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Seasonal variation in the age distribution of influenza A cases suggests that factors other than age shape susceptibility to medically attended infection. We ask whether these differences can be partly explained by protection conferred by childhood influenza infection, which has lasting impacts on immune responses to influenza and protection against new influenza A subtypes (phenomena known as original antigenic sin and immune imprinting). Fitting a statistical model to data from studies of influenza vaccine effectiveness (VE), we find that primary infection appears to reduce the risk of medically attended infection with that subtype throughout life. This effect is stronger for H1N1 compared to H3N2. Additionally, we find evidence that VE varies with both age and birth year, suggesting that VE is sensitive to early exposures. Our findings may improve estimates of age-specific risk and VE in similarly vaccinated populations and thus improve forecasting and vaccination strategies to combat seasonal influenza., Competing Interests: PA, EB, SC No competing interests declared, HM has received funding from Seqirus, unrelated to this work. The author has no other competing interests to declare, (© 2020, Arevalo et al.)

Background: The severity of the 2017-2018 influenza season in the United States was high, with influenza A(H3N2) viruses predominating. Here, we report influenza vaccine effectiveness (VE) and estimate the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the 2017-2018 influenza season., Methods: We used national age-specific estimates of 2017-2018 influenza vaccine coverage and disease burden. We estimated VE against medically attended reverse-transcription polymerase chain reaction-confirmed influenza virus infection in the ambulatory setting using a test-negative design. We used a compartmental model to estimate numbers of influenza-associated outcomes prevented by vaccination., Results: The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%-43%), including 22% (95% CI, 12%-31%) against influenza A(H3N2), 62% (95% CI, 50%-71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%-57%) against influenza B. We estimated that influenza vaccination prevented 7.1 million (95% CrI, 5.4 million-9.3 million) illnesses, 3.7 million (95% CrI, 2.8 million-4.9 million) medical visits, 109 000 (95% CrI, 39 000-231 000) hospitalizations, and 8000 (95% credible interval [CrI], 1100-21 000) deaths. Vaccination prevented 10% of expected hospitalizations overall and 41% among young children (6 months-4 years)., Conclusions: Despite 38% VE, influenza vaccination reduced a substantial burden of influenza-associated illness, medical visits, hospitalizations, and deaths in the United States during the 2017-2018 season. Our results demonstrate the benefit of current influenza vaccination and the need for improved vaccines., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Introduction: A recent study reported an association between inactivated influenza vaccine (IIV) and spontaneous abortion (SAB), but only among women who had also been vaccinated in the previous influenza season. We sought to estimate the association between IIV administered in three recent influenza seasons and SAB among women who were and were not vaccinated in the previous influenza season., Methods: We conducted a case-control study over three influenza seasons (2012-13, 2013-14, 2014-15) in the Vaccine Safety Datalink (VSD). Cases (women with SAB) and controls (women with live births) were matched on VSD site, date of last menstrual period, age group, and influenza vaccination status in the previous influenza season. Of 1908 presumptive cases identified from the electronic record, 1236 were included in the main analysis. Administration of IIV was documented in several risk windows, including 1-28, 29-56, and >56 days before the SAB date., Results: Among 627 matched pairs vaccinated in the previous season, no association was found between vaccination in the 1-28 day risk window and SAB (adjusted odds ratio (aOR) 0.9; 95% confidence interval (CI) 0.6-1.5). The season-specific aOR ranged from 0.5 to 1.7 with all CIs including the null value of 1.0. Similarly, no association was found among women who were not vaccinated in the previous season; the season-specific aOR in the 1-28 day risk window ranged from 0.6 to 0.7 and the 95% CI included 1.0 in each season. There was no association found between SAB and influenza vaccination in the other risk windows, or when vaccine receipt was analyzed relative to date of conception., Conclusion: During these seasons we found no association between IIV and SAB, including among women vaccinated in the previous season. These findings lend support to current recommendations for influenza vaccination at any time during pregnancy, including the first trimester., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Statin medications have immunomodulatory effects. Several recent studies suggest that statins may reduce influenza vaccine response and reduce influenza vaccine effectiveness (VE)., Methods: We compared influenza VE in statin users and nonusers aged ≥45 years enrolled in the US Vaccine Effectiveness Network study over 6 influenza seasons (2011-2012 through 2016-2017). All enrollees presented to outpatients clinics with acute respiratory illness and were tested for influenza. Information on vaccination status, medical history, and statin use at the time of vaccination were collected by medical and pharmacy records. Using a test-negative design, we estimated VE as (1 - OR) × 100, in which OR is the odds ratio for testing positive for influenza virus among vaccinated vs unvaccinated participants., Results: Among 11692 eligible participants, 3359 (30%) were statin users and 2806 (24%) tested positive for influenza virus infection; 78% of statin users and 60% of nonusers had received influenza vaccine. After adjusting for potential confounders, influenza VE was 36% (95% confidence interval [CI], 22%-47%) among statin users and 39% (95% CI, 32%-45%) among nonusers. We observed no significant modification of VE by statin use. VE against influenza A(H1N1)pdm09, A(H3N2), and B viruses were similar among statin users and nonusers., Conclusions: In this large observational study, influenza VE against laboratory-confirmed influenza illness was not affected by current statin use among persons aged ≥45 years. Statin use did not modify the effect of vaccination on influenza when analyzed by type and subtype., (Published by Oxford University Press for the Infectious Diseases Society of America 2018.)

Self-reported influenza vaccination is generally accurate for the current season, but the accuracy of self-report for vaccination in prior seasons is largely unknown. This study evaluated the accuracy of self-report for current and prior season influenza vaccination among patients with medically attended acute respiratory illness enrolled in a study of influenza vaccine effectiveness during the 2014-15 influenza season. It demonstrates there is a greater potential for exposure misclassification when prior season vaccinations are ascertained by self-report. Percent agreement between self-report and final status was high for both current and prior season vaccination: 97.7% and 93.2%, respectively., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Importance: Some studies have reported negative effects of prior-season influenza vaccination. Prior-season influenza vaccination effects on vaccine effectiveness (VE) in children are not well understood., Objective: To assess the association of prior-season influenza vaccination with subsequent VE in children aged 2 to 17 years., Design, Setting, and Participants: This multiseason, test-negative case-control study was conducted in outpatient clinics at 4 US sites among children aged 2 to 17 years with a medically attended febrile acute respiratory illness. Participants were recruited during the 2013-2014, 2014-2015, and 2015-2016 seasons when influenza circulated locally. Cases were children with influenza confirmed by reverse-transcription polymerase chain reaction. Test-negative control individuals were children with negative test results for influenza., Exposures: Vaccination history, including influenza vaccine type received in the enrollment season (live attenuated influenza vaccine [LAIV], inactivated influenza vaccine [IIV], or no vaccine) and season before enrollment (LAIV, IIV, or no vaccine), determined from medical records and immunization registries., Main Outcomes and Measures: LAIV and IIV effectiveness by influenza type and subtype (influenza A[H1N1]pdm09, influenza A[H3N2], or influenza B), estimated as 100 × (1 - odds ratio) in a logistic regression model with adjustment for potential confounders. Prior season vaccination associations were assessed with an interaction term., Results: Of 3369 children (1749 [52%] male; median age, 6.6 years [range, 2-17 years]) included in the analysis, 772 (23%) had a positive test result for influenza and 1674 (50%) were vaccinated in the enrollment season. Among LAIV recipients, VE against influenza A(H3N2) was higher among children vaccinated in both the enrollment and 1 prior season (50.3% [95% CI, 17.0% to 70.2%]) than among those without 1 prior season vaccination (-82.4% [95% CI, -267.5% to 9.5%], interaction P < .001). The effectiveness of LAIV against influenza A(H1N1)pdm09 was not associated with prior season vaccination among those with prior season vaccination (47.5% [95% CI, 11.4% to 68.9%]) and among those without prior season vaccination (7.8% [95% CI, -101.9% to 57.9%]) (interaction P = .37). Prior season vaccination was not associated with effectiveness of IIV against influenza A(H3N2) (38.7% [95% CI, 6.8% to 59.6%] among those with prior-season vaccination and 23.2% [95% CI, -38.3% to 57.4%] among those without prior-season vaccination, interaction P = .16) or with effectiveness of IIV against influenza A[H1N1]pdm09 (72.4% [95% CI, 56.0% to 82.7%] among those with prior season vaccination and 67.5% [95% CI, 32.1% to 84.4%] among those without prior season vaccination, interaction P = .93). Residual protection from prior season vaccination only (no vaccination in the enrollment season) was observed for influenza B (LAIV: 60.0% [95% CI, 36.8% to 74.7%]; IIV: 60.0% [36.9% to 74.6%]). Similar results were observed in analyses that included repeated vaccination in 2 and 3 prior seasons., Conclusions and Relevance: Influenza VE varied by influenza type and subtype and vaccine type, but prior-season vaccination was not associated with reduced VE. These findings support current recommendations for annual influenza vaccination of children.

Background: Influenza-like illness and inflammation are known risk factors for venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). However, few studies have characterized the risk of VTE following influenza vaccination. We examined VTE risk after vaccination in adults 50years old and older within the Vaccine Safety Datalink (VSD)., Methods: We used the self-controlled case series method to determine the risk of VTE among age-eligible adults who received influenza vaccine (with or without pandemic H1N1) and experienced a VTE during the months of September through December in 2007 through 2012. Presumptive VTE cases were identified among VSD participants using diagnostic codes, diagnostic tests, and oral anticoagulant prescription. Potential cases were validated by medical record review. The VTE incidence rate ratio was calculated among confirmed cases for the risk window 1 to 10days after vaccination relative to all other person-time from September through December., Results: Of the 1,488 presumptive cases identified, 508 were reviewed, of which 492 (97%) were confirmed cases of VTE. The analysis included 396 incident, confirmed cases. Overall, there was no increased risk of VTE in the 1 to 10days after influenza vaccination (IRR=0.89, 95% CI 0.69-1.17) compared to the control period. Results were similar when all person-time was censored before vaccination. A post hoc analysis showed an increased risk among current tobacco smokers (IRR=2.57, 95% CI 1.06-6.23). No clustering of VTE was observed in the 1-42days after vaccination., Discussion: Overall, there was no evidence that inactivated influenza vaccine was associated with VTE in adults ≥50years old. An increased risk was found among current smokers in a post hoc analysis. These findings are consistent with previous research and support the safety of annual vaccination in this population., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Human papillomavirus (HPV) vaccine coverage rates remain low. This is believed to reflect parental hesitancy, but few studies have examined how changes in parents' attitudes impact HPV vaccine uptake. This study examined the association between changes in parents' vaccine attitudes and HPV vaccine receipt in their adolescent children., Methods: A baseline and 1-year follow-up survey of HPV vaccine attitudes was administered to parents of 11-17 year olds who had not completed the HPV vaccine series. Changes in attitudinal scores (barriers, harms, ineffectiveness, and uncertainties) from the Carolina HPV Immunization Attitudes and Beliefs Scale were assessed. Two outcomes were measured (in parents' adolescent children) over an 18-month period and analyzed using multivariable regression; receipt of next scheduled HPV vaccine dose and 3-dose series completion., Results: There were 221 parents who completed the baseline survey (11% response rate) and 164 with available follow-up data; 60% of their adolescent children received a next HPV vaccine dose and 38% completed the vaccine series at follow-up. Decrease in parents' uncertainties was a significant predictor of vaccine receipt, with each 1-point reduction in uncertainties score associated with 4.9 higher odds of receipt of the next vaccine dose. Higher baseline harms score was the only significant predictor of lower series completion., Conclusions: Reductions in parents' uncertainties appeared to result in greater likelihood of their children receiving the HPV vaccine. Only baseline concerns about vaccine harms were associated with lower series completion rate. Education for parents should emphasize the HPV vaccine's safety profile.

Introduction: Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

Background: The predominant strain during the 2013-2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009., Methods: The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2-17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed., Results: We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR-confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%-61%). Among fully vaccinated children aged 2-17 years, the effectiveness of LAIV4 was 17% (95% CI, -39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%-74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season., Conclusions: During 2013-2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Few studies have examined the effectiveness of full versus partial vaccination with inactivated trivalent influenza vaccines (IIV3) as defined by the US CDC Advisory Committee on Immunization Practices., Methods: Respiratory swabs were collected from outpatients aged 6 months to 8 years with acute cough for ≤7 days in clinics in 5 states during the 2011-2012 and 2012-2013 influenza seasons. Influenza was confirmed by real-time reverse transcription polymerase chain reaction assay. Receipt of current season IIV3 and up to 4 prior vaccinations was documented from medical records and immunization registries. Using a test-negative design, vaccine effectiveness (VE) was estimated adjusting for age, race/ethnicity, medical conditions, study site and month of enrollment., Results: We did not observe higher VE for children fully versus partially vaccinated with IIV3, as defined by US Advisory Committee on Immunization Practice, although our sample of partially vaccinated children was relatively small. However, among children aged 2-8 years in both seasons and against A(H3N2) and B influenza illness separately, VE point estimates were consistently higher for children who had received 2 doses in the same prior season compared with those without (VE range of 58%-80% vs. 33%-44%, respectively). Across seasons, the odds of A(H3N2) illness despite IIV3 vaccination were 2.4-fold (95% confidence interval: 1.4-4.3) higher among children who had not received 2 doses in the same prior season. We also noted residual protection among unvaccinated children who were vaccinated the previous season (VE range = 36%-40% across outcomes)., Conclusion: Vaccination with IIV3 may provide preventive benefit in subsequent seasons, including possible residual protection if vaccination is missed. Two vaccine doses in the same season may be more effective than alternative priming strategies.

Background: Recent studies suggest that influenza vaccination in the previous season may influence the effectiveness of current-season vaccination, but this has not been assessed in a single population over multiple years., Methods: Patients presenting with acute respiratory illness were prospectively enrolled during the 2004-2005 through 2012-2013 influenza seasons. Respiratory swabs were tested for influenza and vaccination dates obtained from a validated registry. Vaccination status was determined for the current, previous, and prior 5 seasons. Vaccine effectiveness (VE) was calculated for participants aged ≥9 years using logistic regression models with an interaction term for vaccination history., Results: There were 7315 enrollments during 8 seasons; 1056 (14%) and 650 (9%) were positive for influenza A(H3N2) and B, respectively. Vaccination during current only, previous only, or both seasons yielded similar protection against H3N2 (adjusted VE range, 31%-36%) and B (52%-66%). In the analysis using 5 years of historical vaccination data, current season VE against H3N2 was significantly higher among vaccinated individuals with no prior vaccination history (65%; 95% confidence interval [CI], 36%-80%) compared with vaccinated individuals with a frequent vaccination history (24%; 95% CI, 3%-41%; P = .01). VE against B was 75% (95% CI, 50%-87%) and 48% (95% CI, 29%-62%), respectively (P = .05). Similar findings were observed when analysis was restricted to adults 18-49 years., Conclusions: Current- and previous-season vaccination generated similar levels of protection, and vaccine-induced protection was greatest for individuals not vaccinated during the prior 5 years. Additional studies are needed to understand the long-term effects of annual vaccination., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Purpose: We conducted weekly surveillance for pre-specified adverse events following receipt of the 2012-2013 influenza vaccines in the Vaccine Safety Datalink (VSD)., Methods: For each outcome, risk intervals (i.e., period after vaccination with a potentially increased risk) were defined on the basis of biologic plausibility and prior literature. Seizures following inactivated influenza vaccine (IIV) were monitored in children in three age groups (6-23 months, 24-59 months, and 5-17 years) using a self-controlled risk interval design. We also monitored for Guillain-Barré syndrome, encephalitis, and anaphylaxis following IIV in patients ≥6 months of age using a cohort design with historical controls. In the risk intervals following live attenuated influenza vaccine (LAIV), we collected weekly counts of Guillain-Barré syndrome, encephalitis, and anaphylaxis in patients ages 2-49. Among LAIV vaccinees, numbers of expected events based on rates in historical controls were calculated, adjusted for age and site., Results: At the end of surveillance, approximately 3.6 million first doses of IIV and 250 000 first doses of LAIV had been administered in the VSD. No elevated risks were identified in risk intervals following 2012-2013 IIV, as compared with a self-matched control interval or to historical controls. For each outcome, fewer than three events occurred in the risk interval following 2012-2013 LAIV, and we thus were unable to estimate measures of relative risks., Conclusions: No increased risk was identified for any of the pre-specified outcomes following 2012-2013 influenza vaccinations in the VSD. Published 2014. This article is a U.S. Government work and is in the public domain in the USA., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Each year, the US Influenza Vaccine Effectiveness Network examines the effectiveness of influenza vaccines in preventing medically attended acute respiratory illnesses caused by influenza., Methods: Patients with acute respiratory illnesses of ≤ 7 days' duration were enrolled at ambulatory care facilities in 5 communities. Specimens were collected and tested for influenza by real-time reverse-transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or immunization registries. Vaccine effectiveness was estimated in adjusted logistic regression models by comparing the vaccination coverage in those who tested positive for influenza with those who tested negative., Results: The 2011-2012 season was mild and peaked late, with circulation of both type A viruses and both lineages of type B. Overall adjusted vaccine effectiveness was 47% (95% confidence interval [CI], 36-56) in preventing medically attended influenza; vaccine effectiveness was 65% (95% CI, 44-79) against type A (H1N1) pdm09 but only 39% (95% CI, 23-52) against type A (H3N2). Estimates of vaccine effectiveness against both type B lineages were similar (overall, 58%; 95% CI, 35-73). An apparent negative effect of prior year vaccination on current year effectiveness estimates was noted, particularly for A (H3N2) outcomes., Conclusions: Vaccine effectiveness in the 2011-2012 season was modest overall, with lower effectiveness against the predominant A (H3N2) virus. This may be related to antigenic drift, but past history of vaccination might also play a role.

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., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Guillain-Barré Syndrome (GBS) can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1) pandemic in the United States, monovalent inactivated influenza vaccine (MIV) availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited., Methods: We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009-10 MIV, 2010-11 trivalent inactivated influenza vaccine (TIV), and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls., Results: Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009-10 MIV recipients and 2.80 million 2010-11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009-10 MIV/2010-11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI), 0.59-3.99; risk difference = 0.93 per million doses, 95% CI, -0.71-5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60-16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49-26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior vaccination shorter than 6 weeks., Conclusions: After adjusting for antecedent infections, we found no evidence for an elevated GBS risk following 2009-10 MIV/2010-11 TIV influenza vaccines. However, the association between GBS and antecedent infection was strongly elevated.

Background: Serologic response to influenza vaccination declines with age. Few other host factors are known to be associated with serologic response. Our objective was to determine whether obesity and vulnerability independently predicted serologic response to influenza vaccination., Methods: Adults ≥ 50 years were recruited during the 2008-2009 influenza season. Subjects provided pre- and post-vaccination sera for measuring antibody titers to 2008-2009 vaccine components. Body mass index (BMI) was calculated as weight (kg)/height (m(2)). Data were collected on vulnerability using the vulnerable elders survey (VES13). Logistic regression evaluated the associations between obesity and vulnerability and the serologic response to vaccination (both seroprotection and seroconversion), adjusting for gender, age, comorbidities, pre-vaccination titer, and site., Results: Mean (± standard deviation) age of 415 study subjects was 65 ± 10 years; 40% were obese. Mean BMI was 29 ± 5.6 kg/m(2); mean VES13 was 1.6 ± 1.8. The proportions of subjects who seroconverted and had seroprotective titers were 40% and 49%, respectively, for A/Brisbane/59 (H1N1); 73% and 80% for A/Brisbane/10 (H3N2); and 34% and 94% for B/Florida. Modified VES-13 (score 0-10, with 10 being most vulnerable) was not associated with seroprotection against H1N1 or H3N2, and VES-13 was directly associated with seroconversion to H1N1 but not H3N2 or B. Obesity (BMI ≥ 30 kg/m(2) vs. BMI 18.5-30 kg/m(2)) was not associated with seroprotection for H1N1 or H3N2; obesity was directly associated with seroconversion to H3N2 but not H1N1 or B. Age was inversely associated with seroprotection and seroconversion against H1N1 and with seroconversion to influenza B., Conclusion: Based on this sample of older healthy subjects, there were no consistent relationships between VES 13 or obesity and either seroprotection or seroconversion to three influenza vaccine antigens., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Estimates of influenza vaccine effectiveness from observational studies that rely on physician-ordered influenza tests may be biased if physician testing behavior is influenced by patient vaccination status. To assess the potential for differential diagnostic testing of children by vaccine status, we examined the association between receipt of a commercial influenza diagnostic test and influenza vaccination among children aged 6-59 months who sought care at the Marshfield Clinic for acute respiratory or febrile illnesses during the 2004-05 through 2007-08 influenza seasons. There was no significant association between prior influenza vaccination and receipt of a diagnostic test for influenza. These findings suggest that estimates of vaccine effectiveness derived from observational studies among children are unlikely to be biased due to differential diagnostic testing., (Copyright © 2011. Published by Elsevier Ltd.)

Objective: In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine., Methods: Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses., Results: MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6)., Conclusions: Among 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.

Several case reports have described immune hemolytic anemia (IHA) following vaccination in children. We examined the risk of IHA in the 42 days following vaccination exposure using a self-controlled case series study design. In our population-based cohort of nearly 4.5 million children in the Vaccine Safety Datalink, we identified 55 confirmed cases of new-onset IHA from 1991 through 2000. We found no association between IHA and diphtheria-pertussis-tetanus vaccination (incidence rate ratio (IRR)=0.65, 95% CI: 0.19-2.24), hepatitis B vaccination (IRR=1.73, 95% CI: 0.59-5.01), or any vaccination (IRR=1.04, 95% CI: 0.46-2.32).

Background: Local reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td) vaccine and the risk of local reactions may increase with number of prior Td vaccinations., Methods: To estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004., Results: Overall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations) was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV) in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2). Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics., Conclusion: Medically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.

Background: Pneumococcal polysaccharide vaccine (PPV) is recommended for all adults 65 years of age and older and for younger adults with high-risk conditions. While data from national surveys provide information on the proportion of adults 65 years of age and older reporting ever receipt of PPV they do not collect more detailed information, such as age at vaccination or the total number of vaccinations received. In addition, there is relatively little information available on PPV coverage in younger adults with chronic conditions. To assess contemporary patterns of pneumococcal vaccination and revaccination of adults, we conducted a cross-sectional study of adults enrolled in medical care organizations (MCOs) participating in the Vaccine Safety Datalink project., Methods: The study population included 1.5 million adults 25 years of age and older enrolled in the four participating MCOs on December 1, 2006. PPVs administered to members of the study population prior to that date were identified from computerized immunization registries maintained by the MCOs., Results: Among the general population of adults 25 through 64 years of age, vaccine coverage increased from 2% in the 25-29 year old age-group to 26% in the 60-64 year old age-group. In all age-groups, coverage was substantially higher in persons defined as having a chronic high risk condition. This was particularly true for diabetes mellitus, with vaccine coverage of over 50% in the lower age-groups and 75% in those 60-64 years of age. Among adults 65 years of age and older, 82% had received at least one PPV and 18% had received two or more PPVs., Conclusion: We found higher levels of PPV coverage among adults 65 years of age and older and among younger adults with diabetes mellitus than reported by national surveys and for those groups PPV coverage approached the Healthy People 2010 national objectives. These results suggest that achieving those objectives for PPV is possible and that high vaccination coverage may be facilitated by vaccine tracking and reminder systems.

Background: Persons with atopic dermatitis or eczema, regardless of disease severity or activity, may develop eczema vaccinatum if they or their close contacts receive the smallpox vaccine. According to current recommendations, a preexposure vaccination program should identify these persons and exclude them from participating., Objective: To determine the prevalence of diagnosed atopic dermatitis and eczema in a defined population and assess the sensitivity of screening questions to identify patients who have received these diagnoses., Design: Population-based prevalence survey and telephone interview., Setting: 14 ZIP code regions in Wisconsin., Patients: Persons given a diagnosis of atopic dermatitis or eczema in 2000 and 2001 were identified from a population-based cohort. Persons with a history of atopic dermatitis diagnosed since 1979 were eligible for the telephone survey., Measurements: Prevalence of diagnosed atopic dermatitis or eczema; proportions of respondents able to recall a past diagnosis of atopic dermatitis, eczema, or recurrent rash., Results: The prevalence of atopic dermatitis or eczema diagnosis in 2000 or 2001 was 0.8%. At least 2.4% of the cohort would be ineligible for smallpox vaccination because of active skin disease in themselves or household members. Among 94 adult respondents with atopic dermatitis, 55 (59%) correctly self-reported skin disease. Seventy-nine (60%) of 133 household contacts of adults with atopic dermatitis correctly reported the presence of skin disease in a household member. Parental recall of skin disease in children with atopic dermatitis was 70% (123 of 177)., Conclusions: Identifying dermatologic contraindications to smallpox vaccination by relying only on a self-reported history of rash illnesses is likely to miss a substantial proportion of individuals who should not receive smallpox vaccine in a preexposure vaccination campaign.