Influenza Vaccine In Children Research Articles

Immunogenicity and safety of the first indigenously developed Indian tetravalent influenza vaccine (split virion) in healthy children (6 months to 17 years of age): a randomized, multicenter, phase III clinical trial

ABSTRACT This phase III clinical trial was conducted to evaluate the immunogenicity and safety of the Tetravalent Influenza Vaccine (Split virion) I.P. (TetIV), containing two strains each of influenza A and B, developed indigenously in the country for the first time by M/s Cadila Healthcare Limited, India for use in the pediatric population (6 months −17 years of age), and compare it to that of a licensed seasonal Trivalent Influenza Vaccine (TriIV) of Sanofi Pasteur India Private Limited, containing two influenza A and one influenza B strains. Three hundred six subjects of either sex, 6 months to 17 years of age, were randomized in a 1:1 ratio to receive either TetIV or TriIV. Immunogenicity assessments (antibodies against A/H1N1, A/H3N2, B/Phuket, and B/Brisbane) were performed using the hemagglutination inhibition assay at baseline and 28 days after the last vaccination. TetIV was found to fulfill the criteria set by the United States Food and Drug Administration on the requirements of clinical data for licensure of seasonal inactivated influenza vaccines for the pediatric population. The seroconversion rates with TetIV were 94.6% for A/H1N1, 93.9% for A/H3N2, 91.2% for B/Brisbane, and 87.2% for B/Phuket strains. TetIV showed non-inferiority and superiority in immune response, as compared to TriIV, against the shared strains and an additional B strain, respectively. Both the vaccines were tolerated well by all the study participants, and an addition of the fourth strain in TetIV did not compromise the safety as compared to that of TriIV. The most common adverse event reported in both groups was fever.

Key role of pediatricians and disease for influenza vaccination in children with high-risk chronic diseases.

Annual influenza vaccination is recommended for children with chronic diseases. Studies on influenza vaccines, following controversies related to the 2009 H1N1 influenza, are scarce in Europe. Our aim was to evaluate the influenza vaccination coverage in such children in a French tertiary hospital. Secondary objectives were the evaluation of the influenza vaccination coverage trend and the identification of factors influencing the vaccination status. A prospective and descriptive study by questionnaire was performed at the end of 2017 in 402 French hospital outpatients with various underlying chronic diseases eligible to the influenza vaccination. The 2016-2017 vaccination coverage was 46.5%. Figures of 75% or greater were only found in patients with cystic fibrosis and sickle cell disease. CART analysis identified vaccination in the previous year, medical recommendation for vaccination, and maternal influenza vaccination as a child's decisive factors for being vaccinated.Conclusion: Influenza vaccination coverage remains insufficient in children receiving hospital follow-up for chronic diseases. Its implementation clearly depends on pediatricians' recommendation to vaccinate and on the type of chronic disease. What is Known: • Despite health policy recommendations, the rate of annual influenza vaccination in children with chronic diseases is low What is New: • Influenza vaccination coverage depends on the type of chronic disease and on the pediatricians' counseling to vaccine.

Effectiveness of trivalent inactivated influenza vaccines in children during 2017–2018 season in Korea: Comparison of test-negative analysis by rapid and RT-PCR influenza tests

ObjectivesIn Korea, the National Immunization Program provided trivalent inactivated influenza vaccines (IIV3) to all children aged 6–59 months during the 2017–2018 season. In this study, we aimed to evaluate the vaccine effectiveness (VE) of IIV3 in children during the 2017–2018 season. MethodsChildren aged 6–59 months who were tested for influenza for their acute respiratory illness in four hospitals during the 2017–2018 influenza season were included. We estimated the VE of IIV3 by test-negative case-control design based on the rapid influenza diagnostic test (RIDT) or reverse transcription polymerase chain reaction (RT-PCR) test results. ResultsA total of 4738 children were included in this study. The number of laboratory-confirmed influenza cases was 845 (17.8%), and there were 478 cases of influenza A and 362 cases of influenza B. The adjusted VE based on RT-PCR was 53.4% (95% CI, 25.3–70.5) against any influenza, 68.8% (95% CI, 38.7–84.1) against influenza A, and 29.7% (95% CI, −35.1 to 61.8) for influenza B. The adjusted VE based on RIDT was 14.8% (95% CI, −4.4 to 30.0) against any influenza, 24.2% (95% CI, 3.1–40.2) against influenza A, and −5.1% (95% CI, −42.6 to 21.4) against influenza B. Age-specific VE based on RT-PCR against any influenza was 44.1% (95% CI, −0.2 to 67.8) in children aged 6 months to 2 years and 59.3% (95% CI, 8.8–81.9) in children aged 3–<5 years. ConclusionOur results suggest moderate protection (53.4%) of IIV3 against RT-PCR laboratory-confirmed influenza in children in the 2017–2018 influenza season. However, the RIDT hampered the validity to assess VE during influenza season. Caution is needed when interpreting an RIDT-based test negative design influenza VE study.

A randomized controlled trial of antibody response to 2018–19 cell-based vs. egg-based quadrivalent inactivated influenza vaccine in children

BackgroundCurrent influenza vaccine effectiveness (VE) improvement efforts focus on minimizing egg adaptation mutations during manufacture. This study compared immune response of two FDA-approved quadrivalent inactivated influenza vaccines in an unblinded randomized controlled trial. MethodsParticipants were 144 community dwelling, healthy children/adolescents aged 4–20 years, randomized 1:1 in blocks of 4 to a vaccine grown in cell culture (ccIIV4 [Flucelvax®]; n = 85); or in egg medium (IIV4 [Fluzone ®]; n = 83). Blood was drawn at day 0 prevaccination and at day 28 (19–35 days) post vaccination. Hemagglutination inhibition (HI) assays against A/H1N1 and both B strains and microneutralization (MN) assays against egg-based and cell-based A/H3N2 strains were conducted. The primary outcome measure was seroconversion (day 28/day 0 titer ratio ≥ 4 with day 28 titer ≥ 40). Secondary outcomes were elevated titers (day 28 HI titer ≥ 1:110), geometric mean titers (GMTs) and mean fold rise (MFR) in titers. Outcomes were compared for 74 ccIIV4 recipients and 70 IIV4 recipients, and for those vaccinated and unvaccinated the previous year. Only the HI and MN laboratory analysis team was blinded to group assignment. ResultsIn this racially diverse (81% non-white) group of children with a median age of 14 years, baseline demographics did not differ between vaccine groups. At day 0, half or more in each vaccine group had elevated HI or MN titers. Low seroconversion rates (14%-35%) were found; they did not differ between groups. Among 2018–19 ccIIV4 recipients, those unvaccinated in the previous season showed significantly higher MFR against A/H1N1 and A/H3N2 cell-grown virus than the previously vaccinated. Similar results were found for MFR against B/Victoria among 2018–2019 IIV4 recipients. ConclusionIn mostly older children with high baseline titers, no differences in seroconversion or other measures of antibody titers were found between ccIIV4 and IIV4 recipients against egg- and cell-grown influenza vaccine viruses. Clinical Trials NoNCT03614975.

A hidden vulnerable population: Young children up-to-date on vaccine series recommendations except influenza vaccines.

Very young children (under 2 years old) have high risk for influenza-related complications. Children 6 months or older in the US are recommended to receive influenza vaccination annually, yet uptake is substantially lower than other routinely-recommended vaccines. Existing nationally-representative studies on very young child influenza vaccine uptake has several limitations: few examine provider-verified influenza vaccination (relying on parental report), few contain parental vaccine attitudes variables (known to be crucial to vaccine uptake), and none to our knowledge consider intersectionality of social disadvantage nor how influenza vaccine determinants differ from those of other recommended vaccines. This nationally-representative study examines provider-verified data on 7,246 children aged 6-23 months from the most recent (2011) National Immunization Survey to include the restricted Parental Concerns module, focusing on children up-to-date on a series of vaccines (the 4:3:1:3:3:1:4 series) but not influenza vaccines ("hidden vulnerability to influenza"). About 71% of children were up-to-date on the series yet only 33% on influenza vaccine recommendations by their second birthday; 44% had hidden vulnerability to influenza. Independent of parental history of vaccine refusal and a myriad of health services use factors, no parental history of delaying vaccination was associated with 7.5% (2.6-12.5) higher probability of hidden vulnerability to influenza despite being associated with 15.5% (10.8-20.2) lower probability of being up-to-date on neither the series nor influenza vaccines. Thus, parental compliance with broad child vaccine recommendations and lack of vaccine hesitancy may not indicate choice to vaccinate children against influenza. Examination of intersectionality suggests that maternal college education may not confer improved vaccination among non-Hispanic Black and Hispanic children despite that it does for non-Hispanic White children. Policymakers and researchers from public health, sociology, and other sectors need to collaborate to further examine how vaccine hesitancy and intersectional social disadvantage interact to affect influenza vaccine uptake in young US children.

Seasonal influenza vaccination for children with special risk medical conditions: Does policy meet practice?

Ensuring children with special risk medical conditions (SRMC) are protected from influenza is important. The study objective was to describe influenza vaccination practices of medical professionals caring for children with SRMC and explore characteristics associated with a vaccine recommendation. Design: Cross-sectional survey. Treating paediatric specialists and general practitioners of children with confirmed SRMCs. Postal questionnaire administered from March to September 2018 (option for online response). Characteristics associated with providing a recommendation were explored using univariable and multivariable analyses. Overall response rate of 24.8% with the sample representative of the eligible population in terms of practice location and years practicing medicine. There was a higher response from females and sub-specialists. Of the 198 completed survey responders, 97.8% were aware of the recommendation, yet only 38.4% reported they 'always' routinely recommended influenza vaccine and fewer (19.5%) were very confident in understanding all 'medically at risk' conditions. Medical professionals were more likely to provide a recommendation always or mostly, if they received annual influenza vaccination themselves (adjusted odds ratio (aOR) 3.96, confidence interval (CI) 1.12-14.03), had confidence in understanding all 'medically at risk' conditions (aOR 1.82, CI 1.04-3.17) and perceived ownership of the responsibility to provide the recommendation (aOR 7.35, CI 1.67-32.26). Regional practising medical professionals were less likely to provide a recommendation (aOR 0.25 CI 0.10-0.70). We need to improve medical professionals' knowledge through reminders and access to consistent and concise information about what constitutes a SRMC. Increasing medical professionals' engagement in the influenza vaccination programme could also provide a sense of responsibility fostering provider endorsement.

Effect of State Immunization Information System Based Reminder/Recall for Influenza Vaccinations: A Randomized Trial of Autodialer, Text, and Mailed Messages

To evaluate the effect of different modalities of centralized reminder/recall (autodialer, text, mailed reminders) on increasing childhood influenza vaccination. Two simultaneous randomized clinical trials conducted from October 2017 to April 1, 2018, in New York State and Colorado. There were 61 931 children in New York (136 practices) and 23 845 children in Colorado (42 practices) who were randomized to different centralized reminder/recall modalities-4 arms in New York (autodialer, text, mailed, and no reminder control) and 3 arms in Colorado (autodialer, mailed, and no reminder control). The message content was similar across modalities. Up to 3 reminders were sent for intervention arms. The main outcome measure was receipt of ≥1 influenza vaccine. In New York, compared with the control arm (26.6%), postintervention influenza vaccination rates in the autodialer arm (28.0%) were 1.4 percentage points higher (adjusted risk ratio, 1.06; 95% CI, 1.02-1.10), but the rates for text (27.6%) and mail (26.8%) arms were not different from controls. In Colorado, compared with the control arm (29.9%), postintervention influenza vaccination rates for the autodialer (32.9%) and mail (31.5%) arms were 3.0 percentage points (adjusted risk ratio, 1.08; 95% CI, 1.03-1.12) and 1.6 percentage points (adjusted risk ratio, 1.06; 95% CI, 1.02-1.10) higher, respectively. Compared with the control arm, the incremental cost per additional vaccine delivered was $20 (New York) and $16 (Colorado) for autodialer messages. Centralized reminder/recall for childhood influenza vaccine was most effective via autodialer, less effective via mail, and not effective via text messages. The impact of each modality was modest. Compared with no reminders, the incremental cost per additional vaccine delivered was also modest for autodialer messages. ClinicalTrials.gov: NCT03294473 and NCT03246100.

A longitudinal study using parental cognitions based on the theory of planned behavior to predict childhood influenza vaccination

BackgroundThe World Health Organization recommends young children aged 6–59 months receive influenza vaccination (IV) annually. This study investigated the IV incidence in a 12-month follow-up period among 24–59 month-old children and identified its predictors based on the theory of planned behavior (TPB). MethodsA population-based random telephone survey was conducted at baseline (March–June 2011) among Chinese parents of 24–59 month-old children in Hong Kong, China, and a follow-up survey was conducted 12 months afterwards (N=440). ResultsThe IV prevalence was 63.2% at follow-up (3% increased from baseline). The IV incidence during the follow-up period for all sampled, ever-vaccinated, and never-vaccinated children was 35.6, 58.5, and 7.7 per 100 person-years, respectively. Stratified analyses of logistic regression were performed for the ever-vaccinated and never-vaccinated children. After adjusting for significant socio-demographic variable(s), parental positive attitude, norm, and behavioral intention were significant predictors of IV at follow-up among ever-vaccinated children, while intention was the only significant predictor among never-vaccinated children. ConclusionsMost of the IVs received during the follow-up period were re-vaccinations rather than first-time vaccinations. Efforts should target never-vaccinated children's parents, who reported low incidence and intention. TPB also worked less well among never-vaccinated children, and thus research for other predictors of never-vaccinated children's first-time vaccination are warranted. Promotion programs should consider segmentation by children's prior vaccination status.

Why do parents not re-vaccinate their child for influenza? A prospective cohort study

Child influenza vaccination rates for the UK are published annually, however there are no publicly available data on how many children are re-vaccinated the following year. This prospective cohort study aimed to identify factors associated with not re-vaccinating one’s child. Participants (n = 270) completed a questionnaire before their child was vaccinated for influenza in the 2016/17 season, and follow-up questionnaires three days and one month after their child’s vaccination. Re-vaccination data were collected at the end of the 2017/18 influenza season (n = 232, response rate 85.9%). Forty-one children (17.7%) were not re-vaccinated for influenza in 2017/18. Parental report of severe side-effects three days after vaccination (p = .04) and worry about side-effects one month after vaccination (p = .05) were associated with not re-vaccinating. However, the restricted sample size reduced the statistical power of these analyses. Decreasing parental worry about side-effects may help improve re-vaccination rates.Clinical trial registration: The study was registered on ClinicalTrials.gov (NCT02909855).

Higher PIK3C2B gene expression of H1N1+ specific B-cells is associated with lower H1N1 immunogenicity after trivalent influenza vaccination in HIV infected children

Perinatally HIV-infected children (PHIV), despite successful antiretroviral therapy, present suboptimal responses to vaccinations compared to healthy-controls (HC). Here we investigated phenotypic and transcriptional signatures of H1N1-specific B-cells (H1N1-Sp) in PHIV, differentially responding to trivalent-influenza-vaccine (TIV), and HC. Patients were categorized in responders (R) and non-responders (NR) according to hemagglutination-inhibition-assay at baseline and 21 days after TIV. No differences in H1N1-Sp frequencies were found between groups. H1N1-Sp transcriptional analysis revealed a distinct signature between PHIV and HC. NR presented higher PIK3C2B and NOD2 expression compared to R, confirmed by downregulation of PIK3C2B in resting-memory of R after H1N1 in-vitro stimulation. In conclusion this study confirms that qualitative rather than quantitative analyses are needed to characterize immune responses in PHIV. These results further suggest that higher PIK3C2B in H1N1-Sp of NR is associated with lower H1N1 immunogenicity and may be targeted by future modulating strategies to improve TIV responses in PHIV.

Differential gene expression in peripheral blood mononuclear cells from children immunized with inactivated influenza vaccine

ABSTRACT The human immune response to inactivated influenza vaccine is dynamic and impacted by age and preexisting immunity. Our goal was to identify postvaccination transcriptomic changes in peripheral blood mononuclear cells from children. Blood samples were obtained before and at 3 or 7 days postvaccination with 2016–2017 quadrivalent inactivated influenza vaccine and RNA sequencing was performed. There were 1,466 differentially expressed genes (DEGs) for the Day 0–Day 3 group and 513 DEGs for the Day 0–Day 7 group. Thirty-three genes were common between the two groups. The majority of the transcriptomic changes at Day 3 represented innate inflammation and apoptosis pathways. Day 7 DEGs were characterized by activation of cellular processes, including the regulation of cytoskeleton, junctions, and metabolism, and increased expression of immunoglobulin genes. DEGs at Day 3 were compared between older and younger children revealing increased inflammatory gene expression in the older group. Vaccine history in the year prior to the study was characterized by robust DEGs at Day 3 with decreased phagosome and dendritic cell maturation in those who had been vaccinated in the previous year. PBMC responses to inactivated influenza vaccination in children differed significantly by the timing of sampling, patient age, and vaccine history. These data provide insight into the expected molecular pathways to be temporally altered by influenza vaccination in children.

Early Induction of Cross-Reactive CD8+ T-Cell Responses in Tonsils After Live-Attenuated Influenza Vaccination in Children.

BackgroundLive-attenuated influenza vaccine (LAIV) was licensed for prophylaxis of children 2–17 years old in Europe in 2012 and is administered as a nasal spray. Live-attenuated influenza vaccine induces both mucosal and systemic antibodies and systemic T-cell responses. Tonsils are the lymph nodes serving the upper respiratory tract, acting as both induction and effector site for mucosal immunity.MethodsHere, we have studied the early tonsillar T-cell responses induced in children after LAIV. Thirty-nine children were immunized with trivalent LAIV (containing A/H1N1, A/H3N2, and B viruses) at days 3, 7, and 14 before tonsillectomy. Nonvaccinated controls were included for comparison. Tonsils and peripheral blood (pre- and postvaccination) were collected to study T-cell responses.ResultsTonsillar and systemic T-cell responses differed between influenza strains, and both were found against H3N2 and B viruses, whereas only systemic responses were observed against A/H1N1. A significant increase in cross-reactive tonsillar CD8+ T cells recognizing conserved epitopes from a broad range of seasonal and pandemic viruses occurred at day 14. Tonsillar T cells showed significant cytokine responses (Th1, Th2, and granulocyte-macrophage colony-stimulating factor).ConclusionsOur findings support the use of LAIV in children to elicit broadly cross-reactive T cells, which are not induced by traditional inactivated influenza vaccines and may provide protection to novel virus strains.

Respuesta inmune humoral inducida por la vacuna influenza en niños con diagnóstico de leucemia linfoblástica aguda

Patients with acute lymphoblastic leukemia (ALL) have high risk of severe influenza infection and vaccination is highly recommended. The immunogenicity and effectiveness of vaccination are lower than in healthy people. To evaluate the immune response induced by influenza vaccine in children with ALL and observe effectiveness. Children with ALL in maintenance phase and healthy children were recruited. Blood samples were taken at vaccination day (D0) and at day 28 (D28). Humoral response was evaluated by hemaglutination inhibition test (HAI) against H1N1. Patients were followed up for one year, clinical data and influenza episodes were recorded. 34 children with ALL and 9 healthy children were included. Concerning HAI on D28, 12/34 patients and 5/8 healthy children had titers ≥ 1/40, with seroprotection rates of 35 and 63% respectively. Seroprotected children were older than non-seroprotected ones. During follow-up, only 3 patients non seroprotected, presented influenza infection, without oxygen supplementation or critical care support. Children with ALL had a lower seroprotection rate than healthy children. Nevertheless, none of the seroprotected children presented influenza infection, reinforcing the annual vaccination recommendation.

Cost-effectiveness of inactivated influenza vaccination in children with medical risk conditions in the Netherlands

BackgroundIn many countries, annual immunization with inactivated influenza vaccine (IIV) is recommended for children with medical risk conditions. Prior cost-effectiveness analyses found such immunization to be cost saving, but assumed effectiveness against non-severe influenza outcomes and a higher effectiveness against severe influenza outcomes than recent studies would suggest. However, recent vaccine studies do not indicate any reduction in community or outpatient disease episodes in IIV immunized individuals. We therefore evaluated cost-effectiveness of IIV immunization in children with medical risk conditions in the Netherlands, assuming that IIV reduces influenza-related hospitalization and death, but has no meaningful impact on non-severe health outcomes. MethodsA health economic decision tree model was developed to evaluate health effects and costs of annual IIV immunization versus no immunization. Model inputs were based on our study on influenza-related primary care visits and other literature. Immunization was considered cost effective if associated costs were less than €20,000 per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analyses were performed to assess robustness of results, and one-way sensitivity analyses and scenario analyses were done to assess the influence of individual parameters. ResultsAnnual IIV prevents an average of 1.59 influenza-related hospitalizations and 0.02 deaths per 1,000 children with medical risk conditions. This results in an expected QALY gain of 0.43 at incremental costs of €21,564 per 1,000 children, corresponding to an incremental cost-effectiveness ratio (ICER) of €50,297/QALY compared to no immunization. Under base case assumptions, immunization had a 5% probability of being cost effective. Results were most influenced by vaccine efficacy against fatal influenza, QALY loss due to death, and mortality rate. ConclusionsIf IIV only reduces severe disease outcomes, as current evidence suggests, annual immunization of medical risk children is unlikely to be cost effective. Results should however be interpreted with caution as cost-effectiveness is largely dependent on incidence and QALY losses for fatal influenza, for which evidence is scarce.

The impact of new universal child influenza programs in Australia: Vaccine coverage, effectiveness and disease epidemiology in hospitalised children in 2018

BackgroundNew jurisdictionally-based vaccination programs were established providing free quadrivalent influenza vaccine (QIV) for preschool Australian children in 2018. This was in addition to the National Immunisation Program (NIP) funded QIV for Indigenous children and children with comorbid medical conditions. We assessed the impact of this policy change on influenza disease burden and vaccine coverage, as well as report on 2018 vaccine effectiveness in a hospital-based surveillance system. MethodsSubjects were recruited prospectively from twelve PAEDS-FluCAN sentinel hospital sites (April until October 2018). Children aged ≤16 years hospitalised with an acute respiratory illness (ARI) and laboratory-confirmed influenza were considered cases. Hospitalised children with ARI who tested negative for influenza were considered controls. VE estimates were calculated from the adjusted odds ratio of vaccination in cases and controls. ResultsA total of 458 children were hospitalised with influenza: 31.7% were <2 years, 5.0% were Indigenous, and 40.6% had medical comorbidities predisposing to severe influenza. Influenza A was detected in 90.6% of children (A/H1N1: 38.0%; A/H3N2: 3.1%; A/unsubtyped 48.6%). The median length of stay was 2 days (IQR: 1,3) and 8.1% were admitted to ICU. Oseltamivir use was infrequent (16.6%). Two in-hospital deaths occurred (0.45%). 12.0% of influenza cases were vaccinated compared with 36.0% of test-negative controls. Vaccine effectiveness of QIV for preventing influenza hospitalisation was estimated at 78.8% (95%CI: 66.9; 86.4). ConclusionsCompared with 2017 (n = 1268 cases), a significant reduction in severe influenza was observed in Australian children, possibly contributed to by improved vaccine coverage and high vaccine effectiveness. Despite introduction of jurisdictionally-funded preschool programs and NIP-funded vaccine for children with risk factors for severe disease, improved coverage is required to ensure adequate protection against paediatric influenza morbidity and mortality.

Use of traditional serological methods and oral fluids to assess immunogenicity in children aged 2–16 years after successive annual vaccinations with LAIV

BackgroundThe UK introduced quadrivalent live attenuated influenza vaccine (qLAIV) for children in 2013/2014. The impact of annual vaccination on effectiveness and immunogenicity is being assessed. MethodA phase III/IV open-label study of the immunogenicity of annual vaccination with qLAIV (Fluenz™) was conducted over three consecutive years (2014/15–2016/17) in 254, 249 and 162 children respectively. Serum responses to vaccine components were measured by Haemagglutination Inhibition (HAI) and anti-A(H1N1)pdm09 Neuraminidase (NAI) assays, stratified according to previous receipt of AS03B-adjuvanted A(H1N1)pdm09 pandemic vaccine in 2009/10. Antibody levels to the A(H1N1)pdm09 and H3N2 vaccine components in oral fluids (OF) were explored using an ELISA. FindingsMore paired pre- and post-vaccination oral fluids (96%) than paired sera (87%) were obtained. Geometric mean titre rises using HAI assays were limited, with maximum rises seen in year one for both influenza B strains when 39% and 43% of subjects seroconverted (95% confidence interval 33–46% and 36–50%, respectively) and year two for influenza H3N2, when 40% (33–46%) individuals seroconverted. Prior pandemic vaccine receipt resulted in higher pre- and post-vaccination A(H1N1)pdm09 HAI titres and lower pre-and post-vaccination NAI (N1 neuraminidase) titres in all three years. OF results were congruent with HAI results; assay specificity compared to HAI was 88.1 and 71.6 percent, and sensitivity was 86.4 and 74.8 percent respectively for A(H1N1)pdm09 and H3N2. ConclusionIn all three study years, vaccination with qLAIV resulted in poor antibody responses. However, OFs are an alternative specimen type that allows self sampling, can easily be obtained from children, and their analysis leads to similar conclusions as classic serology by HAI. Their suitability for seroprevalence studies should be investigated. We demonstrated a sustained effect from prior receipt of the AS03B-adjuvanted A(H1N1)pdm09 vaccine, even after repeat vaccination with qLAIV indicating that early exposure to influenza antigens has a significant long lasting effect.

Timeliness of signal detection for adverse events following influenza vaccination in young children: a simulation case study

ObjectivesTo determine how soon after commencement of the seasonal influenza vaccination programme, the AusVaxSafety active vaccine safety surveillance system, currently in use across Australia, would have detected a safety signal...

A model of influenza infection and vaccination in children aged under 5 years in Beijing, China

ABSTRACT Background Children aged under 5 years are particularly vulnerable to influenza infection. In this study, we aim to estimate the number and incidence of influenza among young children and estimate the impact of childhood vaccination in different scenarios from 2013/14 to 2016/17 seasons. Methods The number and incidence rate of influenza infections among children aged under 5 years in Beijing was estimated by scaling up observed surveillance data. Then, we used a susceptible–exposed–infected–recovery (SEIR) model to reproduce the weekly number of influenza infections estimated in Beijing during the study seasons, and to estimate the number and proportion of influenza-attributed medically attended acute respiratory infections (I-MAARI) averted by vaccination in each season. Finally, we evaluated the impact of alternative childhood vaccination programs with different coverage and speed of vaccine distribution. Results The estimated average annual incidence of influenza in children aged under 5 years was 33.9% (95% confidence interval (CI): 27.5%, 47.2%) during the study period. With the actual coverage during the included seasons at around 2.9%, an average of 3.9% (95%CI: 3.5%, 4.4%) I-MAARI was reduced compared to a no-vaccination scenario. Reaching 20%, 40%, 50%, 60%, 80% and 100% vaccine coverage would lead to an overall I-MAARI reduction of 25.3%, 42.7%, 51.9%, 57.0%, 65.3% and 71.2%. At 20% coverage scenario, an average of 28.8% I-MAARI will be prevented if intensive vaccination implemented in 2 months since the vaccine released. Conclusion In Beijing, the introduction of a program for vaccinating young children, even at relatively low vaccine coverage rates, would considerably reduce I-MAARI, particularly if the vaccines can be quickly delivered.

Oil-in-water emulsion adjuvants for pediatric influenza vaccines: a systematic review and meta-analysis

Standard inactivated influenza vaccines are poorly immunogenic in immunologically naive healthy young children, who are particularly vulnerable to complications from influenza. For them, there is an unmet need for better influenza vaccines. Oil-in-water emulsion-adjuvanted influenza vaccines are promising candidates, but clinical trials yielded inconsistent results. Here, we meta-analyze randomized controlled trials with efficacy data (3 trials, n = 15,310) and immunogenicity data (17 trials, n = 9062). Compared with non-adjuvanted counterparts, adjuvanted influenza vaccines provide a significantly better protection (weighted estimate for risk ratio of RT-PCR-confirmed influenza: 0.26) and are significantly more immunogenic (weighted estimates for seroprotection rate ratio: 4.6 to 7.9) in healthy immunologically naive young children. Nevertheless, in immunologically non-naive children, adjuvanted and non-adjuvanted vaccines provide similar protection and are similarly immunogenic. These results indicate that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy young children at the first-time seasonal influenza vaccination.

Vaccinating children against influenza: overall cost-effective with potential for undesirable outcomes

BackgroundThe present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands. This requires an evaluation of the long-term impact of such a program on the burden of influenza across all age groups, using a transmission model that accounts for the seasonal variability in vaccine effectiveness and the shorter duration of protection following vaccination as compared to natural infection.MethodsWe performed a cost-effectiveness analysis based on a stochastic dynamic transmission model that has been calibrated to reported GP visits with influenza-like illness in the Netherlands over 11 seasons (2003/2004 to 2014/2015). We analyzed the costs and effects of extending the current program with vaccination of children aged 2–16 years at 50% coverage over 20 consecutive seasons. We measured the effects in quality-adjusted life-years (QALYs) and we adopted a societal perspective.ResultsThe childhood vaccination program is estimated to have an average incremental cost-effectiveness ratio (ICER) of €3944 per QALY gained and is cost-effective in the general population (across 1000 simulations; conventional Dutch threshold of €20,000 per QALY gained). The childhood vaccination program is not estimated to be cost-effective for the target-group itself with an average ICER of €57,054 per QALY gained. Uncertainty analyses reveal that these ICERs hide a wide range of outcomes. Even though introduction of a childhood vaccination program decreases the number of infections, it tends to lead to larger epidemics: in 23.3% of 1000 simulations, the childhood vaccination program results in an increase in seasons with a symptomatic attack rate larger than 5%, which is expected to cause serious strain on the health care system. In 6.4% of 1000 simulations, the childhood vaccination program leads to a net loss of QALYs. These findings are robust across different targeted age groups and vaccination coverages.ConclusionsModeling indicates that childhood influenza vaccination is cost-effective in the Netherlands. However, childhood influenza vaccination is not cost-effective when only outcomes for the children themselves are considered. In approximately a quarter of the simulations, the introduction of a childhood vaccination program increases the frequency of seasons with a symptomatic attack rate larger than 5%. The possibility of an overall health loss cannot be excluded.