Efficacy and safety of a quadrivalent influenza vaccine in children aged 6–35 months: A global,multiseasonal, controlled,randomized Phase III study

BackgroundChildren are an important target group for influenza vaccination, but few studies have prospectively evaluated influenza vaccine efficacy (VE) in children under 3 years of age. This was a randomized Phase III trial to assess the efficacy, immunogenicity, and safety of an inactivated quadrivalent influenza vaccine (QIV) in young children (EudraCT: 2016–004904–74).MethodsInfluenza-naïve children aged 6–35 months were randomized during three influenza seasons to receive vaccination with QIV or a non-influenza control vaccine. One group of participants was revaccinated with QIV in the subsequent influenza season. The primary efficacy endpoint was the absolute VE of QIV against influenza caused by any circulating strain. Key secondary efficacy endpoints included the absolute VE of QIV against influenza due to antigenically matching strains and immunogenicity. Safety and reactogenicity were also evaluated.ResultsIn total, 1005 children received QIV and 995 received control vaccine. Influenza A/B infection due to any circulating influenza strain occurred less frequently in children who received QIV versus children receiving a control vaccine. The absolute VE of QIV against any circulating influenza strain was 54% (95% confidence interval [CI]: 37%, 66%). The absolute VE of QIV against antigenically matching influenza strains was 68% (95% CI: 45%, 81%). Mean hemagglutination inhibition titers for all influenza strains in the QIV group increased post-vaccination, whereas increases were minimal in the control vaccine group; results from virus neutralization and neuraminidase-inhibition assays were generally consistent with the hemagglutination inhibition assay findings. Approximately 12 months after primary vaccination with QIV, antibody titers remained higher than pre-vaccination titers for most strains. In participants who were revaccinated, QIV elicited strong antibody responses. The overall safety profile and reactogenicity of QIV was comparable with control vaccine.ConclusionPrimary vaccination with QIV was well tolerated and effective in protecting children aged 6–35 months against influenza.     

Cost-effectiveness analysis of switching from a trivalent to a quadrivalent inactivated influenza vaccine in the Peruvian immunisation programme

BackgroundSeasonal influenza is an acute respiratory infection mostly caused by type A and B influenza viruses. The severe form of the infection can be life-threatening and lead to a significant burden. Vaccination is the most efficient way of preventing influenza infections and limit this burden.ObjectivesTo assess the cost-effectiveness of switching from a trivalent influenza vaccine (TIV) to a quadrivalent influenza vaccine (QIV) in the vaccination programme in Peru, and to evaluate the health and economic impact of reaching the vaccination coverage rate targeted by the Ministry of Health.MethodsA decision-analytic static cost-effectiveness model, was adapted to the Peruvian setting under both payer and societal perspectives.ResultsA switch from TIV to QIV would prevent 29,126 additional cases (including 12,815 consultations), 54 hospitalisations, and 23 deaths related to influenza, mostly in the population <2 years-old and >60 years-old. This would lead to a saving of US $505,206 under the payer perspective, that would partially offset the investment necessary to introduce QIV into the immunisation programme. The resulting incremental cost-effectiveness ratio (ICER) is $16,649 per QALYs gained. The main drivers of the model results were vaccine efficacy against influenza B viruses, degree of match, vaccines prices and proportion of cases attributable to influenza B. The robustness of the results seems satisfactory as QIV has the probability of being a cost-effective strategy of 83.8% (considering a threshold of three GDP per capita). Reaching the coverage targeted by the Ministry of Health would result in health benefits and disease management savings, and lower ICERs.ConclusionIntroducing QIV instead of TIV in the Peruvian immunisation programme is expected to be a cost-effective strategy, especially in younger children and the elderly. The benefit of QIV would be even more important if the coverage targeted by the Ministry of Health would be reached in the most vulnerable groups.     

Effectiveness of quadrivalent influenza vaccination in the first year of a funded childhood program in Queensland,Australia, 2018

BackgroundFollowing high influenza activity in 2017, the state of Queensland, Australia, funded a quadrivalent inactivated influenza vaccination program for children aged 6 months to <5 years in 2018. We calculated influenza vaccine effectiveness (VE) among children eligible for this program.MethodsA matched case-control study was conducted. Cases were identified using Queensland 2018 influenza notification data among children age-eligible for funded vaccination. Controls were drawn from Australian Immunisation Register records of Queensland resident children age-eligible for funded influenza vaccine. Up to 10 controls per case were matched for location and birthdate. First dose vaccination was valid if received ≥14 days prior to specimen collection; a second dose was valid if received ≥28 days after first dose receipt. VE was calculated for vaccine doses and adherence to national recommendations for two doses in the first season (schedule completeness) and adjusted (VE_adj) for sex and First Nations status.ResultsThere were 1,125 cases and 10,645 matched controls analysed. Overall VE_adj against laboratory-confirmed influenza was 51% (95% confidence interval (CI) 41–60). VE_adj was 60% (95% CI 46–70) for children who received two doses in 2018, and 60% (95% CI 48–69) for children vaccinated appropriately according to schedule completeness. VE increased with age.ConclusionsModerate vaccine effectiveness was observed for children eligible for the funded program in Queensland in 2018, adding to the sparse evidence for influenza vaccine use in Australian children. Adhering to the national first season two dose schedule for influenza vaccine receipt in children ensures maximum protection.     

Influenza vaccination coverage among persons seeking outpatient medical care for acute respiratory illness in five states in the United States, 2011–2012 through 2018–2019

BackgroundIn the United States (U.S.), annual influenza vaccination has been recommended for all persons aged ≥6 months with the Healthy People 2020 coverage target of 70%. However, vaccination coverage has remained around 42–49% during the past eight influenza seasons. We sought to quantify influenza vaccination coverage and factors associated with vaccination in persons seeking outpatient medical care for an acute respiratory illness (ARI).MethodsWe enrolled outpatients aged ≥6 months with ARI from >50 U.S. clinics from 2011 to 2012 through 2018–2019 influenza seasons and tested for influenza with molecular assays. Vaccination status was based on documented receipt of the current season’s influenza vaccine. We estimated vaccination coverage among influenza-negative study participants by study site, age, and season, and compared to state-level influenza coverage estimates in the general population based on annual immunization surveys. We used multivariable logistic regression to examine factors independently associated with receipt of influenza vaccines.ResultsWe enrolled 45,424 study participants with ARI who tested negative for influenza during the study period. Annual vaccination coverage among influenza-negative ARI patients and the general population in the participating states averaged 55% (range: 47–62%), and 52% (range: 46–54%), respectively. Among enrollees, coverage was highest among adults aged ≥65 years (82%; range, 80–85%) and lowest among adolescents aged 13–17 years (38%; range, 35–41%). Factors significantly associated with non-vaccination included non-White race, no college degree, exposure to cigarette smoke, absence of high-risk conditions, and not receiving prior season influenza vaccine.ConclusionsInfluenza vaccination coverage over eight seasons among outpatients with non-influenza respiratory illness was slightly higher than coverage in the general population but 15% lower than national targets. Increased efforts to promote vaccination especially in groups with lower coverage are warranted to attain optimal health benefits of influenza vaccine.     

Cost-effectiveness analysis of quadrivalent seasonal influenza vaccines in Beijing: A modeling analysis

BackgroundSince 2007, Beijing has offered a free trivalent influenza vaccine (TIV) for residents aged ≥ 60 years and school students. The quadrivalent influenza vaccine (QIV) was administered to school children in 2018 and will be administered to elderly adults in the future. In addition, health care workers (HCWs) who are involved in the prevention and control of COVID-19 were included in the program in 2020. This study aimed to analyze the cost-effectiveness of a comprehensive list of combined strategies of TIV and QIV for school children, elderly adults, and HCWs to identify the most cost-effective strategy.MethodsA decision tree was developed to compare 1-year outcomes of TIV vs. QIV in three risk groups: school children, elderly adults, and HCWs. The outcome was incremental cost per quality-adjusted life-year (QALY). Probabilistic sensitivity analyses and scenario analyses were developed to assess the robustness of the results.ResultsFrom the perspective of society, this study found that the introduction of QIVs can be cost-effective for any and all targeted groups with a willingness-to-pay threshold of 3-fold GDP per capita. Among all programs, program H (all school children, elderly adults, and HCWs received the QIV) showed a 79% probability of being cost-effective with an incremental cost-effectiveness ratio (ICER) of 13,580 (95% CI: 13,294, 13,867) US$/QALY and was the preferred option in the base case scenario.ConclusionThe introduction of QIVs to school children, elderly adults, or HCWs is likely to be cost-effective, either separately or collectively. The introduction of QIV to school children, elderly adults, and health care workers simultaneously showed the highest probability of being cost-effective and was the preferred option.     

Safety and immunogenicity of a seasonal quadrivalent influenza vaccine (GC3110A) in healthy participants aged ≥ 65 years

BackgroundSeasonal Influenza is still considered associated with seasonal morbidity and hospitalization in the elderly population. The World Health Organization (WHO) recommended seasonal quadrivalent influenza vaccine (QIV) to reduce burden of two currently circulating influenza B lineages. Until 2019 Korean National Immunization Program (NIP) recommended trivalent influenza vaccine (TIV) after ongoing debates on cost effectiveness of QIV for elderly population. Although influenza vaccine only showed modest effect on reducing influenza in elderly, this study aimed to evaluate the immunogenicity and safety of inactivated QIV in healthy participants ≥ 65 years of age.MethodsA total of 274 healthy participants aged ≥ 65 years received a QIV. Seroconversion-based vaccine efficacy of 4 strains of seasonal influenza was assessed 21 days after vaccination and adverse events were monitored until 180 days after vaccination.ResultsThe percentages of participants seroconverted after vaccination on HI antibody against each strain were 36.5% (99/271) to A/H1N1, 47.6% (129/271) to A/H3N2, 40.6% (110/271) to B Yamagata, and 49.1% (133/271) to B Victoria. The percentages of participants seroprotected after vaccination on HI antibody against each strain were 81.2% (220/271) to A/H1N1, 98.5% (267/271) to A/H3N2, 95.2% (258/271) to B Yamagata, and 93.7% (254/271) to B Victoria. There was no serious adverse event (SAE) related with the study vaccine.ConclusionThe quadrivalent split influenza vaccine is expected to offer seroprotection against influenza A and both influenza B lineages even in the elderly population.     

Trends in effectiveness of inactivated influenza vaccine in children by age groups in seven seasons immediately before the COVID-19 era

BackgroundWe have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6–11 months) and older (6–15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups.MethodsThe overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6–11 months, 1–2, 3–5, 6–12, and 13–15 years old) with adjustments including influenza seasons.ResultsA total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% [95% confidence interval (CI), 41–47], 63% [95 %CI, 51–72], and 37% [95 %CI, 32–42], respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% [95 %CI, 55–65] and 52% [95 %CI, 41–61], respectively). Analysis for the 2020/21 season was not performed because no cases were reported.ConclusionsThis is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.     

Repeated exposure to an MF-59 adjuvanted quadrivalent subunit influenza vaccine (aQIV) in children: Results of two revaccination studies

BackgroundPediatric adjuvanted seasonal influenza vaccines induce higher immune responses and have the potential to confer better protection against influenza among young vaccine-naïve children. Limited data describe benefits and risks of repeated administration of adjuvanted influenza vaccines in children. Two revaccination studies assess the safety and immunogenicity of repeated exposure to an MF59-adjuvanted quadrivalent influenza vaccine (aQIV; Fluad®) compared to routine non-adjuvanted quadrivalent influenza vaccine (QIV).MethodsChildren previously enrolled in the parent study, who received vaccination with aQIV or nonadjuvanted influenza vaccine (TIV or QIV), were recruited in Season 1 (n = 607) or Season 2 (n = 1601) of the extension trials. Season 1 participants remained in their original randomization groups (aQIV-aQIV or TIV-QIV); Season 2 subjects were re-randomized to either vaccine, resulting in four groups (aQIV-aQIV, aQIV-QIV, QIV-aQIV, or QIV-QIV). All subjects received a single-dose vaccination. Blood samples were taken for immunogenicity assessment prior to vaccination and 21 and 180 days after vaccination. Reactogenicity (Days 1–7) and safety were assessed in all subjects.ResultsHemagglutination inhibition (HI) geometric mean titer (GMT) ratios demonstrated superiority of aQIV revaccination over QIV revaccination for all strains in Season 1 and for A/H1N1, B/Yamagata, and B/Victoria in Season 2. Higher HI titers against heterologous influenza strains were observed after aQIV vaccination during both seasons. Mild to moderate severity and short duration reactogenicity was more common in the aQIV than QIV groups, but the overall safety profiles were similar to the parent study.ConclusionThe safety and immunogenicity results from this study demonstrate benefit of aQIV for both priming and revaccination of children aged 12 months to 7 years.     

Lineage-matched versus mismatched influenza B vaccine effectiveness following seasons of marginal influenza B circulation

BackgroundSeveral countries have recently transitioned from the trivalent inactivated influenza vaccine (TIV) to the quadrivalent inactivated influenza vaccine (QIV) in order to outweigh influenza B vaccine-mismatch. However, few studies thus far evaluated its benefits versus the TIV in a systematic manner. Our objective was to compare the QIV VE with lineage-mismatched TIV VE.MethodsWe estimated the 2015–2016, 2017–2018, 2019–2020 end-of season influenza B VE against laboratory-confirmed influenza-like illness (ILI) among community patients, using the test-negative design. VE was estimated for pre-determined age groups and for moving age intervals of 15 years.ResultsSince 2011–2012 season, alternate seasons in Israel were dominated by influenza B circulation. Compared with the lineage-mismatched TIV used during the 2015–2016 and 2017–2018 seasons, the 2019–2020 QIV showed the highest all-ages VE, with VE estimates of 56.9 (95% CI 30.1 to 73.4), 16.5 (95% CI –22.5 to 43.1) and ?25.8 (95% CI ?85.3 to 14.6) for the 2019–2020, 2017–2018 and 2015–2016 seasons, respectively. The 2019–2020 VE point estimated were the highest for the 0.5–4, 5–17 and 18–44 years age groups and for more 15-year age intervals as compared to the other seasons.ConclusionsOur results support the rapid transition from the TIV to the QIV.     

Comparison of the immunogenicity and safety of quadrivalent and tetravalent influenza vaccines in children and adolescents

BackgroundChildren and adolescents are susceptible to influenza. Vaccination is the most important strategy for preventing influenza, yet there are few studies on the immunogenicity and safety of quadrivalent inactivated influenza vaccine (QIV) containing two A strains (H1N1 and H3N2) and two B lineages (Victoria and Yamagata). Therefore, to further clarify the immunogenicity and safety of QIV in children and adolescents, a meta-analysis was performed to provide a reference for the development of influenza prevention strategies.MethodsPubMed, EMBASE and Cochrane Library were searched for articles published as of February 12, 2019. Random clinical trials comparing the immunogenicity and safety of QIV and TIV among children and adolescents were selected. The main outcomes were comparisons of immunogenicity (seroprotection rate [SPR] and seroconversion rate [SCR] and adverse events using risk ratios (RRs). The meta-analysis was performed using random-effects models.ResultsAmong the 6 months up to 3 years group, QIV showed a higher SPR for B lineages than for TIV-B/Yamagata, with pooled RRs of 3.07 (95% CI: 2.58–3.66) and 1.06 (95% CI: 1.01–1.11), respectively. For the 3 years through 18 years, QIV had a higher SCR and SPR for the Yamagata lineage than for TIV-B/Victoria, with pooled RRs of 2.30 (95% CI: 1.83–2.88) and 1.16 (95% CI: 1.03–1.30), respectively. Compared to TIV-B/Yamagata, a higher SCR and SPR for the Victoria lineage was found for QIV, with RRs of 3.09 (95% CI: 1.99–4.78) and 1.72 (95% CI: 1.22–2.41), respectively. Regarding adverse events, only pain was more frequently reported for QIV than TIV ; the RR was 1.09 (95% CI: 1.02–1.17).ConclusionsThe immunogenicity of QIV for common ingredients was similar to that of TIV, but the former exhibited significantly higher immunogenicity for the unique lineage. QIV also had the same reliable safety as TIV.     

Cost-effectiveness of quadrivalent versus trivalent influenza vaccine for elderly population in China

BackgroundInfluenza-associated excess death occurred most in the elderly. We aimed to assess the cost-effectiveness of quadrivalent influenza vaccine (QIV) versus trivalent influenza vaccine (TIV) for prevention of influenza infection among elderly population in China.MethodsA decision-analytic model was developed to compare 1-year clinical and economic outcomes of three influenza vaccination options (no vaccination, TIV, and QIV) in a hypothetical cohort of Chinese elderly aged 69 years. Outcome measures included cost, influenza infection rate, influenza-related mortality rate, quality-adjusted life-years (QALY) loss, and incremental cost-effectiveness ratio (ICER) from societal perspective. Sensitivity analyses were performed to examine the uncertainty of model inputs.ResultsBase-case results showed no vaccination was dominated (more costly at higher QALY loss) by TIV and QIV. QIV was more costly (USD56.29 versus USD54.28) with lower influenza infection rate (0.608 versus 0.623), mortality rate (0.00199 versus 0.00204), and QALY loss (0.01213 versus 0.01243) than TIV. QIV was cost-effective compared to TIV with ICER of 6,700 USD/QALY below the willingness-to-pay threshold (29,580 USD/QALY). One-way sensitivity analysis found the cost-effectiveness of QIV was subject to the relative risk of vaccine effectiveness of QIV versus TIV, and TIV would be cost-effective if the relative risk was below 1.05. In 10,000 Monte Carlo simulations, the probabilities of QIV, TIV, and no vaccination to be cost-effective were 86.3%, 13.7%, and 0%, respectively.ConclusionQIV appears to be a cost-effective option compared to TIV and no influenza vaccination for elderly population in China.     

Active SMS-based influenza vaccine safety surveillance in Australian children

IntroductionAustralia’s novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration.MethodsParent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia’s National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles.Results7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p < .001). Meningococcal B vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p < .001). Reported fever was strongly associated with medical attendance (OR: 42.6; 95% Confidence Interval (CI): 25.6–71.0). TIV and QIV safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p < .001)). There was no difference in safety profile between brands.DiscussionActive participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually.     

Cost-Effectiveness of Quadrivalent Versus Trivalent Influenza Vaccination in the Dutch National Influenza Prevention Program

ObjectivesAs of 2019, quadrivalent influenza vaccine (QIV) has replaced trivalent influenza vaccine (TIV) in the national immunization program in The Netherlands. Target groups are individuals of 60+ years of age and those with chronic diseases. The objective was to estimate the incremental break-even price of QIV over TIV at a threshold of €20 000 per quality-adjusted life-year (QALY).MethodsAn age-structured compartmental dynamic model was adapted for The Netherlands to assess health outcomes and associated costs of vaccinating all individuals at higher risk for influenza with QIV instead of TIV over the seasons 2010 to 2018. Influenza incidence rates were derived from a global database. Other parameters (probabilities, QALYs and costs) were extracted from the literature and applied according to Dutch guidelines. A threshold of €20 000 per QALY was applied to estimate the incremental break-even prices of QIV versus TIV. Sensitivity analyses were performed to test the robustness of the model outcomes.ResultsRetrospectively, vaccination with QIV instead of TIV could have prevented on average 9500 symptomatic influenza cases, 2130 outpatient visits, 84 hospitalizations, and 38 deaths per year over the seasons 2010 to 2018. This translates into 385 QALYs and 398 life-years potentially gained. On average, totals of €431 527 direct and €2 388 810 indirect costs could have been saved each year.ConclusionUsing QIV over TIV during the influenza seasons 2010 to 2018 would have been cost-effective at an incremental price of maximally €3.81 (95% confidence interval, €3.26-4.31). Sensitivity analysis showed consistent findings on the incremental break-even price in the same range.     

Burden of medically attended influenza infection and cases averted by vaccination – United States, 2016/17 through 2018/19 influenza seasons

BackgroundEpidemics of seasonal influenza vary in intensity annually, and influenza vaccine effectiveness (VE) fluctuates based in part on antigenic match to circulating viruses. We estimated the incidence of influenza and influenza cases averted by vaccination in four ambulatory care sites in the United States, during seasons when overall influenza VE ranged from 29% to 40%.MethodsWe conducted active surveillance for influenza at ambulatory care settings at four sites within the United States Influenza Vaccine Effectiveness Network. We extrapolated the total number of influenza cases in the source populations served by these organizations based on incidence of medically attended acute respiratory illness in the source population and influenza test results in those actively tested for influenza. We estimated the number of medically attended influenza cases averted based on incidence, vaccine coverage, and VE.ResultsFrom 2016/17 through 2018/19, incidence of ambulatory visits for laboratory-confirmed influenza ranged from 31 to 51 per 1,000 population. Incidence was highest in children aged 9–17 years (range, 56 to 81 per 1,000) and lowest in adults aged 18–49 years (range, 23–32 per 1,000). Medically attended cases averted by vaccination ranged from a high of 46.6 (95 % CI, 12.1– 91.9) per 1,000 vaccinees in children aged 6 months to 8 years, to a low of 6.9 (95 % CI, ?5.1– 27.3) per 1,000 vaccinees in adults aged ≥ 65 years.DiscussionEven in seasons with low vaccine effectiveness for a particular virus subtype, influenza vaccines can still lead to clinically meaningful reductions in ambulatory care visits for influenza.     

Effectiveness of seasonal trivalent influenza vaccination against hospital-attended acute respiratory infections in pregnant women: A retrospective cohort study

BackgroundPregnant women are at risk of serious influenza infection. Although previous studies indicate maternal influenza vaccination can prevent hospitalisation in young infants, there is limited evidence of the effect in mothers.MethodsA cohort of 34,701 pregnant women delivering between 1 April 2012 and 31 December 2013 was created using birth records. Principal diagnosis codes from hospital emergency department (ED) and inpatient records were used to identify episodes of acute respiratory illness (ARI) during the 2012 and 2013 southern hemisphere influenza seasons. Cox regression models were used to calculate adjusted hazard ratios (aHRs) by maternal vaccination status, controlling for Indigenous status, socioeconomic level, medical conditions, and week of delivery.Results3,007 (8.7%) women received a seasonal influenza vaccine during pregnancy. Vaccinated women were less likely to visit an ED during pregnancy for an ARI (9.7 visits per 10,000 person-days vs. 35.5 visits per 10,000 person-days; aHR: 0.19, 95% CI: 0.05−0.68). Vaccinated women were also less likely to be hospitalised with an ARI compared to unvaccinated women (16.2 hospitalisations per 10,000 person-days vs. 34.0 hospitalisations per 10,000 person-days; aHR: 0.35, 95% CI: 0.13−0.97).ConclusionsInfluenza vaccination during pregnancy was associated with significantly fewer hospital attendances for ARI in pregnant women.     

Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States

BackgroundTest-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls.MethodsAdults hospitalized at 21 medical centers in 18 states March 11–August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group.Results5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18–64 years, VE was 93 % (95 % CI: 90–94) using syndrome-negative controls and 91 % (95 % CI: 88–93) using test-negative controls.ConclusionsDespite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.     

Effectiveness of influenza vaccination during pregnancy to prevent severe infection in children under 6 months of age,Spain, 2017–2019

IntroductionInfluenza vaccination is recommended to pregnant women in Spain to reduce the risk of influenza-related complications. Influenza related hospitalizations pose a significant disease burden in children every year. Although children below 6 months are too young to be vaccinated, they can receive protection against influenza through vaccination of their mothers during pregnancy. We estimated the effectiveness of maternal influenza vaccination to prevent influenza hospitalizations in infants under 6 months of age.MethodsThis is a retrospective pilot study, using data from the Severe Hospitalized Confirmed Influenza Cases (SHCIC) surveillance system in seasons 2017/18 and 2018/19 in Spain. Maternal vaccination status during pregnancy was collected for cases in children 6 months and younger hospitalized with confirmed influenza infection. Influenza vaccine effectiveness was estimated using the screening method, by comparing the proportion of children with vaccinated mothers during pregnancy (proportion of cases vaccinated, PCV), with the vaccination coverage among pregnant women in Spain (proportion of population vaccinated, PPV).ResultsFor all the study period, the PCV was 17% and the PPV was 35%. Influenza vaccination in mothers during pregnancy prevented influenza confirmed hospitalizations in infants aged 6 months and younger with a 61% (95%CI: 27–79%) effectiveness.ConclusionsIn line with evidence from other countries, influenza vaccination during pregnancy protects infants up to 6 months of age from influenza hospitalizations in Spain. These results support current recommendations of influenza vaccination in pregnant women, and more studies are needed in Spain to confirm the double protection of maternal vaccination in mothers and infants.