Assessment of temporally-related acute respiratory illness following influenza vaccination

BackgroundA barrier to influenza vaccination is the misperception that the inactivated vaccine can cause influenza. Previous studies have investigated the risk of acute respiratory illness (ARI) after influenza vaccination with conflicting results. We assessed whether there is an increased rate of laboratory-confirmed ARI in post-influenza vaccination periods.MethodsWe conducted a cohort sub-analysis of children and adults in the MoSAIC community surveillance study from 2013 to 2016. Influenza vaccination was confirmed through city or hospital registries. Cases of ARI were ascertained by twice-weekly text messages to household to identify members with ARI symptoms. Nasal swabs were obtained from ill participants and analyzed for respiratory pathogens using multiplex PCR. The primary outcome measure was the hazard ratio of laboratory-confirmed ARI in individuals post-vaccination compared to other time periods during three influenza seasons.ResultsOf the 999 participants, 68.8% were children, 30.2% were adults. Each study season, approximately half received influenza vaccine and one third experienced ≥1 ARI. The hazard of influenza in individuals during the 14-day post-vaccination period was similar to unvaccinated individuals during the same period (HR 0.96, 95% CI [0.60, 1.52]). The hazard of non-influenza respiratory pathogens was higher during the same period (HR 1.65, 95% CI [1.14, 2.38]); when stratified by age the hazard remained higher for children (HR 1·71, 95% CI [1.16, 2.53]) but not for adults (HR 0.88, 95% CI [0.21, 3.69]).ConclusionAmong children there was an increase in the hazard of ARI caused by non-influenza respiratory pathogens post-influenza vaccination compared to unvaccinated children during the same period. Potential mechanisms for this association warrant further investigation. Future research could investigate whether medical decision-making surrounding influenza vaccination may be improved by acknowledging patient experiences, counseling regarding different types of ARI, and correcting the misperception that all ARI occurring after vaccination are caused by 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.     

Vaccine effectiveness for laboratory-confirmed influenza in children 6-59 months of age, 2005-2007

To estimate the effectiveness of influenza vaccine against medical care visits for laboratory-confirmed influenza in young children we conducted a matched case-control study in children with acute respiratory illness or fever from 2005-2007. Influenza vaccine effectiveness (VE) was calculated using cases with laboratory-confirmed influenza and controls who tested negative for influenza. The effectiveness of influenza vaccine in fully vaccinated children 6-59 months of age was 56% (95% CI: 25%-74%); a significant VE was not found for partial vaccination.     

Change in the efficacy of influenza vaccination after repeated inoculation under antigenic mismatch: A systematic review and meta-analysis

ObjectivesTo examine the effects of repeated influenza vaccination on medically-attended influenza (MAI) and acute respiratory illness (ARI) risk according to the antigenic matching between vaccine and circulating virus strains.MethodsWe performed a systematic review and meta-analysis of randomized studies that compared the risk of MAI and ARI between subjects who had been vaccinated for two consecutive seasons (multiple vaccine group) and those who had been vaccinated in the current season and not in the previous season (single vaccine group).ResultsOf 1467 articles identified, eight studies covering ten seasons were included in meta-analyses. Six studies assessed efficacy against MAI in children, yielding the risk ratios (RR) of 2.04 (95% CI 1.29–3.22) when circulating strains mismatched vaccine strains, and 0.64 (0.33–1.22) when circulating strains matched vaccine strains. When stratified by vaccine types, the reduced efficacy was significant for live-attenuated influenza vaccine only. Three studies investigated efficacy against ARI in children, with the RR of 0.96 (0.81–1.15). The results on adults and the elderly were scarce.ConclusionsInfluenza vaccine efficacy against mismatch strains was lower in repeatedly vaccinated children as compared with those vaccinated for the current season only. The scarcity of available studies may call for further randomized controlled trials on repeated influenza vaccination.     

Influenza vaccine for pregnant women in resource-constrained countries: a review of the evidence to inform policy decisions

Seasonal influenza is responsible for three to five million severe cases of disease annually, and up to 500,000 deaths worldwide. Pregnant women and infants suffer disproportionately from severe outcomes of influenza. The excellent safety profile and reliable immunogenicity of inactivated influenza vaccine support WHO recommendations that pregnant women be vaccinated to decrease complications of influenza disease during pregnancy. Nevertheless, influenza vaccine is not routinely used in most low-and middle-income countries and is not widely used in pregnant women worldwide.Two recent prospective, controlled trials of maternal influenza vaccination in Bangladesh and US Native American reservations demonstrated that inactivated influenza vaccine given to pregnant women can decrease laboratory-confirmed influenza virus infection in their newborn children. These studies support consideration of the feasibility of targeted influenza vaccine programs in resource-constrained countries.Platforms exist for the delivery of influenza vaccine to pregnant women worldwide. Even in the least developed countries, an estimated 70% of women receive antenatal care, providing an opportunity for targeted influenza vaccination. Challenges to the introduction of maternal influenza vaccination in resource-constrained countries exist, including issues regarding vaccine formulation, availability, and cost. Nonetheless, maternal influenza vaccination remains an important and potentially cost-effective approach to decrease influenza morbidity in two high-risk groups - pregnant women and young infants.     

Association between seasonal influenza vaccination with pre- and postnatal outcomes

Objective

Influenza vaccination during pregnancy is known to prevent severe influenza illness but its effects on other outcomes and the extent to which its safety is affected by timing of vaccination, maternal race/ethnicity and the type of vaccine is less clear. Therefore, we examined this in a large retrospective cohort.

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.     

Birth outcomes for Australian mother-infant pairs who received an influenza vaccine during pregnancy, 2012–2014: The FluMum study

IntroductionIn Australia, influenza vaccination is recommended for all women who will be pregnant during the influenza season. Vaccine safety and effectiveness are key concerns and influencers of uptake for both vaccine providers and families. We assessed the safety of receiving an influenza vaccination during any trimester of pregnancy with respect to preterm births and infant birthweight.MethodsWe conducted a nested retrospective cohort study of ‘FluMum’ participants (2012–2014). Our primary exposure of interest was influenza vaccination during pregnancy. The primary outcomes of interest were infant birthweight and weeks’ gestation at birth for live singleton infants. Analyses included comparisons of these birth outcomes by vaccination status and trimester of pregnancy an influenza vaccine was given. We calculated means, proportions, and relative risks and performed multivariable logistic regression for potential confounding factors.ResultsIn the 7126 mother-infant pairs enrolled in this study, mean maternal age at infant birth was 31.7 years. Influenza vaccine uptake in pregnancy was 34%. Most mothers with a known date of vaccination received a vaccine in the second trimester (51%). Those mothers with a co-morbidity or risk factor were 13% more likely to have influenza vaccine during pregnancy compared to other mothers (RR 1.13, 95% CI 1.04–1.24, p = 0.007). Mean weeks’ gestation at birth was 38.7 for the vaccinated and 38.8 for the unvaccinated group (p = 0.051). Infants in the vaccinated group weighed 15 g less in birthweight compared to the unvaccinated infants (95% CI −12.8 to 42.2, p = 0.29).ConclusionResults arising from this large Australian cohort study are reassuring with respect to two critical safety outcomes; preterm births and low infant birthweights. Studies examining a broader range of birth outcomes following influenza vaccination during pregnancy are required, particularly now that maternal vaccination in pregnancy has expanded to include pertussis as well as influenza.     

Influenza vaccination and risk of hospitalization among adults with laboratory confirmed influenza illness

Background

Influenza vaccine is moderately effective for preventing influenza illness. It is not known if vaccination reduces the risk of subsequent hospital admission among patients with vaccine failure and laboratory confirmed influenza illness.

Methods

Patients in a community cohort presenting with acute respiratory illness were prospectively enrolled and tested for influenza during 8 seasons to estimate seasonal vaccine effectiveness. Hospital admissions within 14 days after illness onset were identified for all participants aged ≥20 years with laboratory confirmed influenza. The association between vaccination and hospital admission was examined in a propensity score adjusted logistic regression model. The model was validated by examining the association between vaccination and hospital admission in participants without influenza.

Results

Influenza was identified in 1393 (28%) of 4996 participants. Sixty-two (6%) of 1020 with influenza A and 17 (5%) of 369 with influenza B were hospitalized. Vaccination was not associated with a reduced risk of hospital admission among all participants with influenza [adjusted odds ratio (aOR) = 1.08; 95% CI: 0.62, 1.88]; or among those with influenza A (aOR = 1.35; 95% CI: 0.71, 2.57) or influenza B (aOR = 0.67; 95% CI: 0.21, 2.15). Influenza vaccination was not associated with hospitalization after non-influenza respiratory illness (aOR = 1.14; 95% CI: 0.84, 1.54).

Conclusions

Influenza vaccination did not reduce the risk of subsequent hospital admission among patients with vaccine failure. These findings do not support the hypothesis that vaccination mitigates influenza illness severity.     

“The flu… is a little more complicated than a cold”: Knowledge,beliefs, and practices related to influenza and influenza vaccination among at-risk populations and health professionals in Peru

BackgroundInfluenza is a major source of morbidity and mortality with an annual global attack rate estimated at 5–10% in adults and 20–30% in children. Influenza vaccination is the main strategy for reducing influenza-related morbidity and mortality. Like several other countries, Peru has low vaccination coverage, estimated at 25–50% among young children and older adults. Therefore, the study objective was to explore the knowledge, beliefs, attitudes, and practices related to influenza vaccination among populations at higher risk for infection and/or complications and health professionals in Peru, and their perspectives on health communication channels.MethodsThis qualitative study was carried out in three cities. We held nine focus groups with pregnant and postpartum women, parents of young children, and older adults. We carried out 25 in-depth interviews with health professionals (HPs) working in, leading or advising immunization-related programs.ResultsHPs correctly identified the causes of influenza and HPs and at risk community members identified major symptoms. Community members had poor awareness of the potential severity of influenza and were generally unaware of influenza-related mortality. Both HPs and community members greatly underestimated the prevalence of influenza in Peru. HPs in our study overestimated major side effects of the influenza vaccine and community members perceived that the vaccine caused illness. HPs missed important opportunities to promote vaccination in patients with minor illness (runny nose, allergies, colds) and community members did not understand that the vaccine should be received annually.ConclusionsThere is no single strategy that will increase influenza vaccination rates to World Health Organization recommended levels. Instead, it requires multi-faceted commitment from HPs, other healthcare authorities and the government. Addressing important knowledge barriers, specifically negative views regarding the influenza vaccine and the severe morbidity and mortality associated with influenza illness, both in the community and especially among HPs, could have significant impacts.     

Knowledge and attitudes towards influenza and influenza vaccination among pregnant women in Kenya

BackgroundInfluenza vaccination during pregnancy benefits mothers and children. Kenya and other low- and middle-income countries have no official influenza vaccination policies to date but are moving towards issuing such policies. Understanding determinants of influenza vaccine uptake during pregnancy in these settings is important to inform policy decisions and vaccination rollout.MethodsWe interviewed a convenience sample of women at antenatal care facilities in four counties (Nairobi, Mombasa, Marsabit, Siaya) in Kenya. We described knowledge and attitudes regarding influenza vaccination and assessed factors associated with willingness to receive influenza vaccine.ResultsWe enrolled 507 pregnant women, median age was 26 years (range 15–43). Almost half (n = 240) had primary or no education. Overall, 369 (72.8%) women had heard of influenza. Among those, 288 (78.1%) believed that a pregnant woman would be protected if vaccinated, 252 (68.3%) thought it was safe to receive a vaccine while pregnant, and 223 (60.4%) believed a baby would be protected if mother was vaccinated. If given opportunity, 309 (83.7%) pregnant women were willing to receive the vaccine. Factors associated with willingness to receive influenza vaccine were mothers’ belief in protective effect (OR 3.87; 95% CI 1.56, 9.59) and safety (OR 5.32; 95% CI 2.35, 12.01) of influenza vaccines during pregnancy.ConclusionApproximately one third of pregnant women interviewed had never heard of influenza. Willingness to receive influenza vaccine was high among women who had heard about influenza. If the Kenyan government recommends influenza vaccine for pregnant women, mitigation of safety concerns and education on the benefits of vaccination could be the most effective strategies to improve vaccine acceptance.     

孕妇流感疫苗接种相关研究进展

流感是由流感病毒引起的急性呼吸道传染病, 妊娠期间因生理和免疫功能的变化, 孕妇罹患流感及发生相关并发症的风险较高。接种流感疫苗是预防流感的有效手段。WHO和许多国家均将孕妇列为流感疫苗接种的优先推荐人群, 但目前我国孕妇流感疫苗接种率偏低, 且部分产品使用说明将孕妇列为接种禁忌人群, 推动孕妇流感疫苗接种工作仍存在诸多挑战。本文就近年来国内外流感对孕妇及其胎儿的影响以及孕妇接种流感疫苗研究进展进行综述, 并针对目前孕妇流感疫苗接种的现状, 提出促进孕妇接种流感疫苗的策略并进行探讨, 以期为我国相关工作的开展和政策制定提供参考。     

Longitudinal,population-based cohort study of prenatal influenza vaccination and influenza infection in childhood

BackgroundInfluenza vaccination is recommended to protect mothers and their infants from influenza infection. Few studies have evaluated the health impacts of in utero exposure to influenza vaccine among children more than six months of age.MethodsWe used probabilistically linked administrative health records to establish a mother–child cohort to evaluate the risk of influenza and acute respiratory infections associated with maternal influenza vaccination. Outcomes were laboratory-confirmed influenza (LCI) and hospitalization for influenza or acute respiratory infection (ARI). Adjusted hazard ratios (aHRs) accounted for child’s Aboriginal status and were weighted by the inverse-probability of treatment.Results14,396 (11.5%) children were born to vaccinated mothers. Maternally vaccinated infants aged < 6 months had lower risk of LCI (aHR: 0.33; 95% CI: 0.13, 0.85), influenza-associated hospitalization (aHR: 0.39; 95% CI: 0.16, 0.94) and ARI-associated hospitalization (aHR: 0.85; 95% CI: 0.77, 0.94) compared to maternally unvaccinated infants. With the exception of an increased risk of LCI among children aged 6 months to < 2 years old following first trimester vaccination (aHR: 2.28; 95% CI: 1.41, 3.69), there were no other differences in the risk of LCI, influenza-associated hospitalization or ARI-associated hospitalization among children aged > 6 months.ConclusionStudy results show that maternal influenza vaccination is effective in preventing influenza in the first six months and had no impact on respiratory infections after two years of age.     

A multi-country investigation of influenza vaccine coverage in pregnant individuals, 2010–2016

BackgroundMany countries recommend influenza vaccination during pregnancy. Despite this recommendation, influenza vaccine among pregnant individuals remains under-utilized and uptake varies by country. Factors associated with influenza vaccine uptake during pregnancy may also vary across countries.MethodsAs members of the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), five sites from four countries (Australia, Canada, Israel, and the United States) retrospectively identified cohorts of individuals aged 18–50 years who were pregnant during pre-defined influenza seasons. Influenza vaccine coverage estimates were calculated for the 2010–11 through 2015–16 northern hemisphere and the 2012 through 2015 southern hemisphere influenza seasons, by site. Sites used electronic health records, administrative data, and immunization registries to collect information on pregnancy, health history, demographics, and vaccination status. Each season, vaccination coverage was calculated as the percentage of individuals who received influenza vaccine among the individuals in the cohort that season. Characteristics were compared between those vaccinated and unvaccinated, by site.ResultsMore than two million pregnancies were identified over the study period. Influenza vaccination coverage ranged from 5% to 58% across sites and seasons. Coverage increased consistently over the study period at three of the five sites (Western Australia, Alberta, and Israel), and was highest in all seasons at the United States study site (39–58%). Associations with vaccination varied by country and across seasons; where available, parity >0, presence of a high-risk medical condition, and urban residence were consistently associated with increased likelihood of vaccination.ConclusionsThough increasing, uptake of influenza vaccine among pregnant individuals remains lower than recommended. Coverage varied substantially by country, suggesting an ongoing need for targeted strategies to improve influenza vaccine uptake in this population.     

Preliminary assessment of the effectiveness of the 2003-04 inactivated influenza vaccine--Colorado, December 2003

Influenza activity started earlier than usual in the United States this season, with widespread influenza activity reported in 10 states by November 22, 2003. The predominant influenza viruses (A/Fujian/411/2002 [H3N2]-like viruses) circulating this season differ antigenically from the 2003-04 influenza A (H3N2) vaccine strain. A retrospective cohort study was conducted among workers at a Colorado hospital to provide preliminary data on the effectiveness of trivalent inactivated influenza vaccine (TIV) against influenza-like illness (ILI). This report summarizes the results of that study, which indicated that TIV had no or low effectiveness against ILI. However, additional studies are needed to evaluate the effectiveness of the 2003-04 vaccine against laboratory-confirmed influenza and influenza-related complications, including hospitalization and death. Influenza vaccine continues to be recommended, particularly for persons at increased risk for influenza-related complications, their household contacts, and health-care personnel.     

Tetanus,diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections

BackgroundTo protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36 weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants <2 months of age.MethodsThis retrospective cohort study included 99,434 infants born to active duty military women in the Department of Defense Birth and Infant Health Registry from 2006 through 2013. Multivariable log-binomial regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at <2 months of age.ResultsInfants of mothers who received Tdap vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at <2 months of age (RR, 0.91; 95% CI, 0.84–0.99), and the risk was 17% lower if vaccination was received between 27 and 36 weeks of pregnancy (RR, 0.83; 95% CI, 0.74–0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36 weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74–0.98).ConclusionsMaternal Tdap vaccination between 27 and 36 weeks of pregnancy was consistently protective against infant ARI in the first 2 months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy.     

Cost-effectiveness of seasonal inactivated influenza vaccination among pregnant women

ObjectiveTo evaluate the cost-effectiveness of seasonal inactivated influenza vaccination among pregnant women using data from three recent influenza seasons in the United States.Design, setting, and participantsWe developed a decision-analytic model following a cohort of 5.2 million pregnant women and their infants aged <6 months to evaluate the cost-effectiveness of vaccinating women against seasonal influenza during pregnancy from a societal perspective. The main outcome measures were quality-adjusted life-year (QALY) gained and cost-effectiveness ratios. Data sources included surveillance data, epidemiological studies, and published vaccine cost data. Sensitivity analyses were also performed. All costs and outcomes were discounted at 3% annually.Main outcome measuresTotal costs (direct and indirect), effects (QALY gains, averted case numbers), and incremental cost-effectiveness of seasonal inactivated influenza vaccination among pregnant women (cost per QALY gained).ResultsUsing a recent benchmark of 52.2% vaccination coverage among pregnant women, we studied a hypothetical cohort of 2,753,015 vaccinated pregnant women. With an estimated vaccine effectiveness of 73% among pregnant women and 63% among infants <6 months, QALY gains for each season were 305 (2010–2011), 123 (2011–2012), and 610 (2012–2013). Compared with no vaccination, seasonal influenza vaccination during pregnancy was cost-saving when using data from the 2010–2011 and 2012–2013 influenza seasons. The cost-effectiveness ratio was greater than $100,000/QALY with the 2011–2012 influenza season data, when CDC reported a low attack rate compared to other recent seasons.ConclusionsInfluenza vaccination for pregnant women can reduce morbidity from influenza in both pregnant women and their infants aged <6 months. Seasonal influenza vaccination during pregnancy is cost-saving during moderate to severe influenza seasons.