Does influenza vaccination attenuate the severity of breakthrough infections? A narrative review and recommendations for further research

The effect of influenza vaccination on influenza severity remains uncertain. We reviewed the literature for evidence to inform the question of whether influenza illness is less severe among individuals who received influenza vaccination compared with individuals with influenza illness who were unvaccinated prior to their illnesses. We conducted a narrative review to identify published findings comparing severity of influenza outcomes by vaccination status among community-dwelling adults and children ≥ 6 months of age with laboratory-confirmed influenza illness. When at least four effect estimates of the same type (e.g., odds ratio) were available for a specific outcome and age category (children versus adults), data were pooled with meta-analysis to generate a summary effect estimate. We identified 38 published articles reporting ≥ 1 association between influenza vaccination status and one of 21 indicators of severity of influenza illness among individuals with laboratory-confirmed influenza. Study methodologies and effect estimates were highly heterogenous, with only five severity indicators meeting criteria for calculating a combined effect. Among eight studies, influenza vaccination was associated with 26% reduction in odds of ICU admission among adults with influenza-associated hospitalization (OR = 0.74, 95% CI 0.58, 0.93). Among five studies of adults with influenza-associated hospitalization, vaccinated patients had 31% reduced risk of death compared with unvaccinated patients (OR = 0.69, 95% CI 0.52, 0.92). Among four studies of children with influenza virus infection, vaccination was associated with an estimated 45% reduction in the odds of manifesting fever (OR = 0.55, 95% CI 0.42, 0.71). Vaccination was not significantly associated with receiving a clinical diagnosis of pneumonia among adults hospitalized with influenza (OR = 0.92, 95% CI 0.82, 1.04) or with risk of hospitalization following outpatient influenza illness among adults (OR = 0.60, 95% CI 0.28, 1.28). Overall, our findings support the hypothesis that influenza vaccination may attenuate the course of disease among individuals with breakthrough influenza virus infection.     

The effectiveness of influenza vaccination in pregnancy in relation to child health outcomes: Systematic review and meta-analysis

ObjectivesTo determine the effectiveness of influenza vaccination during pregnancy on child health outcomes.DesignSystematic review/meta-analysis.Data sourcesClinical Trials.gov, Cochrane Library, EMBASE, Medline, Medline in process, PubMed and Web of Science, from 1st January 1996 to 29th June 2018. An updated Medline search was performed 30th June 2018 to 31st October 2019.MethodsRandomised controlled trials (RCTs) and observational studies reporting health outcomes of infants and children born to women who received inactivated influenza vaccine during pregnancy. The primary outcome was infant laboratory confirmed influenza (LCI). Secondary outcomes included influenza-like illness (ILI), other respiratory illnesses, primary care, clinic visit or hospitalisations due to influenza illness and long-term respiratory childhood outcomes.Results19 studies were included; 15 observational studies and 4 primary RCTs with an additional 3 papers reporting secondary outcomes of these RCTs. In a random effects meta-analysis of 2 RCTs including 5742 participants, maternal influenza vaccination was associated with an overall reduction of LCI in infants of 34% (95% confidence interval 15–50%). However, there was no effect of maternal influenza vaccination on ILI in infants ≤6 months old. Two RCTs were excluded from the meta-analysis for the outcome of LCI in infants (different controls used). Both of these studies showed a protective effect for infants from LCI, with a vaccine efficacy of up to 70%.Overall observational studies showed an inverse (protective) association between maternal influenza vaccination and infant LCI, hospitalisation and clinic visits due to LCI or ILI in infants and other respiratory illness in infants ≤6 months old.ConclusionsThis systematic review supports maternal influenza vaccination as a strategy to reduce LCI and influenza-related hospitalisations in young infants. Communicating these benefits to pregnant women may support their decision to accept influenza vaccination in pregnancy and increase vaccine coverage in pregnant women.RegistrationPROSPERO CRD42018102776.     

Estimated influenza illnesses and hospitalizations averted by influenza vaccination among children aged 6–59 months in Suzhou,China, 2011/12 to 2015/16 influenza seasons

BackgroundThere are few estimates of vaccination-averted influenza-associated illnesses in China.MethodsWe used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% confidence intervals (CI) of influenza-associated outcomes (hospitalization, illness, and medically-attended (MA) illness) averted by vaccination among children aged 6–59 months in Suzhou from October 2011–September 2016. Influenza illnesses included non-hospitalized MA influenza illnesses and non-MA influenza illnesses. The numbers of influenza-associated outcomes averted by vaccination were the difference between the expected burden if there were no vaccination given and the observed burden with vaccination. The model incorporated the disease burden estimated based on surveillance data from Suzhou University Affiliated Children’s Hospital (SCH) and data from health utilization surveys conducted in the catchment area of SCH, age-specific estimates of influenza vaccination coverage in Suzhou from the Expanded Program on Immunization database, and influenza vaccine effectiveness estimates from previous publications. Averted influenza estimations were presented as absolute numbers and in terms of the prevented fraction (PF). A hypothetical scenario with 50% coverage (but identical vaccine effectiveness) over the study period was also modeled.ResultsIn ~250,000 children, influenza vaccination prevented an estimated 731 (CI: 549–960) influenza hospitalizations (PF: 6.2% of expected, CI: 5.8–6.6%) and 10,024 (7593–12,937) influenza illnesses (PF: 6.5%, 6.4–6.7%), of which 8342 (6338–10,768) were MA (PF: 6.6%, 6.4–6.7%) from 2011 to 2016. The PFs declined each year along with decreasing influenza vaccination coverage. If 50% of the study population had been vaccinated over time, the estimated numbers of averted cases during the study period would have been 4059 (3120–5762) influenza hospitalizations (PF: 27.2%, 26.4–27.9%) and 56,215 (42,925–78,849) influenza illnesses (PF: 28.5%, 28.3–28.7%), of which 46,596 (35,662–65,234) would be MA (PF: 28.5%, 28.3–28.7%).ConclusionInfluenza vaccination is estimated to have averted influenza-associated illness outcomes even with low coverage in children aged 6–59 months in Suzhou. Increasing influenza vaccination coverage in this population could further reduce illnesses and hospitalizations.     

Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis

BackgroundThe clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines.MethodsWe searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR) 1 100. Narrative synthesis was undertaken where meta-analysis was not possible.ResultsWe identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE = 80%; 95% confidence interval [CI] 59–90%; unadjuvanted: VE = 66%; 95% CI 47–78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14–82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18–64 years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes.ConclusionsAdjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.     

Parental perceptions of childhood seasonal influenza vaccination in Singapore: A cross-sectional survey

PurposeSeasonal influenza vaccination is recommended in children aged 6–59 months, but little is known about child vaccination coverage and determinants in Asian settings. We report the results of a survey of knowledge, attitudes, practices, and determinants of child influenza vaccination in Singapore.MethodsIn December 2015-March 2016, we conducted a survey of 332 parents of children aged 6 months to 5 years attending pre-schools. We assessed child influenza vaccine coverage and parental knowledge, attitudes, and practices of child influenza vaccination. We used multivariable regression and structural equation models to identify factors associated with child influenza vaccination.ResultsKnowledge about influenza, perceived benefit of vaccination, and willingness to vaccinate were high. However, only 32% of children had ever received influenza vaccine, and only 15% in the past year. Factors independently associated with child influenza vaccination included: being recommended influenza vaccine by a child’s doctor (prevalence ratio (PR) = 2.47, 95% CI: 1.75–3.48); receiving influenza vaccine information from a private general practitioner (PR = 1.47, 95% CI: 1.05–2.04); regularly receiving pre-travel influenza vaccine (PR = 1.64, 95% CI: 1.19–2.25); higher willingness to vaccinate (PR = 1.58, 95% CI:1.24–2.04 per unit increase in willingness score); and feeling well-informed about influenza vaccine (PR = 1.44, 95% CI: 1.04–1.99). Parents who obtained influenza vaccine information from television were less likely to have vaccinated their child (PR = 0.44, 95% CI: 0.23–0.85). Path analysis indicated that being recommended vaccination by a child's doctor increased willingness to vaccinate and self-efficacy (feeling well-informed about influenza vaccine). Median willingness-to-pay for a dose of influenza vaccine was SGD30 (interquartile range: SGD20-SGD50), and was higher in parents of vaccinated compared with unvaccinated children (SGD45 vs SGD30, p = 0.0012).ConclusionKnowledge and willingness to vaccinate was high in this parent population, but influenza vaccine uptake in children was low. Encouraging medical professionals to recommend vaccination of eligible children is key to improving uptake.     

Knowledge,attitudes, and practices regarding seasonal influenza vaccination during pregnancy in Costa Rica: A mixed-methods study

BackgroundInfluenza increases stillbirth risk, morbidity and mortality in pregnant women. Vaccination protects pregnant women against severe disease and indirectly protects their infants, but coverage among pregnant women remains low worldwide. We aimed to describe knowledge, attitudes, and practices (KAP) regarding seasonal influenza vaccination among postpartum women and prenatal care physicians in Costa Rica.MethodsWe conducted cross-sectional KAP surveys to women one to three days after childbirth at Costa Rican Social Security Fund maternity hospitals, and obstetricians and general practitioners who provided prenatal care in 2017. Principal components analysis, multiple imputation, and logistic regression were used to examine associations between influenza vaccination and demographics, prenatal care, and sources of information—separately for postpartum women and physicians. We also held two focus groups of six healthcare workers each to further describe vaccination KAP.ResultsWe surveyed 642 postpartum women and 146 physicians in maternity hospitals in five Costa Rican provinces of whom 85.5 % (95 % CI: 82.6 %-88.0 %) and 57.9 % (95 % CI: 49.6 %-65.7 %) were vaccinated for influenza, respectively. Factors associated with influenza vaccination for postpartum women included tetanus vaccination (aOR: 3.62, 95 % CI: 1.89–6.92); received vaccination recommendations from clinicians during prenatal check-ups (aOR: 3.39, 95 % CI: 2.06–5.59); had other children in household vaccinated for influenza (aOR: 2.25, 95 % CI: 1.08–4.68); and secondary/university education (aOR: 0.15–0.31) with no formal education as reference. For postpartum women, reasons for vaccination were perceived benefits for mother and infant, whereas not being offered vaccines was most cited for non-vaccination. Most prenatal care physicians recommended influenza vaccines during prenatal check-ups but believed vaccination causes flu-like symptoms.ConclusionVaccination campaigns and provisions of free vaccines effectively increased knowledge and coverage among women in Costa Rica. To improve access, women should be offered vaccines during prenatal care appointments. Educating healthcare workers about vaccine benefits for themselves and patients is needed to mitigate safety concerns.     

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.     

Effectiveness of the influenza vaccine at reducing adverse events in patients with heart failure: A systematic review and meta-analysis

BackgroundThe association between influenza and adverse vascular events in patients with heart failure is well documented. The effect of the influenza vaccine on preventing such adverse events is uncertain. This systematic review and meta-analysis addressed whether vaccination against influenza reduces adverse vascular events and mortality in heart failure patients.MethodsMEDLINE and EMBASE databases were comprehensively searched, study screening and quality assessment were completed, and data was synthesized. Eligible studies investigated heart failure patients who received the influenza vaccine, and reported outcomes within 12 months, compared to heart failure patients who did not receive the influenza vaccine. The following 6 outcomes were assessed: all-cause mortality, cardiovascular-related mortality, all-cause hospitalization, cardiovascular-related hospitalization, non-fatal myocardial infarction, and non-fatal stroke. Risk of bias was assessed using the Newcastle-Ottawa Scale and a GRADE assessment was completed. A random-effects meta-analysis was performed to estimate the pooled risk ratio (RR), 95% confidence intervals (CIs), and heterogeneity using I² statistics.ResultsAfter synthesizing data from 7 non-randomized studies (247,842 patients), the results demonstrate the risk of all-cause mortality is significantly reduced within 12 months of a heart failure patient receiving the influenza vaccine (RR = 0.75, 95% CI 0.71–0.79; P<0.0001); very low certainty of evidence. The risk of cardiovascular-related mortality was significantly reduced (RR = 0.77, 95% CI 0.73–0.81; P<0.0001); low certainty of evidence. The pooled risk of all-cause hospitalization was higher among vaccinated heart failure patients (RR = 1.24, 95% CI 1.13–1.35; P<0.0001), based on two studies; very low certainty of evidence and considerable heterogeneity (I² = 90%). No eligible studies assessed cardiovascular-related hospitalization, non-fatal myocardial infarction, or non-fatal stroke.ConclusionsInfluenza vaccination appears to reduce adverse cardiovascular events, although the certainty of the evidence is low or very low. Rigorous randomized controlled trial evidence is needed to further examine the protective effect of the influenza vaccine in heart failure patients.     

No association between influenza vaccination during pregnancy and adverse birth outcomes

BackgroundPregnant women are recommended to receive inactivated influenza vaccination anytime during pregnancy. Studies have investigated the impact of influenza vaccination during pregnancy on birth outcomes and results on preterm birth have been inconsistent.MethodsWe conducted a retrospective cohort study among children born at a gestational age ≥ 24 weeks from January 1, 2010 to December 31, 2015 at Kaiser Permanente Northern California facilities (KPNC). We evaluated the association between maternal influenza vaccination during pregnancy and risk of preterm birth, small and large for gestational age, admission to the neonatal intensive care unit (NICU), respiratory distress syndrome, low birth weight, and low Apgar score. We ascertained the dates of maternal influenza vaccination, conception, and delivery, as well as birth outcomes from KPNC inpatient and outpatient databases. Conditional multivariate Cox regression and logistic regression analyses were used to determine the association between maternal vaccination during pregnancy and risk of each birth outcome.ResultsThe study included 145,869 children. Maternal influenza vaccination during pregnancy was not associated with risk of small or large for gestational age births, preterm birth, need for mechanical ventilation at birth, respiratory distress syndrome, admission to the NICU, low birth weight, or low Apgar score. However, when we did not control for immortal time bias, the risk of preterm birth (odds ratio [OR] = 0.69, 95% confidence interval [CI] 0.66–0.72) was lower among infants of vaccinated mothers.ConclusionWe found no association between maternal influenza vaccination during pregnancy and adverse birth outcomes. When investigating preterm birth outcome in association with vaccination during pregnancy, immortal time bias should be taken into account in the analysis.     

Influenza vaccine effectiveness against influenza-associated hospitalization in children: A systematic review and meta-analysis

Vaccination remains the most effective way to prevent influenza infection, albeit vaccine effectiveness (VE) varies by year. Compared to other age groups, children and elderly adults have the highest risk of developing influenza-related complications and requiring hospitalization. During the last years, “test negative design” (TND) studies have been implemented in order to estimate influenza VE. The aim of this systematic review and meta-analysis was to summarize the findings of TND studies reporting influenza VE against laboratory-confirmed influenza-related hospitalization in children aged 6 months to 17 years. We searched the PubMed and Embase databases and identified 2615 non-duplicate studies that required detailed review. Among them, 28 met our inclusion criteria and we performed a random-effects meta-analysis using adjusted VE estimates. In our primary analysis, influenza vaccine offered significant protection against any type influenza-related hospitalization (57.48%; 95% CI 49.46–65.49). When we examined influenza VE per type and strain, VE was higher against H1N1 (74.07%; 95% CI: 54.85–93.30) and influenza B (50.87%; 95% CI: 41.75–59.98), and moderate against H3N2 (40.77%; 95% CI: 25.65–55.89). Notably, influenza vaccination offered higher protection in children who were fully vaccinated (61.79%; 95% CI: 54.45–69.13), compared to those who were partially vaccinated (33.91%; 95% CI: 21.12 – 46.69). Also, influenza VE was high in children less than 5 years old (61.71%; 95% CI: 49.29–74.12) as well as in children 6–17 years old (54.37%; 95% CI: 35.14–73.60). In conclusion, in the pediatric population, influenza vaccination offered significant protection against influenza-related hospitalization and complete annual vaccination should be encouraged.     

Seasonal influenza vaccine effectiveness against medically attended influenza illness among children aged 6–59 months,October 2011–September 2012: A matched test-negative case–control study in Suzhou,China

BackgroundSeasonal influenza infections among young children in China lead to substantial numbers of hospitalizations and financial burden. This study assessed the seasonal influenza vaccine effectiveness (VE) against laboratory confirmed medically attended influenza illness among children in Suzhou, China, from October 2011–September 2012.MethodsWe conducted a test-negative case–control study among children aged 6–59 months who sought care at Soochow University Affiliated Children's Hospital (SCH) from October 2011–September 2012. A case was defined as a child with influenza-like illness (ILI) or severe acute respiratory infection (SARI) with an influenza-positive nasopharyngeal swab by rRT-PCR. Controls were selected from children presenting with ILI or SARI without laboratory confirmed influenza. We conducted 1:1 matching by age and admission date. Vaccination status was verified from the citywide immunization system database. VE was calculated with conditional logistic regression: (1 − OR) × 100%.ResultDuring the study period, 2634 children aged 6–59 months presented to SCH with ILI (1975) or SARI (659) and were tested for influenza. The vaccination records were available for 69% (1829; ILI: 1354, SARI: 475). Among those, 23% (427) tested positive for influenza, and were included as cases. Among influenza positive cases, the vaccination rates were 3.2% for SARI and 4.5% for ILI. Among controls, the vaccination rates were 13% for SARI, and 11% for ILI. The overall VE against lab-confirmed medically attended influenza virus infection was 67% (95% CI: 41–82). The VE for SARI was 75% (95% CI: 11–93) and for ILI was 64% (95% CI: 31–82).ConclusionsThe seasonal influenza vaccine was effective against medically attended lab-confirmed influenza infection in children aged 6–59 months in Suzhou, China in the 2011–12 influenza season. Increasing seasonal influenza vaccination among young children in Suzhou may decrease medically attended influenza-associated ILI and SARI cases in this population.     

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.     

Influenza vaccine effectiveness against influenza-associated hospitalization in 2015/16 season,Beijing, China

BackgroundVaccination is recommended to prevent influenza virus infection and associated complications. This study aimed to estimate the influenza vaccine effectiveness (VE) against hospitalization in the 2015/16 season in Beijing.MethodsPatients who were hospitalized in the 5 study hospitals between 1 Oct 2015 and 15 May 2016 were recruited. Influenza vaccination status was obtained for PCR-confirmed influenza patients and the selected controls who tested negative for the virus. Conditional logistic regression was used to estimate the influenza VE matching by calendar week, and adjusting for age, study sites, underlying medical conditions, smoking status, and hospital admissions over the past 12 months.ResultsThe overall VE was −37.9% (95% CI: −103.3, 6.5) against laboratory-confirmed influenza-associated hospitalization. The 2015–16 seasonal vaccine was had −61.9% (95% CI: −211.9, 15.9), −5.4% (95% CI: −108.1, 46.6) and −45.2% (95% CI: −152.6, 16.5) effectiveness to prevent infection from A(H1N1)pdm09, A(H3N2) and influenza B, respectively.ConclusionsInfluenza vaccination did not show effective protection against hospitalization with influenza in 2015/16 season in Beijing.     

Evaluation of non-specific effects of human rotavirus vaccination in medical risk infants

BackgroundThe WHO recommends research into non-specific effects of vaccination. For rotavirus vaccines, these have not yet been well established. We studied non-specific effects up to 18 months of age using data from a quasi-experimental before-after study comparing cohorts of rotavirus vaccinated and unvaccinated infants with medical risk conditions.MethodsInfants were enrolled at six weeks of age before and after a stepped-wedge implementation of a hospital-based risk-group rotavirus vaccination program. Other infant vaccinations were administered according to the Dutch National Immunization Program and similar in both cohorts. Non-specific effect outcomes were prospectively collected using monthly questionnaires and included acute hospitalization (excluding for acute gastroenteritis), monthly incidence of acute respiratory illness and eczema. We used time-to-event analysis and negative binomial regression to assess the effect of at least one dose of rotavirus vaccination for each of these outcomes.FindingsThe analysis included 496 rotavirus unvaccinated and 719 vaccinated medical risk infants. In total, 1067 (88%) were premature, 373 (31%) small for gestational age and 201 (17%) had a congenital pathology. The adjusted hazard ratio for first acute hospitalization was 0·91 (95 %CI 0·76;1·16) for rotavirus vaccinated versus unvaccinated infants. Adjusted incidence rate ratio for acute respiratory illness was 1·05 (95 %CI 0·96;1·15) and for eczema 0·89 (95 %CI 0·69;1·15).ConclusionThe results suggest no, or minimal non-specific effects from rotavirus vaccination on acute hospitalization, acute respiratory illness or eczema in medical risk infants.Trial registration: as NTR5361 in the Dutch trial registry, www.trialregister.nl.     

Duration of influenza vaccine effectiveness in the elderly in Japan: A retrospective cohort study using large-scale population-based registry data

BackgroundThe immune response to influenza vaccination in the elderly is likely to be lower than that in young adults. Clinical protection may not persist year-round in the elderly. However, the effectiveness of influenza vaccine in the elderly has not been adequately studied, especially in terms of the duration of effectiveness.MethodsWe used a linked database of healthcare administrative claims data and vaccination records maintained by the municipality of a city in Kanto region of Japan. We studied individuals who were aged 65 years or older at baseline and were followed up between April 1, 2014 to March 31, 2020. The duration of influenza vaccine effectiveness by age category was analyzed using a time-dependent piecewise Cox proportional hazard model with time-dependent vaccine status, prior season vaccination and covariates confirmed in the baseline period (age, sex, cancer, diabetes, chronic obstructive pulmonary diseases, asthma, chronic kidney diseases, and cardiovascular diseases).ResultsWe identified an analysis population of 83,146 individuals, of which 7,401 (8.9%) had experienced influenza and 270 (0.32%) underwent influenza-related hospitalization. Individuals who were vaccinated during the first season (n = 47,338) were older than non-vaccinated individuals (n = 35,808) (average age, 75.8 vs. 74.1 years, respectively). The multivariable analysis showed a lower incidence of influenza in vaccinated individuals (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.43–0.51; P < 0.001), while the incidence of hospitalization for influenza did not differ significantly by vaccination status (HR, 0.79; 95% CI, 0.53–1.18; P = 0.249). Protective effectiveness against incidence was maintained for 4 or 5 months after vaccination in those aged 65–69 and 80-years, 5 months in 70–79 years.ConclusionsOur study identified moderate vaccine effectiveness in preventing the incidence of influenza in the Japanese elderly. Vaccine effectiveness showed a trend of gradual attenuation. Clinicians should suspect influenza infection even in those vaccinated, especially in elderly individuals who had received vaccination more than 4 or 5 months previously.     

History of pandemic H1N1-containing influenza vaccination and risk for spontaneous abortion and birth defects

BackgroundOne recent study suggested an association between receipt of pandemic H1N1 (pH1N1)-containing vaccines in consecutive influenza seasons and spontaneous abortion, but corroborating scientific evidence is limited. In the present study, we leveraged a population of vaccine-compliant pregnant military women to examine history of pH1N1-containing influenza vaccination and adverse pregnancy outcomes. Because seasonal influenza vaccination is compulsory for military service, safety concerns regarding repeat vaccination are particularly relevant in this population.MethodsPregnancies and live births from Department of Defense Birth and Infant Health Research program data were linked with military personnel immunization records to identify women vaccinated with a pH1N1-containing vaccine in pregnancy prior to 21 6/7 weeks’ gestation, October 2009–April 2015. Cox and modified Poisson regression models estimated associations between vaccination with pH1N1- versus non–pH1N1-containing influenza vaccine in the season prior to the index pregnancy, and spontaneous abortion and birth defects, respectively. Cox models were calculated for two periods of follow-up: through (1) 21 6/7 weeks’ gestation and (2) 28 days postvaccination.ResultsOf 26,264 pregnancies, 21,736 (82.8%) were among women who received a dose of pH1N1-containing vaccine in the prior influenza season and 4,528 (17.2%) were among women who received non–pH1N1-containing vaccine in the prior influenza season. Among 23,121 infants, 19,365 (83.8%) and 3,756 (16.2%) had mothers exposed and unexposed to pH1N1-containing vaccine in the prior influenza season, respectively. The adjusted hazard ratio (aHR) for spontaneous abortion approximated 1.0 across the complete follow-up period (95% confidence interval [CI]: 0.89–1.13) and was slightly elevated when censored at 28 days postvaccination, though the CI was imprecise (aHR: 1.19; 95% CI: 0.97–1.46). No associations with birth defects were observed.ConclusionThis work lends additional safety evidence and support for vaccination against pH1N1 in pregnancy, regardless of the vaccine received in the prior influenza season.     

Risk factors associated with hospitalisation for influenza-associated severe acute respiratory illness in South Africa: A case-population study

BackgroundInfluenza is a common cause of severe respiratory illness, but risk factors for hospitalisation in low income settings with a high HIV prevalence are not well described. We aimed to assess risk factors associated with influenza-associated severe acute respiratory illness (SARI) hospitalisation in South Africa.MethodsWe conducted a case-population study using data on risk conditions in patients hospitalised with SARI and the national prevalence of these conditions. Data on hospitalised cases were from the national SARI surveillance program while data on the referent population were from the latest national census or health and demographic surveillance surveys.FindingsFrom 2009 to 2012, we identified 3646 (7.9%) of 46,031 enrolled cases of SARI that were associated with influenza infection. Risk factors associated with hospitalisation included previous history of smoking [case-population ratio (CPR) 3.82, 95% confidence interval (CI) 3.5–4.16], HIV infection (CPR 3.61, 95% CI 3.5–3.71), asthma (CPR 2.45, 95% CI 2.19–2.73), previous history of hospital admission in the past 12 months (CPR 2.07, 95% CI 1.92–2.23), and tuberculosis (CPR 1.85, 95% CI 1.68–2.02). When stratified by age, there is increased risk of hospitalisation in those ⩽5 years of age (CPR 3.07, 95% CI 2.93–3.21) and among those 35 years of age and above (CPR 1.23, 95% CI 1.28–1.18). Male sex (CPR 0.85, 95% CI 0.82–0.88) and completion of pneumococcal conjugate vaccination schedule in children <5 years of age (CPR 0.74, 95% CI 0.71–0.77) were associated with decreased risk of hospitalisation.ConclusionThese results identify groups at high-risk for severe influenza who should be considered potential targets for influenza vaccination in South Africa and similar settings.     

Economic assessment of a high-dose versus a standard-dose influenza vaccine in the US Veteran population: Estimating the impact on hospitalization cost for cardio-respiratory disease

ObjectiveTo compare the economic impact of high-dose trivalent (HD) versus standard-dose trivalent (SD) influenza vaccination on direct medical costs for cardio-respiratory hospitalizations in adults aged 65 years or older enrolled in the United States (US) Veteran’s Health Administration (VHA).MethodsLeveraging a relative vaccine effectiveness study of HD versus SD over five respiratory seasons (2010/11 through 2014/15), we collected cost data for healthcare provided to the same study population both at VHA and through Medicare services. Our economic assessment compared the costs of vaccination and hospital care for patients experiencing acute cardio-vascular or respiratory illness.ResultsWe analyzed 3.5 million SD and 158,636 HD person-seasons. The average cost of HD and SD vaccination was $23.48 (95% CI: $21.29 - $25.85) and $12.21 (95% CI: $11.49 - $13.00) per recipient, respectively, while the hospitalization rates for cardio-respiratory disease in HD and SD recipients were 0.114 (95% CI: 0.108–0.121) and 0.132 (95% CI: 0.132–0.133) per person-season, respectively. Attributing the average cost per hospitalization of $11,796 (95% CI: $11,685 - $11,907) to the difference in hospitalization rates, we estimated savings attributable to HD to be $202 (95% CI: $115 – $280) per vaccinated recipient.ConclusionsFor the five-season period of 2010/11 through 2014/15, HD influenza vaccination was associated with net cost savings due to fewer hospitalizations, and therefore lower direct medical costs, for cardio-respiratory disease as compared to SD influenza vaccination in the senior US VHA population.