SARS-CoV-2 incidence, seroprevalence, and antibody dynamics in a rural, population-based cohort: March 2020 - July 2022.

Studies of SARS-CoV-2 incidence are important for response to continued transmission and future pandemics. We followed a rural community cohort with broad age representation with active surveillance for SARS-CoV-2 identification from November 2020 through July 2022. Participants provided serum specimens at regular intervals and following SARS-CoV-2 infection or vaccination. We estimated the incidence of SARS-CoV-2 infection identified by study RT-PCR, electronic health record documentation or self-report of a positive test, or serology. We also estimated the seroprevalence of SARS-CoV-2 spike and nucleocapsid antibodies measured by ELISA. Overall, 65% of the cohort had ≥1 SARS-CoV-2 infection by July 2022, and 19% of those with primary infection were reinfected. Infection and vaccination contributed to high seroprevalence, 98% (95% CI: 95%, 99%) of participants were spike or nucleocapsid seropositive at the end of follow-up. Among those seropositive, 82% were vaccinated. Participants were more likely to be seropositive to spike than nucleocapsid following infection. Infection among seropositive individuals could be identified by increases in nucleocapsid, but not spike, ELISA optical density values. Nucleocapsid antibodies waned more quickly after infection than spike antibodies. High levels of SARS-CoV-2 population immunity, as found in this study, are leading to changing epidemiology necessitating ongoing surveillance and policy evaluation.

Detection of Blastomyces gilchristii via metagenomic sequencing in outbreak-associated soils.

Cases of blastomycosis, a serious fungal disease globally rare but endemic to North America, can appear both sporadically and in outbreaks. Tracing these outbreaks to their environment has traditionally used culturing and polymerase chain reaction. Here, we present our method for metagenomic detection of Blastomyces in a 2015 outbreak soil sample from central Wisconsin. By sequencing this sample to multiple depths, we simulated the minimum required depth to detect Blastomyces in this outbreak. Our methods and recommendations can be used to identify the sources of blastomycosis during outbreaks and to learn about the ecology of Blastomyces.

Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).

Interim Estimates of 2022-23 Seasonal Influenza Vaccine Effectiveness - Wisconsin, October 2022-February 2023.

In the United States, 2022-23 influenza activity began earlier than usual, increasing in October 2022, and has been associated with high rates of hospitalizations among children* (1). Influenza A(H3N2) represented most influenza viruses detected and subtyped during this period, but A(H1N1)pdm09 viruses cocirculated as well. Most viruses characterized were in the same genetic subclade as and antigenically similar to the viruses included in the 2022-23 Northern Hemisphere influenza vaccine (1,2). Effectiveness of influenza vaccine varies by season, influenza virus subtype, and antigenic match with circulating viruses. This interim report used data from two concurrent studies conducted at Marshfield Clinic Health System (MCHS) in Wisconsin during October 23, 2022-February 10, 2023, to estimate influenza vaccine effectiveness (VE). Overall, VE was 54% against medically attended outpatient acute respiratory illness (ARI) associated with laboratory-confirmed influenza A among patients aged 6 months-64 years. In a community cohort of children and adolescents aged <18 years, VE was 71% against symptomatic laboratory-confirmed influenza A virus infection. These interim analyses indicate that influenza vaccination substantially reduced the risk for medically attended influenza among persons aged <65 years and for symptomatic influenza in children and adolescents. Annual influenza vaccination is the best strategy for preventing influenza and its complications. CDC recommends that health care providers continue to administer annual influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating (2).

Household Transmission of Influenza A Viruses in 2021-2022.

Importance: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. Objective: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. Design, Setting, and Participants: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. Exposures: Household contacts living with a primary case. Main Outcomes and Measures: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. Results: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. Conclusions and Relevance: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.

SARS-CoV-2 Virus Dynamics in Recently Infected People-Data From a Household Transmission Study.

We used daily real-time reverse-transcription polymerase chain reaction (RT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study, conducted April 2020-May 2021, to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration. Ct values varied across RT-PCR platforms and by participant age. Specimens collected from children and adolescents had higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms, with the lowest Ct value occurring 2-6 days after symptom onset.

Multicenter Clinical Evaluation of Modified Two-Tiered Testing Algorithms for Lyme Disease Using Zeus Scientific Commercial Assays.

Modified two-tiered testing (MTTT) algorithms for Lyme disease (LD), which involve the sequential use of orthogonal enzyme immunoassays (EIAs) without immunoblotting, are acceptable alternatives to standard two-tiered testing (STTT; EIA followed by immunoblots) provided the EIAs have been FDA-cleared for this intended use. We evaluated four Zeus Scientific LD EIAs used in two distinct MTTT algorithms for FDA review. MTTT 1 used a VlsE1/pepC10 polyvalent EIA followed by a whole-cell sonicate (WCS) polyvalent EIA. MTTT 2 used the same first-tier EIA followed by separate IgM and IgG WCS EIAs. In a retrospective phase, we compared each MTTT algorithm to STTT using archived samples from LD patients or control subjects. In a prospective phase, we used the same algorithms to analyze consecutive excess samples submitted for routine LD serology to three clinical laboratories. For the retrospective phase, MTTTs 1 and 2 were more sensitive (56% and 74%) than STTT (41%; P ≤ 0.03) among 61 patients with acute erythema migrans (EM). In LD patients with neuroborreliosis, carditis, or arthritis (n = 75), sensitivity was comparable between algorithms (96 to 100%; P = 1.0). Among 190 control subjects without past LD, all algorithms were highly and comparably specific (≥99%, P = 0.48). For the prospective phase, (n = 2,932), positive percent-agreement (PPA), negative percent-agreement (NPA), and overall agreement of MTTT 1 with STTT were 93%, 97.7% and 97.4% (kappa 0.80). MTTT 2 yielded higher PPA (98%) but lower NPA (96.1%) and overall agreement (96.2%, kappa 0.74; all P < 0.05). Compared with STTT, both MTTT algorithms provided increased sensitivity in EM patients, comparable sensitivity in later disease and non-inferior specificity.

A gene-based recessive diplotype exome scan discovers FGF6, a novel hepcidin-regulating iron-metabolism gene.

Standard analyses applied to genome-wide association data are well designed to detect additive effects of moderate strength. However, the power for standard genome-wide association study (GWAS) analyses to identify effects from recessive diplotypes is not typically high. We proposed and conducted a gene-based compound heterozygosity test to reveal additional genes underlying complex diseases. With this approach applied to iron overload, a strong association signal was identified between the fibroblast growth factor-encoding gene, FGF6, and hemochromatosis in the central Wisconsin population. Functional validation showed that fibroblast growth factor 6 protein (FGF-6) regulates iron homeostasis and induces transcriptional regulation of hepcidin. Moreover, specific identified FGF6 variants differentially impact iron metabolism. In addition, FGF6 downregulation correlated with iron-metabolism dysfunction in systemic sclerosis and cancer cells. Using the recessive diplotype approach revealed a novel susceptibility hemochromatosis gene and has extended our understanding of the mechanisms involved in iron metabolism.

Suspected Neuro-invasive Powassan Virus Infection in a Pediatric Patient.

Powassan virus lineage II (POWV), also known as deer tick virus, is an emerging tick-borne pathogen transmitted by Ixodes scapularis, the natural vector for the organisms that causes Lyme disease, babesiosis, and anaplasmosis. POWV is the only tick-borne flavivirus in North America known to cause disease in humans. We present a suspected pediatric case of POWV infection in northern Wisconsin.

Urine Antigen Testing is Equally Sensitive to B. dermatitidis and B. gilchristii Infections.

INTRODUCTION: Blastomycosis is endemic in Wisconsin with Blastomyces dermatitidis and B. gilchristii responsible for infections. Urine antigen testing is a non-invasive diagnostic method for blastomycosis with up to 93% test sensitivity. However, the test's sensitivity has not been evaluated with relationship to B. gilchristii infections. METHODS: We aimed to assess physician use of the urine antigen assay and its sensitivity to B. gilchristii and B. dermatitidis infections in a retrospective study. Culture confirmed clinical cases of blastomycosis from 2008-2016 were identified within Marshfield Clinic Health System (MCHS) and UW Hospital and Clinics (UWHC) medical records. Clinical data were abstracted from each medical record and included the following: patient demographics, presence of immune compromising and underlying medical conditions, treatment drugs, presence of isolated pulmonary or disseminated disease, death, urine antigen testing, timeframe of testing, and quantitative test values (EIA units or ng/mL). RESULTS: A total of 140 blastomycosis cases were included in this study, with MCHS contributing 114 cases to the study and UWHC contributing 26 cases. The majority of UWHC cases (n=22; 85%) were caused by B. dermatitidis and the majority of MCHS cases (n=73; 64%) were caused by B. gilchristii. UWHC physicians were significantly more likely to treat with multiple drugs during the course of infection and were more likely to prescribe amphotericin B and voriconazole. Urine antigen testing was more frequently used at UWHC (n=24; 92%) than MCHS (n=51; 45%; P < 0.00001). In this study, the urine antigen assay demonstrated 79% sensitivity. Sensitivity was significantly associated with the timeframe of testing (P < 0.05), with most true positive urine antigen tests (83%) being performed ≤ 7 days from diagnosis. In this study, the urine antigen assay was capable of detecting both B. dermatitidis and B. gilchristii at about equal sensitivity. Urine antigen concentration (ng/mL) trended higher in B. dermatitidis infections. CONCLUSION: This study found that the urine antigen assay is capable of detecting both species of Blastomyces at about the same sensitivity. We recommend continued use of the urine antigen assay for diagnosis of blastomycosis and recommend that the assay be used early in the diagnostic process to minimize the chance of false negative results.

Molecular detection of Blastomyces in an air sample from an outbreak associated residence.

Based on epidemiologic data during a blastomycosis outbreak, exposure within the home was suspected for two case patients that resided together. Soil and air samples were collected from the basement of their residence. Samples were tested for Blastomyces by culture and polymerase chain reaction (PCR) to compare with an available clinical isolate. An air sample from the basement of the residence was PCR positive for Blastomyces. Sequence data from the air sample and the outbreak clinical isolate were identified as different Blastomyces spp. Despite this, our findings suggest that the basement was suitable for the growth of Blastomyces and airborne organism was circulating.

Infectious Mononucleosis and Lyme Disease as Confounding Diagnoses: A Report of 2 Cases.

Lyme disease and infectious mononucleosis are common illnesses that share similar clinical presentations. Significant cross-reactivity is known to occur between Lyme and EBV serologic assays complicating the diagnosis. To date, no prior cases of concurrent acute Lyme and EBV infections have been reported. We describe the clinical presentation of two children with confirmed early Lyme disease and features suggestive of infectious mononucleosis, including one case of probable Lyme and EBV co-infection.

Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans.

UNLABELLED: Influenza vaccines must be frequently reformulated to account for antigenic changes in the viral envelope protein, hemagglutinin (HA). The rapid evolution of influenza virus under immune pressure is likely enhanced by the virus's genetic diversity within a host, although antigenic change has rarely been investigated on the level of individual infected humans. We used deep sequencing to characterize the between- and within-host genetic diversity of influenza viruses in a cohort of patients that included individuals who were vaccinated and then infected in the same season. We characterized influenza HA segments from the predominant circulating influenza A subtypes during the 2012-2013 (H3N2) and 2013-2014 (pandemic H1N1; H1N1pdm) flu seasons. We found that HA consensus sequences were similar in nonvaccinated and vaccinated subjects. In both groups, purifying selection was the dominant force shaping HA genetic diversity. Interestingly, viruses from multiple individuals harbored low-frequency mutations encoding amino acid substitutions in HA antigenic sites at or near the receptor-binding domain. These mutations included two substitutions in H1N1pdm viruses, G158K and N159K, which were recently found to confer escape from virus-specific antibodies. These findings raise the possibility that influenza antigenic diversity can be generated within individual human hosts but may not become fixed in the viral population even when they would be expected to have a strong fitness advantage. Understanding constraints on influenza antigenic evolution within individual hosts may elucidate potential future pathways of antigenic evolution at the population level. IMPORTANCE: Influenza vaccines must be frequently reformulated due to the virus's rapid evolution rate. We know that influenza viruses exist within each infected host as a "swarm" of genetically distinct viruses, but the role of this within-host diversity in the antigenic evolution of influenza has been unclear. We characterized here the genetic and potential antigenic diversity of influenza viruses infecting humans, some of whom became infected despite recent vaccination. Influenza virus between- and within-host genetic diversity was not significantly different in nonvaccinated and vaccinated humans, suggesting that vaccine-induced immunity does not exert strong selective pressure on viruses replicating in individual people. We found low-frequency mutations, below the detection threshold of traditional surveillance methods, in nonvaccinated and vaccinated humans that were recently associated with antibody escape. Interestingly, these potential antigenic variants did not reach fixation in infected people, suggesting that other evolutionary factors may be hindering their emergence in individual humans.

Influenza and respiratory syncytial virus in infants study (IRIS) of hospitalized and non-ill infants aged <1 year in four countries: study design and methods.

BACKGROUND: This multi-country prospective study of infants aged <1 year aims to assess the frequency of influenza virus and respiratory syncytial virus (RSV) infections associated with hospitalizations, to describe clinical features and antibody response to infection, and to examine predictors of very severe disease requiring intensive care. METHODS/DESIGN: We are enrolling a hospital-based cohort and a sample of non-ill infants in four countries (Albania, Jordan, Nicaragua, and the Philippines) using a common protocol. We are currently starting year 2 of a 2- to 3-year study and will enroll approximately 3,000 infants hospitalized for any acute illness (respiratory or non-respiratory) during periods of local influenza and/or RSV circulation. After informed consent and within 24 h of admission, we collect blood and respiratory specimens and conduct an interview to assess socio-demographic characteristics, medical history, and symptoms of acute illness (onset ≤10 days). Vital signs, interventions, and medications are documented daily through medical record abstraction. A follow-up health assessment and collection of convalescent blood occurs 3-5 weeks after enrollment. Influenza and RSV infection is confirmed by singleplex real time reverse transcriptase polymerase chain reaction (rRT-PCR) assays. Serologic conversion will be assessed comparing acute and convalescent sera using hemagglutination inhibition assay for influenza antibodies and enzyme-linked immunosorbent assay (ELISA) for RSV. Concurrent with hospital-based enrollment, respiratory specimens are also being collected (and tested by rRT-PCR) from approximately 1,400 non-ill infants aged <1 year during routine medical or preventive care. DISCUSSION: The Influenza and RSV in Infants Study (IRIS) promises to expand our knowledge of the frequency, clinical features, and antibody profiles of serious influenza and RSV disease among infants aged <1 year, quantify the proportion of infections that may be missed by traditional surveillance, and inform decisions about the potential value of existing and new vaccines and other prevention and treatment strategies.

Development and validation of a novel single nucleotide polymorphism (SNP) panel for genetic analysis of Blastomyces spp. and association analysis.

BACKGROUND: Single nucleotide polymorphism (SNP) genotyping is increasingly being utilized for molecular typing of pathogens and is cost-effective, especially for large numbers of isolates. The goals of this study were 1) to develop and validate a SNP assay panel for genetic analysis of Blastomyces spp., 2) ascertain whether microsatellite genotyping and the SNP genotyping with the developed panel resolve identical genetic groups, and 3) explore the utility of SNPs for examining phylogenetic and virulence questions in humans. METHODS: Three hundred sixty unique Blastomyces spp. isolates previously genotyped with microsatellite markers were genotyped with the MassARRAY® SNP genotyping system (Agena Bioscience™, San Diego, CA), for a custom panel of 28 SNPs. Clinical presentation data was analyzed for association with SNP variants. RESULTS: Three hundred twenty-three Blastomyces spp. isolates (90 %) were successfully genotyped by SNP analysis, with results obtained for at least 27 of 28 assays. For 99.7 % of isolates tested by both genotyping methods, microsatellite genetic group assignment correlated with species assignment based on internal transcribed spacer 2 (ITS2) genotyping, with Group 1 (Gr 1) being equivalent to B. gilchristii and Group 2 (Gr 2) being equivalent to B. dermatitidis. Thirteen isolates were genetic hybrids by one or both methods of genotyping and were difficult to assign to a particular genetic group or species. Fifteen SNP loci showed significantly different alleles in cases of pulmonary vs disseminated disease, at a p-value of <0.01 or less. CONCLUSIONS: This study is the largest genotyping study of Blastomyces spp. isolates and presents a new method for genetic analysis with which to further explore the relationship between the genetic diversity in Blastomyces spp. and clinical disease presentation. We demonstrated that microsatellite Gr 1 is equivalent to B. gilchristii and Gr 2 is equivalent to B. dermatitidis. We also discovered potential evidence of infrequent recombination between the two Blastomyces spp. Several Blastomyces spp. SNPs were identified as associated with dissemination or pulmonary disease presentation, but additional work is needed to examine virulence SNPs separately within B. dermatitidis and B. gilchristii.

Optimizing Virus Identification in Critically Ill Children Suspected of Having an Acute Severe Viral Infection.

OBJECTIVES: Multiplex rapid viral tests and nasopharyngeal flocked swabs are increasingly used for viral testing in PICUs. This study aimed at evaluating how the sampling site and the type of diagnostic test influence test results in children with suspected severe viral infection. DESIGN: Prospective cohort study. SETTING: PICUs at 21 tertiary pediatric referral centers in the United States. PATIENTS: During the 2010-2011 and 2011-2012 influenza seasons, we enrolled children (6 mo to 17 yr old) who were suspected to have severe viral infection. INTERVENTIONS: We collected samples by using a standardized protocol for nasopharyngeal aspirate and nasopharyngeal flocked swabs in nonintubated patients and for endotracheal tube aspirate and nasopharyngeal flocked swabs in intubated patients. MEASUREMENTS AND MAIN RESULTS: Viral testing included a single reverse transcription-polymerase chain reaction influenza test and the GenMark Respiratory Viral Panel (20 viruses). We enrolled 90 endotracheally intubated and 133 nonintubated children. We identified influenza in 45 patients with reverse transcription-polymerase chain reaction testing; the multiplex panel was falsely negative for influenza in two patients (4.4%). Six patients (13.3%) had not been diagnosed with influenza in the PICU. Non-influenza viruses were identified in 172 of 223 children (77.1%). In nonintubated children, the same virus was identified by nasopharyngeal flocked swabs and nasopharyngeal aspirate in 133 of 183 paired samples (72.7%), with +nasopharyngeal aspirate/-nasopharyngeal flocked swabs in 32 of 183 paired samples (17.4%). In intubated children, the same virus was identified by nasopharyngeal flocked swabs and endotracheal tube aspirate in 67 of 94 paired samples (71.3%), with +nasopharyngeal flocked swabs/- endotracheal tube aspirate in 22 of 94 paired samples (23.4%). Most discrepancies were either adenovirus or rhinovirus in both groups. CONCLUSIONS: Standardized specimen collection and sensitive diagnostic testing with a reverse transcription-polymerase chain reaction increased the identification of influenza in critically ill children. For most pathogenic viruses identified, results from nasopharyngeal flocked swabs agreed with those from nasopharyngeal or endotracheal aspirates.

Influenza vaccine effectiveness in the United States during 2012-2013: variable protection by age and virus type.

BACKGROUND: During the 2012-2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza B lineage viruses in the United States. METHODS: Patients with acute cough illness for ≤7 days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as [100% × (1 - adjusted odds ratio)] for vaccination in cases versus test-negative controls. RESULTS: Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval [CI], 43%-55%) overall, 39% (95% CI, 29%-47%) against influenza A(H3N2), 66% (95% CI, 58%-73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%-63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50-64 years (52%; 95% CI, 33%-65%) and persons aged 6 months-8 years (51%; 95% CI, 32%-64%) and lowest among persons aged ≥65 years (11%; 95% CI, -41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011-2012 vaccine 1 year earlier. CONCLUSIONS: The 2012-2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation.

Medically attended respiratory syncytial virus infections in adults aged ≥ 50 years: clinical characteristics and outcomes.

BACKGROUND: Few studies have examined respiratory syncytial virus (RSV) infections in adults. We assessed the characteristics and outcomes of RSV relative to other viral infections. METHODS: Patients ≥ 50 years old with acute respiratory illness were recruited for studies of influenza vaccine effectiveness from 2004 through 2010. Nasopharyngeal swabs from enrollees were analyzed for the presence of RSV and other respiratory viruses by multiplex reverse transcription polymerase chain reaction. Clinical data were obtained from interview and medical records. RESULTS: A total of 2225 samples were tested across all seasons. The mean age was 64.2 (SD, 10.7) years; the mean interval from illness onset to sample collection was 4 (SD, 2.2) days. One or more viruses were detected in 1202 (54%) participants. In a multivariable logistic regression model, RSV was associated with ages 65-79 years (vs 50-64 years), symptoms of cough, nasal congestion and wheezing, and longer interval from illness onset to clinical encounter. RSV was not associated with the presence of chronic obstructive pulmonary disease or congestive heart failure in univariate analyses. Hospital admission within 30 days after illness onset was less common among patients with RSV compared to those with influenza (unadjusted odds ratio = 0.54 [95% confidence interval, .29-1.01], P = .06). CONCLUSIONS: RSV is a common cause of acute respiratory illness in adults aged ≥ 50 years; the risk of infection increases with age. Delays in healthcare seeking and reduced risk of hospital admission in patients with RSV suggest a milder course of illness relative to influenza.

Impact of repeated vaccination on vaccine effectiveness against influenza A(H3N2) and B during 8 seasons.

BACKGROUND: Recent studies suggest that influenza vaccination in the previous season may influence the effectiveness of current-season vaccination, but this has not been assessed in a single population over multiple years. METHODS: Patients presenting with acute respiratory illness were prospectively enrolled during the 2004-2005 through 2012-2013 influenza seasons. Respiratory swabs were tested for influenza and vaccination dates obtained from a validated registry. Vaccination status was determined for the current, previous, and prior 5 seasons. Vaccine effectiveness (VE) was calculated for participants aged ≥9 years using logistic regression models with an interaction term for vaccination history. RESULTS: There were 7315 enrollments during 8 seasons; 1056 (14%) and 650 (9%) were positive for influenza A(H3N2) and B, respectively. Vaccination during current only, previous only, or both seasons yielded similar protection against H3N2 (adjusted VE range, 31%-36%) and B (52%-66%). In the analysis using 5 years of historical vaccination data, current season VE against H3N2 was significantly higher among vaccinated individuals with no prior vaccination history (65%; 95% confidence interval [CI], 36%-80%) compared with vaccinated individuals with a frequent vaccination history (24%; 95% CI, 3%-41%; P = .01). VE against B was 75% (95% CI, 50%-87%) and 48% (95% CI, 29%-62%), respectively (P = .05). Similar findings were observed when analysis was restricted to adults 18-49 years. CONCLUSIONS: Current- and previous-season vaccination generated similar levels of protection, and vaccine-induced protection was greatest for individuals not vaccinated during the prior 5 years. Additional studies are needed to understand the long-term effects of annual vaccination.