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Background Data on the true prevalence of respiratory syncytial virus (RSV) among medically attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over 3 seasons, which is informative in light of the recommendations for shared decision making for vaccination in older adults. Methods Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated multimorbidity-weighted index (MWI) were collected by in-person survey and electronic medical record review. Results Over 3 surveillance seasons (fall 2017 to spring 2020), 9.9% (n = 441) of 4442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months to 4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). Conclusions RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision making for vaccination. [ABSTRACT FROM AUTHOR]

Background: Serological responses from influenza vaccination or infection are typically measured by hemagglutinin inhibition (HAI) or microneutralization (MN). Both methods are limited in feasibility, standardization, and generalizability to recent strains. We developed a luciferase MN (LMN) assay that combines the advantages of the conventional MN assay with the ease of the HAI assay. Methods: Sera were obtained from the HIVE study, a Michigan household cohort. Reverse genetics was used to generate recombinant influenza viruses expressing the hemagglutinin and neuraminidase of test strains, all other viral proteins from an A/WSN/1933 backbone, and a NanoLuc reporter. Serum neutralization of luciferase‐expressing targets was quantified as a reduction in light emission from infected cells. Neutralization titers were measured for cell‐ and egg‐adapted versions of A/Hong Kong/4801/2014 and A/Singapore/INFIMH‐16‐0019/2016 and compared to HAI titers against egg‐grown antigens. Results: Three hundred thirty‐three sera were collected from 259 participants between May 2016 and July 2018. Sampled participants were 7–68 years of age, and >80% were vaccinated against influenza. HAI and LMN titers were correlated for A/Hong Kong/4801/2014 (ρ = 0.52, p ≤ 0.01) and A/Singapore/INFIMH‐16‐0019/2016 (ρ = 0.79, p ≤ 0.01). LMN titers were lower for cell strains compared to egg strains (A/Hong Kong/4801/2014 mean log2 fold change = −2.66, p ≤ 0.01 and A/Singapore/INFIMH‐16‐0019/2016 mean log2 fold change = −3.15, p ≤ 0.01). Conclusions: The LMN assay was feasible using limited sample volumes and able to differentiate small antigenic differences between egg‐adapted and cell‐derived strains. The correspondence of these results with the commonly used HAI confirms the utility of this assay for high‐throughput studies of correlates of protection and vaccine response. [ABSTRACT FROM AUTHOR]

A study was conducted to compare the efficacy of inactivated as against live attenuated influenza vaccines. Results indicated that inactivated vaccines were more effective in preventing symptomatic influenza A in healthy adults, and was also more effective than live attenuated vaccines.

A clinical trial is carried out to determine the efficacy as measured by laboratory confirmation of influenza, of both the inactivated and live attenuated influenza vaccines in the healthy adult population during the influenza season. It is observed that the inactivated and live attenuated influenza vaccines are efficacious in preventing laboratory-confirmed symptomatic illnesses from influenza in healthy adults but the live attenuated vaccines are less efficacious.

Introduction: In Southeast Michigan, active surveillance studies monitor influenza activity in hospitals, ambulatory clinics, and community households. Across five respiratory seasons, we assessed the contribution of data from each of the three networks towards improving our overall understanding of regional influenza circulation. Methods: All three networks used case definitions for acute respiratory illness (ARI) and molecularly tested for influenza from research‐collected respiratory specimens. Age‐ and network‐stratified epidemic curves were created for influenza A and B. We compared stratified epidemic curves visually and by centering at seasonal midpoints. Results: Across all seasons (from 2014/2015 through 2018/2019), epidemic curves from each of the three networks were comparable in terms of both timing and magnitude. Small discrepancies in epidemics recorded by each network support previous conclusions about broader characteristics of particular influenza seasons. Conclusion: Influenza surveillance systems based in hospital, ambulatory clinic, and community household settings appear to provide largely similar information regarding regional epidemic activity. Together, multiple levels of influenza surveillance provide a detailed view of regional influenza epidemics, but a single surveillance system—regardless of population subgroup monitored—appears to be sufficient in providing vital information regarding community influenza epidemics. [ABSTRACT FROM AUTHOR]

Background The evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (ie, indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort. Methods Using longitudinal data from the HIVE cohort from 2010–11 through 2017–18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households. Results The pooled, direct VE against any influenza was 30.2% (14.0–43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8) and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (−6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccination coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VE was 56.4% (30.1–72.9) in low coverage, 43.2% (19.5–59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households. Conclusions Influenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. Although there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated. [ABSTRACT FROM AUTHOR]

While influenza virus diversity and antigenic drift have been well characterized on a global scale, the factors that influence the virus’ rapid evolution within and between human hosts are less clear. Given the modest effectiveness of seasonal vaccination, vaccine-induced antibody responses could serve as a potent selective pressure for novel influenza variants at the individual or community level. We used next generation sequencing of patient-derived viruses from a randomized, placebo-controlled trial of vaccine efficacy to characterize the diversity of influenza A virus and to define the impact of vaccine-induced immunity on within-host populations. Importantly, this study design allowed us to isolate the impact of vaccination while still studying natural infection. We used pre-season hemagglutination inhibition and neuraminidase inhibition titers to quantify vaccine-induced immunity directly and to assess its impact on intrahost populations. We identified 166 cases of H3N2 influenza over 3 seasons and 5119 person-years. We obtained whole genome sequence data for 119 samples and used a stringent and empirically validated analysis pipeline to identify intrahost single nucleotide variants at ≥1% frequency. Phylogenetic analysis of consensus hemagglutinin and neuraminidase sequences showed no stratification by pre-season HAI and NAI titer, respectively. In our study population, we found that the vast majority of intrahost single nucleotide variants were rare and that very few were found in more than one individual. Most samples had fewer than 15 single nucleotide variants across the entire genome, and the level of diversity did not significantly vary with day of sampling, vaccination status, or pre-season antibody titer. Contrary to what has been suggested in experimental systems, our data indicate that seasonal influenza vaccination has little impact on intrahost diversity in natural infection and that vaccine-induced immunity may be only a minor contributor to antigenic drift at local scales. [ABSTRACT FROM AUTHOR]

Background Out-of-home child care (CC) is a risk factor for viral acute respiratory infection (ARI) in young children. Little is known, however, about differences in frequencies of viral infection between CC children and those cared for exclusively at home. Methods Using surveillance data from the HIVE household cohort in southeast Michigan from 2014–2018 (4 seasons), we analyzed 1022 illness cases from 354 children aged 0–6 years. Age groups were dichotomized as infants (aged <2 years) and toddlers/preschoolers (aged 2–6 years). Households were prospectively enrolled and nasal respiratory swabs were collected from children upon report of acute illness symptoms. We used real-time RT–PCR to test for 18 respiratory viruses. Results We detected at least one virus in 855 illness cases (83% of all illnesses reported). Age at first illness onset in all four seasons was significantly younger among CC children than homecare children (P < 0.001) across all 4 years (average difference = 1.25 years). CC children <2 years had slightly lower odds of viral detection during illness (OR = 0.89, 95% CI [0.49, 1.61]) but higher odds at ages 2–6y (1.07 [0.65, 1.76]); neither was statistically significant. Neither CC nor homecare children were significantly more or less at risk for any particular pathogen—expect for rhinovirus in the <2-year group, where odds of rhinovirus infection were 58% lower (OR = 0.42) in CC children compared with homecare counterparts (95% CI, 0.21–0.83). Conversely, CC attendees under 3 more frequently had influenza, RSV, hMPV, parainfluenza, and coronavirus; however, none of these associations were significant. Odds of coinfection (> 1 virus detected) were higher among CC children, but not significant (OR = 1.4 [0.63, 2.96] and 1.2 [0.77, 1.88] in <2 year and 2–6 year age groups, respectively). Among all children <7 year, the mean number of pathogens detected was not different between CC and homecare individuals (1.20 vs. 1.23, P = 0.16). Conclusion As expected, results indicated that CC attendees aged 0–6y experienced illness episodes earlier in life compared with homecare children. Our analysis also indicated that, compared with children cared for at home, CC children were less at risk for rhinovirus infection when young but could potentially be at higher risk for viruses of greater clinical concern. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Highlights • Serum collected at hospital admission can be used to assess influenza protection. • There was no trend in antibody among influenza cases by day of collection (0–10). • Inpatients who received influenza vaccination had more antibody than unvaccinated. • Associations between antibody and infection paralleled vaccine effectiveness. Abstract Background Influenza vaccines are important for prevention of influenza-associated hospitalization. However, the effectiveness of influenza vaccines can vary by year and influenza type and subtype and mechanisms underlying this variation are incompletely understood. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness in hospitalized populations. Methods We enrolled adults hospitalized for treatment of acute respiratory illnesses during the 2014–2015 and 2015–2016 influenza seasons whose symptoms began <10 days prior to enrollment. Influenza infection status was determined by RT-PCR. Influenza vaccination status was defined by self-report and medical record/registry documentation. Serum specimens collected at hospital admission were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated how well antibody measured in these specimens represented pre-infection immune status, and measured associations between antibody and influenza vaccination and infection. Results Serum specimens were retrieved for 315 participants enrolled during the 2014–2015 season and 339 participants during the 2015–2016 season. Specimens were collected within 3 days of illness onset from 65% of participants. Geometric mean titers (GMTs) did not vary by the number of days from illness onset to specimen collection among influenza positive participants suggesting that measured antibody was representative of pre-infection immune status rather than a de novo response to infection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated. HAI titers against the 2014–2015 A(H3N2) vaccine strain did not correlate with protection from infection with antigenically-drifted A(H3N2) viruses that circulated that season. In contrast, higher HAI titers against the A(H1N1)pdm09 vaccine strain were associated with reduced odds of A(H1N1)pdm09 infection in 2015–2016. Conclusions Serum collected shortly after illness onset at hospital admission can be used to assess correlates of protection against influenza infection. Broader implementation of similar studies would provide an opportunity to understand the successes and shortcomings of current influenza vaccines. [ABSTRACT FROM AUTHOR]