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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 5 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 subtype/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. Results Among 8845 enrollees, 2722 (31%) tested positive for influenza, including 1209 (44%) for B/Victoria and 1405 (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. [ABSTRACT FROM AUTHOR]

Background A third measles-mumps-rubella vaccine (MMR) dose (MMR3) is recommended in the United States for persons at increased risk for mumps during outbreaks. MMR3 is also likely given to persons who might have received 2 doses of MMR but lack documentation. Since MMR3 safety data are limited, we describe adverse events in persons receiving MMR3 in a nonoutbreak setting. Methods Young adults with 2 documented MMR doses were administered MMR3. From 2 weeks before until 4 weeks after MMR3 receipt, participants reported daily on 11 solicited, common symptoms potentially associated with MMR. Weekly rate differences in post- vs prevaccination (baseline) were evaluated by Poisson regression. Baseline rates were subtracted from postvaccination rates of significantly different symptoms to estimate the number and percentage of participants with excess risk for symptoms post-MMR3. Descriptive analyses were performed for 3 postvaccination injection-site symptoms. Results The 662 participants were aged 18–28 years (median = 20 years); 56% were women. Headache, joint problems, diarrhea, and lymphadenopathy rates were significantly higher postvaccination vs baseline. We estimate that 119 participants (18%) reported more symptoms after MMR3 than prevaccination. By symptom, 13%, 10%, 8%, and 6% experienced increased symptoms of headache, joint problems, diarrhea, and lymphadenopathy, respectively, after MMR3. The median onset was Days 3–6 postvaccination; the median duration was 1–2 days. One healthcare visit for a potential vaccination-related symptom (urticaria) was reported. Injection-site symptoms were reported by 163 participants (25%); the median duration was 1–2 days. Conclusions Reported systemic and local events were mild and transient. MMR3 is safe and tolerable among young adults. [ABSTRACT FROM AUTHOR]

Background: Preexisting antibodies to influenza, shaped by early infection and subsequent exposures, may impact responses to influenza vaccination.Methods: We enrolled 72 children (aged 7-17 years) in 2015-2016; all received inactivated influenza vaccines. Forty-one were also vaccinated in 2014-2015, with 12 becoming infected with A(H3N2) in 2014-2015. Thirty-one children did not have documented influenza exposures in the prior 5 seasons. Sera were collected pre- and postvaccination in both seasons. We constructed antibody landscapes using hemagglutination inhibition antibody titers against 16 A(H3N2) viruses representative of major antigenic clusters that circulated between 1968 and 2015.Results: The breadth of the antibody landscapes increased with age. Vaccine-induced antibody responses correlated with boosting of titers to previously encountered antigens. Postvaccination titers were the highest against vaccine antigens rather than the historic A(H3N2) viruses previously encountered. Prevaccination titers to the vaccine were the strongest predictors of postvaccination titers. Responses to vaccine antigens did not differ by likely priming virus. Influenza A(H3N2)-infected children in 2014-2015 had narrower antibody landscapes than those uninfected, but prior season infection status had little effect on antibody landscapes following 2015-2016 vaccination.Conclusions: A(H3N2) antibody landscapes in children were largely determined by age-related immune priming, rather than recent vaccination or infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly. Methods The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011–2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013–2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients. Results Trivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45–59) for IIV4 versus 45% (95% CI, 34–54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency. Conclusions The uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally. [ABSTRACT FROM AUTHOR]

Background The effects of repeated influenza vaccination in children are not well understood. In this study, we evaluated previous vaccination effects on antibody response after vaccination with trivalent inactivated influenza vaccine (IIV) or quadrivalent live-attenuated influenza vaccine (LAIV) among school-aged children (5–17 years) across 3 seasons. Methods Children were enrolled in the fall of 2013, 2014, and 2015. The participants received IIV or LAIV according to parent preference (2013–2014) or our randomization scheme (2014–2015). All study children received IIV in 2015–2016. Hemagglutination-inhibition assays measured antibody response to egg-grown vaccine strains from prevaccination and postvaccination serum samples. Geometric mean titers (GMTs) and increases in GMTs from before to after vaccination (geometric mean fold rise [GMFR]) were estimated from repeated-measures linear mixed models. Results We enrolled 161 children in 2013–2014, 128 in 2014–2015, and 126 in 2015–2016. Among the IIV recipients, responses to the influenza A(H1N1)pdm09 and B vaccine strains were lowest among children who had received a previous-season IIV. The GMFRs for strains A(H1N1)pdm09 and B were 1.5 to 2.3 for previous-season IIV and 4.3 to 12.9 for previous-season LAIV or no previous vaccine. GMFRs were lower for strain A(H3N2), and differences according to previous-season vaccination history were smaller and not significant in most seasons. Most children had a post-IIV vaccination titer of ≥40 for vaccine strains in all seasons, regardless of previous-season vaccination history. Little to no increase in antibody levels was observed after vaccination with LAIV. Conclusions Serologic response to vaccination was greatest for IIV, but previous-season vaccination modified IIV response to A(H1N1)pdm09 and B. Influenza A(H3N2) responses were low in all groups, and LAIV generated minimal serologic response against all strains. [ABSTRACT FROM AUTHOR]

Purpose The objective was to develop a natural language processing (NLP) algorithm to identify vaccine‐related anaphylaxis from plain‐text clinical notes, and to implement the algorithm at five health care systems in the Vaccine Safety Datalink. Methods: The NLP algorithm was developed using an internal NLP tool and training dataset of 311 potential anaphylaxis cases from Kaiser Permanente Southern California (KPSC). We applied the algorithm to the notes of another 731 potential cases (423 from KPSC; 308 from other sites) with relevant codes (ICD‐9‐CM diagnosis codes for anaphylaxis, vaccine adverse reactions, and allergic reactions; Healthcare Common Procedure Coding System codes for epinephrine administration). NLP results were compared against a reference standard of chart reviewed and adjudicated cases. The algorithm was then separately applied to the notes of 6 427 359 KPSC vaccination visits (9 402 194 vaccine doses) without relevant codes. Results: At KPSC, NLP identified 12 of 16 true vaccine‐related cases and achieved a sensitivity of 75.0%, specificity of 98.5%, positive predictive value (PPV) of 66.7%, and negative predictive value of 99.0% when applied to notes of patients with relevant diagnosis codes. NLP did not identify the five true cases at other sites. When NLP was applied to the notes of KPSC patients without relevant codes, it captured eight additional true cases confirmed by chart review and adjudication. Conclusions: The current study demonstrated the potential to apply rule‐based NLP algorithms to clinical notes to identify anaphylaxis cases. Increasing the size of training data, including clinical notes from all participating study sites in the training data, and preprocessing the clinical notes to handle special characters could improve the performance of the NLP algorithms. We recommend adding an NLP process followed by manual chart review in future vaccine safety studies to improve sensitivity and efficiency. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background In recent influenza seasons, the effectiveness of inactivated influenza vaccines against circulating A(H3N2) virus has been lower than against A(H1N1)pdm09 and B viruses, even when circulating viruses remained antigenically similar to vaccine components. Methods During the 2016–2017 influenza season, vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design that compared the odds of vaccination among reverse transcription polymerase chain reaction–confirmed influenza positives and negatives. Results Among 7083 enrollees, 1342 (19%) tested positive for influenza A(H3N2), 648 (9%) were positive for influenza B (including B/Yamagata, n = 577), and 5040 (71%) were influenza negative. Vaccine effectiveness was 40% (95% confidence interval [CI], 32% to 46%) against any influenza virus, 33% (95% CI, 23% to 41%) against influenza A(H3N2) viruses, and 53% (95% CI, 43% to 61%) against influenza B viruses. Conclusions The 2016–2017 influenza vaccines provided moderate protection against any influenza among outpatients but were less protective against influenza A(H3N2) viruses than B viruses. Approaches to improving effectiveness against A(H3N2) viruses are needed. [ABSTRACT FROM AUTHOR]

Background Statin medications have immunomodulatory effects. Several recent studies suggest that statins may reduce influenza vaccine response and reduce influenza vaccine effectiveness (VE). Methods We compared influenza VE in statin users and nonusers aged ≥45 years enrolled in the US Vaccine Effectiveness Network study over 6 influenza seasons (2011–2012 through 2016–2017). All enrollees presented to outpatients clinics with acute respiratory illness and were tested for influenza. Information on vaccination status, medical history, and statin use at the time of vaccination were collected by medical and pharmacy records. Using a test-negative design, we estimated VE as (1 – OR) × 100, in which OR is the odds ratio for testing positive for influenza virus among vaccinated vs unvaccinated participants. Results Among 11692 eligible participants, 3359 (30%) were statin users and 2806 (24%) tested positive for influenza virus infection; 78% of statin users and 60% of nonusers had received influenza vaccine. After adjusting for potential confounders, influenza VE was 36% (95% confidence interval [CI], 22%–47%) among statin users and 39% (95% CI, 32%–45%) among nonusers. We observed no significant modification of VE by statin use. VE against influenza A(H1N1)pdm09, A(H3N2), and B viruses were similar among statin users and nonusers. Conclusions In this large observational study, influenza VE against laboratory-confirmed influenza illness was not affected by current statin use among persons aged ≥45 years. Statin use did not modify the effect of vaccination on influenza when analyzed by type and subtype. [ABSTRACT FROM AUTHOR]

Over five seasons, we determined the proportion of outpatients with laboratory‐confirmed, influenza‐associated illness who were hospitalized within 30 days following the outpatient visit. Overall, 136 (1.7%) of 7813 influenza‐positive patients were hospitalized a median of 4 days after an outpatient visit. Patients aged ≥ 65 years and those with high‐risk conditions were at increased risk of hospitalization. After controlling for age and high‐risk conditions, vaccination status and infecting influenza virus type were not associated with hospitalization risk among adults. [ABSTRACT FROM AUTHOR]