaccination claims for privately-insured children and adults increased and shifted earlier from 2007 through 2009-2011. During the 2011-2012 influenza season, 25.4% of children aged 6 months-17 years and 12.3% of adults aged 18-64 years were vaccinated. Increasing influenza vaccination should remain a priority, and alternative venues for seasonal influenza vaccination should be considered in order to meet the Healthy People 2020 goal of 80% to 90% coverage among children.

A systematic review of the efficacy of live attenuated influenza vaccine upon revaccination of children

Abstract Four randomized, double-blind, placebo-controlled studies in 6090 children that investigated the efficacy of live attenuated influenza vaccine (LAIV) upon revaccination of children against laboratory-confirmed cases of influenza in consecutive seasons were reviewed. The efficacy in season 2 of LAIV administered over 2 consecutive seasons was 86.7% (95 % CI: 76.8%, 92.4%) against strains antigenically similar to those contained in the vaccine. The additional efficacy of LAIV administered in season 2 compared to LAIV recipients in season 1 only was 58.4% (28.3%, 75.9%). LAIV administered over 2 consecutive seasons also was more efficacious than was LAIV administered in season 2 only (relative efficacy: 53.9% [17.4%, 74.3%]). Residual efficacy of LAIV administered in season 1 only compared to placebo administered in two consecutive seasons was 56.4% (37.0%, 69.8%). This review did not find any evidence of decreasing efficacy of LAIV when administered during 2 consecutive seasons.