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BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses. METHODS: We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children’s stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year–vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive–vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone. RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year–vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive–vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification. CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.

Background As of 2017 (WHO, 2017), diarrheal disease ranked second as a cause of worldwide mortality for children under five years of age. Approximately 50-70% of acute gastroenteritis (AGE) is viral in etiology, with commonly detected viruses including norovirus, rotavirus, and adenovirus. However, the epidemiology of less commonly detected viruses, specifically enterovirus (EV) and parechovirus A (PeV-A), associated AGE in the United States is not well described. The purpose of our study was to determine the prevalence of EV and PeV-A in children with AGE vs. healthy controls (HC) over a 7-year period. Methods From December 2011 – November 2018, we screened stool samples from children less than 18 years of age prospectively enrolled in Children’s Mercy-Kansas City’s (CM-KC) site for the CDC’s New Vaccine Surveillance Network; 3005 samples from subjects presenting with AGE and 1097 from HC. Samples from 2011 – 2016 (AGE: 2453; HC:752) and 2017 – 2018 (AGE:552; HC:344) were tested at CDC and CM-KC respectively by a real-time-PCR assay using specific EV and PeV-A primers targeting the highly conserved 5’ untranslated region. Demographic data were collected from EMR. Results Among 3005 AGE samples, EV was detected in 12.5% (n=386/3004), and PeV-A in 10.3% (n=252/3005). Among 1097 HC samples, EV was detected in 9.0% (99/1096), and PeV-A in 11.9% (130/1097). In 2014-2015 EV detection in AGE was highest (17.9%) among all years and significantly higher (p=0.004) than in HC samples (9.1%), whereas PeV-A detection in AGE was 9.5% vs. 15.6% in HC samples, p=0.008 (Table 1). Co-infections with EV and PeV-A were seen in 55 AGE and 21 HC. Most EV detections (45.1%) were in 1- to 2-year-olds, whereas PeV-A detections (47.3%) were in children < 1 year old (Table 2). Both EV (58.3%) and PeV-A (48.4%) detections were significantly more frequent in male children (p=0.006). The highest frequency of EV detections was in summer to fall months, and for PeV-A in late summer through early winter. Conclusion We report a higher prevalence of EV infections in AGE, and PeV-A infections in HC during 2011 to 2018, plus their seasonal and age distributions. Although our data do not currently demonstrate an association between detection of EV or PeV-A types and AGE, additional data could provide more clarity into a potential association. Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Mary E. Moffatt, M.D., Becton and Dickinson and Company: Stocks/Bonds|Biogen: Stocks/Bonds|Coloplast B: Stocks/Bonds|Express Scripts: Stocks/Bonds|Novo Nordisk A/S Spons ADR: Stocks/Bonds|Novo Nordisk A/S-B: Stocks/Bonds|Steris PLC: Stocks/Bonds|Stryker Corp: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background Non-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotypes have been detected in pediatric CSF, e.g. Echovirus (E) 6 and E30. CSF innate immune responses to EV genotypes remain poorly defined. Most data are from EV-A71 or E30 CNS infections and do not compare responses between these or other EV types. We sought to better define innate immune responses to EV genotypes in CSF. Methods Salvaged standard of care CSF samples from ≤6 month olds (real time EV PCR(+) or EV PCR(-) controls) from Jan 2010 - Dec 2020 were tested in duplicate on a 21- cytokine bead panel (MilliporeSigma). EV positive samples were previously genotyped by sequencing the viral capsid gene. Cytokine levels calculated from the standard curve were compared by Kruskal-Wallis and post-hoc analysis (GraphPad Prism 8.4.3). Natural partitioning of participants was explored using principal component analysis and cluster analysis (IBM SPSS v27). The utility of cytokine signatures in predicting EV status was explored using discriminant analysis and ROC analysis (IBM SPSS v27). Results Data from 72 CSF with E6 (N=16), E9 (N= 9), E18 (N=9), and E30 (N=21) showed significant differences among EV genotypes vs. controls for 20 cytokines (IL-17 was excluded). Significant differences in cytokine levels in EV CSF vs controls were seen: E6 for all 20 cytokines; E9 for Fractalkine, IP10, and MCP1; E18 for Fractalkine and MCP1; E30 19 cytokines (not GM-CSF). PCA revealed only minor overlap of controls and EV positives; EV types overlapped, except E30, differing most from E9 and E18 but overlapping E6. The most important type-differentiating cytokines by PCA were MCP1, Fractalkine, IL-8, and IL-10. Patterns in DA resembled PCA; controls clearly separated from EV CSF, E30 being the most distinct. Overall, the discriminant model correctly classified EV type or controls at a 63% rate - highest for controls (94.1%) and E30 (74.1%). In the DA model, the most important cytokines were IP-10, IL-2, IL-1Ra, and Fractalkine. Discriminant scores had the largest area under the curve (AUC), 0.990. Among cytokines, IFNa2 had the largest AUC, 0.987. Conclusion Preliminary data show significant EV-genotype differences in innate immune response to CNS infections. Cytokine patterns may serve as a key predictor for discerning EV genotypes. Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background Mycoplasma pneumoniae (MP), a common pediatric pneumonia pathogen, has 2 subtypes based on P1 adhesin gene variation. Macrolide-resistant MP (MRMP), seen since 2000 in many countries, has been subtype associated. Limited U.S. pediatric data exist on MP subtype or MRMP frequency and their clinical importance. Methods During 2015–2020, mid-turbinate nasal swab (MTNS) specimens and/or throat swabs were collected from children with acute respiratory illness (ARI) enrolled in emergency department (ED) or outpatient and inpatient settings at 4 CDC-funded New Vaccine Surveillance Network sites (Cincinnati, Seattle, Houston, and Kansas City). Specimens were tested for MP and common respiratory viruses by singleplex or multiplex polymerase chain reaction assay (PCR). P1-subtyping for MP positive specimens used multiplex TaqMan real-time PCR while MR was assessed by real time PCR with melt curve analysis (Lightmix®, TIBMolbiol). Select demographic/clinical data were analyzed by P1 subtype (P1–1 vs. P1–2). Results Of 208 MTNS specimens from 208 children (median age 5.5 years), 110 (53%) were P1–1, 89 (43%) P1–2, and 9 (4%) untypeable. Of 199 typeable specimens, 111 (56%) came from inpatients while 88 (44%) came from ED/outpatients.Overall MRMP prevalence during 2015–2020 was low (3/208,1.4%); all MRMP (Houston: 1 each in 2016–2017 and 2019–2020, Seattle: 1 in 2018–2019) were P1–1. Differences in P1–2 vs. P1–1 proportions were significant in 2 years: P1–2 dominated in 2015–2016; P1-1 in 2019–2020 (Figure 1). Common clinical symptoms for 199 MP-positive patients were fever (84%, mean 102.5±1.5oF), shortness of breath (82%), wheezing (67%), and cough (60%). Clinical manifestations, hospitalization, and antibiotic use did not differ in P1-1 vs. P1-2 patients. Antibiotics were used in 59/199 (30%) patients overall; amoxicillin was most frequent (48/199, 24%), followed by cefdinir (9/199, 5%) and azithromycin (5/199, 3%). Conclusion MP subtypes co-circulated during 2015–2020; P1-2 dominated in 2015–2016, P1-1 in 2018–2019. Signs/symptoms were similar for P1-1 and P1-2. MRMP detection was uncommon among our pediatric subjects. Ongoing surveillance is important to assess potential changes in MR prevalence and temporal subtype variation. Disclosures Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Mary E. Moffatt, M.D., Becton and Dickinson and Company: Stocks/Bonds|Biogen: Stocks/Bonds|Coloplast B: Stocks/Bonds|Express Scripts: Stocks/Bonds|Novo Nordisk A/S Spons ADR: Stocks/Bonds|Novo Nordisk A/S-B: Stocks/Bonds|Steris PLC: Stocks/Bonds|Stryker Corp: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds Janet A. Englund, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccine: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|SanofiPasteur: Advisor/Consultant.

Background An optimal specimen collection method is important for pathogen detection in respiratory surveillance studies. Mid-turbinate swab (MTS) in combination with throat swab (TS) were used for collecting samples from children enrolled in Kansas City site of the New Vaccine Surveillance Network (NVSN), a prospective surveillance network for acute respiratory infections. A standalone MTS is used for standard of care (SOC) testing. We compared detections from NVSN MTS+TS vs. SOC MTS samples collected ±1 day of each other to evaluate the sensitivity of the single MTS collection in children. Methods Nucleic acid extracts from NVSN MTS+TS samples were tested by Luminex NxTag Respiratory Pathogen Panel (NxTag RPP). SOC MTS samples were tested by BioFire® Respiratory Panel 1.7. (FilmArray). All children, aged < 18 years enrolled in the inpatient and Emergency Department for NVSN (November 2015 to May 2019) with available historical MTS SOC testing results ±1 day of enrollment were included in the study. Concordance between results of NVSN MTS+TS and SOC MTS testing was measured. Results Paired NVSN and SOC samples were available from 315 subjects with median age of 16.8 months (IQR 5.0 months – 61.7 months); 59.3% (189/315) were from male subjects. An overall positivity of 93.6% was noted with 295 detections by one sample or the other. Of the 295 detections, 231 (78%) detections were in both samples; 35 (12%) detections by MTS+TS; and 29 (10%) detections by MTS only. High concordance ( >90%) and very good Kappa values (Table 1) between the 2 specimen collection methods was noted for most pathogens. 72% of discrepant samples were from children with median age 13.2 months (IQR 8.0 months – 38.6 months). Conclusion We observed high concordance between MTS and MTS+TS for all targets. Most discrepant samples were from young children in whom adequate sampling can be challenging, perhaps reducing sensitivity. Differences in time of collection and testing, and platform differences (NxTag RPP vs. FilmArray) may have impacted our data, e.g. due to variable assay sensitivities for specific targets. Regardless of these differences, our data show comparable performance between MTS alone and MTS+TS suggesting that MTS alone may be sufficient for respiratory pathogen surveillance in children. Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background Adenovirus (AdV) is a common cause of acute respiratory illness (ARI). Multiple respiratory AdV types have been identified in humans, but it remains unclear which are the most common in U.S. children with ARI. Methods We conducted a multicenter, prospective viral surveillance study at seven U.S. children’s hospitals, the New Vaccine Surveillance Network, during 12/1/16–11/30/19, prior to the COVID-19 pandemic. Children < 18 years of age seen in the emergency department or hospitalized with fever and/or respiratory symptoms were enrolled, and mid-turbinate nasal +/- throat swabs were tested using multiplex respiratory pathogen assays or real time polymerase chain reaction (PCR) test for AdV, respiratory syncytial virus (RSV), human metapneumovirus, rhinovirus/enterovirus (RV), influenza, parainfluenza viruses, and endemic coronaviruses. AdV-positive specimens were subsequently typed using single-plex qPCR assays targeting sequences in the hexon gene specific for types 1-7, 11, 14, 16 and 21. Demographics, clinical characteristics, and outcomes were compared between AdV types. Results Of 29,381 enrolled children, 2,106 (7.2%) tested positive for AdV. The distribution of types among the 1,330 (63.2%) successfully typed specimens were as follows: 31.7% AdV-2, 28.9% AdV-1, 15.3% AdV-3, 7.9% AdV-5, 5.9% AdV-7, 1.4% AdV-4, 1.2% AdV-6, 0.5% AdV-14, 0.2% AdV-21, 0.1% AdV-11, and 7.0% ≥1 AdV type. Most children with AdV-1 or AdV-2 detection were < 5 years of age (Figure 1a). Demographic and clinical characteristics varied by AdV types, including age, race/ethnicity, smoke exposure, daycare/school attendance, and hospitalization (Table 1). Co-detection with other viruses was common among all AdV types, with RV and RSV being the most frequently co-detected (Figure 1b). Fever and cough were the most common symptoms for all AdV types (Figure 2). Children with AdV-7 detected as single pathogen had higher odds of hospitalization (adjusted odds ratio 6.34 [95% CI: 3.10, 12.95], p= 0.027). Conclusion AdV-2 and AdV-1 were the most frequently detected AdV types among children over the 3-year study period. Notable clinical heterogeneity of the AdV types warrants further surveillance studies to identify AdV types that could be targeted for pediatric vaccine development. Disclosures Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|National Institute of Health: Grant/Research Support|Uptodate: Royalties Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Mary E. Moffatt, M.D., Becton and Dickinson and Company: Stocks/Bonds|Biogen: Stocks/Bonds|Coloplast B: Stocks/Bonds|Express Scripts: Stocks/Bonds|Novo Nordisk A/S Spons ADR: Stocks/Bonds|Novo Nordisk A/S-B: Stocks/Bonds|Steris PLC: Stocks/Bonds|Stryker Corp: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds Geoffrey A. Weinberg, MD, Merck & Co.: Honoraria|Merck & Co.: Honoraria for composing and reviewing textbook chapters, Merck Manual of Therapeutics Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

Background Children ≤5 years of age have the highest rates of pneumococcal colonization and play an important role in the spread of pneumococcus. Our objective was to determine whether the public health measures (physical distancing, masking, and shelter-in-place orders) implemented to slow the spread of SARS-CoV-2 pandemic had an impact on pneumococcal colonization rates among children aged ≤5 years with and without respiratory symptoms during the first year of SARS-CoV-2 pandemic (4/1/20 to 3/31/21). Methods This is a single center retrospective cohort study. The study period was divided in 3 four-month periods to represent the initial period of strict adherence to public health measures (period 1: Apr-Jul), relaxation of some of these measures (period 2: Aug-Nov) and Northern hemisphere winter season (period 3: Dec-Mar). We used salvaged mid-turbinate samples obtained as part of routine care from patients without respiratory symptoms but screened for SARS-CoV-2 prior to surgery or aerosol generating procedures (asymptomatic) or from patients with respiratory symptoms tested for SARS-CoV-2 and/or other respiratory viruses (symptomatic). Samples were evaluated for pneumococcal colonization by real-time PCR using CDC lytA primers. Sample size was calculated based on the assumption of lower colonization rates in period 1 and gradual increase (10-15%) in the following study periods. Results A total of 311 patients were included (185 asymptomatic and 126 symptomatic). Demographics, SARS-CoV-2 PCR and pneumococcal colonization results are shown in Table 1. Pneumococcal colonization rates for asymptomatic and symptomatic children were 14% and 22% (p=0.06), respectively. The odds of colonization of asymptomatic children were similar during period 2 (OR 0.96 [95%CI 0.34-2.67]) and period 3 (OR 0.53 [95%CI 0.17-1.62]), using period 1 as reference and after adjusting for age, sex, and SARS-COV-2 results. The odds of colonization of symptomatic children were also similar across the 3 study periods (period 2 OR 1.28 [95%CI 0.41-4.01] and period 3 OR 0.73 [95% CI 0.24-2.18]). Table 1.Characteristics of asymptomatic and symptomatic groups Conclusion Pneumococcal colonization rates were not significantly impacted by public health measures implemented during the first year of the SARS-CoV-2 pandemic and did not correlate with SARS-CoV-2 positivity. Disclosures Liset Olarte, MD, MSc, GSK: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support Douglas S. Swanson, MD, Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J. Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric News: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background According to the 2018 Infectious Diseases Society of America (IDSA) clinical practice guidelines and Centers for Disease Control and Prevention (CDC) guidance, clinicians should start antiviral treatment as soon as possible for children who are hospitalized with suspected or confirmed influenza. We assessed the use of influenza-specific antiviral therapy in children hospitalized with symptoms of acute respiratory illness and laboratory-confirmed influenza. Methods We conducted active, population-based surveillance of children hospitalized with fever and/or respiratory symptoms (12/01/2016–02/28/2020) at the seven U.S. medical centers that comprise the CDC New Vaccine Surveillance Network. We excluded children who did not undergo clinical testing (by rapid antigen testing or nucleic acid amplification test [NAAT]) or research testing (by NAAT) for influenza, those who presented out of influenza season (site- and season-specific), and those whose date of antiviral therapy or whether antiviral therapy was given was unknown. We assessed the use of influenza-specific antiviral therapy in this cohort and defined timely antiviral therapy as administration within 2 days of hospitalization. Results Of 11,275 eligible children, 1,149 (10.2%) tested positive for influenza by clinical and/or research assays (Table 1). Overall, 154 influenza cases (13.4%) were detected by clinical testing only, 428 (37.2%) by research testing only, and 567 (49.3%) by both. During their influenza-associated hospitalization, 620 children (54.0%) received influenza-specific antivirals, and therapy was timely in 572 cases (92.3%). Of those who tested positive clinically, 445/721 (61.7%) received timely antiviral therapy, 38 (5.3%) received delayed antiviral therapy, and 238 (33.0%) received no antiviral therapy. Oseltamivir was the antiviral used in all treated cases. The distribution of antiviral-treated cases varied by race and Hispanic origin and study site, but not by age at presentation or influenza season (Figure 1). Table 1 Demographic characteristics of 1,149 children with influenza enrolled in the New Vaccine Surveillance Network over four influenza seasons between December 1, 2016, and February 28, 2020. Figure 1Proportions of children with influenza enrolled in the New Vaccine Surveillance Network who received timely, delayed, or no antiviral therapy by age at presentation, race and Hispanic origin, study site, and influenza season (N=1,149). Conclusion Although antiviral therapy is recommended for all influenza-associated hospitalizations in children, antiviral prescribing remains suboptimal. Further studies would help identify and address barriers to antiviral therapy in children with influenza. Disclosures John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|National Institute of Health: Grant/Research Support|Uptodate: Royalties Geoffrey A. Weinberg, MD, Merck & Co.: Honoraria|Merck & Co.: Honoraria for composing and reviewing textbook chapters, Merck Manual of Therapeutics Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

Enterovirus D68 (EV-D68) is associated with a broad spectrum of illnesses, including mild to severe acute respiratory illness (ARI) and acute flaccid myelitis (AFM). Enteroviruses, including EV-D68, are typically detected in the United States during late summer through fall, with year-to-year fluctuations. Before 2014, EV-D68 was infrequently reported to CDC (1). However, numbers of EV-D68 detection have increased in recent years, with a biennial pattern observed during 2014-2018 in the United States, after the expansion of surveillance and wider availability of molecular testing. In 2014, a national outbreak of EV-D68 was detected (2). EV-D68 was also reported in 2016 via local (3) and passive national (4) surveillance. EV-D68 detections were limited in 2017, but substantial circulation was observed in 2018 (5). To assess recent levels of circulation, EV-D68 detections in respiratory specimens collected from patients aged18 years* with ARI evaluated in emergency departments (EDs) or admitted to one of seven U.S. medical centers

Antiviral treatment is recommended for all hospitalized children with suspected or confirmed influenza, regardless of their risk profile. Few data exist on adherence to these recommendations, so we sought to determine factors associated with influenza testing and antiviral treatment in children.Hospitalized children18 years of age with acute respiratory illness (ARI) were enrolled through active surveillance at pediatric medical centers in seven cities between 11/1/2015 and 6/30/2016; clinical information was obtained from parent interview and chart review. We used generalized linear mixed-effects models to identify factors associated with influenza testing and antiviral treatment.Of the 2299 hospitalized children with ARI enrolled during one influenza season, 51% (n = 1183) were tested clinically for influenza. Clinicians provided antiviral treatment for 61 of 117 (52%) patients with a positive influenza test versus 66 of 1066 (6%) with a negative or unknown test result. In multivariable analyses, factors associated with testing included neuromuscular disease (aOR = 5.35, 95% CI [3.58-8.01]), immunocompromised status (aOR = 2.88, 95% CI [1.66-5.01]), age (aOR = 0.93, 95% CI [0.91-0.96]), private only versus public only insurance (aOR = 0.78, 95% CI [0.63-0.98]), and chronic lung disease (aOR = 0.64, 95% CI [0.51-0.81]). Factors associated with antiviral treatment included neuromuscular disease (aOR = 1.86, 95% CI [1.04, 3.31]), immunocompromised state (aOR = 2.63, 95% CI [1.38, 4.99]), duration of illness (aOR = 0.92, 95% CI [0.84, 0.99]), and chronic lung disease (aOR = 0.60, 95% CI [0.38, 0.95]).Approximately half of children hospitalized with influenza during the 2015-2016 influenza season were treated with antivirals. Because antiviral treatment for influenza is associated with better health outcomes, further studies of subsequent seasons would help evaluate current use of antivirals among children and better understand barriers for treatment.

Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.Using NONMEM v7.3, Monte Carlo simulations (N=10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 hours (standard-dose), AMOX 45 mg/kg/dose PO every 12 hours (high-dose), and PENG 62,500 units/kg/day IV every 6 hours using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fTMIC) across the population of pneumococci for 30-50% of the dosing interval.In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared with CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fTMIC in the serum at the susceptible MICs, standard-dose AMOX achieved4% PTA (CLSI) and86% PTA (EUCAST); high-dose AMOX achieved73% PTA (CLSI) and99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved71%,93%, and 100% PTA, respectively, in the serum at 30-50%fTMIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens.Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.

Background Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014–2016 Methods A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing. Results A total of 795 (76%) samples contained detectable RVA when tested at the CDC. Rotavirus disease was highest in children < 3 years of age. Four G types (G1, G2, G9, and G12) accounted for 94.6% of strains while 2 P types (P[4] and P[8]) accounted for 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all 3 seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty-four percent of RVA-positive specimens contained other AGE pathogens. Conclusions G12P[8] predominated over 3 seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the postvaccine era.

Ceftolozane/tazobactam (C/T), a cephalosporin/beta-lactamase inhibitor combination, was evaluated in vitro vs. 10 comparators against 299 pediatric extended-spectrum-cephalosporin-resistant or carbapenem-resistant (ESC-R/CR) Gram-negative Enterobacteriaceae from three freestanding pediatric centers. Isolates were from urine or other sterile sites of children and adolescents through 21 years of age. Susceptibilities were assayed by microbroth dilution via custom Sensititre plates (Thermo Fisher Scientific). Susceptibility was determined using the Sensititre Vizion® system (Thermo Fisher Scientific). Susceptibility breakpoint criteria were those of the Clinical and Laboratory Standards Institute (CLSI) for 2017, except for colistin (EUCAST 2019). Overall, 87.5% isolates were C/T susceptible (MIC ≤2 μg/ml; MIC50/90, 0.25/4 μg/ml). Susceptibility to C/T was detected more frequently as compared to all other antimicrobials tested except for colistin (95.4%) and meropenem (97.4%). Percent susceptibility to C/T was high for E. coli (91%) and Klebsiella spp. (73.3%). C/T demonstrated good in-vitro activity and high potency against most beta-lactam resistant pediatric Enterobacteriaceae from three geographically diverse U.S. regions.

It is now well documented that mercury is extremely toxic to both humans and the environment. A close-packed gold nanorod (Au-NR) monolayer was deposited on a titanium-based quartz crystal microbalance (QCM) and its performance for elemental mercury (Hg0) vapor sorption and detection was compared with that of a typical gold thin film (Au CTRL) based QCM device. The developed Au-NR based Hg0 sensor showed an up to ∼1.7 times higher response magnitude than its Au CTRL counterpart when exposed to Hg0 vapor concentrations of 0.21 to 3.26 mg m−3 at two different operating temperatures of 30 and 75 °C. The repeatability of the Au-NR sensor was calculated to be >90% when exposed to a series of sorption/desorption events with a Hg0 vapor concentration of 3.26 mg m−3. The calibration curves (i.e. response magnitudes vs. Hg0 concentrations) of the Au-NR sensor were found to follow the Langmuir extension isotherm, indicating the sensor's suitability to detect relatively low concentrations (ppb levels) of Hg0 vapor. Furthermore, the newly developed Au-NR sensor showed good selectivity (∼97%) toward Hg0 vapor when acetaldehyde co-existed in the gas mix. However, the selectivity of the sensor decreased to 66% and 67% when Hg0 vapor was detected in the presence of ammonia and water vapor, respectively. The selectivity data from the tested sensors were analysed to understand the selectivity performance of Au NRs toward Hg0 vapor in the presence of different gas species in order to implement improvements in developing the sensor for real world applications.

OBJECTIVES: Diagnosing Clostridioides difficile infections in young children with high asymptomatic colonization is challenging. We compared the frequency of C difficile detection by polymerase chain reaction (PCR) in healthy control (HC) children with those with acute gastroenteritis (AGE) and evaluated fecal-lactoferrin and organism load as possible indicators of true C difficile infection disease. METHODS: Stool was collected from children RESULTS: Of 524 stools collected from 524 children (250 with AGE, 274 HCs), C difficile was detected less in children with AGE (14%, 36 of 250) than in HCs (28%, 76 of 274) stools (P < .0001). Among infants CONCLUSIONS: HC children

The fusion (F) protein of respiratory syncytial virus (RSV) is the major target of immunoprophylactic monoclonal antibodies (mAbs) and vaccines. Recently reported mutations in F gene antigenic sites can vary among RSV types A and B. To further understand mutations in RSV F proteins, we performed subtyping and F gene sequencing on 400 RSV-positive respiratory samples collected at four pediatric hospitals within the United States from children under 2 years old between 2018 and 2020. RSV B was predominant in 2018-2019 and RSV A in 2019-2020 (55.5% and 85.5% respectively). Compared to the reference sequence, all RSV B samples had at least one antigenic polymorphism with the most changes at sites AM14/V (100%) and Ø (93.3%) followed by II (5.8%), IV (3.9%), and p27 (2.9%). The most frequent mutations among RSV B for AM14/V site were in L172Q (100%), S173L (100%), and K191R (95.2%) while for Ø site they were in I206M (93.3%) and Q209R (93.3%). Conversely, polymorphisms were observed in only 15.3% of RSV A samples overall, specifically at antigenic sites p27 (5.9%), IV (3.0%), II (2.5%), AM14/V (2.0%), I (2.0%), and Ø (0.5%). Among RSV A cases, T122A at p27 (n = 10) and S276N at II (n = 3) were the most common substitution sites. S276N at site II was found in both RSV types. Although polymorphisms in F proteins of RSV B were more common than those in RSV A samples, changes in both subtypes were observed in key F antigenic sites which could potentially impact the efficacy of mAb therapies and vaccines.

An estimated 12.8 million pediatric SARS-CoV-2 infections have occurred within the United States as of March 1 2022, with multiple epidemic waves due to emergence of several SARS-CoV-2 variants. The aim of this study was to compare demographics, clinical presentation, and detected respiratory co-infections during COVID-19 waves to better understand changes in pediatric SARS-CoV-2 epidemiology over time.

To offer: (1) Insight into the antivaccine movement's use of social media negatively impacting vaccine hesitancy and disease outbreaks, (2) Examples via case observations, and (3) Selected resources to combat vaccine hesitancy.For the past 25 years, daily social media usage has risen continually, allowing information to spread widely to a reading/listening/viewing audience via mostly unvetted social media sites. During a pandemic/epidemic (e.g., coronavirus disease 2019 pandemic), an overabundance of information from many sources, including social media, has led to what is now termed as an 'infodemic'. Infodemics arise from overwhelming amounts of both correct and incorrect information from experts and nonexperts alike. Differentiating correct from incorrect information is difficult for social media users who can be swayed by nonscientific 'influencers' or fear-mongering more than by vetted expert scientific information. Consequently, vaccine misinformation is steadily increasing via social media, the use of which is often believed to be associated with vaccine hesitancy. Stopping the spread of misinformation has been a difficult task.Vaccine misinformation on social media has been detrimental to public health. Vaccine advocates must increase the use of social media to the advantage of public health in the persistent struggle against vaccine hesitancy/refusal.

Background Human adenovirus (HAdV) is commonly associated with acute respiratory illnesses (ARI) in children and is also frequently co-detected with other viral pathogens. We compared clinical presentation and outcomes in young children with HAdV detected alone vs co-detected with other respiratory viruses. Methods We used data from a multicenter, prospective, viral surveillance study of children seen in the emergency department and inpatient pediatric settings at seven US sites. Children less than 18 years old with fever and/or respiratory symptoms were enrolled between 12/1/16 and 10/31/18 and tested by molecular methods for HAdV, human rhinovirus/enterovirus (HRV/EV), respiratory syncytial virus (RSV), parainfluenza (PIV, types 1–4), influenza (flu, types A-C), and human metapneumovirus (HMPV). Our primary measure of illness severity was hospitalization; among hospitalized children, secondary severity outcomes included oxygen support and length of stay (LOS). Results Of the 18,603 children enrolled, HAdV was detected in 1,136 (6.1%), among whom 646 (56.9%) had co-detection with at least one other respiratory virus. HRV/EV (n = 293, 45.3%) and RSV (n = 123, 19.0%) were the most frequent co-detections. Children with HRV/EV (aOR = 1.61; 95% CI = [1.11–2.34]), RSV (aOR = 4.48; 95% CI = [2.81–7.14]), HMPV (aOR = 3.39; 95% CI = [1.69–6.77]), or ≥ 2 co-detections (aOR = 1.95; 95% CI = [1.14–3.36]) had higher odds of hospitalization compared to children with HAdV alone. Among hospitalized children, HAdV co-detection with RSV or HMPV was each associated with higher odds of oxygen support, while co-detection with PIV or influenza viruses was each associated with higher mean LOS. Conclusions HAdV co-detection with other respiratory viruses was associated with greater disease severity among children with ARI compared to HAdV detection alone.

Cyanopyridone-based oligothiophene donors with both hydrophobic and hydrophilic characters have been evaluated as active layers within simple capacitive devices for humidity sensing at room temperature. Surface studies using atomic force microscopy revealed a self-assembled nanofibrous network with a thin needle-like structure for the terminal hydroxy example (CP6), devoid in the methyl example (CP1). The sensing performance of each sensor was investigated over a broad range of relative humidity levels as a function of capacitance at room temperature. The sensor CP6 demonstrated favourable features such as high sensitivity (12.2 pF/%RH), quick response/recovery (13 s/20.7 s), wide working range of relative humidity (10%–95% RH), low hysteresis (0.57%), outstanding recyclability, and excellent long-term stability. From the results obtained, hydrophilicity and hydrogen bonding appear to play a vital role in enhancing humidity sensing performance, leading to possible new design directions for simple organic semiconductor-based sensors.

Studies have shown egg-adaptive mutations in influenza vaccine strains that might have impaired protection against circulating A(H3N2) influenza viruses during the 2016–2017 and 2017–2018 seasons. We used the test-negative design and multivariable models to assess vaccine effectiveness against influenza-associated hospitalization and emergency department visits among children (

Background Despite vaccine-induced decreases in US rotavirus (RV) disease, acute gastroenteritis (AGE) remains relatively common. We evaluated AGE pathogen distribution in hospitalized US children in the post–RV vaccine era. Methods From December 2011 to June 2016, the New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based surveillance in hospitalized children with AGE. We tested stools from 2 NVSN sites (Kansas City, Houston) with Luminex x-TAG Gastrointestinal Pathogen Panels (Luminex GPP) and analyzed selected signs and symptoms. Results For 660 pediatric AGE inpatients and 624 age-matched healthy controls (HCs), overall organism detection was 51.2% and 20.6%, respectively (P 1 virus in 39% and >1 bacterium in 14% of specimens. Detection frequencies for AGE subjects vs HCs were norovirus (NoV) 18.5% vs 6.6%, RV 16.1% vs 9.8%, adenovirus 7.7% vs 1.4%, Shigella 4.8% vs 1.0%, Salmonella 3.1% vs 0.1%, and Clostridioides difficile in ≥2-year-olds 4.4% vs 2.4%. More co-detections occurred among AGE patients (37/660, 5.6%) than HCs (14/624, 2.2%; P = .0024). Per logistic regression analysis, ill contacts increased risk for NoV, RV, and Shigella (P Conclusions NoV detection was most frequent; however, RV remained important in hospitalized AGE in the post–RV vaccine era. Continued active surveillance is important to document ongoing vaccine effects, pathogen emergence, and baseline disease burden for new vaccines.

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.

Objective In response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children. Study design This multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21 days apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6–35 months of age received 7.5mcg or 15mcg of hemagglutinin (HA)/dose; children 3–17 years of age received 15mcg HA/dose. Safety and reactogenicity were assessed by measuring the occurrence of solicited injection site and systemic reactions in the 7 days after each vaccination; adverse events were assessed for 42 days and serious adverse events for 7 months after the first vaccination. Immunogenicity was evaluated by measuring hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies to H3N2v prior to and 21 days after each vaccination. Cross-reactivity against seasonal H3N2 strains was evaluated. Results The H3N2v vaccine was well tolerated. Transient mild to moderate injection site tenderness, pain and erythema was observed, with the most commonly reported systemic reactogenicity being irritability in children 6–35 months, and headache and fatigue in children 9–17 years old. Children 6–35 months old, whether they received 7.5mcg or 15mcg/dose, had low HAI and Neut antibody responses after two doses compared to older children. Children under 9 years of age required two doses of vaccine to demonstrate a response, while 9–17 year olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 9–17 years of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses. Conclusion The H3N2v vaccine was safe and immunogenic in children and adolescents. Age-related increases in immunogenicity against H3N2v and seasonal H3N2 viruses were observed, suggesting prior priming via infection and/or immunization. Clinical trial registry: The trial is registered with clinicaltrial.gov: NCT02100436 .

In this report, the gas sensing performance of zinc titanate (ZnTiO3) nanoarrays (NAs) synthesized by coating hydrothermally formed zinc oxide (ZnO) NAs with TiO2 using low-temperature chemical vapor deposition is presented. By controlling the annealing temperature, diffusion of ZnO into TiO2 forms a mixed oxide of ZnTiO3 NAs. The uniformity and the electrical properties of ZnTiO3 NAs made them ideal for light-activated acetone gas sensing applications for which such materials are not well studied. The acetone sensing performance of the ZnTiO3 NAs is tested by biasing the sensor with voltages from 0.1 to 9 V dc in an amperometric mode. An increase in the applied bias was found to increase the sensitivity of the device toward acetone under photoinduced and nonphotoinduced (dark) conditions. When illuminated with 365 nm UV light, the sensitivity was observed to increase by 3.4 times toward 12.5 ppm acetone at 350 °C with an applied bias of 9 V, as compared to dark conditions. The sensor was also observed to have significantly reduced the adsorption time, desorption time, and limit of detection (LoD) when excited by the light source. For example, LoD of the sensor in the dark and under UV light at 350 °C with a 9 V bias is found to be 80 and 10 ppb, respectively. The described approach also enabled acetone sensing at an operating temperature down to 45 °C with a repeatability of >99% and a LoD of 90 ppb when operated under light, thus indicating that the ZnTiO3 NAs are a promising material for low concentration acetone gas sensing applications.

Acute viral respiratory infections are a major health burden in children worldwide. In recent years, rapid and sensitive multiplex nucleic acid amplification tests (NAATs) have replaced conventional methods for routine virus detection in the clinical laboratory.We compared BioFire® FilmArray® Respiratory Panel (FilmArray V1.7), Luminex NxTag® Respiratory Pathogen Panel (NxTag RPP) and Applied Biosystems TaqMan Array Card (TAC) for the detection of eight viruses in pediatric respiratory specimens. Results from the three platforms were analyzed with a single-plex real-time RT-PCR (rRT-PCR) assay for each virus.Of the 170/210 single-plex virus-positive samples, FilmArray detected a virus in 166 (97.6%), TAC in 163 (95.8%) and NxTag RPP in 160 (94.1%) samples. The Positive Percent Agreement (PPA) of FilmArray, NxTag RPP and TAC was highest for influenza B (100%, 100% and 95.2% respectively) and lowest for seasonal coronaviruses on both FilmArray (90.2%) and NxTag RPP (81.8%), and for parainfluenza viruses 1- 4 on TAC (84%). The Negative Percent Agreement (NPA) was lowest for rhinovirus/enterovirus (92.9%, 96.7% and 97.3%) on FilmArray, NxTag RPP and TAC respectively. NPA for all three platforms was highest (100%) for both parainfluenza viruses 1- 4 and influenza A and B, and 100% for human metapneumovirus with TAC as well.All three multiplex platforms displayed high overall agreement (gt;90%) and high NPA (gt;90%), while PPA was pathogen dependent and varied among platforms; high PPA (gt;90%) was observed for FilmArray for all eight viruses, TAC for six viruses and NxTag RPP for 4 viruses.

OBJECTIVES Nonpharmaceutical interventions against coronavirus disease 2019 likely have a role in decreasing viral acute respiratory illnesses (ARIs). We aimed to assess the frequency of respiratory syncytial virus (RSV) and influenza ARIs before and during the coronavirus disease 2019 pandemic. METHODS This study was a prospective, multicenter, population-based ARI surveillance, including children seen in the emergency departments and inpatient settings in 7 US cities for ARI. Respiratory samples were collected and evaluated by molecular testing. Generalized linear mixed-effects models were used to evaluate the association between community mitigation and number of eligible and proportion of RSV and influenza cases. RESULTS Overall, 45 759 children were eligible; 25 415 were enrolled and tested; 25% and 14% were RSV-positive and influenza-positive, respectively. In 2020, we noted a decrease in eligible and enrolled ARI subjects after community mitigation measures were introduced, with no RSV or influenza detection from April 5, 2020, to April 30, 2020. Compared with 2016–2019, there was an average of 10.6 fewer eligible ARI cases per week per site and 63.9% and 45.8% lower odds of patients testing positive for RSV and influenza, respectively, during the 2020 community mitigation period. In all sites except Seattle, the proportions of positive tests for RSV and influenza in the 2020 community mitigation period were lower than predicted. CONCLUSIONS Between March and April 2020, rapid declines in ARI cases and the proportions of RSV and influenza in children were consistently noted across 7 US cities, which could be attributable to community mitigation measures against severe acute respiratory syndrome coronavirus 2.

Background Adult studies have demonstrated intra-season declines in influenza vaccine effectiveness (VE) with increasing time since vaccination; however, data in children are limited. Methods We conducted a prospective, test-negative study of children ages 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers each season in the New Vaccine Surveillance Network during the 2015-2016 through 2019-2020 influenza seasons. Cases were children with an influenza-positive molecular test; controls were influenza-negative children. Controls were matched to cases by illness onset date using 3:1 nearest neighbor matching. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥ 1 dose of influenza vaccine ≥ 14 days before the onset of illness that resulted in hospitalization among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date during each season were estimated using multivariable logistic regression models. Results Of 8,430 hospitalized children (4,781 [57%] male; median age 2.4 years), 4,653 (55%) received ≥ 1 dose of influenza vaccine. On average, 48% and 85% of children were vaccinated by the end of October and December, respectively. Influenza-positive cases (n=1,000; 12%) were less likely to be vaccinated than influenza-negative controls (39% vs. 61%, p< 0.001) and overall VE against hospitalization was 53% (95% CI: 46%, 60%). Pooling data across 5 seasons, the odds of any influenza-associated hospitalization increased 0.96% (95% CI: -0.76%, 2.71%) per week with a corresponding weekly decrease in VE of 0.45% (p=0.275). Odds of hospitalization with time since vaccination increased 0.66% (95% CI: -0.76%, 2.71%) per week in children ≤ 8 years (n=3,084) and 2.16% (95% CI: -1.68%, 6.15%) per week in children 9-17 years (n=771). No significant differences were observed by virus subtype or lineage. Figure 1. Declines in influenza VE over time from 2015-2016 through 2019-2020, overall (a) and by age group (b: ≤ 8 years; c: 9-17 years) Conclusion We observed minimal intra-season declines in VE against influenza-associated hospitalization in U.S. children. Vaccination following Advisory Committee on Immunization Practices guidelines and current timing of vaccine receipt is the best strategy for prevention of influenza-associated hospitalization in children. Disclosures Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)

Parechovirus A (PeV-A) has emerged as a leading cause of infant central nervous system (CNS) infections. Risk factors associated with infant acquisition of PeV-A are not well understood.We conducted prospective PeV-A/enterovirus (EV) CNS infection surveillance, enrolling 461 hospitalized infants90 days old who underwent sepsis evaluations and lumbar puncture during 2011-2012. Infants were grouped by RT-PCR detection of PeV-A, EV, or neither virus (Neg) in CSF. We collected demographic/clinical data and tested specimens from all infants. For 427 mothers, we collected demographic/clinical data and evaluated PeV-A3 and EV shedding, and PeV-A3 neutralizing antibody for 147 mothers.PeV-A was detected in 40 infants (8.7%), 4 in 2011 and 36 in 2012. EV was detected in 35 infants (7.6%), 16 in 2011, and 19 in 2012. PeV-A infected infants presented with irritability, abdominal discomfort, fever, and tachycardia, plus both lymphopenia and absence of CSF pleocytosis which help differentiate PeV-A from EV CNS infection. PeV-A was detected in 9/427 maternal throat swabs; eight of their infants also had PeV-A CNS infection. Infants whose mothers had PeV-A3-positive throat swabs were more likely to be PeV-A3-positive than infants whose mothers had negative throat swabs (relative risk [RR], 13.4 [95% CI, 8.6 - 20.7]). Maternal PeV-A3 seropositivity decreased with increasing maternal age. Mothers of PeV-A-positive infants had lower median PeV-A3 neutralizing titers and were more likely seronegative.Maternal viral shedding, serostatus and neutralization titers appear to be important factors in infant PeV-A3 CNS infections.

Background Parent-reported influenza vaccination history may be valuable clinically and in influenza vaccine effectiveness (VE) studies. Few studies have assessed the validity of parental report among hospitalized children. Methods Parents of 2597 hospitalized children 6 months–17 years old were interviewed from November 1, 2015 to June 30, 2016, regarding their child’s sociodemographic and influenza vaccination history. Parent-reported 2015–2016 influenza vaccination history was compared with documented vaccination records (considered the gold standard for analysis) obtained from medical records, immunization information systems, and providers. Multivariable logistic regression analyses were conducted to determine potential factors associated with discordance between the 2 sources of vaccination history. Using a test-negative design, we estimated VE using vaccination history obtained through parental report and documented records. Results According to parental report, 1718 (66%) children received the 2015–2016 influenza vaccine, and of those, 1432 (83%) had documentation of vaccine receipt. Percent agreement was 87%, with a sensitivity of 96% (95% confidence interval [CI], 95%–97%) and a specificity of 74% (95% CI, 72%–77%). In the multivariable logistic regression, study site and child’s age 5–8 years were significant predictors of discordance. Adjusted VE among children who received ≥1 dose of the 2015–2016 influenza vaccine per parental report was 61% (95% CI, 43%–74%), whereas VE using documented records was 55% (95% CI, 33%–69%). Conclusions Parental report of influenza vaccination was sensitive but not as specific compared with documented records. However, VE against influenza-associated hospitalizations using either source of vaccination history did not differ substantially. Parental report is valuable for timely influenza VE studies.

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

For over a decade, the New Vaccine Surveillance Network (NVSN) has conducted active rotavirus (RVA) strain surveillance in the USA. The evolution of RVA in the post-vaccine introduction era and the possible effects of vaccine pressure on contemporary circulating strains in the USA are still under investigation. Here, we report the whole-gene characterization (eleven ORFs) for 157 RVA strains collected at seven NVSN sites during the 2014 through 2016 seasons. The sequenced strains included 52 G1P[8], 47 G12P[8], 18 G9P[8], 24 G2P[4], 5 G3P[6], as well as 7 vaccine strains, a single mixed strain (G9G12P[8]), and 3 less common strains. The majority of the single and mixed strains possessed a Wa-like backbone with consensus genotype constellation of G1/G3/G9/G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, while the G2P[4], G3P[6], and G2P[8] strains displayed a DS-1-like genetic backbone with consensus constellation of G2/G3-P[4]/P[6]/P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Two intergenogroup reassortant G1P[8] strains were detected that appear to be progenies of reassortment events between Wa-like G1P[8] and DS-1-like G2P[4] strains. Two Rotarix® vaccine (RV1) and two RV5 derived (vd) reassortant strains were detected. Phylogenetic and similarity matrices analysis revealed 2–11 sub-genotypic allelic clusters among the genes of Wa- and DS-1-like strains. Most study strains clustered into previously defined alleles. Amino acid (AA) substitutions occurring in the neutralization epitopes of the VP7 and VP4 proteins characterized in this study were mostly neutral in nature, suggesting that these RVA proteins were possibly under strong negative or purifying selection in order to maintain competent and actual functionality, but fourteen radical (AA changes that occur between groups) AA substitutions were noted that may allow RVA strains to gain a selective advantage through immune escape. The tracking of RVA strains at the sub-genotypic allele constellation level will enhance our understanding of RVA evolution under vaccine pressure, help identify possible mechanisms of immune escape, and provide valuable information for formulation of future RVA vaccines.

Ceftolozane/tazobactam (C/T), a cephalosporin/beta-lactamase inhibitor combination, was evaluated