Direct and Indirect Protection with Pediatric Quadrivalent Live-Attenuated Influenza Vaccination in Europe Estimated by a Dynamic Transmission Model.

Objectives: To estimate the public health impact of annual vaccination of children with a quadrivalent live-attenuated influenza vaccine (QLAIV) across Europe. Methods: A deterministic, age-structured, dynamic model was used to simulate influenza transmission across 14 European countries, comparing current vaccination coverage using a quadrivalent inactivated vaccine (QIV) to a scenario whereby vaccination coverage was extended to 50% of 2-17 year-old children, using QLAIV. Differential equations described demographic changes, exposure to infectious individuals, recovery and immunity dynamics. For each country, the basic reproduction number (R0) was calibrated to published influenza incidence statistics. Assumed vaccine efficacy for children was 80% (QLAIV) and 59% (QIV). Symptomatic cases cumulated over 10 years were calculated per 100 000 person-years. One-way sensitivity analyses were conducted on QLAIV efficacy in 7-17 year-olds (59% instead of 80%), durations of natural (±3 years; base case: 6, 12 years for influenza A, B respectively) and QLAIV vaccine-induced immunity (100% immunity loss after 1 season; base case: 30%), and R0 (+/-10% around all-year average value). Results: Across countries, annual QLAIV vaccination additionally prevents 1366-3604 symptomatic cases per 100 000 population (average 2495 /100 000, ie, a reduction of 47.6% of the cases which occur in the reference scenario with QIV vaccination only). Among children (2-17 years), QLAIV prevents 551-1555 cases per 100 000 population (average 990 /100 000, ie, 67.2% of current cases). Among adults, QLAIV indirectly prevents 726-2047 cases per 100 000 population (average 1466 /100 000, ie, 40.0% of current cases). The most impactful drivers of total protection were duration of natural immunity against influenza A, R0 and QLAIV immunity duration and efficacy. In all evaluated scenarios, there was a large direct and even larger indirect protection compared with the reference scenario. Conclusions: The model highlights direct and indirect protection benefits when vaccinating healthy children with QLAIV in Europe, across a range of demographic structures, contact patterns and vaccination coverage rates.

Translation of the UK Pediatric Influenza Vaccination Programme in Primary Schools to 13 European Countries Using a Dynamic Transmission Model.

Objectives: To simulate the impact of a pediatric influenza vaccination programme using quadrivalent live attenuated influenza vaccine (QLAIV) in Europe by applying coverage rates achieved in the United Kingdom during the 2014-2015 season and to compare the model outcomes to the UK results. Methods: We used a deterministic, age-structured, dynamic transmission model adapted to the demography, contact patterns and influenza incidence of 13 European countries, with a 10-year horizon. The reference strategy was the unchanged country-specific coverage rate, using quadrivalent inactivated vaccine (assumed efficacy against infection from 45% in 1-year-old children to 60% in healthy adults). In the evaluated strategy, 56.8% of 5-10-year-old children were additionally vaccinated with QLAIV (assumed efficacy 80%), as was the case in 2014-2015 in the United Kingdom's primary school pilot areas. Symptomatic influenza cases and associated medical resources (primary care consultations [PCC], hospitalization, intensive care unit [ICU] admissions) were calculated. The evaluated versus reference strategies were compared using odds ratios (ORs) for PCC in the target (aged 5-10-years) and non-target adult (aged >17 years) populations as well as number needed to vaccinate (NNV) with QLAIV to avert one PCC, hospitalization or ICU admission. Model outcomes, averaged over 10 seasons, were compared with published real-life data from the United Kingdom for the 2014-2015 season. Results: Over 13 countries and 10 years, the evaluated strategy prevented 32.8 million of symptomatic influenza cases (172.3 vs 205.2 million). The resulting range of ORs for PCC was 0.18-0.48 among children aged 5-10-years, and the published OR in the United Kingdom was 0.06 (95% confidence interval [0.01; 0.62]). In adults, the range of ORs for PCC was 0.60-0.91 (UK OR=0.41 [0.19; 0.86]). NNV ranges were 6-19 per averted PCC (UK NNV=16), 530-1524 per averted hospitalization (UK NNV=317) and 5298-15 241 per averted ICU admission (UK NNV=2205). Conclusions: Across a range of European countries, our model shows the beneficial direct and indirect impact of a paediatric vaccination programme using QLAIV in primary school-aged children, consistent with what was observed during a single season in the United Kingdom. Recommendations for the implementation of pediatric vaccination programmes are, therefore, supported in Europe.

Estimates of the Public Health Impact of a Pediatric Vaccination Program Using an Intranasal Tetravalent Live-Attenuated Influenza Vaccine in Belgium.

OBJECTIVES: Our objectives were to estimate the public health outcomes of vaccinating Belgian children using an intranasal tetravalent live-attenuated influenza vaccine (QLAIV) combined with current coverage of high-risk/elderly individuals using the trivalent inactivated vaccine. METHODS: We used a deterministic, age-structured, dynamic model to simulate seasonal influenza transmission in the Belgian population under the current coverage or after extending vaccination with QLAIV to healthy children aged 2-17 years. Differential equations describe demographic changes, exposure to infectious individuals, infection recovery, and immunity dynamics. The basic reproduction number (R 0) was calibrated to the observed number of influenza doctor visits/year. Vaccine efficacy was 80 % (live-attenuated) and 59-68 % (inactivated). The 10-year incidence of symptomatic influenza was calculated with different coverage scenarios (add-on to current coverage). RESULTS: Model calibration yielded R 0 = 1.1. QLAIV coverage of 75 % of those aged 2-17 years averted 374,000 symptomatic cases/year (57 % of the current number), 244,000 of which were among adults (indirect effect). Vaccinating 75 % of those aged 2-11 years and 50 % of those aged 12-17 years averted 333,200 cases/year (213,000 adult cases/year). Vaccinating only healthy children aged 2-5 years generated direct protection but limited indirect protection, even with 90 % coverage (40,800 averted adult cases/year; -8.4 %). Targeting all children averted twice as many high-risk cases as targeting high-risk children only (8485 vs. 4965/year with 75 % coverage). Sensitivity analyses showed the robustness of results. CONCLUSIONS: The model highlights the direct and indirect protection benefits when vaccinating healthy children with QLAIV in Belgium. Policies targeting only high-risk individuals or the youngest provide limited herd protection, as school-age children are important influenza vectors in the community.

An evaluation of a low-density DNA microarray using cytochrome P450 inducers.

The aim of this study was to validate a low-density DNA microarray "Rat HepatoChip", which contains 59 genes from a range of potential toxic markers and drug metabolism-related genes. Liver mRNA was isolated from rats dosed with six different chemicals, dexamethasone, troleandomycin, miconazole, clotrimazole, and methylclofanapate, which are all known to induce different cytochrome P450 genes, and isoniazid, which does not cause histopathological changes. Replicate microarrays were used to measure the variability in the chips and in the process. The average variability in signal between different chips observed in triplicate experiments was 33% ranging from 21 to 39% depending on genes. We also demonstrated a strong correlation between the liver histopathology and the gene expression profiles indicating that the gene expression profile reflects histopathological changes. These results suggest that the Rat HepatoChip microarray may provide a fast and effective tool for assessing the toxicity profile of developmental drug candidates during the drug discovery process.