Influenza vaccine effectiveness among patients with high-risk medical conditions in the United States, 2012–2016

Abstract Background Demonstration of influenza vaccine effectiveness (VE) against hospitalized illness in addition to milder outpatient illness may strengthen vaccination messaging. Our objective was to compare patient characteristics and VE between United States (US) inpatient and outpatient VE networks. Methods We tested adults with acute respiratory illness (ARI) for influenza within 1 outpatient-based and 1 hospital-based VE network from 2015 through 2018. We compared age, sex, and high-risk conditions. The test-negative design was used to compare vaccination odds in influenza-positive cases vs influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time to testing from, season (overall VE), and underlying conditions. VE differences (ΔVE) were assessed with 95% confidence intervals (CIs) determined through bootstrapping with significance defined as excluding the null. Results The networks enrolled 14 573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median, 62 years vs 49 years) and had more high-risk conditions (median, 4 vs 1). Overall VE across seasons was 31% (95% CI, 26%–37%) among outpatients and 36% (95% CI, 27%–44%) among inpatients. Strain-specific VE (95% CI) among outpatients vs inpatients was 37% (25%–47%) vs 53% (37%–64%) against H1N1pdm09; 19% (9%–27%) vs 23% (8%–35%) against H3N2; and 46% (38%–53%) vs 46% (31%–58%) against B viruses. ΔVE was not significant for any comparison across all sites. Conclusions Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health among inpatients, influenza vaccination was effective in preventing influenza-associated hospitalizations.

Download Full-text

Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa800 ◽

2020 ◽

Author(s):

Mark W Tenforde ◽

H Keipp Talbot ◽

Christopher H Trabue ◽

Manjusha Gaglani ◽

Tresa M McNeal ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Current Season ◽

Hospital Resources ◽

Negative Controls

Abstract Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

Download Full-text

Influenza Vaccine Effectiveness in the United States During the 2016–2017 Season

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.1151 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S451-S452

Author(s):

Brendan Flannery ◽

Jessie Chung ◽

Arnold S Monto ◽

Emily T Martin ◽

Edward Belongia ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

The United States ◽

Vaccine Effectiveness

Download Full-text

150. Relative Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults—United States, 2015–2017

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy209.020 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S10-S10

Author(s):

Joshua Doyle ◽

Lauren Beacham ◽

Elif Alyanak ◽

Manjusha Gaglani ◽

Emily T Martin ◽

...

Keyword(s):

United States ◽

Older Adults ◽

Influenza Vaccine ◽

Influenza A ◽

Standard Dose ◽

Relative Effectiveness ◽

The United States ◽

Vaccine Effectiveness ◽

High Dose ◽

Research Grant

Abstract Background Seasonal influenza causes substantial morbidity and mortality, and older adults are disproportionately affected. Newer vaccines have been developed for use in people 65 years and older, including a trivalent inactivated vaccine with a 4-fold higher dose of antigen (IIV-HD). In recent years, the use of IIV-HD has increased sufficiently to evaluate its effectiveness compared with standard-dose inactivated influenza vaccines (IIV-SD). Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in 4 states participating in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Predominant influenza A virus subtypes were H1N1 and H3N2, respectively, during these seasons. All enrolled patients were tested for influenza virus with polymerase chain reaction. Receipt and type of influenza vaccine was determined from electronic records and chart review. Odds of laboratory-confirmed influenza were compared among vaccinated and unvaccinated patients. Relative odds of laboratory-confirmed influenza were determined for patients who received IIV-HD or IIV-SD, and adjusted for potential confounding variables via logistic regression. Results Among 1,744 enrolled patients aged ≥ 65 years, 1,105 (63%) were vaccinated; among those vaccinated, 621 (56%) received IIV-HD and 484 (44%) received IIV-SD. Overall, 315 (18%) tested positive for influenza, including 97 (6%) who received IIV-HD, 86 (5%) who received IIV-SD, and 132 (8%) who were unvaccinated. Controlling for age, race, sex, enrollment site, date of illness, index of comorbidity, and influenza season, the adjusted odds of influenza among patients vaccinated with IIV-HD vs. IIV-SD were 0.72 (P = 0.06, 95% CI: 0.52 to 1.01). Conclusion Comparison of high-dose vs. standard-dose vaccine effectiveness during 2 recent influenza seasons (1 H1N1 and 1 H3N2-predominant) suggested relative benefit (nonsignificant) of high-dose influenza vaccine in protecting against influenza-associated hospitalization among persons aged 65 years and older; additional years of data are needed to confirm this finding. Disclosures H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

Download Full-text

Influenza Vaccine Effectiveness in the United States During the 2016–2017 Season

Clinical Infectious Diseases ◽

10.1093/cid/ciy775 ◽

2018 ◽

Vol 68 (11) ◽

pp. 1798-1806 ◽

Cited By ~ 34

Author(s):

Brendan Flannery ◽

Jessie R Chung ◽

Arnold S Monto ◽

Emily T Martin ◽

Edward A Belongia ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

The United States ◽

Vaccine Effectiveness

Download Full-text

Influenza Vaccine Effectiveness in the United States during the 2015–2016 Season

New England Journal of Medicine ◽

10.1056/nejmoa1700153 ◽

2017 ◽

Vol 377 (6) ◽

pp. 534-543 ◽

Cited By ~ 140

Author(s):

Michael L. Jackson ◽

Jessie R. Chung ◽

Lisa A. Jackson ◽

C. Hallie Phillips ◽

Joyce Benoit ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

The United States ◽

Vaccine Effectiveness

Download Full-text

A Real-World Clinical and Economic Analysis of Cell-derived Quadrivalent Influenza Vaccine Compared to Standard Egg-derived Quadrivalent Influenza Vaccines During the 2019-20 Influenza Season in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab604 ◽

2021 ◽

Author(s):

Victoria Divino ◽

Vamshi Ruthwik Anupindi ◽

Mitch DeKoven ◽

Joaquin Mould-Quevedo ◽

Stephen I Pelton ◽

...

Keyword(s):

High Risk ◽

Influenza Vaccine ◽

Influenza Season ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Vaccines ◽

Sensitivity Analyses ◽

Administrative Claims ◽

Adaptive Mutations ◽

Quadrivalent Influenza Vaccine

Abstract Background Cell-derived influenza vaccines are not subject to egg adaptive mutations that have potential to decrease vaccine effectiveness. This retrospective analysis estimated the relative vaccine effectiveness (rVE) of cell-derived quadrivalent influenza vaccine (IIV4c) compared to standard egg-derived quadrivalent influenza vaccines (IIV4e) among recipients aged 4-64 years in the US during the 2019-20 influenza season. Methods The IQVIA PharMetrics® Plus administrative claims database was utilized. Study outcomes were assessed post-vaccination through the end of the study period (March 7, 2020). Inverse probability of treatment weighting (IPTW) was implemented to adjust for covariate imbalance. Adjusted rVE against influenza-related hospitalizations/emergency room (ER) visits and other clinical outcomes was estimated through IPTW-weighted Poisson regression models for the IIV4c and IIV4e cohorts and for the subgroup with ≥1 high-risk condition. Sensitivity analyses modifying the outcome assessment period as well as a doubly-robust analysis were also conducted. IPTW-weighted generalized linear models were used to estimate predicted annualized all-cause costs. Results The final sample comprised 1,138,969 IIV4c and 3,926,357 IIV4e recipients following IPTW adjustment. IIV4c was more effective in preventing influenza-related hospitalizations/ER visits as well as respiratory-related hospitalizations/ER visits compared to IIV4e. IIV4c was also more effective for the high-risk subgroup and across the sensitivity analyses. IIV4c was also associated with significantly lower annualized all-cause total costs compared to IIV4e (-$467), driven by lower costs for outpatient medical services and inpatient hospitalizations. Conclusions IIV4c was significantly more effective in preventing influenza-related hospitalizations/ER visits compared to IIV4e and was associated with significantly lower all-cause costs.

Download Full-text

1341. Relative Vaccine Effectiveness Against Influenza-related Hospitalizations and Respiratory Events During the 2019/20 Influenza seAson in U.S. Children and Adults. A Real-World Evidence Comparison Between Quadrivalent Cell-based and Egg-based Influenza Vaccines

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1533 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S758-S758

Author(s):

Stephen I Pelton ◽

Maarten Postma ◽

Victoria Divino ◽

Joaquin F Mould-Quevedo ◽

Ruthwik Anupindi ◽

...

Keyword(s):

High Risk ◽

Influenza Vaccine ◽

Influenza Season ◽

Standard Dose ◽

The United States ◽

Negative Control ◽

Vaccine Effectiveness ◽

Administrative Claims ◽

Real World Evidence ◽

Quadrivalent Influenza Vaccine

Abstract Background Non-egg-based influenza vaccine manufacturing reduces egg adaptation and therefore has the potential to increase vaccine effectiveness. This study evaluated whether the cell-based quadrivalent influenza vaccine (QIVc) improved relative vaccine effectiveness (rVE) compared to standard-dose egg-based quadrivalent influenza vaccine (QIVe-SD) in the reduction of influenza-related and respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season. Methods A retrospective analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the United States of America (U.S.) (IQVIA PharMetrics® Plus). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders. Post-IPTW, the number of events and rates (per 1,000 vaccinated subject-seasons) of influenza-related hospitalizations/ER visits, respiratory-related hospitalizations/ER visits and all-cause hospitalizations were assessed. Poisson regression was used to estimate adjusted rVE. To avoid any influenza outcome misclassification with COVID-19 infection, the study period ended March 7,2020. A sub-analysis for a high-risk subgroup was conducted. Urinary tract infection (UTI) hospitalization was assessed as a negative control endpoint. Results During the 2019/20 influenza season, 1,150,134 QIVc and 3,924,819 QIVe-SD recipients were identified post-IPTW. Overall adjusted analyses (4-64 years old) found that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95% CI: 0.5%-9.9%]), all-cause hospitalizations (14.5% [95% CI: 13.1%-15.8%]) and any respiratory-related hospitalization/ER visit (8.2% [95% CI: 6.5%-9.8%]). A similar trend was seen for the high-risk subgroup; for instance, rVE for QIVc compared to QIVe-SD against influenza-related hospitalizations/ER visits was 10.5% [95% CI: 2.9%-17.4%]. No effect was identified for the negative control outcome. Conclusion QIVc was significantly more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits, as well as all-cause hospitalizations, compared to QIVe-SD. Disclosures Stephen I. Pelton, MD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Victoria Divino, PhD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)

Download Full-text

Effects of Influenza Vaccination in the United States During the 2018–2019 Influenza Season

Clinical Infectious Diseases ◽

10.1093/cid/ciz1244 ◽

2020 ◽

Vol 71 (8) ◽

pp. e368-e376 ◽

Cited By ~ 7

Author(s):

Jessie R Chung ◽

Melissa A Rolfes ◽

Brendan Flannery ◽

Pragati Prasad ◽

Alissa O’Halloran ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Influenza Season ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Monte Carlo Algorithm ◽

Medical Visits ◽

The Us

Abstract Background Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018–2019 influenza season in the United States included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season. Methods We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UIs) of influenza-associated outcomes prevented by vaccination in the United States. The model incorporated age-specific estimates of national 2018–2019 influenza vaccine coverage, influenza virus–specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network. Results Influenza vaccination prevented an estimated 4.4 million (95%UI, 3.4 million–7.1 million) illnesses, 2.3 million (95%UI, 1.8 million–3.8 million) medical visits, 58 000 (95%UI, 30 000–156 000) hospitalizations, and 3500 (95%UI, 1000–13 000) deaths due to influenza viruses during the US 2018–2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among children aged 6 months–4 years. Conclusions Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the United States, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated healthcare utilization even in a season in which a vaccine component does not match to a circulating virus.

Download Full-text

Relative and Absolute Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults—United States, 2015–2017

Clinical Infectious Diseases ◽

10.1093/cid/ciaa160 ◽

2020 ◽

Cited By ~ 3

Author(s):

Joshua D Doyle ◽

Lauren Beacham ◽

Emily T Martin ◽

H Keipp Talbot ◽

Arnold Monto ◽

...

Keyword(s):

United States ◽

Older Adults ◽

Influenza Vaccine ◽

Standard Dose ◽

Relative Effectiveness ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

High Dose ◽

Confounding Variables

Abstract Background Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged ≥65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. Results Among 1487 enrolled patients aged ≥65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV, and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] −42%, 38%) and that of HD-IIV was 32% (95% CI −3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95% CI −1%, 48%). Conclusions During 2 US influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged ≥65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

Download Full-text