The effectiveness of influenza vaccination in preventing hospitalisation in children in Western Australia

BackgroundThere is increasing evidence demonstrating influenza vaccine effectiveness (VE) in the prevention of influenza in children, including the very young. Data demonstrating the effectiveness against severe disease, including hospitalisation, are limited. We aimed to determine the VE of the southern hemisphere trivalent inactivated influenza vaccine (TIV) in preventing laboratory-confirmed influenza-associated hospitalisation in children.Patients and MethodsLaboratory records were used to identify children with confirmed influenza hospitalised (i.e., cases) during a 5 year period (2008, 2010–2013) at the only tertiary paediatric facility in Western Australia. Cases and time, age and ward matched controls were retrospectively reviewed to determine risk factors, vaccination status and outcome. Adjusted odds ratios and VE estimates were derived using conditional logistic regression models.ResultsThree hundred and eighty five cases were identified (Influenza A, 64.9%; Influenza B, 35.1%). Influenza-like illness and pneumonia were the most frequent presentation (74.5% and 23.9%, respectively). The median length of stay was 2 days (Interquartile range 1–4 days). Twenty children (5.2%) required admission to the intensive care unit. Vaccine uptake in cases and controls was low (4.9% and 8.5%, respectively). Three hundred and six case-control pairs were included in the VE analysis, of which 19 pairs were informative with discrepant vaccination status. VE (fully vaccinated vs. unvaccinated) was estimated to be 62.3% (95% CI: −6.6%, 86.7%).ConclusionIn this study, the point estimate for the effectiveness of TIV in preventing influenza-associated hospitalisation in children was similar to that reported for emergency or outpatient attended, laboratory-confirmed influenza, yet confidence intervals were wide. Vaccine uptake remains low. Studies, enroling larger numbers of children, ideally with higher vaccine uptake, are needed to provide additional evidence on TIV protection against influenza hospitalisation in children.     

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.     

The European I-MOVE Multicentre 2013–2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2)

BackgroundIn the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013–2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013–2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season.MethodsPractitioners systematically selected ILI patients to swab within eight days of symptom onset.We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I² index and Cochrane's Q test. If the I² was <50%, we estimated pooled VE as (1 minus the OR) × 100 using a one-stage model with study site as a fixed effect. If the I² was >49% we used a two-stage random effects model.ResultsWe included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p = 0.695) and the I² index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4–67.0).For A(H3N2), the I² was 51.5% (p = 0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: −34.4–63.2).ConclusionsThe results suggest a moderate 2013–2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses.     

Influenza vaccine effectiveness against laboratory confirmed influenza in Greece during the 2013–2014 season: A test-negative study

BackgroundIn 2013–2014 Greece experienced a resurgence of severe influenza cases, coincidental with a shift to H1N1pdm09 predominance. We sought to estimate Vaccine Effectiveness (VE) for this season using available surveillance data from hospitals (including both inpatients and outpatients).MethodsSwab samples were sent by hospital physicians to one of three laboratories, covering the entire country, to be tested for influenza using RT-PCR. The test-negative design was employed, with patients testing positive serving as cases and those testing negative serving as controls. VE was estimated using logistic regression, adjusted for age group, sex, region and calendar time, with further adjustment for unknown vaccination status using inverse response propensity weights. Additional age group stratified estimates and subgroup estimates of VE against H1N1pdm09 and H3N2 were calculated.ResultsOut of 1310 patients with known vaccination status, 124 (9.5%) were vaccinated, and 543 patients (41.5%) tested positive for influenza. Adjusted VE was 34.5% (95% CI: 4.1–55.3%) against any influenza, and 56.7% (95% CI: 22.8–75.7%) against H1N1pdm09. VE estimates appeared to be higher for people aged 60 and older, while in those under 60 there was limited evidence of effectiveness. Isolated circulating strains were genetically close to the vaccine strain, with limited evidence of antigenic drift.ConclusionsThese results suggest a moderate protective effect of the 2013–2014 influenza vaccine, mainly against H1N1pdm09 and in people aged 60 and over. Vaccine coverage was very low in Greece, even among groups targeted for vaccination, and substantial efforts should be made to improve it. VE can and should be routinely monitored, and the results taken into account when deciding on influenza vaccine composition for next season.     

Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010–11 and 2011–12

IntroductionInactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).MethodsWe conducted a case-control study over two influenza seasons (2010–11, 2011–12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1–28 days before the SAB.ResultsThe overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1–3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1–28 days was 3.7 (95% CI 1.4–9.4) in 2010–11 and 1.4 (95% CI 0.6–3.3) in 2011–12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1–28 days was 7.7 (95% CI 2.2–27.3); the aOR was 1.3 (95% CI 0.7–2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.ConclusionSAB was associated with influenza vaccination in the preceding 28 days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.     

Post hoc analysis of the efficacy of the 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia in at-risk older adults

BackgroundIndividuals with certain chronic medical conditions are at higher risk of developing pneumonia and pneumococcal disease than those without. Using data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), this post hoc analysis assessed the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥65 years with at-risk conditions.MethodsThe Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) was a double-blind, parallel-group, randomized, placebo-controlled study in the Netherlands in which adults aged ≥65 years received either PCV13 or placebo. Outcomes of interest were identified using prespecified clinical criteria, radiographic confirmation, routine microbiologic testing, and a serotype-specific urinary antigen detection assay.In this post hoc analysis, participants were classified by at-risk status based on self-reporting of any of the following chronic medical conditions: heart disease, lung disease, asthma, diabetes, liver disease, and smoking. The objective of this analysis was to assess PCV13 vaccine efficacy (VE) against a first episode of vaccine-serotype community-acquired pneumonia (VT-CAP) in at-risk participants.ResultsOf the 84,496 adults enrolled in the study, 41,385 (49.2%) were considered at risk owing to chronic medical conditions. Of the 139 VT-CAP cases, 115 (82.7%) occurred in these participants. VE of PCV13 against a first episode of VT-CAP among participants with at-risk conditions was 40.3% (95.2% CI: 11.4%, 60.2%). Average duration of follow-up since vaccination was 3.95 years for at-risk participants; protection did not wane over the study period.ConclusionsThis post hoc analysis of the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) showed significant and persistent efficacy of PCV13 against VT-CAP in at-risk older adults.ClinicalTrials.gov identifier: NCT00744263.     

Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults

PurposeHigh-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50–64 year-olds.MethodsMarkov model CE analysis compared 5 strategies in 50–64 year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided.ResultsThe least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values.ConclusionsBased on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted.     

Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season

BackgroundRecent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2).MethodsPatients with acute respiratory illness were actively recruited during the 2007–2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders.ResultsThere were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p = 0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable.ConclusionsIdentification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season.     

Characteristics and health behaviors of diabetic patients receiving influenza vaccination

ObjectiveEpidemiological research has posited a ‘healthy user’ bias in patients receiving influenza vaccination; thus we sought to evaluate potential healthy-user attributes and their associations with influenza vaccination.Research design & methodsBetween 2011 and 2013, adults with type 2 diabetes were enrolled in a prospective cohort in Alberta, Canada. Information collected included sociodemographics, diabetes-related data (e.g., duration, complications), health behaviors (e.g., smoking status), functional health status, and satisfaction with healthcare. Data were collected by a mailed, self-administered survey. Multivariable logistic regression analyses were used to identify potential healthy-user attributes independently associated with influenza vaccination.ResultsFrom a cohort of 2040 patients, 1287 (63%) reported receiving the influenza vaccine in the previous year. Average age of the cohort was 64 years (standard deviation 11) and 55% were male. In multivariable analysis, attributes independently associated with influenza vaccination included receiving preventive medications: aspirin (64% vs 44%; adjusted odds ratio, aOR 1.65, 95% CI 1.34–2.04); blood pressure medications (76% vs 56%; aOR 1.36, 95% CI 1.07–1.71); and cholesterol-lowering medications (74% vs 53%; aOR 1.50, 95% CI 1.19–1.89), as well as having a healthcare professional check feet for lesions (47% vs 31%; aOR 1.39, 95% CI 1.12–1.74). Additional covariates independently associated with influenza vaccination included: age over 65 years, respiratory disease, the number of additional comorbidities, and higher ratings of healthcare experience.ConclusionVaccinated diabetic patients exhibit many postulated attributes of ‘healthy users’, which has implications for the interpretation of epidemiological studies of influenza vaccine effectiveness, as well as targeting future vaccination campaigns.     

The changing epidemiology of invasive pneumococcal disease after PCV13 vaccination in a country with intermediate vaccination coverage

BackgroundWe studied the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of invasive pneumococcal disease (IPD) and serotype distribution in a region with intermediate levels of vaccination (around 64% in children aged <2 years).MethodsSurveillance data on IPD cases reported by microbiologists participating in the Microbiological Reporting System of Catalonia during 2006–2014 were analysed. We compared estimated incidence rate (IR) ratios for serotypes included in PCV7, PCV10non7, PCV13non10 and non-PCV13 between the PCV7 (2006–2009) and PCV13 periods (2010–2014). IR were corrected for missing serotypes according to year and age groups: <2 years, 2–4 years, 5–64 years and ≥65 years.ResultsA total of 9338 IPD cases were reported. Overall IPD incidence declined by 26.2% (from 16.4 to 12.1) in the PCV13 period. The largest decrease was observed in children aged 2–4 years (44.5%, from 37.4 to 20.8). Pneumonia fell in all age groups with the largest reduction in children aged 2–4 years (49.3%) and <2 years (42%). PCV13 serotypes decreased significantly in all age groups, from 52% (31.6 to 15.1) in children aged 2–4 years to 35% (22.8 to 14.8) in adults aged ≥65 years. Non-PCV13 serotypes rose by 13% (14.8 to 16.8) in people aged ≥65 years.ConclusionsIn a region with intermediate vaccination coverage, the introduction of PCV13 has reduced the overall incidence of IPD, mainly due to the decrease in PCV13 serotypes in all age groups, suggesting herd immunity. Non-PCV13 serotypes have increased in adults aged ≥65 years, suggesting serotype replacement. Higher PCV13 vaccination coverage in children will further reduce IPD incidence in all age groups.     

Impact of elementary school-located influenza vaccinations: A stepped wedge trial across a community

BackgroundInfluenza vaccination rates among children are low and novel strategies are needed to raise coverage. We measured the impact of school-located influenza vaccination (SLIV) on coverage, examined whether SLIV substitutes for practice-based influenza vaccination (“substitution”), and estimated whether a second year of experience with SLIV increases its impact.MethodsWe implemented a stepped wedge study design with schools as clusters. In Year 1, we randomly allocated schools to SLIV or control. In Year 2, all schools performed SLIV. We used emails (suburban schools) or backpack fliers (both urban and suburban schools) to notify parents, and offered web-based (suburban) or paper-based vaccination (urban) consent forms. Local health department nurses administered SLIV vaccinations and billed insurers. We analyzed state immunization registry data to measure influenza vaccination rates.Results42 schools (38,078 children) participated over 2 years. Overall vaccination rates were 5 and 7 percentage points higher among SLIV- school children versus control-school children in suburban (aOR 1.36, 95% CI 1.25–1.49 in Years 1–2 SLIV vs. Year 1 control schools) and urban schools (aOR 1.22, 95% CI 1.10–1.36), respectively, adjusting for prior year’s vaccination and other covariates. While no substitution occurred among children attending suburban schools, some substitution occurred among children attending urban schools, although overall vaccination rates were still higher in urban schools due to SLIV. Compared to an initial year of SLIV, more children were vaccinated in a second year of SLIV at urban (8.3% vs. 6.8%, aOR 1.24, 95% CI 1.04–1.47) but not suburban schools (3.5% vs. 2.7%, aOR 1.24, 95% CI 0.98–1.57).ConclusionsIn this stepped wedge trial, SLIV increased overall influenza vaccination rates in suburban and urban schools. Some substitution for primary care vaccination occurred in urban settings. A second year of SLIV expanded its reach slightly in urban schools.     

A phase II randomized study to determine the safety and immunogenicity of the novel PIKA rabies vaccine containing the PIKA adjuvant using an accelerated regimen

BackgroundHuman Rabies infection continues to be potentially fatal despite the availability of post-exposure prophylaxis with rabies vaccine. The PIKA Rabies vaccine adjuvant is a TLR3 agonist and has been shown to be safe and immunogenic in clinical phase I studies.MethodsWe conducted a phase II, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA rabies vaccine under an accelerated regimen. 126 subjects were randomized into two groups: control vaccine classic regimen (“control-classic”) and PIKA vaccine accelerated regimen (“PIKA-accelerated”). Subjects were followed up for safety and rabies virus neutralizing antibodies (RVNA).ResultsBoth the control and PIKA vaccines were generally well tolerated. 57.6% of subjects in the PIKA vaccine group, compared with 43.8% of subjects in the control-classic group, achieved the target RVNA titer of ≥0.5 IU/mL by Day 7. All subjects achieved the target RVNA titer by Day 14. The RVNA geometric mean titer at Day 7 was 0.60 IU/ml in the PIKA vaccine group and 0.39 IU/ml in the control-classic group. At Day 14, the RVNA geometric mean titer was 18.25 IU/ml in the PIKA-accelerated group and 19.24 IU/ml in the control-classic group. The median time taken to reach the target RVNA titer level of ≥0.5 IU/mL was 7.0 days (95% CI: 7.0–42.0 days) in the PIKA-accelerated group and 14.0 days (95% CI: 7.0–42.0 days) in the control-classic group.ConclusionThe accelerated regimen using the investigational PIKA Rabies vaccine was well-tolerated and demonstrated non-inferior immunogenicity compared to the classic regimen using the commercially available vaccine in healthy adults.Clinical trial registry: The study was registered with clinicaltrials.gov (NCT02956421).     

Evaluating the effectiveness of the universal immunization program against varicella in Japanese children

ObjectiveMatched case control study was conducted to elucidate the effectiveness of the Oka/Biken vaccine immediately after implementation of the universal immunization program in Japan.MethodsCases were laboratory confirmed varicella patient under 15 years of age diagnosed at 14 designated pediatric clinics between September 2015 and September 2016. Controls were selected from patients who visited the same practice for different reasons as the varicella case within 2 weeks. Swab samples were collected from varicella suspected patients and molecular diagnostic assays were used to confirm varicella cases. Matched odds ratio were used to calculate vaccine effectiveness (VE).ResultsVaricella zoster virus DNA was detected in 183 (81.3%) of 225 suspected cases. One sample was excluded because it was positive for the Oka vaccine strain (182/225, 80.9%). Three hundred twenty-three control subjects were enrolled. The effectiveness of 1 dose of the Oka/Biken vaccine compared with no vaccine was 76.7% (95% confidence interval [CI]: 58.6–86.9%; P < 0.001). The effectiveness of 2 doses of the Oka/Biken vaccine was 94.2% (95% CI: 85.7–97.6%; P < 0.001). After adjusting for potential confounding effects, the adjusted VE of 1 and 2 doses of varicella vaccine were 76.9% (95% CI: 58.1–87.3%; P < 0.001) and 94.7% (95% CI: 86.0–98.0%; P < 0.001), respectively.ConclusionsVE of one dose of Oka/Biken varicella vaccine was insufficient to control varicella. Therefore, two doses of Oka/Biken varicella vaccine is significant for controlling varicella in Japan.     

Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in adults 65 years of age and older: A phase II,observer-blind,randomized, controlled trial

BackgroundH7 influenza strains can cause severe and often fatal human infections, especially in the elderly. This phase II, observer-blind, randomized trial (www.ClinicalTrials.gov: NCT01949090) assessed the immunogenicity and safety of a novel AS03-adjuvanted H7N1 vaccine that may serve as a model H7-subtype vaccine.Methods360 adults ≥65 years of age in stable health received either 1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3.75 μg or 7.5 μg hemagglutinin adjuvanted with either AS03_A or AS03_B) or saline placebo, given as a 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays for the per-protocol cohort, comprising 332 participants at 21 days post-each dose, 332 at month 6, and 309 at month 12 (HI assay only). Safety was assessed up to month 12 for all participants who had received ≥1 dose (360 participants).ResultsFor H7N1 HI antibody assessment at day 42 (21 days post-dose 2), seroprotection rates (SPR) in the vaccinated groups were 69.6%–88.7%, seroconversion rates (SCR) 69.6%–88.5%, mean geometric increase (MGI) 11.0–18.9, and HI geometric mean titers (GMTs) 55.0–104.8. These parameters declined by month 6 and month 12. Microneutralization GMTs were 46.2–74.7 in the vaccinated groups at day 42, while vaccine response rate (VRR; proportion with ≥4-fold increase in MN titer) was 46.4%–81.5%. For the cross-reactive H7N9 strain, at day 42, HI GMT were 64.3–201.3, SPR 78.6%–96.3%, SCR 79.3%–96.3%, and MGI 14.1–37.7; MN GMTs were 44.0–85.6, and VRR 46.4–85.2%.The most frequent solicited symptom was injection site pain (41.7%–65.0% of vaccine recipients). In total, 40 participants reported 67 serious adverse events; none were considered causally related to vaccination.ConclusionsIn adults aged ≥65 years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile.www.ClinicalTrials.gov: NCT01949090.     

A follow-up comparative safety analysis of pandemic H1N1 vaccination during pregnancy and risk of infant birth defects among U.S. military mothers

ObjectiveTo update a previous assessment of birth defects among infants born to active duty U.S. military mothers who received the 2009–2010 pandemic H1N1 vaccine, in comparison to the 2008–2009 seasonal influenza vaccine, during pregnancy. Here, we updated the previous comparative analyses with a more refined definition for birth defects using an additional year of follow-up data from both inpatient and outpatient medical encounters.MethodsThe study population included 15,510 live born infants born to active duty mothers vaccinated during pregnancy with either the 2009–2010 pandemic H1N1 vaccine (n = 9033) or the 2008–2009 seasonal influenza vaccine (n = 6477). Birth defect cases were defined as those infants who received a birth defect diagnosis on one inpatient record or two outpatient records on different days within the first year of life. Multivariable logistic regression models were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between birth defects and maternal vaccination during pregnancy with pandemic H1N1 vaccine versus seasonal influenza vaccine.ResultsInfants born to mothers vaccinated during pregnancy with the pandemic H1N1 vaccine, versus the seasonal influenza vaccine, were not at increased odds of birth defects in univariable (OR: 1.13, 95% CI: 0.95–1.34) or multivariable (OR: 1.14, 95% CI: 0.96–1.35) models. Findings were not significant when further limited to first trimester exposure. Multivariable models were adjusted for infant sex and plurality; maternal age, race/ethnicity, marital status, service branch, military rank, and occupation; timing of vaccination; and receipt of vaccination(s) not routinely recommended during pregnancy.ConclusionComparable to our previous analyses assessing birth defects diagnosed at birth, no significant association was found between the pandemic H1N1 vaccination during pregnancy and birth defects, versus the seasonal influenza vaccine. These findings are reassuring and provide additional support for H1N1-containing seasonal influenza vaccination during pregnancy.     

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study

BackgroundVaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014–2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18 years.MethodsParticipants (n = 3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n = 1741), IIV3-YAM (n = 871), or IIV3-VIC (n = 872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI] ≤ 1.5) and seroconversion rate (SCR) difference (IIV3 – IIV4; upper bound of two-sided 95% CI ≤ 10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7 days postvaccination, AEs recorded for 28 days postvaccination, and serious AEs for 6 months postvaccination.ResultsIIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were −1.1 (−4.5, 2.3), −1.7 (−5.0, 1.7), −3.2 (IIV3-YAM; −7.4, 0.9), and −1.6 (IIV3-VIC; −5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%).ConclusionsIIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains not contained in IIV3 comparators. Safety/tolerability profiles were similar across vaccine groups.Funding: Seqirus; Clinicaltrials.gov: NCT02214225.     

Impact of rotavirus vaccination on the burden of acute gastroenteritis in Nagoya city,Japan

BackgroundIn Nagoya city, Japan, rotavirus (RV) vaccination has been available since 2011 with estimated coverage reaching 92% by 2015 after the introduction of a public subsidy in 2012. This study assessed the impact of vaccination on the RV gastroenteritis (RVGE) burden in children aged <5 years old (y) by comparing RVGE hospitalizations and outpatient visits during pre-vaccination (2007–2011), transition (2011–2012) and subsidization (2012–2016) periods.MethodsAll hospitalizations and outpatient visits in children aged <5 y from 2 administrative districts of Nagoya city were identified from the hospital-based electronic databases of 4 hospitals. RVGE cases were identified by diagnostic code and/or positive results of diagnostic kits.ResultsCompared to the pre-vaccination period, there was a decrease in RVGE hospitalizations for children <5 y from 5.59 per 1000 person-year (kPY) to 3.65/kPY in the subsidization period (i.e. 34.69%). In children <1 y, the incidence of RVGE hospitalizations decreased continuously from 6.62/kPY in the pre-vaccination period to 1.84/kPY in the subsidization period (i.e. 72.19%). The highest decrease was observed in the subsidization season i.e. when high coverage was reached: 69% and 75.57% in the 2013/2014 season for 2–3 y and 3–4 y, and 74.03% in the 2014/2015 season for 4–5 y, respectively. Proportion of RVGE outpatient visits decreased by 87.44% for children <1 y and 57.05% for <5 y from the pre-vaccination to the subsidization period. This decrease started the first year of subsidization for children <1 y, 1–2 y and 2–3 y (78.89%, 18.86% and 5.80%) and the second year (2013/2014 season) for children 3–4 y and 4–5 y (87.73% and 51.78%).ConclusionsAlthough yearly fluctuations have been observed, the introduction of vaccination significantly decreased pediatric RVGE hospitalizations and outpatient visits, especially in the age group eligible for vaccination. During the second and third year of subsidization, we observed a herd protection effect on other age groups <5 y who were not eligible for vaccination.Clinicaltrial.gov.registered#:NCT01733862.     

Do parents prefer inactivated or live attenuated influenza vaccine for their children?

ObjectivesTo determine the proportion of children whose parents prefer them to receive live, attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV), examine reasons for preferences, and determine what percentage of vaccinated children receive other than the preferred type of vaccine and why.MethodsParental-reported data for the 2014–15 and 2015–16 influenza seasons from the National Immunization Survey-Flu (NIS-Flu), a random-digit-dialed, dual frame (landline and cellular telephone) survey of households with children, were analyzed. We calculated the proportions of vaccinated children aged 2–17 years whose parents preferred LAIV, IIV, or had no preference, and the proportions that were vaccinated with other than the preferred type of vaccine.ResultsFor the 2014–15 and 2015–16 seasons, 55.2% and 53.7%, respectively, of vaccinated children had parents who reported no preference for either IIV or LAIV. The percentage who preferred LAIV was 22.7% and 21.7%, and IIV was 22.1% and 24.7%. The most common reason given by parents for preferring LAIV was the child’s fear of needles (70.9%) and for preferring IIV was belief that the shot is more effective (29.0%). Approximately one-third of vaccinated children whose parents preferred LAIV received IIV only.ConclusionsThe main finding of this study was that most parents do not have a vaccine type preference for their children. The lack of overwhelming preference is advantageous for the maintenance of vaccination coverage levels during times when one vaccine type is not available or not recommended such as in the 2016–17 and 2017–18 seasons when there was a temporary recommendation not to administer LAIV.     

Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study on immunogenicity and controlled field trials

B lineage mismatch prompted introduction of quadri-valent influenza vaccines (QIV) with two influenza B viruses representing distinct antigenic lineages. To explore the impact on antibody induction and vaccine effectiveness predicted from antibody (VEab), we performed a systematic literature search on immunogenicity studies conducted to assess antibody superiority of QIV over trivalent influenza vaccine (TIV). Thirteen relevant articles described 31 trials from 2007 and 2013. Log-transformed GMT trial estimates and their variances were converted to clinical protection rates predicted from antibody (PRab). VEab estimates were calculated from pre- and post-vaccination PRab. Without specific pre-vaccination immunity, average VEab was 69% for match, and −4% for lineage mismatch. With increasing pre-vaccination seropositivity, mismatch impact declined to 2%. We also performed an umbrella literature search for randomised controlled trials and test-negative case-control trials with TIV, and estimated vaccine effectiveness against laboratory-confirmed influenza B (VEf). Sixty-eight eligible clinical articles described 110 season-trials from 1965 to 2012, covering seasons with B lineage match (n = 52), lineage drift (n = 15) and lineage mismatch (n = 43). With no pre-vaccination antibody levels determined, we used chance of previous exposure to influenza B (Ppe) as pre-seasonal immunity measure. When Ppe was 0%, average VEf for matched seasons was 67%, and for mismatched seasons 35%, indicating a moderate, yet significant mismatch impact on VEf. With increasing Ppe, mismatch impact declined to 3%. Thus serological and field trials indicate that B lineage mismatch impact is negatively related to pre-seasonal immunity and that the gain of QIV over TIV most benefits infants and children not yet exposed to influenza B.