Publications by authors named "Suzanne E Ohmit"

45 Publications

The Household Influenza Vaccine Effectiveness Study: Lack of Antibody Response and Protection Following Receipt of 2014-2015 Influenza Vaccine.

Clin Infect Dis 2017 Oct;65(10):1644-1651

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: Antigenically drifted A(H3N2) viruses circulated extensively during the 2014-2015 influenza season. Vaccine effectiveness (VE) was low and not significant among outpatients but in a hospitalized population was 43%. At least one study paradoxically observed increased A(H3N2) infection among those vaccinated 3 consecutive years.

Methods: We followed a cohort of 1341 individuals from 340 households. VE against laboratory-confirmed influenza was estimated. Hemagglutination-inhibition and neuraminidase-inhibition antibody titers were determined in subjects ≥13 years.

Results: Influenza A(H3N2) was identified in 166 (12%) individuals and B(Yamagata) in 34 (2%). VE against A(H3N2) was -3% (95% confidence interval [CI]: -55%, 32%) and similarly ineffective between age groups; increased risk of infection was not observed among those vaccinated in 2 or 3 previous years. VE against influenza B(Yamagata) was 57% (95% CI: -3%, 82%) but only significantly protective in children <9 years (87% [95% CI: 43%, 97%]). Less than 20% of older children and adults had ≥4-fold antibody titer rise against influenza A(H3N2) and B antigens following vaccination; responses were surprisingly similar for antigens included in the vaccine and those similar to circulating viruses. Antibody against A/Hong Kong/4801/14, similar to circulating 2014-2015 A(H3N2) viruses and included in the 2016-2017 vaccine, did not significantly predict protection.

Conclusions: Absence of VE against A(H3N2) was consistent with circulation of antigenically drifted viruses; however, generally limited antibody response following vaccination is concerning even in the context of antigenic mismatch. Although 2014-2015 vaccines were not effective in preventing A(H3N2) infection, no increased susceptibility was detected among the repeatedly vaccinated.
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http://dx.doi.org/10.1093/cid/cix608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850544PMC
October 2017

Application of an Individual-Based Transmission Hazard Model for Estimation of Influenza Vaccine Effectiveness in a Household Cohort.

Am J Epidemiol 2017 Dec;186(12):1380-1388

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan.

Household cohort studies are an important design for the study of respiratory virus transmission. Inferences from these studies can be improved through the use of mechanistic models to account for household structure and risk as an alternative to traditional regression models. We adapted a previously described individual-based transmission hazard (TH) model and assessed its utility for analyzing data from a household cohort maintained in part for study of influenza vaccine effectiveness (VE). Households with ≥4 individuals, including ≥2 children <18 years of age, were enrolled and followed during the 2010-2011 influenza season. VE was estimated in both TH and Cox proportional hazards (PH) models. For each individual, TH models estimated hazards of infection from the community and each infected household contact. Influenza A(H3N2) infection was laboratory-confirmed in 58 (4%) subjects. VE estimates from both models were similarly low overall (Cox PH: 20%, 95% confidence interval: -57, 59; TH: 27%, 95% credible interval: -23, 58) and highest for children <9 years of age (Cox PH: 40%, 95% confidence interval: -49, 76; TH: 52%, 95% credible interval: 7, 75). VE estimates were robust to model choice, although the ability of the TH model to accurately describe transmission of influenza presents continued opportunity for analyses.
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http://dx.doi.org/10.1093/aje/kwx217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860432PMC
December 2017

Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains.

J Infect Dis 2016 Dec 7;214(12):1947-1951. Epub 2016 Oct 7.

Wistar Institute.

During the 2013-2014 influenza season, nearly all circulating 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) strains possessed an antigenically important mutation in hemagglutinin (K166Q). Here, we performed hemagglutination-inhibition (HAI) assays, using sera collected from 382 individuals prior to the 2013-2014 season, and we determined whether HAI titers were associated with protection from A(H1N1)pdm09 infection. Protection was associated with HAI titers against an A(H1N1)pdm09 strain possessing the K166Q mutation but not with HAI titers against the current A(H1N1)pdm09 vaccine strain, which lacks this mutation. These data indicate that contemporary A(H1N1)pdm09 strains are antigenically distinct from the current A(H1N1)pdm09 vaccine strain.
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http://dx.doi.org/10.1093/infdis/jiw479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142093PMC
December 2016

Influenza Vaccine Effectiveness Against Antigenically Drifted Influenza Higher Than Expected in Hospitalized Adults: 2014-2015.

Clin Infect Dis 2016 10 1;63(8):1017-25. Epub 2016 Jul 1.

Department of Epidemiology, University of Michigan, School of Public Health.

Background: The 2014-2015 influenza season was severe, with circulating influenza A (H3N2) viruses that were antigenically drifted from the vaccine virus. Reported vaccine effectiveness (VE) estimates from ambulatory care settings were markedly decreased.

Methods: Adults, hospitalized at 2 hospitals in southeast Michigan for acute respiratory illnesses, defined by admission diagnoses, of ≤10 days duration were prospectively enrolled. Throat and nasal swab specimens were collected, combined, and tested for influenza by real-time reverse transcription polymerase chain reaction. VE was estimated by comparing the vaccination status of those testing positive for influenza with those testing negative in logistic regression models adjusted for age, sex, hospital, calendar time, time from illness onset to specimen collection, frailty score, and Charlson comorbidity index (CCI).

Results: Among 624 patients included in the analysis, 421 (68%) were vaccinated, 337 (54%) were female, 220 (35%) were age ≥65 years, and 92% had CCI > 0, indicating ≥1 comorbid conditions. Ninety-eight (16%) patients tested positive for influenza A (H3N2); among 60 (61%) A (H3N2) viruses tested by pyrosequencing, 53 (88%) belonged to the drifted 3C.2a genetic group. Adjusted VE was 43% (95% confidence interval [CI], 4-67) against influenza A (H3N2); 40% (95% CI, -13 to 68) for those <65 years, and 48% (95% CI, -33 to 80) for those ≥65 years. Sensitivity analyses largely supported these estimates.

Conclusions: VE estimates appeared higher than reports from similar studies in ambulatory care settings, suggesting that the 2014-2015 vaccine may have been more effective in preventing severe illness requiring hospitalization.
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http://dx.doi.org/10.1093/cid/ciw432DOI Listing
October 2016

Enhanced Genetic Characterization of Influenza A(H3N2) Viruses and Vaccine Effectiveness by Genetic Group, 2014-2015.

J Infect Dis 2016 10 6;214(7):1010-9. Epub 2016 May 6.

Influenza Division, Centers for Disease Control and Prevention.

Background: During the 2014-2015 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of the genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE).

Methods: A novel pyrosequencing assay was used to determine genetic group, based on hemagglutinin (HA) gene sequences, of influenza A(H3N2) viruses from patients enrolled at US Influenza Vaccine Effectiveness Network sites. VE was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients.

Results: Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2) virus; genetic characterization of 1397 viruses showed that 1134 (81%) belonged to 1 HA genetic group (3C.2a) of antigenically drifted influenza A(H3N2) viruses. Effectiveness of 2014-2015 influenza vaccination varied by influenza A(H3N2) virus genetic group from 1% (95% confidence interval [CI], -14% to 14%) against illness caused by antigenically drifted influenza A(H3N2) virus group 3C.2a viruses versus 44% (95% CI, 16%-63%) against illness caused by vaccine-like influenza A(H3N2) virus group 3C.3b viruses.

Conclusions: Effectiveness of 2014-2015 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in HA genes related to antigenic drift were associated with reduced VE.
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http://dx.doi.org/10.1093/infdis/jiw181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812259PMC
October 2016

Modest Waning of Influenza Vaccine Efficacy and Antibody Titers During the 2007-2008 Influenza Season.

J Infect Dis 2016 10 19;214(8):1142-9. Epub 2016 Apr 19.

Department of Epidemiology.

Background: Antibody titers decrease with time following influenza vaccination, raising concerns that vaccine efficacy might wane. However, the relationship between time since vaccination and protection is unclear.

Methods: Time-varying vaccine efficacy (VE[t]) was examined in healthy adult participants (age range, 18-49 years) in a placebo-controlled trial of inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) performed during the 2007-2008 influenza season. Symptomatic respiratory illnesses were laboratory-confirmed as influenza. VE(t) was estimated by fitting a smooth function based on residuals from Cox proportional hazards models. Subjects had blood samples collected immediately prior to vaccination, 30 days after vaccination, and at the end of the influenza season for testing by hemagglutination inhibition and neuraminidase inhibition assays.

Results: Overall efficacy was 70% (95% confidence interval [CI], 50%-82%) for IIV and 38% (95% CI, 5%-59%) for LAIV. Statistically significant waning was detected for IIV (P = .03) but not LAIV (P = .37); however, IIV remained significantly efficacious until data became sparse at the end of the season. Similarly, antibody titers against influenza virus hemagglutinin and neuraminidase significantly decreased over the season among IIV recipients.

Conclusions: Both vaccines were efficacious but LAIV less so. IIV efficacy decreased slowly over time, but the vaccine remained significantly efficacious for the majority of the season.
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http://dx.doi.org/10.1093/infdis/jiw105DOI Listing
October 2016

Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013-2014 in the United States.

J Infect Dis 2016 May 6;213(10):1546-56. Epub 2016 Jan 6.

Centers for Disease Control and Prevention, Atlanta, Georgia.

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.
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http://dx.doi.org/10.1093/infdis/jiv577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837903PMC
May 2016

Substantial Influenza Vaccine Effectiveness in Households With Children During the 2013-2014 Influenza Season, When 2009 Pandemic Influenza A(H1N1) Virus Predominated.

J Infect Dis 2016 Apr 23;213(8):1229-36. Epub 2015 Nov 23.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: We examined the influenza vaccine effectiveness (VE) during the 2013-2014 influenza season, in which 2009 pandemic influenza A(H1N1) virus (influenza A[H1N1]pdm09) predominated. In 2 previous years when influenza A(H3N2) virus predominated, the VE was low and negatively affected by prior year vaccination.

Methods: We enrolled and followed 232 households with 1049 members, including 618 children; specimens were collected from subjects with acute respiratory illnesses. The VE in preventing laboratory-confirmed influenza A(H1N1)pdm09 infection was estimated in adjusted models. Preseason hemagglutination-inhibition and neuraminidase-inhibition antibody titers were determined to assess susceptibility.

Results: Influenza A(H1N1)pdm09 was identified in 25 households (10.8%) and 47 individuals (4.5%). Adjusted VE against infection with influenza A(H1N1)pdm09 was 66% (95% confidence interval [CI], 23%-85%), with similar point estimates in children and adults, and against both community-acquired and household-acquired infections. VE did not appear to be different for live-attenuated and inactivated vaccines among children aged 2-8 years, although numbers were small. VE was similar for subjects vaccinated in both current and prior seasons and for those vaccinated in the current season only; susceptibility titers were consistent with this observation.

Conclusions: Findings, including substantial significant VE and a lack of a negative effect of repeated vaccination on VE, were in contrast to those seen in prior seasons in which influenza A(H3N2) virus predominated.
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http://dx.doi.org/10.1093/infdis/jiv563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799665PMC
April 2016

Illness Severity and Work Productivity Loss Among Working Adults With Medically Attended Acute Respiratory Illnesses: US Influenza Vaccine Effectiveness Network 2012-2013.

Clin Infect Dis 2016 Feb 12;62(4):448-455. Epub 2015 Nov 12.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: Influenza causes significant morbidity and mortality, with considerable economic costs, including lost work productivity. Influenza vaccines may reduce the economic burden through primary prevention of influenza and reduction in illness severity.

Methods: We examined illness severity and work productivity loss among working adults with medically attended acute respiratory illnesses and compared outcomes for subjects with and without laboratory-confirmed influenza and by influenza vaccination status among subjects with influenza during the 2012-2013 influenza season.

Results: Illnesses laboratory-confirmed as influenza (ie, cases) were subjectively assessed as more severe than illnesses not caused by influenza (ie, noncases) based on multiple measures, including current health status at study enrollment (≤7 days from illness onset) and current activity and sleep quality status relative to usual. Influenza cases reported missing 45% more work hours (20.5 vs 15.0; P < .001) than noncases and subjectively assessed their work productivity as impeded to a greater degree (6.0 vs 5.4; P < .001). Current health status and current activity relative to usual were subjectively assessed as modestly but significantly better for vaccinated cases compared with unvaccinated cases; however, no significant modifications of sleep quality, missed work hours, or work productivity loss were noted for vaccinated subjects.

Conclusions: Influenza illnesses were more severe and resulted in more missed work hours and productivity loss than illnesses not confirmed as influenza. Modest reductions in illness severity for vaccinated cases were observed. These findings highlight the burden of influenza illnesses and illustrate the importance of laboratory confirmation of influenza outcomes in evaluations of vaccine effectiveness.
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http://dx.doi.org/10.1093/cid/civ952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725387PMC
February 2016

Quantifying Protection Against Influenza Virus Infection Measured by Hemagglutination-inhibition Assays in Vaccine Trials.

Epidemiology 2016 Jan;27(1):143-51

From the aSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; bLi Ka Shing Faculty of Medicine, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China; cDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI; and dYale-NUS College, National University of Singapore, Singapore, Singapore.

Background: Correlations between hemagglutination-inhibition titers (hereafter "titers") and protection against infection have been identified in historical studies. However, limited information is available about the dynamics of how titer influences protection.

Methods: Titers were measured in randomized, placebo-controlled vaccine trials in Hong Kong among pediatrics during September 2009-December 2010 and the United States among adults during Oct 2007-April 2008. Intermediate unobserved titers were imputed using three interpolation methods. As participants were recruited at different times leading to varying exposure to infection relative to entry, a modified proportional hazards model was developed to account for staggered entry into the studies and to quantify the correlation of titers with protection against influenza infections, adjusting for waning in titers. The model was fitted using Markov chain Monte Carlo and importance sampling.

Results: A titer of 1:40 was associated with a reduced infection risk of 40%-70% relative to a titer of 1:10, depending on the circulating strain; the corresponding protection associated with a titer of 1:80 was 54%-84%. Results were robust across interpolation methods. The trivalent-inactivated vaccine reduced cumulative incidence of influenza B and influenza A(H3N2) infections by six percentage points (pp; 95% credible interval = 2 pp, 10 pp) and 1 pp (95% credible interval = 0.3 pp, 2 pp) respectively, but not for influenza A(H1N1)pdm09. The live-attenuated vaccine showed little efficacy against influenza A(H3N2) infections.

Conclusions: Titers are correlated with protection against influenza infections. The trivalent inactivated vaccine can reduce the risk of influenza A(H3N2) and influenza B infections in the community.
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http://dx.doi.org/10.1097/EDE.0000000000000402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658669PMC
January 2016

Persistence of Antibodies to Influenza Hemagglutinin and Neuraminidase Following One or Two Years of Influenza Vaccination.

J Infect Dis 2015 Dec 26;212(12):1914-22. Epub 2015 May 26.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: Antibody titers to influenza hemagglutinin (HA) and neuraminidase (NA) surface antigens increase in the weeks after infection or vaccination, and decrease over time thereafter. However, the rate of decline has been debated.

Methods: Healthy adults participating in a randomized placebo-controlled trial of inactivated (IIV) and live-attenuated (LAIV) influenza vaccines provided blood specimens immediately prior to vaccination and at 1, 6, 12, and 18 months postvaccination. Approximately half had also been vaccinated in the prior year. Rates of hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) titer decline in the absence of infection were estimated.

Results: HAI and NAI titers decreased slowly over 18 months; overall, a 2-fold decrease in antibody titer was estimated to take >600 days for all HA and NA targets. Rates of decline were fastest among IIV recipients, explained in part by faster declines with higher peak postvaccination titer. IIV and LAIV recipients vaccinated 2 consecutive years exhibited significantly lower HAI titers following vaccination in the second year, but rates of persistence were similar.

Conclusions: Antibody titers to influenza HA and NA antigens may persist over multiple seasons; however, antigenic drift of circulating viruses may still necessitate annual vaccination. Vaccine seroresponse may be impaired with repeated vaccination.
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http://dx.doi.org/10.1093/infdis/jiv313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655854PMC
December 2015

Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection.

J Infect Dis 2015 Oct 8;212(8):1191-9. Epub 2015 Apr 8.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: Laboratory correlates of influenza vaccine protection can best be identified by examining people who are infected despite vaccination. While the importance of antibody to viral hemagglutinin (HA) has long been recognized, the level of protection contributed independently by antibody to viral neuraminidase (NA) has not been determined.

Methods: Sera from a controlled trial of the efficacies of inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV) were tested by hemagglutination inhibition (HAI) assay, microneutralization (MN) assay, and a newly standardized lectin-based neuraminidase inhibition (NAI) assay.

Results: The NAI assay detected a vaccine response in 37% of IIV recipients, compared with 77% and 67% of participants in whom responses were detected by the HAI and MN assays, respectively. For LAIV recipients, the NAI, HAI, and MN assays detected responses in 6%, 21%, and 17%, respectively. In IIV recipients, as NAI assay titers rose, the frequency of infection fell, similar to patterns seen with HAI and MN assays. HAI and MN assay titers were highly correlated, but NAI assay titers exhibited less of a correlation. Analyses suggested an independent role for NAI antibody in protection, which was similar in the IIV, LAIV, and placebo groups.

Conclusions: While NAI antibody is not produced to a large extent in response to current IIV, it appears to have an independent role in protection. As new influenza vaccines are developed, NA content should be considered.

Clinical Trials Registration: NCT00538512.
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http://dx.doi.org/10.1093/infdis/jiv195DOI Listing
October 2015

Influenza vaccine effectiveness in households with children during the 2012-2013 season: assessments of prior vaccination and serologic susceptibility.

J Infect Dis 2015 May 21;211(10):1519-28. Epub 2014 Nov 21.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: There are recognized needs to identify determinants of influenza vaccine effectiveness (VE), including the effect of repeated annual vaccination.

Methods: We recruited 321 households with 1426 members, including 833 children, and followed them during the 2012-2013 influenza season; specimens were collected from subjects with reported acute respiratory illnesses. We estimated the effectiveness of documented influenza vaccination in preventing laboratory-confirmed influenza, using adjusted Cox proportional hazards models. Antibody titers in a subset of subjects were determined by a hemagglutination inhibition assay to determine the subjects' preseason susceptibility to influenza.

Results: Influenza was identified in 76 (24%) households and 111 (8%) individuals. VE point estimates indicated significant protection in adults (48%; 95% confidence interval [CI], 1%-72%), similar protection in children aged 9-17 years (49%; 95% CI, -16% to 78%), but no evidence of effectiveness in children aged <9 years (-4%; 95% CI, -110% to 49%). Lower VE was observed in those vaccinated in both the current and prior seasons, compared with those vaccinated in the current season only; susceptibility titers against type A but not type B were consistent with this observation. Residual protection from vaccination in the prior season was indicated by both VE and serologic results.

Conclusions: Prior vaccination appears to modify VE by both residual protection and reduced vaccine response.
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http://dx.doi.org/10.1093/infdis/jiu650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462665PMC
May 2015

Influenza vaccine effectiveness in the United States during 2012-2013: variable protection by age and virus type.

J Infect Dis 2015 May 18;211(10):1529-40. Epub 2014 Nov 18.

Marshfield Clinic Research Foundation, Wisconsin.

Background: During the 2012-2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza B lineage viruses in the United States.

Methods: Patients with acute cough illness for ≤7 days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as [100% × (1 - adjusted odds ratio)] for vaccination in cases versus test-negative controls.

Results: Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval [CI], 43%-55%) overall, 39% (95% CI, 29%-47%) against influenza A(H3N2), 66% (95% CI, 58%-73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%-63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50-64 years (52%; 95% CI, 33%-65%) and persons aged 6 months-8 years (51%; 95% CI, 32%-64%) and lowest among persons aged ≥65 years (11%; 95% CI, -41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011-2012 vaccine 1 year earlier.

Conclusions: The 2012-2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation.
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http://dx.doi.org/10.1093/infdis/jiu647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407759PMC
May 2015

Frequency of acute respiratory illnesses and circulation of respiratory viruses in households with children over 3 surveillance seasons.

J Infect Dis 2014 Dec 6;210(11):1792-9. Epub 2014 Jun 6.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

Background: The household has traditionally been the site for studying acute respiratory illnesses (ARIs). Most studies were conducted many years ago, and more broadly sensitive laboratory methods to determine ARI etiology are now available.

Methods: We recruited and followed households with children over 3 annual surveillance periods and collected respiratory tract specimens from subjects with reported ARI. Virus etiology was determined by real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis.

Results: Individuals in larger households (defined as households with >4 members) and those in households with children aged <5 years had significantly higher ARI frequencies than others. ARI frequency generally declined with increasing age. Virus etiology was most likely to be determined in young children, who were also most likely to have virus coinfection. Overall, 16% of ARIs with 1 virus identified had ≥1 coinfecting virus. Rhinoviruses and coronaviruses were the most frequently identified agents of ARI in all age categories. Influenza virus and adenovirus were less frequently identified but were most likely to cause ARI that required medical attention.

Conclusions: Longitudinal studies in families remain a valuable way to study respiratory infections. RT-PCR has increased the sensitivity of virus detection, including coinfecting viruses, and expanded our ability to detect viruses now known to cause ARI.
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http://dx.doi.org/10.1093/infdis/jiu327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296188PMC
December 2014

Interim estimates of 2013-14 seasonal influenza vaccine effectiveness - United States, February 2014.

MMWR Morb Mortal Wkly Rep 2014 Feb;63(7):137-42

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months. Each season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended acute respiratory illness (ARI). This report uses data from 2,319 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness (Flu VE) Network during December 2, 2013-January 23, 2014, to estimate an interim adjusted effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with medically attended ARI. During this period, overall vaccine effectiveness (VE) (adjusted for study site, age, sex, race/ethnicity, self-rated health, and days from illness onset to enrollment) against influenza A and B virus infection associated with medically attended ARI was 61%. The influenza A (H1N1)pdm09 (pH1N1) virus that emerged to cause a pandemic in 2009 accounted for 98% of influenza viruses detected. VE was estimated to be 62% against pH1N1 virus infections and was similar across age groups. As of February 8, 2014, influenza activity remained elevated in the United States, the proportion of persons seeing their health-care provider for influenza-like illness was lower than in early January but remained above the national baseline, and activity still might be increasing in some parts of the country. CDC and the Advisory Committee on Immunization Practices routinely recommend that annual influenza vaccination efforts continue as long as influenza viruses are circulating. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated. Antiviral medications are an important second line of defense to treat influenza illness and should be used as recommended among suspected or confirmed influenza patients, regardless of patient vaccination status. Early antiviral treatment is recommended for persons with suspected influenza with severe or progressive illness (e.g., hospitalized persons) and those at high risk for complications from influenza, no matter how severe the illness.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584757PMC
February 2014

Factors associated with influenza vaccine receipt in community dwelling adults and their children.

Vaccine 2014 Apr 12;32(16):1841-7. Epub 2014 Feb 12.

University of Michigan School of Public Health, Department of Epidemiology, 1415 Washington Heights, Ann Arbor, MI 48109, USA.

Background: Factors associated with influenza vaccine receipt are well studied in healthcare personnel, pregnant women, and the elderly. There has been substantially less research in community dwelling adults and children, and none among entire households. Many studies determine vaccination status by self-report or behavioral intention, outcomes susceptible to misclassification. Given that vaccine is recommended for everyone over six months, re-evaluating these factors is warranted.

Methods: The Household Influenza Vaccine Effectiveness (HIVE) study is a prospective cohort of households with children. In 2010-2011, 549 adults representing 312 households completed surveys evaluating knowledge, attitudes, and practices regarding influenza vaccination for themselves and their children. Using the health belief model (HBM) as a framework, we examined factors associated with documented seasonal influenza vaccine receipt using log-binomial regression models.

Results: In multivariate models, cues to action such as doctor recommendation, (RR 1.62, 95% CI: 1.25-2.10), perceived benefits (RR 1.25, 95% CI: 1.04-1.50), and perceived susceptibility (RR 1.21, 95% CI: 1.03-1.42) were significantly associated with increased likelihood of vaccine receipt among adults while high perceived barriers were associated with decreased likelihood (RR 0.38, 95% CI: 0.25-0.59). Similarly, parents reporting higher barriers were less likely (RR 0.58, 95% CI: 0.42-0.79) and those perceiving greater benefits (RR 4.16, 95% CI: 2.28-7.59) and severity (RR 1.13, 95% CI: 1.00-1.27 were more likely to vaccinate their children. The observed effects of perceptions of susceptibility, severity, and benefits were more pronounced at low cues to action for children, as were the effects of perceptions of barriers and severity among adults.

Conclusion: Perceived benefits and barriers are most strongly associated with vaccine receipt. However, the effects of various factors were most pronounced in the absence of cues to action, which may be an important component of targeted interventions.
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http://dx.doi.org/10.1016/j.vaccine.2014.01.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084780PMC
April 2014

Influenza vaccine effectiveness in the 2011-2012 season: protection against each circulating virus and the effect of prior vaccination on estimates.

Clin Infect Dis 2014 Feb 13;58(3):319-27. Epub 2013 Nov 13.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.

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.
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http://dx.doi.org/10.1093/cid/cit736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007111PMC
February 2014

Influenza transmission in a cohort of households with children: 2010-2011.

PLoS One 2013 25;8(9):e75339. Epub 2013 Sep 25.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.

Background: Households play a major role in community spread of influenza and are potential targets for mitigation strategies.

Methods: We enrolled and followed 328 households with children during the 2010-2011 influenza season; this season was characterized by circulation of influenza A (H3N2), A (H1N1)pdm09 and type B viruses. Specimens were collected from subjects with acute respiratory illnesses and tested for influenza in real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays. Influenza cases were classified as community-acquired or household-acquired, and transmission parameters estimated.

Results: Influenza was introduced to 78 (24%) households and transmission to exposed household members was documented in 23 households. Transmission was more likely in younger households (mean age <22 years) and those not reporting home humidification, but was not associated with household vaccination coverage. The secondary infection risk (overall 9.7%) was highest among young children (<9 years) and varied substantially by influenza type/subtype with the highest risk for influenza A (H3N2). The serial interval (overall 3.2 days) also varied by influenza type and was longest for influenza B. Duration of symptomatic illness was shorter in children compared with adults, and did not differ by influenza vaccination status.

Discussion: Prospective study of households with children over a single influenza season identified differences in household transmission by influenza type/subtype, subject age, and home humidification, suggesting possible targets for interventions to reduce transmission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0075339PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783407PMC
July 2014

Influenza vaccine effectiveness in the community and the household.

Clin Infect Dis 2013 May 14;56(10):1363-9. Epub 2013 Feb 14.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Background: There is a recognized need to determine influenza vaccine effectiveness on an annual basis and a long history of studying respiratory illnesses in households.

Methods: We recruited 328 households with 1441 members, including 839 children, and followed them during the 2010-2011 influenza season. Specimens were collected from subjects with reported acute respiratory illnesses and tested by real-time reverse transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or an immunization registry. The effectiveness of 2010-2011 influenza vaccination in preventing laboratory-confirmed influenza was estimated using Cox proportional hazards models adjusted for age and presence of high-risk condition, and stratified by prior season (2009-2010) vaccination status.

Results: Influenza was identified in 78 (24%) households and 125 (9%) individuals; the infection risk was 8.5% in the vaccinated and 8.9% in the unvaccinated (P = .83). Adjusted vaccine effectiveness in preventing community-acquired influenza was 31% (95% confidence interval [CI], -7% to 55%). In vaccinated subjects with no evidence of prior season vaccination, significant protection (62% [95% CI, 17%-82%]) against community-acquired influenza was demonstrated. Substantially lower effectiveness was noted among subjects who were vaccinated in both the current and prior season. There was no evidence that vaccination prevented household transmission once influenza was introduced; adults were at particular risk despite vaccination.

Conclusions: Vaccine effectiveness estimates were lower than those demonstrated in other observational studies carried out during the same season. The unexpected findings of lower effectiveness with repeated vaccination and no protection given household exposure require further study.
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http://dx.doi.org/10.1093/cid/cit060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693492PMC
May 2013

Effectiveness of seasonal influenza vaccines in the United States during a season with circulation of all three vaccine strains.

Clin Infect Dis 2012 Oct 25;55(7):951-9. Epub 2012 Jul 25.

Department of Medicine, University of Rochester Medical Center, NY, USA.

Background: Influenza vaccines may be reformulated annually because of antigenic drift in influenza viruses. However, the relationship between antigenic characteristics of circulating viruses and vaccine effectiveness (VE) is not well understood. We conducted an assessment of the effectiveness of US influenza vaccines during the 2010-2011 season.

Methods: We performed a case-control study comparing vaccination histories between subjects with acute respiratory illness with positive real-time reverse transcription polymerase chain reaction for influenza and influenza test-negative controls. Subjects with acute respiratory illness of ≤7 days duration were enrolled in hospitals, emergency departments, or outpatient clinics in communities in 4 states. History of immunization with the 2010-2011 vaccine was ascertained from vaccine registries or medical records. Vaccine effectiveness was estimated in logistic regression models adjusted for study community, age, race, insurance status, enrollment site, and presence of a high-risk medical condition.

Results: A total of 1040 influenza-positive cases and 3717 influenza-negative controls were included from the influenza season, including 373 cases of influenza A(H1N1), 334 cases of influenza A(H3N2), and 333 cases of influenza B. Overall adjusted VE was 60% (95% confidence interval [CI], 53%-66%). Age-specific VE estimates ranged from 69% (95% CI, 56%-77%) in children aged 6 months-8 years to 38% (95% CI, -16% to 67%) in adults aged ≥65 years.

Conclusions: The US 2010-2011 influenza vaccines were moderately effective in preventing medically attended influenza during a season when all 3 vaccine strains were antigenically similar to circulating viruses. Continued monitoring of influenza vaccines in all age groups is important, particularly as new vaccines are introduced.
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http://dx.doi.org/10.1093/cid/cis574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657521PMC
October 2012

Editorial commentary: seasonal influenza vaccines during the 2009 pandemic: help or harm?

Clin Infect Dis 2012 Sep 5;55(5):703-5. Epub 2012 Jun 5.

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http://dx.doi.org/10.1093/cid/cis526DOI Listing
September 2012

Influenza hemagglutination-inhibition antibody titer as a correlate of vaccine-induced protection.

J Infect Dis 2011 Dec 12;204(12):1879-85. Epub 2011 Oct 12.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

Background: Antibody to influenza virus hemagglutinin has been traditionally associated with protection. Questions have been raised about its use as a surrogate for vaccine efficacy, particularly with regard to an absolute titer indicating seroprotection.

Methods: We examined hemagglutination-inhibition (HAI) antibody titers in subjects from a placebo-controlled trial of inactivated and live attenuated vaccines and compared titers in subjects with symptomatic influenza (cases) to those without influenza infection (noncases).

Results: Prevaccination and postvaccination geometric mean titers were both significantly lower for cases compared with noncases in all intervention groups. Frequency of postvaccination seroconversion did not significantly differ for cases and noncases in either vaccine group. Among live attenuated vaccine and placebo recipients, cases were less likely than noncases to have postvaccination HAI titers ≥32 or 64. Nearly all recipients of inactivated vaccine had postvaccination titers of at least 64, and the small number of vaccine failures were scattered across titers ranging from 64 to 2048.

Conclusions: While HAI antibody is the major correlate of protection, postvaccination titers alone should not be used as a surrogate for vaccine efficacy. Vaccine failures from clinical trials need to be examined to determine why seemingly protective HAI titers may not protect. Clinical Trials Registration. NCT00538512.
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http://dx.doi.org/10.1093/infdis/jir661DOI Listing
December 2011

Effectiveness of non-adjuvanted pandemic influenza A vaccines for preventing pandemic influenza acute respiratory illness visits in 4 U.S. communities.

PLoS One 2011 12;6(8):e23085. Epub 2011 Aug 12.

Department of Preventive Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.

We estimated the effectiveness of four monovalent pandemic influenza A (H1N1) vaccines (three unadjuvanted inactivated, one live attenuated) available in the U.S. during the pandemic. Patients with acute respiratory illness presenting to inpatient and outpatient facilities affiliated with four collaborating institutions were prospectively recruited, consented, and tested for influenza. Analyses were restricted to October 2009 through April 2010, when pandemic vaccine was available. Patients testing positive for pandemic influenza by real-time RT-PCR were cases; those testing negative were controls. Vaccine effectiveness was estimated in logistic regression models adjusted for study community, patient age, timing of illness, insurance status, enrollment site, and presence of high-risk medical conditions. Pandemic virus was detected in 1,011 (15%) of 6,757 enrolled patients. Fifteen (1%) of 1,011 influenza positive cases and 1,042 (18%) of 5,746 test-negative controls had record-verified pandemic vaccination >14 days prior to illness onset. Adjusted effectiveness (95% confidence interval) for pandemic vaccines combined was 56% (23%, 75%). Adjusted effectiveness for inactivated vaccines alone (79% of total) was 62% (25%, 81%) overall and 32% (-92%, 76%), 89% (15%, 99%), and -6% (-231%, 66%) in those aged 0.5 to 9, 10 to 49, and 50+ years, respectively. Effectiveness for the live attenuated vaccine in those aged 2 to 49 years was only demonstrated if vaccination >7 rather than >14 days prior to illness onset was considered (61%∶ 12%, 82%). Inactivated non-adjuvanted pandemic vaccines offered significant protection against confirmed pandemic influenza-associated medical care visits in young adults.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023085PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155536PMC
February 2012

Efficacy studies of influenza vaccines: effect of end points used and characteristics of vaccine failures.

J Infect Dis 2011 May 4;203(9):1309-15. Epub 2011 Mar 4.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Background: End points used to detect influenza in vaccine efficacy trials have varied. Both the inactivated and live attenuated influenza vaccines are efficacious; however, failure to protect occurs.

Methods: We compared characteristics of influenza A (H3N2) and B cases from 3 years of a comparative placebo-controlled trial of inactivated and live attenuated vaccines, and we evaluated the laboratory end points used to determine efficacy.

Results: Although illness duration and reported symptoms did not differ by intervention, subjects with influenza in the inactivated vaccine group were less likely than those in the placebo group to report medically attended illnesses. All influenza type A (H3N2) and B cases isolated in cell culture were also identified by real-time polymerase chain reaction (rtPCR). However, only 69% of type A (H3N2) cases identified by rtPCR also were isolated in cell culture. Isolation frequency was lowest among live attenuated vaccine failures, a reflection of lower specimen viral loads. Among cases of rtPCR identified influenza A (H3N2), 90% of placebo and 87% of live attenuated vaccine recipients but only 23% of inactivated vaccine recipients demonstrated serologic confirmation of infection.

Conclusions: In influenza vaccine efficacy studies, virus identification using rtPCR is the ideal end point. Isolation in cell culture will miss cases, and a serologic end point alone will overestimate inactivated vaccine efficacy.
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http://dx.doi.org/10.1093/infdis/jir015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069734PMC
May 2011

Comparative efficacy of inactivated and live attenuated influenza vaccines.

N Engl J Med 2009 Sep;361(13):1260-7

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

Background: The efficacy of influenza vaccines may vary from year to year, depending on a variety of factors, and may differ for inactivated and live attenuated vaccines.

Methods: We carried out a randomized, double-blind, placebo-controlled trial of licensed inactivated and live attenuated influenza vaccines in healthy adults during the 2007-2008 influenza season and estimated the absolute and relative efficacies of the two vaccines.

Results: A total of 1952 subjects were enrolled and received study vaccines in the fall of 2007. Influenza activity occurred from January through April 2008, with the circulation of influenza types A (H3N2) (about 90%) and B (about 9%). Absolute efficacy against both types of influenza, as measured by isolating the virus in culture, identifying it on real-time polymerase-chain-reaction assay, or both, was 68% (95% confidence interval [CI], 46 to 81) for the inactivated vaccine and 36% (95% CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50% (95% CI, 20 to 69) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine. The absolute efficacy against the influenza A virus was 72% (95% CI, 49 to 84) for the inactivated vaccine and 29% (95% CI, -14 to 55) for the live attenuated vaccine, with a relative efficacy of 60% (95% CI, 33 to 77) for the inactivated vaccine.

Conclusions: In the 2007-2008 season, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic influenza A (predominately H3N2) in healthy adults. The live attenuated vaccine also prevented influenza illnesses but was less efficacious. (ClinicalTrials.gov number, NCT00538512.)
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http://dx.doi.org/10.1056/NEJMoa0808652DOI Listing
September 2009

Seasonal influenza vaccines: evolutions and future trends.

Expert Rev Vaccines 2009 Apr;8(4):383-9

University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, MI 48104, USA.

Influenza vaccines are among the oldest still in active use. Purity, potency and standardization have been improved over the years. However, they are still produced using the same basic methods as when they were first introduced and evaluated by the US Armed Forces during and after the Second World War. For some time, the trivalent inactivated influenza vaccines have been recognized as having deficiencies. These deficiencies are now being addressed by a number of innovative approaches in vaccine development. These include strategies for broadening the vaccine-induced immune response, increasing the duration of protection, improving the protection induced in older individuals and reducing dependence on the egg supply. Each new vaccine will need to be evaluated carefully, ideally against placebo as well as against a standard vaccine, to determine absolute and relative efficacy. Such data will be necessary to inform decisions on making selections for use.
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http://dx.doi.org/10.1586/erv.09.9DOI Listing
April 2009

Reduced reaction frequencies with repeated inactivated or live-attenuated influenza vaccination.

Vaccine 2009 Feb 16;27(7):1050-4. Epub 2008 Dec 16.

University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

Data collected as part of a multi-year trial examining the efficacies of inactivated and live-attenuated influenza vaccines were used to evaluate the reported occurrence of post-vaccination reactions. Two cohorts were defined: (1) individuals who received the same vaccine over two consecutive years, and (2) individuals who first enrolled in year 2 of the study and received vaccine only in that year. For both vaccines there were significantly fewer reactions reported in year 2 in those subjects who were vaccinated both years. Declines were demonstrated when comparing year 1 and 2 reaction frequencies in subjects vaccinated both years, and differences were seen when comparing year 2 reaction frequencies in subjects vaccinated both years with those first vaccinated in year 2. Reaction reporting peaked on post-vaccination days 0 and 1 following receipt of the inactivated vaccine, and on day 2 following receipt of the live-attenuated vaccine.
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http://dx.doi.org/10.1016/j.vaccine.2008.11.100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665993PMC
February 2009
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