scholarly journals 2734. Lack of Influence of Early Exposure to Influenza A(H3N2) Viruses on Vaccine Effectiveness Against A(H3N2)-Associated Illness in US Children <18 Years, 2016–2018

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S962-S962
Author(s):  
Chandresh N Ladva ◽  
Edward Belongia ◽  
Arnold Monto ◽  
Emily T Martin ◽  
Manjusha Gaglani ◽  
...  

Abstract Background During 2017–2018, influenza vaccine effectiveness (VE) against A(H3N2) illness was highest among children <5 years compared with all other ages. A child’s first influenza infection can shape later immune responses. The emergence of antigenically distinct influenza A(H3N2) viruses in 2014–2015 provided an opportunity to explore potential effects of first virus infection on vaccine effects. We compared VE against influenza A(H3N2) during 2016–2017 and 2017–2018 among children born after and before 2014. Methods Outpatient children aged 6 months–17 years with acute respiratory illness with cough were enrolled in the United States Influenza VE Network and tested for influenza infection by RT–PCR. Vaccination status was derived through medical records and immunization registries. Children with partial or unknown vaccination status were excluded. We used a test-negative design to estimate VE and 95% confidence intervals (CI) from logistic regression, adjusting for potential confounders. Cohorts were defined by birth after or before June 2014; we assumed exposure to the new A(H3N2) virus among children born after June 2014. Results During 2016–2017, among 2,545 children, 445 (18%) tested positive for A(H3N2) and 1,809 (71%) tested negative. VE against A(H3N2) did not differ among children born after June 2014 and among those born before June 2014 [49% (95% CI: −12%, 77%) vs. 43% (27%, 55%); interaction P < 0.75]. During 2017–2018, among 2,936 patients, 631 (22%) tested positive for A(H3N2), and 1,852 (63%) tested negative. VE against A(H3N2) was 59% (36%, 74%) among children born after June 2014 vs. 20% (−1%, 37%) among those born before June 2014 (interaction P < 0.01). Conclusion We did not consistently see differences in VE against A(H3N2) between children potentially exposed to different A(H3N2) viruses. However, error in exposure assignment to A(H3N2) viruses and few seasons since the emergence of the new A(H3N2) viruses limit our interpretation. Future study will include additional A(H3N2) seasons as initial exposures to current circulating viruses increase among young children. Alternative explanations for age-related differences will also be explored, such as prior seasonal vaccination. Disclosures All authors: No reported disclosures.

Author(s):  
Leora R Feldstein ◽  
Constance Ogokeh ◽  
Brian Rha ◽  
Geoffrey A Weinberg ◽  
Mary A Staat ◽  
...  

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.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S26-S27
Author(s):  
Angela P Campbell ◽  
Constance E Ogokeh ◽  
Craig McGowan ◽  
Brian Rha ◽  
Rangaraj Selvarangan ◽  
...  

Abstract Background Annual national estimates of influenza vaccine effectiveness (VE) typically measure protection against outpatient medically attended influenza illness. We assessed influenza VE in preventing laboratory-confirmed influenza hospitalization in children across two influenza A(H3N2)-predominant seasons. Methods Children < 18 years hospitalized with acute respiratory illness were enrolled at 7 pediatric hospitals in the New Vaccine Surveillance Network. We included subjects ≥6 months with ≤10 days of symptoms enrolled during the 2016–2017 and 2017–2018 seasons (date of first through last influenza-positive case for each site). Combined mid-turbinate and throat swabs were tested using molecular assays. We estimated age-stratified VE from a test-negative design using logistic regression to compare the odds of vaccination among cases positive for influenza with controls testing negative, adjusting for age, enrollment month, site, underlying comorbidities, and race/ethnicity. Full/partial vaccination was defined using ACIP criteria. We verified vaccine receipt from state immunization registries and/or provider records. Results Among 3441 children with complete preliminary data, in 2016–2017, 156/1,710 (9%) tested positive for influenza: 91 (58%) with influenza A(H3N2), 5 (3%) with A(H1N1), and 60 (38%) with B viruses. In 2017–2018, 193/1,731 (11%) tested positive: 87 (45%) with influenza A(H3N2), 47 (24%) with A(H1N1), and 58 (30%) with B. VE for all vaccinated children (full and partial) against any influenza was 48% (95% confidence interval, 26%–63%) in 2016–2017 and 45% (24%–60%) in 2017–2018. Combining seasons, VE for fully and partially vaccinated children against any influenza type was 46% (32%–58%); by virus, VE was 30% (4%–49%) for influenza A(H3N2), 71% (46%–85%) for A(H1N1), and 57% (36%–70%) for B viruses. There was no statistically significant difference in VE by age or full/partial vaccination status for any virus (table). Conclusion Vaccination in the 2016–2017 and 2017–2018 seasons nearly halved the risk of children being hospitalized with influenza. These findings support the use of vaccination to prevent severe illness in children. Our study highlights the need for a better understanding of the lower VE against influenza A(H3N2) viruses. Disclosures All Authors: No reported Disclosures.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S68-S68
Author(s):  
Jessie Chung ◽  
Brendan Flannery ◽  
Rodolfo Begue ◽  
Herve Caspard ◽  
Laurie Demarcus ◽  
...  

Abstract Background Quadrivalent live attenuated influenza vaccine (LAIV4) was not recommended for use in the United States for the 2016–2017 and 2017–2018 influenza seasons based on US observational studies of vaccine effectiveness (VE) from 2013–2014 to 2015–2016. We pooled individual patient data on children aged 2–17 years enrolled in 5 US studies during these 3 influenza seasons to further investigate VE by vaccine type. Methods Analyses included 17,173 children enrolled in the US Department of Defense Global Laboratory-based Influenza Surveillance Program, US Influenza Vaccine Effectiveness Network, Influenza Incidence Surveillance Project, Influenza Clinical Investigation for Children, and a Louisiana State University study. Participants’ specimens were tested for influenza by reverse transcription-polymerase chain reaction (RT-PCR), culture, or a combination of rapid antigen testing and RT-PCR. VE was calculated by comparing odds of vaccination with either inactivated influenza vaccine (IIV) or LAIV4 among influenza-positive cases to test-negative controls and calculated as 100 × (1 − odds ratio) in logistic regression models with age, calendar time, influenza season, and study site (random effect). Patients were stratified by prior season vaccination status in a subanalysis. Results Overall, 38% of patients (N = 6,558) were vaccinated in the current season, of whom 30% (N = 1,979) received LAIV4. Pooled VE of IIV against any influenza virus was 51% (95% CI: 47, 54) versus 26% (95% CI: 15, 36) for LAIV4. Point estimates for pooled VE against any influenza by age group ranged from 45% to 58% for IIV and 19% to 34% for LAIV4 during the 3 seasons (Figures 1 and 2). Pooled VE against influenza A(H1N1)pdm09 was 67% (95% CI: 62, 72) for IIV versus 20% (95% CI: −6, 39) for LAIV4. Pooled VE against influenza A(H3N2) was 29% (95% CI: 14, 42) for IIV versus 7% (95% CI: −11, 23) for LAIV4, and VE against influenza B was 52% (95% CI: 42, 60) for IIV and 66% (95% CI: 47, 77) for LAIV4. VE against influenza A(H1N1)pdm09 was lower for LAIV4 versus IIV across all strata of prior season vaccination (Figure 3). Conclusion Consistent with individual studies, our pooled analyses found that LAIV4 effectiveness was reduced for all age groups against influenza A(H1N1)pdm09 compared with IIV. This result did not vary based on prior vaccination status. Disclosures H. Caspard, AstraZeneca: Employee, Salary.


Author(s):  
J M Ferdinands ◽  
M Gaglani ◽  
S Ghamande ◽  
E T Martin ◽  
D Middleton ◽  
...  

Abstract We estimated vaccine effectiveness for prevention of influenza-associated hospitalizations among adults during the 2018-2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network and testing positive for influenza were cases; patients testing negative were controls. Vaccine effectiveness was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09-associated hospitalization was 51% (95%CI 25, 68). Adjusted VE against influenza A(H3N2) virus-associated hospitalization was −2% (95%CI −65, 37) and differed significantly by age, with VE of −130% (95% CI −374, −27) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza-A(H1N1)pdm09-associated hospitalizations, it conferred no protection against influenza A(H3N2)-associated hospitalizations. We observed negative VE for young-and middle-aged adults but cannot exclude residual confounding as a potential explanation.


2019 ◽  
Vol 221 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Brendan Flannery ◽  
Rebecca J Garten Kondor ◽  
Jessie R Chung ◽  
Manjusha Gaglani ◽  
Michael Reis ◽  
...  

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.


Author(s):  
Mark W Tenforde ◽  
H Keipp Talbot ◽  
Christopher H Trabue ◽  
Manjusha Gaglani ◽  
Tresa M McNeal ◽  
...  

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.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S10-S10
Author(s):  
Joshua Doyle ◽  
Lauren Beacham ◽  
Elif Alyanak ◽  
Manjusha Gaglani ◽  
Emily T Martin ◽  
...  

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.


2019 ◽  
Vol 147 ◽  
Author(s):  
N. Komadina ◽  
S. G. Sullivan ◽  
K. Kedzierska ◽  
S. M. Quiñones-Parra ◽  
K. Leder ◽  
...  

Abstract The epidemiology of H5N1 and H7N9 avian viruses of humans infected in China differs despite both viruses being avian reassortants that have inherited six internal genes from a common ancestor, H9N2. The median age of infected populations is substantially younger for H5N1 virus (26 years) compared with H7N9 virus (63 years). Population susceptibility to infection with seasonal influenza is understood to be influenced by cross-reactive CD8+ T cells directed towards immunogenic peptides derived from internal viral proteins which may provide some level of protection against further influenza infection. Prior exposure to seasonal influenza peptides may influence the age-related infection patterns observed for H5N1 and H7N9 viruses. A comparison of relatedness of immunogenic peptides between historical human strains and the two avian emerged viruses was undertaken for a possible explanation in the differences in age incidence observed. There appeared to be some relationship between past exposure to related peptides and the lower number of H5N1 virus cases in older populations, however the relationship between prior exposure and older populations among H7N9 virus patients was less clear.


2017 ◽  
Vol 146 (1) ◽  
pp. 78-88 ◽  
Author(s):  
A. MÖHL ◽  
L. GRÄFE ◽  
C. HELMEKE ◽  
D. ZIEHM ◽  
M. MONAZAHIAN ◽  
...  

SUMMARYInfluenza vaccine effectiveness (VE) has to be estimated anew for every season to explore vaccines’ protective effect in the population. We report VE estimates against laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2) and influenza B among children aged 2–17 years, using test-negative design. Pooled data from two German federal states’ surveillance systems for acute respiratory illness from week 40/2012 to 20/2016 was used, yielding a total of 10 627 specimens. Odds ratios and 95% confidence intervals (95% CIs) for the association between laboratory-confirmed influenza and vaccination status were calculated by multivariate logistic regression adjusting for age, sex, illness onset and federal state. VE was estimated as 1-Odds Ratio. Overall adjusted VE was 33% (95% CI: 24·3–40·7). A strong variation of VE between the seasons and subtypes was observed: highest season- and subtype-specific VE of 86·2% (95% CI: 41·3–96·7) was found against A(H1N1)pdm09 in 7–17-year-olds in 2015/16. Low estimates of VE were observed against A(H3N2) in any season, e.g. 1·5% (95% CI: −39·3–30·3) in 2014/15. Estimates showed a tendency to higher VE among 7–17-year-old children, but differences were not statistically significant. Although our findings are common in studies estimating influenza VE, we discussed several explanations for observed low VE.


2010 ◽  
Vol 21 (4) ◽  
pp. e151-e157
Author(s):  
George Zahariadis ◽  
Ari R Joffe ◽  
James Talbot ◽  
Albert deVilliers ◽  
Patricia Campbell ◽  
...  

BACKGROUND: In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1) strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1) in Canada.METHODS: Enhanced public health and laboratory surveillance for pH1N1 was implemented throughout Alberta on April 24, 2009. Respiratory specimens from all patients with a respiratory illness and travel history or those presenting with a severe respiratory infection requiring hospitalization underwent screening for respiratory viruses using molecular methods. For the first severe case identified and the first death due to pH1N1, histocompatibility leukocyte antigens were compared by molecular methods.RESULTS: The first death (a 39-year-old woman) occurred on April 28, 2009, and on May 1, 2009, a 10-year-old child presented with severe respiratory distress due to pH1N1. Both patients had no travel or contact with anyone who had travelled to Mexico; the cases were not linked. Histocompatibility antigen comparison of both patients did not identify any notable similarity. pH1N1 strains identified in Alberta did not differ from the Mexican strain.CONCLUSION: Rapid transmission of pH1N1 continued to occur in Alberta following the first death and the first severe respiratory infection in Canada, which were identified without any apparent connection to Mexico or the United States. Contact tracing follow-up suggested that oseltamivir may have prevented ongoing transmission of pH1N1.


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