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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

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 Children can present with overlapping symptoms of acute respiratory illness (ARI) and acute gastroenteritis (AGE). In these cases, it is unclear if the etiologic agent is a respiratory pathogen, gastrointestinal pathogen, or both. Methods We analyzed data collected in Nashville, TN (12/01/2016–2/28/2020) as part of the New Vaccine Surveillance Network, a prospective ARI/AGE surveillance study. Children (< 18 years old) who presented to the emergency department or were admitted with fever and/or respiratory symptoms for < 14 days were enrolled as ARI subjects and had mid-turbinate nasal ± throat swabs collected, while children with ≥1 episode of vomiting and/or ≥3 episodes of diarrhea in 24 hours were enrolled as AGE subjects and had stool collected. Children who met both sets of criteria were dually enrolled. Respiratory specimens were tested for common respiratory viruses by molecular testing and stool specimens were tested for common gastrointestinal (GI) pathogens by Luminex GI Pathogen Panel. We compared detection groups using Pearson’s χ2 test. C. difficile detection in children < 2 years old was considered asymptomatic carriage (n=32). Results We identified 501 dual enrollees, among whom 279 (55.7%) had both a respiratory and stool specimen tested. Overall, 127 (45.5%) had only a respiratory virus detected, 33 (11.8%) had only a GI pathogen detected, 39 (14.0%) had both, and 77 (27.6%) had no detection (Table 1). Vomiting and diarrhea were frequently reported ( >50%) in all dual enrollees whether or not a pathogen was detected (Figure 1). Cough was detected in high frequency in all groups with pathogen detection. Children with respiratory-only or dual detection had a higher frequency of wheezing and shortness of breath than those with GI-only or no detection. The distribution of pathogens did not significantly differ between single and co-detected cases (Figure 2). Table 1Demographic characteristics of N=279* children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status.Figure 1Distribution of signs and symptoms in N=279 children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status. p values represent omnibus comparisons of all four groups.Figure 2Distribution of pathogens detected in N=279 children presenting with symptoms of acute respiratory illness and acute gastroenteritis in Nashville, TN, stratified by detection status. Conclusion Children presenting with overlapping symptoms of ARI and AGE were more likely to have an ARI-associated virus. Lower respiratory symptoms (namely, wheezing and shortness of breath) were more specific for ARI-associated viral detection compared with other signs and symptoms. Disclosures Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

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.

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 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.

Background The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), evolved rapidly in the United States. This report describes the demographic, clinical, and epidemiologic characteristics of 544 U.S. persons under investigation (PUI) for COVID-19 with complete SARS-CoV-2 testing in the beginning stages of the pandemic from January 17 through February 29, 2020. Methods In this surveillance cohort, the U.S. Centers for Disease Control and Prevention (CDC) provided consultation to public health and healthcare professionals to identify PUI for SARS-CoV-2 testing by quantitative real-time reverse-transcription PCR. Demographic, clinical, and epidemiologic characteristics of PUI were reported by public health and healthcare professionals during consultation with on-call CDC clinicians and subsequent submission of a CDC PUI Report Form. Characteristics of laboratory-negative and laboratory-positive persons were summarized as proportions for the period of January 17−February 29, and characteristics of all PUI were compared before and after February 12 using prevalence ratios. Results A total of 36 PUI tested positive for SARS-CoV-2 and were classified as confirmed cases. Confirmed cases and PUI testing negative for SARS-CoV-2 had similar demographic, clinical, and epidemiologic characteristics. Consistent with changes in PUI evaluation criteria, 88% (13/15) of confirmed cases detected before February 12, 2020, reported travel from China. After February 12, 57% (12/21) of confirmed cases reported no known travel- or contact-related exposures. Conclusions These findings can inform preparedness for future pandemics, including capacity for rapid expansion of novel diagnostic tests to accommodate broad surveillance strategies to assess community transmission, including potential contributions from asymptomatic and presymptomatic infections.

Background Nasopharyngeal (NP) specimen testing by reverse transcriptase polymerase chain reaction (RT-PCR) is the standard of care for detecting SARS-CoV-2. Data comparing the sensitivity and specificity of the NP specimen to the less invasive, mid-turbinate (MT) nasal specimen in children are limited. Methods Paired clinical NP and research MT specimens were collected from children Results Out of 907 children, 569 (62.7%) had parental consent and child assent when appropriate to participate and provided paired MT and NP specimens a median of 4 days after symptom onset (range 1-14 days). 16.5% (n = 94) of MT specimens were positive for SARS-CoV-2 compared with 20.0% (n = 114) of NP specimens. The sensitivity of research MT compared to clinical NP specimens was 82.5% (95% CI: 74.2%, 88.9%), specificity was 100.0% (95% CI: 99.2%, 100.0%), and overall agreement was 96.1% (κ = 0.87). The sensitivity of MT specimens decreased with time from 100% (95% CI: 59.0%, 100.0%) on day 1 of illness to 82.1% (95% CI: 73.8%, 88.7%) within 14 days of illness onset; sensitivity was generally >90% when specimens were collected within the first week of illness. Conclusion MT specimens, particularly those collected within the first week of illness, have moderately reduced sensitivity and equivalent specificity to less-tolerated NP specimens in pediatric outpatients. MT specimen use in children may represent a viable alternative to NP specimen collection.

Harmful algal bloom events can result from the rapid growth, or bloom, of photosynthesizing organisms in natural bodies of fresh, brackish, and salt water. These events can be exacerbated by nutrient pollution (e.g., phosphorus) and warming waters and other climate change effects (1); have a negative impact on the health of humans, animals, and the environment; and damage local economies (2,3). U.S. harmful algal bloom events of public health concern are centered on a subset of phytoplankton: diatoms, dinoflagellates, and cyanobacteria (also called blue-green algae). CDC launched the One Health Harmful Algal Bloom System (OHHABS) in 2016 to inform efforts to prevent human and animal illnesses associated with harmful algal bloom events. A total of 18 states reported 421 harmful algal bloom events, 389 cases of human illness, and 413 cases of animal illness that occurred during 2016-2018. The majority of harmful algal bloom events occurred during May-October (413; 98%) and in freshwater bodies (377; 90%). Human and animal illnesses primarily occurred during June-September (378; 98%) and May-September (410; 100%). Gastrointestinal or generalized illness signs or symptoms were the most frequently reported (>40% of human cases and >50% of animal cases); however, multiple other signs and symptoms were reported. Surveillance data from harmful algal bloom events, exposures, and health effects provide a systematic description of these occurrences and can be used to inform control and prevention of harmful algal bloom-associated illnesses.

Background The 2019–2020 influenza season was characterized by early onset with B/Victoria followed by A(H1N1)pdm09 viruses. Emergence of new B/Victoria viruses raised concerns about possible vaccine mismatch. We estimated vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department (ED) visits among children in the United States. Methods We assessed VE among children aged 6 months–17 years with acute respiratory illness and ≤10 days of symptoms enrolled at 7 pediatric medical centers in the New Vaccine Surveillance Network. Combined midturbinate/throat swabs were tested for influenza virus using molecular assays. Vaccination history was collected from parental report, state immunization information systems, and/or provider records. We estimated VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive vs negative for influenza. Results Among 2029 inpatients, 335 (17%) were influenza positive: 37% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval [CI], 52%–71%) for influenza-related hospitalizations, 54% (95% CI, 33%–69%) for B/Victoria viruses, and 64% (95% CI, 49%–75%) for A(H1N1)pdm09. Among 2102 ED patients, 671 (32%) were influenza positive: 47% with influenza B/Victoria alone and 42% with influenza A(H1N1)pdm09 alone. VE was 56% (95% CI, 46%–65%) for an influenza-related ED visit, 55% (95% CI, 40%–66%) for B/Victoria viruses, and 53% (95% CI, 37%–65%) for A(H1N1)pdm09. Conclusions Influenza vaccination provided significant protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the 2 predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus subclade.

Influenza A(H1N1)pdm09 viruses initially predominated during the US 2018-2019 season, with antigenically drifted influenza A(H3N2) viruses peaking later. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits among children in the New Vaccine Surveillance Network.We tested children 6 months to 17 years with acute respiratory illness for influenza using molecular assays at 7 pediatric hospitals (ED patients5 years at 3 sites). Vaccination status sources were parental report, state immunization information systems and/or provider records for inpatients, and parental report alone for ED patients. We estimated VE using a test-negative design, comparing odds of vaccination among children testing positive versus negative for influenza using multivariable logistic regression.Of 1792 inpatients, 226 (13%) were influenza-positive: 47% for influenza A(H3N2), 36% for A(H1N1)pdm09, 9% for A (not subtyped), and 7% for B viruses. Among 1944 ED children, 420 (22%) were influenza-positive: 48% for A(H3N2), 35% for A(H1N1)pdm09, 11% for A (not subtyped), and 5% for B viruses. VE was 41% (95% confidence interval [CI], 20% to 56%) against any influenza-related hospitalizations, 41% (95% CI, 11% to 61%) for A(H3N2), and 47% (95% CI, 16% to 67%) for A(H1N1)pdm09. VE was 51% (95% CI, 38% to 62%) against any influenza-related ED visits, 39% (95% CI, 15% to 56%) against A(H3N2), and 61% (95% CI, 44% to 73%) against A(H1N1)pdm09.The 2018-2019 influenza vaccine reduced pediatric influenza A-associated hospitalizations and ED visits by 40% to 60%, despite circulation of a drifted A(H3N2) clade.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalized acute respiratory illness (ARI) among young children. With RSV vaccines and immunoprophylaxis agents in clinical development, we sought to update estimates of US pediatric RSV hospitalization burden. METHODS: Children RESULTS: Among 2969 hospitalized children included in analyses, 1043 (35%) tested RSV-positive; 903 (87%) children who were RSV-positive were CONCLUSIONS: During the 2015–2016 season, RSV infection was associated with one-third of ARI hospitalizations in our study population of young children. Hospitalization rates were highest in infants

IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19.MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20–February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing.ResultsAmong the 12 patients, median age was 53 years (range: 21–68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2–3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients.ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

Background Influenza C virus (ICV) is associated with acute respiratory infection (ARI); however, the burden of ICV is not well-described. We sought to determine the burden and characteristics of ICV in a prospective, population-based cohort. Methods The study was conducted within the New Vaccine Surveillance Network (NVSN), a CDC-led, seven-site network that performs population-based surveillance for ARI in children < 5 years. Nasal/throat swabs were collected from emergency department (ED) or inpatient children with ARI, or healthy controls in clinic, between 12/05/2016-10/31/2019 and tested by real-time RT-PCR for ICV and other respiratory viruses. Preliminary data were extracted and demographic/clinical features of ICV+ cases analyzed. We sequenced the hemagglutinin-esterase (HE) gene from ICV+ Pittsburgh samples. Results Among 19,321 children with ARI or healthy controls enrolled and tested for ICV from 2016-2019, 115/17,668 (0.7%) ARI cases and 8/1653 (0.5%) healthy controls tested positive for ICV. The median age of ICV+ ARI subjects was 19 months (IQR 10,46) and 81(70%) were ≤36 months. 42.6% (49) were white, 33.9% (39) black, and 16.5% (19) Hispanic, with the remainder Asian or unknown; 56.5% (62) attended daycare. Among ICV+ ARI cases, 67.8% (78) had fever, 94.8% (109) cough, and 60.8% (70) wheezing. 45.2% (52) ICV+ cases occurred in 2016-17, 6.5% (8) in 2017-2018, and 47.8% (55) in 2018-19 (Table). 40% (46) of ICV+ cases were seen in the ED, while the remainder were inpatients. Median length of stay was 2d (IQR,1-3) with 15 admitted to ICU. 67.8% (78/115) ARI cases had 1 or 2 co-detected pathogens, with rhinovirus (26), respiratory syncytial virus (26), and adenovirus (14) most frequently co-detected. ARI symptoms including fever, myalgias, chills, and wheezing did not differ significantly between coinfected subjects and those who were only ICV+. HE sequences were in the two currently circulating Kanagawa and Sao Paulo lineages. ICV+ Cases by Site and Year Conclusion ICV was an uncommon cause of ARI symptoms leading to healthcare encounters in young children. The prevalence varied year-to-year and between different geographic regions. Most children infected with ICV were ≤3 years old and had co-detected pathogens. ICV was similarly rarely detected in healthy controls. Disclosures Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial) 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)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member)

Background The 2019–20 influenza season was predominated by early onset B/Victoria viruses followed by A(H1N1)pdm09 virus circulation. Over 95% of circulating B/Victoria viruses were subclade V1A.3, different from the Northern Hemisphere vaccine strain. Annual estimates of influenza vaccine effectiveness (VE) are important because of frequent changes in circulating and vaccine viruses. Methods We assessed VE among children 6 months–17 years old with acute respiratory illness and Results Among 2022 inpatients, 324 (16%) were influenza positive: 38% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone (Table). Among 2066 ED children, 653 (32%) were influenza positive: 45% with influenza B/Victoria alone and 43% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval [CI], 51%–70%) against any influenza-related hospitalizations, 68% (95% CI, 55%–78%) for A(H1N1)pdm09 and 55% (95% CI, 35%–69%) for B/Victoria. VE by age group for any influenza-related hospitalizations was 57% (95% CI, 40%–69%) among children 6 months to < 5 years and 66% (95% CI, 49%–77%) among children 5–17 years. VE was 53% (95% CI, 42%–62%) against any influenza-related ED visits, 46% (95% CI, 28%–60%) for A(H1N1)pdm09 and 54% (95% CI, 39%–66%) for B/Victoria. VE by age group was 52% (95% CI, 37%–63%) among children 6 months to < 5 years and 42% (95% CI, 16%–60%) among children 5–17 years. Conclusion Influenza vaccination in the 2019–20 season provided substantial protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the two predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus V1A.3 subclade. Disclosures Janet A. Englund, MD, AstraZeneca (Scientific Research Study Investigator)GSK group of companies (Scientific Research Study Investigator)Meissa vaccines (Consultant)Merck (Scientific Research Study Investigator)Sanofi Pasteur (Consultant) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (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)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support) Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial)

Background Respiratory syncytial virus (RSV) is a major cause of severe acute respiratory illnesses (ARI) in young children. Circulation of RSV subgroups A and B can vary by season and geographic location, and may have implications for disease susceptibility, outcomes, and prevention measures. We investigated RSV subgroup distribution among samples collected in the New Vaccine Surveillance Network. Methods Prospective active surveillance for hospitalized ARI was conducted from November 1, 2015 to June 30, 2016 among children < 12 months of age at seven pediatric hospital sites. Mid-turbinate nasal and throat flocked swabs (combined when both available) and/or tracheal aspirates were collected and tested for RSV at each site using real-time reverse transcription polymerase chain reaction (rRT–PCR) assays; RSV A/B subgroup results were available from four sites that did their own subgroup testing (Cincinnati, Kansas City, Houston, and Oakland). At three sites (Rochester, Nashville, Seattle), approximately 50 RSV-positive specimens were sampled based on the monthly distribution for each site and 1:1 distribution by gender, and then assayed for subgroup at CDC. Patient information was obtained from medical records; chi-square tests were used to compare the distribution of A and B subgroups by site. Results Of 704 RSV-positive hospitalized infants, subgroup data from 586 were analyzed; 340 (58%) were RSV A and 246 (42%) were RSV B. The median age for both RSV A and RSV B patients was 2 months. Subgroup distribution varied by geographic location, with the overall proportion of RSV A ranging from 18–83% across sites (P < 0.01). Peak RSV A and B detections by month varied by site, occurring from November–February (figure). Conclusion During the 2015–2016 season, RSV A and B subgroups co-circulated among hospitalized infants enrolled at seven US sites. The predominance of RSV subgroup varied by geographic location. Continued surveillance and additional subgroup testing over multiple seasons should improve understanding of the epidemiologic significance of RSV infections by subgroup. Disclosures All authors: No reported disclosures.

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

Background Influenza vaccination has been shown to reduce influenza risk in pregnant women and their infants who are not yet age-eligible for vaccine. Ascertainment of vaccination history is important for vaccine safety and effectiveness evaluations. Our goals were to (a) determine coverage, location, and timing of maternal influenza vaccination and (b) compare a subset of self-reported influenza vaccinations with documented vaccine records. Methods We enrolled children < 18 years. with acute respiratory illness in 7 pediatric hospitals and emergency departments in the New Vaccine Surveillance Network from December 1, 2016 to October 31, 2018. We interviewed all mothers of enrolled infants < 1 year, and obtained mother’s influenza vaccine information while pregnant. As an option, sites obtained maternal influenza vaccine records from reported sources (e.g., registries, provider records, pharmacies). Results Among 5,458 mothers, 2,944 (54%) self-reported receiving influenza vaccine during pregnancy (57% in 2016–2017; 51% in 2017–2018), varying from 49% to 74% by site. Among self-reported vaccinees, 17%, 36%, and 47% received vaccine during their first, second, and third trimester, respectively. Most women (76%) were vaccinated at their OB/GYN or midwife office, 7% at their primary care provider, 7% at their workplace, and 5% at a retail pharmacy. Among 1,338 infants < 6 months. during early influenza season (i.e., born from June to August) and thus ineligible for vaccination, only 46% of mothers reported receiving vaccine during pregnancy (42% reported not receiving it, 12% were unsure). Of 2,242 women for whom vaccine verification was attempted, 1,491 (67%) self-reported receiving influenza vaccine during pregnancy; of those, documentation of vaccine receipt was found for 901 (60%). Conclusion Influenza vaccination coverage among pregnant women was suboptimal, potentially increasing the risk of influenza in unvaccinated pregnant women. Infants born to unvaccinated women, particularly those born from June to August, may also be at higher risk since they are not age-eligible to receive vaccine before influenza season. The optimal approach to ascertainment of maternal vaccination history with accuracy and completeness merits further investigation. Disclosures All authors: No reported disclosures.

Background Respiratory viruses are associated with most asthma exacerbations (AEx) in children; however, the role of different viruses in AEx is unclear. We describe respiratory virus detections among pediatric inpatients with AEx (AEx-inpatients). Methods Through active, prospective surveillance at 7 US medical centers, we enrolled inpatients ( Results We tested 3,897 inpatients with ARI; of whom, 954 were AEx-inpatients. Most AEx-inpatients (741/954 [78%]) reported an asthma/RAD history. Viruses were more frequently detected among AEx-inpatients Conclusion AEx-inpatients Disclosures All authors: No reported disclosures.

Background Acute pharyngitis is mostly of viral etiology; GAS, the leading bacterial cause, comprises 20%–30% of pediatric pharyngitis. Patients with pharyngitis and additional acute respiratory illness (ARI) symptoms more suggestive of viral etiology, including cough, rhinorrhea and conjunctivitis, are not recommended for GAS testing. The use of highly sensitive GAS PCR assays in patients with sore throat and viral ARI symptoms may detect GAS colonization and lead to antibiotic overuse. We evaluated GAS PCR in viral ARI inpatients and asymptomatic healthy controls (HC) to illustrate the potential negative impact of offering GAS PCR test in poorly selected patients. Methods In November 2015–June 2016, 458 ARI inpatients (< 18 years) and 205 HC (< 5 years, no ARI symptoms within 72 hours) in Kansas City were enrolled in the New Vaccine Surveillance Network study. Mid-turbinate and throat swabs were tested by multiplex respiratory panel PCR and leftover nucleic acid extracts were further tested by real-time GAS PCR. Presenting symptoms of cough, rhinorrhea and/or conjunctivitis, plus sore throat were assessed by parent interview. Results Overall, 6.3% of HC < 5 years old and 8.7% of ARI subjects < 18 years were GAS (+); mostly in the 3–15 year old age group (25/40, 62.5%). Among 3–15 year old GAS (+) ARI subjects, 92.8% had cough, 76.2% rhinorrhea and 37.2% conjunctivitis; 80% had > 2 of 3 symptoms noted above. Among 40 GAS (+) ARI subjects, a virus was co-detected in 34 (85%), among which Rhinovirus/Enterovirus were predominant 22/34 (55%). Of the 130 (28%) ARI subjects with sore throat, more tested positive for viruses (107/130, 82.3%) than for GAS (9/130, 6.9%). All GAS (+) HC (13/205, 6.3% overall) were < 3 year olds. Conclusion PCR detected GAS in 6.3% HC < 5 years old and 8.7% ARI subjects < 18 years old; mostly in 3- to 15-year-old ARI subjects. Most GAS (+) ARI children had cough, rhinorrhea or conjunctivitis and/or virus co-detection suggesting GAS carriage. Our data demonstrate that GAS may be detected in patients with a low clinical suspicion for acute GAS pharyngitis. These findings highlight the need to review patient selection and exercise caution in implementing highly sensitive GAS PCR assays especially in such clinical settings. Disclosures All authors: No reported disclosures.

Background Human adenovirus (HAdV) types 1–7, 11, 14, 16, and 21 within species B, C, and E are commonly associated with acute respiratory illnesses (ARI) in children. We sought to compare demographics, clinical characteristics, and outcomes of HAdV types with children who presented with fever and/or respiratory symptoms. Methods Children < 18 years with fever and/or ARI seen at Vanderbilt Children’s Hospital inpatient and emergency department settings from December of 2016 to October of 2018 were enrolled. Interviews and chart abstraction were conducted. Mid-turbinate nose and throat swab specimens were collected and tested by real-time RT-PCR for common respiratory viruses including HAdV. HAdV molecular typing was performed by type-specific real-time PCR assays for types 1–7, 11, 14, 16, and 21 targeting the hexon gene using published methods. Results Of 5111 ARI cases, 206 (4%) were HAdV-positive with a median age of 16 months (IQR 9–30); 57% male, 47% White, 40% Black, 33% Hispanic, 20% admitted, and 24% of hospitalized required oxygen support. Of the 206, 186 (90%) were able to be typed with more than one types detected in 13 (7%) cases. Distribution of HAdV types among single detections (n = 173) is shown in Figure 1; HAdV-1 and HAdV-2 were most common. Children with HAdV-2 were younger (median age 12 months vs. 15 months (HAdV-1) and 59 months (all other types), P < 0.001), and those with HAdV-1 were less likely to be male (44% vs. 65% for both HAdV-2 and other types, P = 0.029). Figure 2 displays HAdV detections over time, with winter and early spring peaks. Co-detection with other respiratory viruses occurred in 47% of cases; the most common among typable HAdV were rhinovirus/enterovirus in 30/186 (16%) and RSV in 19/186 (10%). Distribution among HAdV types is shown in Figure 3. Conclusion HAdV-1 and HAdV-2 were more prevalent than other HAdV types over two respiratory seasons in the Nashville area with peak cases in December-March. Children with HAdV-1 and HAdV-2 had some demographic differences. Further studies with a larger sample size for HAdV typing are needed in the pediatric population to determine whether additional clinically-relevant differences between HAdV types exist. Disclosures All authors: No reported disclosures.

Background Rhinovirus (RV) quantitation by reverse transcription-quantitative PCR is limited by variable amplification efficiency across genotypes. We used a precise viral quantitation method, reverse transcription-digital PCR (RT-dPCR), to characterize the role of viral load in clinical outcomes and in viral co-infections in children presenting to a tertiary hospital emergency department (ED). Methods Children < 18 years with respiratory symptoms for ≤ 14 days were enrolled from December 1, 2016 to December 31, 2018. Participants had nasal and throat specimens obtained and multiplex PCR testing with a commercial assay (FilmArray; bioMerieux). RV positive samples were quantified using RT-dPCR. Samples with sufficient viral load were sequenced at a 543 bp fragment of the RV VP4/VP2 region. RV species were assigned by comparison to RV sequences in GenBank using BLAST. Clinical data were collected into REDCap. T-tests were used to compare mean viral loads between groups. Results Of 1703 children enrolled in the ED, 697 were RV/enterovirus positive by FilmArray [median age 18 months (interquartile range 9–39 months)]. Of 590 subjects with viral load available, 276 (47%) were admitted to the hospital. Among RV mono-infections (N = 434), mean viral load did not differ between subjects admitted vs. discharged from the ED (7.03 log copies/mL for both, P = 0.97). Among admitted subjects with RV mono-infection, viral load also did not differ between subjects requiring supplemental oxygen vs. not (7.01 vs. 7.10 log copies/mL, P = 0.6). Subjects with viral co-infections had lower mean RV viral loads (6.31 log copies/mL) compared with those with RV only (7.03 log copies/mL; P < 0.001) (figure). Significantly different RV viral loads were seen with co-infections with respiratory syncytial virus (RSV), metapneumovirus (MPV) and parainfluenza (PIV), but not with influenza, adenovirus or coronavirus. In 525 sequenced samples (46% RV-A, 4% RV-B, 50% RV-C), viral load did not vary between RV viral species (P = 0.09). Conclusion Precise viral quantitation demonstrates children co-infected with RV and RSV, MPV or PIV have lower nasal viral loads than those with RV alone. Among RV mono-infections, RV viral load was not associated with admission or need for supplemental oxygen. Disclosures All authors: No reported disclosures.

Background Noroviruses are the leading cause of acute gastroenteritis (AGE) outbreaks in the United States. However, outbreaks attributed to norovirus often lack confirmation by diagnostic testing. Clinical and epidemiologic profiles, such as the Kaplan criteria (vomiting in >50% cases, mean incubation period of 24–48 hours, mean duration of illness for 12–60 hours, and negative bacterial stool culture), have been used to distinguish norovirus outbreaks from those caused by bacteria. Methods Kaplan criteria were evaluated among 10 023 outbreaks reported to the National Outbreak Reporting System (NORS) during 2009–2012. An alternate profile for distinguishing norovirus outbreaks from outbreaks caused by nonviral etiologies was identified using classification and regression tree (CART) modeling. Performance of the Kaplan criteria and alternate profile were compared among laboratory-confirmed outbreaks. Results The Kaplan criteria were 63.9% sensitive and 100% specific in discriminating norovirus from nonviral outbreaks, but only 3.3% of norovirus and 1.2% of nonviral outbreaks reported all criteria. Clinical and epidemiologic characteristics identified with CART modeling (ratio of proportion of cases with fever to the proportion of cases with vomiting Conclusions Compared with the Kaplan criteria, the CART-derived profile had higher sensitivity and broader application in reported AGE outbreaks. Thus, this alternate profile may provide a more useful tool for identifying norovirus during outbreak investigations.

Background Antiviral (AV) therapy is recommended for children < 2 years, hospitalized, or with underlying conditions (UC) and suspected influenza (flu). We sought to compare demographic and clinical characteristics by AV prescription in flu-positive children who presented to the emergency department (ED) and determine the percentage of AV prescription in these high-risk children. Methods Children < 18 years who presented with respiratory symptoms and/or fever at seven New Vaccine Surveillance Network sites were enrolled. We conducted interviews, obtained mid-turbinate nasal and/or throat swabs for molecular flu testing (results unknown to providers), and reviewed medical charts for AV prescription after presenting to the ED. These are preliminary data. Results From December 2016 to June 2018, 9,524 subjects were enrolled and tested for flu; 1,260 (13%) were flu-positive by research testing; 54% were male, median age was 41 months, and 23% were prescribed an AV. The frequency of AV prescription differed by study site (Figure 1). Among research-tested flu-positive patients, AV were prescribed to 25% of children < 2 years, 31% of children with UC, and 51% admitted to the hospital from the ED (Table 1). Of the 388 (31%) clinically-tested flu-positive patients, 52%, 66%, and 77% of the same high-risk groups were prescribed an AV, respectively. Conclusion AV prescriptions varied by study site and differences by race, ethnicity, and clinical presentation were noted. Clinical testing was associated with higher use of AV treatment in appropriate target patients. Efforts are needed to understand AV use patterns and improve prescription rates in recommended patients. Disclosures All authors: No reported disclosures.