Influenza Vaccine Effectiveness in Inpatient and Outpatient Settings in the United States, 2015–2018

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.

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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.

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

Vaccine ◽

10.1016/j.vaccine.2018.10.093 ◽

2018 ◽

Vol 36 (52) ◽

pp. 8047-8053 ◽

Cited By ~ 9

Author(s):

Mei Shang ◽

Jessie R. Chung ◽

Michael L. Jackson ◽

Lisa A. Jackson ◽

Arnold S. Monto ◽

...

Keyword(s):

United States ◽

High Risk ◽

Influenza Vaccine ◽

The United States ◽

Vaccine Effectiveness ◽

Medical Conditions

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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.

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995. Effectiveness of Influenza Vaccine for Prevention of Influenza-Associated Hospitalizations Among High-Risk Adults in the United States, 2015–2016

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.832 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S296-S296

Author(s):

Elif Alyanak ◽

Manjusha Gaglani ◽

Emily T Martin ◽

Arnold S Monto ◽

Don Middleton ◽

...

Keyword(s):

High Risk ◽

Influenza Vaccine ◽

Chronic Conditions ◽

Medical Condition ◽

Respiratory Illness ◽

Risk Groups ◽

The United States ◽

Vaccine Effectiveness ◽

Increased Risk ◽

Research Grant

Abstract Background Individuals with cardiopulmonary and other chronic conditions are at increased risk for severe complications of influenza. Few studies have examined influenza vaccine effectiveness (VE) in high-risk groups. We evaluated VE against influenza-associated hospitalization among adults with specific high-risk conditions. Methods Adults hospitalized with acute respiratory illness (ARI) during the 2015–2016 influenza season were enrolled at eight hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Respiratory specimens were tested for influenza by reverse transcription PCR. Measures of illness severity, underlying health status, and vaccination were obtained from medical records and enrollment interviews. The presence of high-risk conditions was determined from clinical codes assigned to prior year medical encounters. We estimated VE using a test-negative design as (1 − adjusted odds ratio), comparing odds of PCR-confirmed influenza among vaccinated patients vs. unvaccinated controls. Multivariate logistic regression was adjusted for age, sex, and other factors, stratifying by chronic conditions. Results Of 1,467 adults hospitalized with ARI, 236 (16%) had PCR-confirmed influenza; 180 (78%) were A(H1N1)pdm09. In all, 1,358 (93%) had ≥1 high-risk medical condition, and 1,026 (70%) had ≥3 conditions. Cardiovascular (n = 835), metabolic (including diabetes) (n = 773) and lung conditions (n = 692) were most common (figure). Patients with ≥1 high-risk conditions were more likely to be vaccinated (70%) vs. patients not at high risk (31%, P < 0.001). Among all patients, VE against any influenza-associated hospitalization was 50% (95% CI: 31–63). VE was similarly high among patients with neurologic (VE = 64%, 95% CI: 26–83), metabolic (VE = 55%, 95% CI: 30–71), and cardiovascular (VE = 53%, 95% CI: 27–69) conditions, though lower for patients with immunosuppression and malignancy (VE = 20%, 95% CI: −42–54). Conclusion Vaccination significantly reduced risk of influenza hospitalization among adults with the most prevalent high-risk cardiovascular, metabolic, and lung conditions. Results support the benefit of vaccinating adults with existing specific chronic conditions. 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.

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Effect of antigenic drift on influenza vaccine effectiveness in the United States – 2019-2020

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1884 ◽

2020 ◽

Author(s):

Mark W Tenforde ◽

Rebecca J Garten Kondor ◽

Jessie R Chung ◽

Richard K Zimmerman ◽

Mary Patricia Nowalk ◽

...

Keyword(s):

United States ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Antigenic Drift ◽

Emerging Viruses ◽

Vaccine Protection ◽

Polymerase Chain ◽

Influenza Illness ◽

Negative Controls

Abstract Background At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses, that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses. Methods We enrolled outpatients aged ≥6 months with acute respiratory illness at five sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus sub-type/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. Results Among 8,845 enrollees, 2,722 (31%) tested positive for influenza, including 1,209 (44%) for B/Victoria and 1,405 (51%) for A(H1N1)pdm09. Effectiveness against any influenza illness was 39% (95% confidence interval [CI]: 32-44), 45% (95%CI: 37-52) against B/Victoria and 30% (95%CI: 21-39) against A(H1N1)pdm09 associated illness. Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95%CI: -14 to 23%) which predominated after January. Conclusions Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed.

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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

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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.

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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

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2741. Seasonal Influenza Vaccine Timing in Children and Adults Hospitalized with Influenza in the United States, FluSurv-NET, 2013–2017

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2418 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S964-S965

Author(s):

Julia C Haston ◽

Shikha Garg ◽

Angela P Campbell ◽

Jill Ferdinands ◽

Alissa O’Halloran ◽

...

Keyword(s):

Influenza Vaccine ◽

Seasonal Influenza ◽

Patient Characteristics ◽

Risk Groups ◽

The United States ◽

Vaccine Effectiveness ◽

Chi Square ◽

Surveillance Network ◽

Seasonal Influenza Vaccine ◽

Hispanic Patients

Abstract Background Seasonal influenza vaccine may attenuate disease severity among people infected with influenza despite vaccination, but vaccine effectiveness may decrease with increasing time between vaccination and infection. Patient characteristics may play a role in the timing of vaccine receipt. Methods We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET) and included patients ≥ 9 years hospitalized with laboratory-confirmed influenza during October 1–April 30 of influenza seasons 2013–2014 through 2016–2017 who received seasonal influenza vaccine ≥ 14 days prior to admission. Vaccine history was obtained from vaccine registries, medical charts, and patient interviews. We defined “early vaccination” as vaccine receipt before October 15 and “late vaccination” as receipt after (date selected using typical season onset and median vaccination dates). Early and late groups were compared using Chi-square or Fisher exact tests. Results Among 21,751 vaccinated patients, 61% received vaccine before October 15, and distribution of vaccination date was similar across seasons (figure). Vaccination occurred earlier with increasing age (45% were vaccinated early among those 9–17 years but 65% in those ≥ 80 years, P < 0.01). White non-Hispanic patients were more likely to receive vaccine early compared with black non-Hispanic and Hispanic patients (63% vs. 55% and 54%; P < 0.01). Those with metabolic disorders, cardiovascular disease, kidney disease, and cancer were vaccinated earlier whereas those with HIV and liver disease were vaccinated later. Vaccine timing also varied by state (P < 0.01) but not by sex. Conclusion Among influenza-vaccinated older children and adults hospitalized with influenza, older age, white race, and certain medical conditions were associated with early receipt of influenza vaccination in unadjusted analysis. This may be due to frequent healthcare encounters and targeted public health strategies in high-risk groups. Understanding how timing of vaccine receipt varies among populations can provide insights into variables that must be controlled for in studying possible vaccine effectiveness waning and attenuation of disease among those who are infected despite vaccination. Disclosures All authors: No reported disclosures.

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