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

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 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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Vaccine Effectiveness Against Influenza Hospitalization Among Children in the United States, 2015–2016

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa017 ◽

2020 ◽

Cited By ~ 1

Author(s):

Leora R Feldstein ◽

Constance Ogokeh ◽

Brian Rha ◽

Geoffrey A Weinberg ◽

Mary A Staat ◽

...

Keyword(s):

United States ◽

Influenza Vaccination ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Limited Data ◽

Surveillance Network ◽

Number Of Children ◽

Influenza Illness ◽

Us Children

Abstract Background Annual United States (US) estimates of influenza vaccine effectiveness (VE) in children typically measure protection against outpatient medically attended influenza illness, with limited data evaluating VE against influenza hospitalizations. We estimated VE for preventing laboratory-confirmed influenza hospitalization among US children. Methods We included children aged 6 months–17 years with acute respiratory illness enrolled in the New Vaccine Surveillance Network during the 2015–2016 influenza season. Documented influenza vaccination status was obtained from state immunization information systems, the electronic medical record, and/or provider records. Midturbinate nasal and throat swabs were tested for influenza using molecular assays. We estimated VE as 100% × (1 – odds ratio), comparing the odds of vaccination among subjects testing influenza positive with subjects testing negative, using multivariable logistic regression. Results Of 1653 participants, 36 of 707 (5%) of those fully vaccinated, 18 of 226 (8%) of those partially vaccinated, and 85 of 720 (12%) of unvaccinated children tested positive for influenza. Of those vaccinated, almost 90% were documented to have received inactivated vaccine. The majority (81%) of influenza cases were in children ≤ 8 years of age. Of the 139 influenza-positive cases, 42% were A(H1N1)pdm09, 42% were B viruses, and 14% were A(H3N2). Overall, adjusted VE for fully vaccinated children was 56% (95% confidence interval [CI], 34%–71%) against any influenza-associated hospitalization, 68% (95% CI, 36%–84%) for A(H1N1)pdm09, and 44% (95% CI, –1% to 69%) for B viruses. Conclusions These findings demonstrate the importance of annual influenza vaccination in prevention of severe influenza disease and of reducing the number of children who remain unvaccinated or partially vaccinated against influenza.

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

Clinical Infectious Diseases ◽

10.1093/cid/ciaa407 ◽

2020 ◽

Author(s):

Mark W Tenforde ◽

Jessie Chung ◽

Emily R Smith ◽

H Keipp Talbot ◽

Christopher H Trabue ◽

...

Keyword(s):

United States ◽

High Risk ◽

Influenza Vaccine ◽

Patient Characteristics ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Activity ◽

Outpatient Settings ◽

Negative Controls

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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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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Effects of Prior Season Vaccination on Current Season Vaccine Effectiveness in the United States Flu Vaccine Effectiveness Network, 2012–2013 Through 2017–2018

Clinical Infectious Diseases ◽

10.1093/cid/ciaa706 ◽

2020 ◽

Author(s):

Sara S Kim ◽

Brendan Flannery ◽

Ivo M Foppa ◽

Jessie R Chung ◽

Mary Patricia Nowalk ◽

...

Keyword(s):

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza B ◽

Time High Risk ◽

Calendar Time ◽

Vaccine Protection ◽

Current Season ◽

The Us ◽

Flu Vaccine

Abstract Background We compared effects of prior vaccination and added or lost protection from current season vaccination among those previously vaccinated. Methods Our analysis included data from the US Flu Vaccine Effectiveness Network among participants ≥9 years old with acute respiratory illness from 2012–2013 through 2017–2018. Vaccine protection was estimated using multivariate logistic regression with an interaction term for effect of prior season vaccination on current season vaccine effectiveness. Models were adjusted for age, calendar time, high-risk status, site, and season for combined estimates. We estimated protection by combinations of current and prior vaccination compared to unvaccinated in both seasons or current vaccination among prior vaccinated. Results A total of 31 819 participants were included. Vaccine protection against any influenza averaged 42% (95% confidence interval [CI], 38%–47%) among those vaccinated only the current season, 37% (95% CI, 33–40) among those vaccinated both seasons, and 26% (95% CI, 18%–32%) among those vaccinated only the prior season, compared with participants vaccinated neither season. Current season vaccination reduced the odds of any influenza among patients unvaccinated the prior season by 42% (95% CI, 37%–46%), including 57%, 27%, and 55% against A(H1N1), A(H3N2), and influenza B, respectively. Among participants vaccinated the prior season, current season vaccination further reduced the odds of any influenza by 15% (95% CI, 7%–23%), including 29% against A(H1N1) and 26% against B viruses, but not against A(H3N2). Conclusions Our findings support Advisory Committee on Immunization Practices recommendations for annual influenza vaccination. Benefits of current season vaccination varied among participants with and without prior season vaccination, by virus type/subtype and season.

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Spread of Antigenically Drifted Influenza A(H3N2) Viruses and Vaccine Effectiveness in the United States During the 2018–2019 Season

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz543 ◽

2019 ◽

Vol 221 (1) ◽

pp. 8-15 ◽

Cited By ~ 17

Author(s):

Brendan Flannery ◽

Rebecca J Garten Kondor ◽

Jessie R Chung ◽

Manjusha Gaglani ◽

Michael Reis ◽

...

Keyword(s):

Influenza A ◽

Influenza Season ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Vaccine Component ◽

Polymerase Chain ◽

H3n2 Vaccine ◽

Respiratory Specimens

Abstract Background Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness (VE) and vaccine strain selection. We used US virologic surveillance and US Influenza Vaccine Effectiveness (Flu VE) Network data to evaluate consequences of this clade. Methods Distribution of influenza viruses was described using virologic surveillance data. The Flu VE Network enrolled ambulatory care patients aged ≥6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by means of reverse-transcriptase polymerase chain reaction and were sequenced. Using a test-negative design, we estimated VE, comparing the odds of influenza among vaccinated versus unvaccinated participants. Results During the 2018–2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2763 Flu VE Network case patients, 1325 (48%) were infected with A(H1N1)pdm09 and 1350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval, 37%–51%) against A(H1N1)pdm09 and 9% (−4% to 20%) against A(H3N2); VE was 5% (−10% to 19%) against A(H3N2) clade 3C.3a viruses. Conclusions The predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018–2019 season was associated with decreased VE, supporting the A(H3N2) vaccine component update for 2019–2020 northern hemisphere influenza vaccines.

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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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Transmission of the Citrus Variegated Chlorosis Bacterium Xylella fastidiosa with the Sharpshooter Oncometopia nigricans

Plant Disease ◽

10.1094/pdis.2002.86.11.1237 ◽

2002 ◽

Vol 86 (11) ◽

pp. 1237-1239 ◽

Cited By ~ 15

Author(s):

R. H. Brlansky ◽

V. D. Damsteegt ◽

J. S. Hartung

Keyword(s):

United States ◽

Polymerase Chain Reaction ◽

Xylella Fastidiosa ◽

The United States ◽

Reliable Indicator ◽

Symptom Development ◽

Chain Reaction ◽

Citrus Variegated Chlorosis ◽

Specific Polymerase Chain Reaction ◽

Polymerase Chain

Citrus variegated chlorosis (CVC) is an economically important, destructive disease in Brazil and is caused by the bacterium Xylella fastidiosa Wells. The bacterium has been found to be transmitted in Brazil by sharpshooter leafhoppers (Cicadellidae). Sharpshooters are present in most citrus growing areas of the United States. The sharpshooter leafhopper, Oncometopia nigricans Walker, frequently is found feeding on citrus in Florida. This sharpshooter transmits the X. fastidiosa strains that cause Pierce's disease of grape and ragweed stunt. Research was initiated to determine if O. nigricans was capable of vectoring the X. fastidiosa that causes CVC. In 59 different transmission tests, using 1 to 57 insects per test, transmission of the bacterium was observed 12 times (20.3%). Symptom development in the greenhouse was not a reliable indicator of transmission. Transmission was verified by specific polymerase chain reaction-based assays. Individual insects were able to transmit the bacterium. This information on sharpshooter transmission of CVC is needed to assess the threat posed by the CVC disease to the citrus industries in the United States.

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