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BackgroundPatterns of respiratory syncytial virus (RSV) co-detection with other viruses may have been disrupted during the coronavirus disease 2019 (COVID-19) pandemic, but the clinical impact of viral co-detections with RSV is not well-established. We aimed to explore the frequency and clinical outcomes associated with RSV single detection and co-detection before and during the pandemic.MethodsWe conducted a single-center retrospective cohort study of all children and adults with respiratory samples tested using a respiratory pathogen panel (RPP; 01/01/2018–11/30/2022), a provider-ordered polymerase chain reaction–based assay that detects respiratory pathogens. We stratified our cohort into age groups: 0–4, 5–17, 18–64, and ≥65 years old. Among RSV-positive samples, we compared the proportion of samples with single RSV detection before and during the pandemic and the patterns of specific viral co-detections. We compared the odds of hospitalization, oxygen use, intensive care unit admission, and intubation between individuals with RSV single detection and those with co-detection.ResultsAmong 57,940 samples collected during the study period, 3,986 (6.9%) were RSV-positive. RSV was co-detected with at least one other virus in 1,231/3,158 (39.0%), 104/348 (29.9%), 49/312 (15.7%), and 21/168 (12.5%) of samples from individuals 0–4, 5–17, 18–64, and ≥65 years old, respectively. The relative frequencies of RSV single detection and co-detection were comparable before and during the pandemic except in children 0–4 years old, in whom single RSV detections were more prevalent before (63.7%) than during (59.5%) the pandemic (p=0.021). In children 0–4 years old, RSV co-detection was associated with lower odds of hospitalization compared to single RSV detection, and RSV co-detection with parainfluenza viruses or human rhinovirus/enterovirus was associated with significantly lower odds of hospitalization, while RSV/SARS-CoV-2 co-detection was associated with higher odds of ICU admission. In adults ≥65 years old, RSV co-detection was associated with lower odds of oxygen use.ConclusionThe proportion of RSV co-detection did not appreciably vary before and during the pandemic, except in young children, though the combinations of co-detected viruses did vary. Our findings suggest that the clinical impact of RSV co-detection with other viruses may be age-associated and virus-specific.

Background Lower respiratory tract infections are the leading cause of mortality in young children globally. In many resource-limited settings clinicians rely on guidelines such as IMCI or ETAT + that promote empiric antibiotic utilization for management of acute respiratory illness (ARI). Numerous evaluations of both guidelines have shown an overall positive response however, several challenges have also been reported, including the potential for over prescribing of unnecessary antibiotics. Methods We conducted a prospective study of children

Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare sequela that typically develops 2–6 weeks after SARS-CoV-2 infection. According to CDC recommendations, children who recover from MIS-C should be vaccinated 90 days after diagnosis, but safety and immunogenicity data are lacking. Our aim was to evaluate the safety and immunogenicity of one dose of the BNT162b2 vaccine in children with a history of MIS-C. Methods We conducted a longitudinal study of children with MIS-C admitted to Monroe Carell Jr. Children's Hospital at Vanderbilt from 7/11/2020 to 3/23/2022. Children were eligible if they met CDC’s MIS-C criteria and had blood collected before and after SARS-CoV-2 vaccination. Clinical data were obtained from medical records and injection site and systemic reactions were recorded for a week following SARS-CoV-2 vaccination via memory aids. IgG against SARS-CoV-2 nucleocapsid (N), spike receptor-binding domain (RBD), and spike extracellular domain (ECD) was detected using an enzyme-linked immunosorbent assay. The first anti-RBD and anti-ECD levels prevaccination and postvaccination were compared using the paired-samples t-test. Results Seven children were included, of whom five were male and five were non-Hispanic White. The first blood sample was collected 3–44 days following admission. The median age at admission was 15.8 years (IQR, 10.5–14.7 years), and the median time from admission to vaccination was 7 months (IQR, 6–8 months). Five children each had injection site or systemic reactions (Figure 1); the majority were mild or moderate and occurred within 2 days of vaccination. Children were followed for a median of 5.6 months (4.3–6.2 months) postvaccination; none developed MIS-C recurrence. Following vaccination, mean anti-RBD and anti-ECD levels increased by 2.0 (1.2–2.9; p < 0.001) and 1.9 (1.2–2.6; p < 0.001) absorbance units, respectively (Figure 2). A sensitivity analysis excluding children with antibody evidence of reinfection (increase in anti-N level ≥ 0.5) showed similar results. Figure 1Safety of SARS-CoV-2 vaccination in children with a history of MIS-C. Figure 2 Immunogenicity of SARS-CoV-2 vaccination in children with a history of MIS-C. The best-fit lines (LOESS) are indicated in black. The dashed line indicates the day of vaccination. Conclusion SARS-CoV-2 vaccination is safe and immunogenic in children with a history of MIS-C, with no documented recurrence of MIS-C–like illness. Further studies are needed to determine the optimal timing, safety, and immunogenicity of vaccination following MIS-C. Disclosures Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

BACKGROUND Little is known about the epidemiology and outcomes of neurologic complications associated with coronavirus disease 2019 (COVID-19) in children. METHODS We performed a cross-sectional study of children 2 months to RESULTS Of 15 137 children hospitalized with COVID-19, 1060 (7.0%) had a concurrent diagnosis of a neurologic complication. The most frequent neurologic complications were febrile seizures (3.9%), nonfebrile seizures (2.3%), and encephalopathy (2.2%). Hospital LOS, ICU admission, ICU LOS, 30 day readmissions, deaths, and hospital costs were higher in children with neurologic complications compared with those without complications. Factors associated with lower odds of neurologic complications included: younger age (adjusted odds ratio [aOR]: 0.97; 95% confidence interval [CI]: 0.96–0.98), occurrence during delta variant predominant time period (aOR: 0.71; 95% CI: 0.57–0.87), presence of a nonneurologic complex chronic condition (aOR: 0.80; 95% CI: 0.69–0.94). The presence of a neurologic complex chronic condition was associated with higher odds of neurologic complication (aOR 4.14, 95% CI 3.48–4.92). CONCLUSIONS Neurologic complications are common in children hospitalized with COVID-19 and are associated with worse hospital outcomes. Our findings emphasize the importance of COVID-19 immunization in children, especially in high-risk populations, such as those with neurologic comorbidity.

Background Whether acute respiratory illnesses (ARIs), often associated with virus detection, are associated with lower risk for subsequent ARI remains unclear. We assessed the association between symptomatic ARI and subsequent ARI in young children. Methods In a prospective cohort of Peruvian children Results Among 983 index ARI, 339 (34%) had an ARI event during follow-up, compared with 876/2826 (31%) matched asymptomatic observations. We found no significant association of index ARI and subsequent ARI risk during follow-up overall (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI], .98–1.23) or when limited to index ARI with respiratory viruses detected (aOR, 1.03; 95% CI, .86–1.24). Similarly, when the outcome was limited to ARI in which viruses were detected, no significant association was seen (aOR, 1.05; 95% CI, .87–1.27). Conclusions ARIs were not associated with short-term protection against subsequent ARI in these children. Additional longitudinal studies are needed to understand drivers of recurrent ARI in young children.

Rhinovirus (RV)-specific surveillance studies in the Middle East are limited. Therefore, we aimed to study the clinical characteristics, outcomes, and seasonality of RV-associated acute respiratory infection among hospitalized young children in Jordan. We conducted a prospective viral surveillance study and enrolled children2 years old admitted to a large public hospital in Amman, Jordan (2010-2013). Demographic and clinical data were collected by structured interviews and chart abstractions. Nasal and/or throat swabs were collected and tested for a panel of respiratory viruses, and RV genotyping and speciation was performed. At least one virus was detected in 2641/3168 children (83.4%). RV was the second most common virus detected (n = 1238; 46.9%) and was codetected with another respiratory virus in 730 cases (59.0%). Children with RV codetection were more likely than those with RV-only detection to have respiratory distress but had similar outcomes. RV-A accounted for about half of RV-positive cases (54.7%), while children with RV-C had a higher frequency of wheezing and reactive airway disease. RV was detected year-round and peaked during winter. In conclusion, though children with RV codetection had worse clinical findings, neither codetection nor species affected most clinical outcomes.

The COVID-19 pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for Infectious Diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, women faculty, underrepresented in medicine and science faculty, and particularly ESF experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic.

Compared to adults, the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness in children has been lower and less severe. However, reports comparing SARS-CoV-2 infection among children and adults are limited. As part of our longitudinal cohort study of adults and children with SARS-CoV-2 infection and their household contacts in Nashville, Tennessee, we compared the clinical characteristics and outcomes of SARS-CoV-2 infections between children and adults. Children were more likely to be asymptomatically infected and had a shorter illness duration compared to adults. The differences observed in clinical presentation across ages may inform symptom-specific testing, screening, and management algorithms.

Purpose of review To review the epidemiological characteristics and clinical features associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children in the United States. Recent findings In the United States, the majority of SARS-CoV-2 infections in children have been mild illnesses, with those 5-17 years of age having the highest frequency. Specifically, the incidence of SARS-CoV-2 in children is two times higher in adolescents (12-17 years) than younger school-aged children (5-11 years). Despite the higher case counts in older children, 10% of pediatric hospitalizations have been in infants less than one year. In addition, severe respiratory and renal complications, hospitalization, and even death have been documented in children. Summary Clinical manifestations of SARS-CoV-2 infection in children range from asymptomatic to severe respiratory distress, with mild nonspecific symptoms being the most commonly reported. The broad clinical presentation and the frequency of asymptomatic or minimally symptomatic infections in children pose challenges for controlling and detecting SARS-CoV-2. However, severe disease has been noted in children with associated medical complications and death. Thus, additional active surveillance and research is needed to understand the burden children contribute to the SARS-CoV-2 pandemic in the United States.

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC).In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data.Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals.Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted.US Centers for Disease Control and Prevention.

While the detection of SARS-CoV-2 in samples preserved in viral transport medium (VTM) by RT-PCR is a standard diagnostic method, this may preclude the study of bacterial respiratory pathogens from the same specimen. It is unclear if the use of skim milk, tryptone, glucose, and glycerin (STGG) transport media, used for study of respiratory bacteria, allows an efficient and concurrent study of SARS-CoV-2 infections.To determine the concordance in SARS-CoV-2 detection by real time RT-PCR between paired nasopharyngeal (NP) swabs preserved in STGG and nasal (NS) swabs preserved in VTM.Paired samples of NP and NS swabs were collected between December 2020 and March 2021 from a prospective longitudinal cohort study of 44 households and 132 participants from a peri-urban community (Lima, Peru). NP and NS swabs were taken from all participants once and twice per week, respectively, independent of respiratory symptoms. STGG medium was used for NP samples and VTM for NS samples. Samples were analyzed for SARS-CoV-2 by RT-PCR for N, S and ORF1ab targets. We calculated the concordance in detections between sample types and compared the RT-PCR cycle thresholds (Ct).Among the 148 paired samples, we observed a high concordance in detections between NP and NS samples (agreement = 94.59%; Kappa = 0.79). Median Ct values were statistically similar between sample types for each RT-PCR target: N, S and ORF1ab (p = 0.11, p = 0.71 and p = 0.11, respectively).NP swabs collected in STGG medium are reliable alternatives to nasal swabs collected in VTM for the study of SARS-CoV-2.

The effects of community closures and relaxing social distancing restrictions on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by occupational risk remain unclear. Therefore, we evaluated the impact of community closures and reopening phases with the prevalence of testing SARS-CoV-2-positive among nonessential and essential workers.We constructed a cross-sectional cohort from March 20 to July 31, 2020, of 344 adults from Metropolitan Nashville, Tennessee. We performed an unconditional logistic regression model to evaluate the impact of community closures and phase implementation on testing SARS-CoV-2 positive by occupation to estimate adjusted prevalence odds ratios (aPORs) and 95% confidence intervals (CIs).During a stay-at-home/Phase I order, those with non-essential occupations had 59% decreased prevalence odds (aPOR:0.41; 95% CI: 0.20-0.84) of testing SARS-CoV-2-positive compared to when no restrictions were in place. Persons with essential occupations had four times the prevalence odds of testing SARS-CoV-2-positive (aPOR:4.19; 95% CI:1.57-11.18) compared with nonessential occupations when no community restrictions were established.Stay-at-home restrictions were associated with a lower risk of SARS-CoV-2 infection in the community for nonessential workers. Essential employees remained at increased risk for SARS-CoV-2, including when no community restrictions were in place and vaccines were not available. This study supports targeting prevention measures for these high-risk occupations.

Antibiotics are widely used in neonatal intensive care units (NICUs). We conducted a cross-sectional analysis of antibiotic use across US NICUs to evaluate overall, broad-spectrum, and combination antibiotic use. Patterns of antibiotic use varied by medical versus surgical service line, hospital, and geographic location.

Background The spectrum of illness and predictors of severity among children with SARS-CoV-2 infection are incompletely understood. Methods Active surveillance was performed for SARS-CoV-2 by polymerase chain reaction among symptomatic pediatric patients in a quaternary care academic hospital laboratory beginning March 12, 2020. We obtained sociodemographic and clinical data 5 (+/-3) and 30 days after diagnosis via phone follow-up and medical record review. Logistic regression was used to assess predictors of hospitalization. Results The first 1000 symptomatic pediatric patients were diagnosed in our institution between March 13, 2020 and September 28, 2020. Cough (52 %), headache (43 %), and sore throat (36 %) were the most common symptoms. Forty-one (4 %) were hospitalized; 8 required ICU admission, and 2 required mechanical ventilation ( Conclusions In 1000 pediatric patients with systematic follow-up, most SARS-CoV-2 infections were mild, brief, and rarely required hospitalization. Pediatric predictors of hospitalization included comorbid conditions, Black race, Hispanic ethnicity, dyspnea and vomiting and were distinct from those reported among adults.

BACKGROUND AND OBJECTIVES:Patient complexity at US children’s hospitals is increasing. Hospitals experience concurrent pressure to reduce length of stay (LOS) and readmissions, yet little is known about how these common measures of resource use and quality have changed over time. Our aim was to examine temporal trends in medical complexity, hospital LOS, and readmissions across a sample of US children’s hospitals.METHODS:Retrospective cohort study of hospitalized patients from 42 children’s hospitals in the Pediatric Health Information System from 2013 to 2017. After excluding deaths, healthy newborns, obstetric care, and low volume service lines, we analyzed trends in medical complexity, LOS, and 14-day all-cause readmissions using generalized linear mixed effects models, adjusting for changes in patient factors and case-mix.RESULTS:Between 2013 and 2017, a total of 3 355 815 discharges were included. Over time, the mean case-mix index and the proportion of hospitalized patients with complex chronic conditions or receiving intensive care increased (P < .001 for all). In adjusted analyses, mean LOS declined 3% (61.1 hours versus 59.3 hours from 2013 to 2017, P < .001), whereas 14-day readmissions were unchanged (7.0% vs 6.9%; P = .03). Reductions in adjusted LOS were noted in both medical and surgical service lines (3.6% and 2.0% decline, respectively; P < .001).CONCLUSIONS:Across US children’s hospitals, adjusted LOS declined whereas readmissions remained stable, suggesting that children’s hospitals are providing more efficient care for an increasingly complex patient population.

Increased nasopharyngeal pneumococcal (Streptococcus pneumoniae) colonization density has been associated with invasive pneumococcal disease, but factors that increase pneumococcal density are poorly understood. We evaluated pneumococcal densities in nasopharyngeal samples from asymptomatic young children from Peru and their association with subsequent acute respiratory illness (ARI). Total pneumococcal densities (encompassing all present serotypes) during asymptomatic periods were significantly higher when a respiratory virus was detected versus when no virus was detected (p

Background Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood. Methods Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types. Results AS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcγ receptor (FcγR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs. Conclusions Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.

Background: Few studies have prospectively evaluated SARS-CoV-2 infections in households. We assessed the prevalence and incidence of SARS-CoV-2 infections in a prospective study of households in Lima, Peru. Methods: We conducted a prospective cohort study in a peri-urban district of Lima, Peru. Households with at least a child, a young adult (age 18 to 50 years) and an older adult age >50 years, were followed with twice-a-week household visits during a two-month period for health surveillance. Nasal swabs and saliva specimens were collected twice weekly, and nasopharyngeal swabs were collected weekly from each participant, regardless of symptoms. Laboratory-confirmed SARS-CoV-2 infection was defined by two RT-PCR tests from any of the collected specimens within a week. Blood samples collected at enrolment and end of follow­-up were tested with rapid serological tests. We calculated the prevalence and incidence of laboratory-confirmed SARS-CoV-2 infections during the study period. Findings: We enrolled 132 participants from 44 households, including 44 children, 44 young adults and 44 older adults. A total of 13 SARS-CoV-2 infections were detected in 9 households, for an overall period prevalence of 9·85% (95% confidence interval [CI]:5·35-16·25). Most (66·67%) infections were symptomatic. Eight of 11 (72·73%) SARS-CoV-2 detections corresponded to the Lambda variant. During 218·79 person-months at risk of follow-up there were six new SARS-CoV-2 infections detected (2·74 per 100 person-month, 95% CI: 1·25– 6·04). At enrollment, 59 of 128 participants tested had positive SARS-CoV-2 IgG serology (46·09%, 95% CI: 37·25-55·12). Five of six new infections occurred among participants with negative baseline serology. Interpretation: We demonstrated high incidence of SARS-CoV-2 infections in households during periods of active circulation of the Lambda variant, especially among subjects without evidence of prior infection, most of them not detected by the Ministry of Health system. Funding Information: Consejo Nacional de Ciencia y Tecnologia – CONCYTEC-PROCIENCIA, Lima, Peru (contract No. 082-2020); Vanderbilt University Medical Center, Nashville TN, USA; and Instituto de Investigacion Nutricional, Lima, Peru. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the ethics review boards (ERBs) of the Instituto de Investigacion Nutricional and Vanderbilt University. All adults signed their own ERB approved written informed consent form (ICF). For individuals under 18 years of age, either the mother or the father signed an ICF. Additionally, children 8 years and older signed a written informed assent form.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen‐specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens—adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia—was matched by date with hydrometeorological variables from a global Earth observation dataset—precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non‐linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7‐day average temperatures—a relative risk of 0.76 (95% confidence interval: 0.69–0.85) above 28°C—while ETEC risk increased by almost half, 1.43 (1.36–1.50), in the 20–35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower‐than‐average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea‐causing agents as the global climate changes., Key Points Many pathogens cause diarrhea in children and are affected in different ways by weather conditions like rainfall, temperature, and humidityDiarrhea‐causing bacteria infections increase in warm, humid weather and when soil is moist, though ETEC is sensitive to rainfall extremesHigh humidity decreases prevalence of several viruses, though only rotavirus increases in cold weather and following heavy surface runoff

Background Parainfluenza virus (PIV) is a leading cause of acute respiratory illness (ARI) in children. However, few studies have characterized the clinical features and outcomes associated with PIV infections among young children in the Middle East. Methods We conducted hospital-based surveillance for ARI among children Results PIV was detected in 221/3168 (7.0%) children hospitalized with ARI. PIV-3 was the most commonly detected serotype (125/221; 57%). Individual clinical features of PIV infections varied little by individual serotype, although admission diagnosis of ‘croup’ was only associated with PIV-1 and PIV-2. Children with PIV-associated ARI had lower frequency of cough (71% vs 83%; p p = 0.68) and infections in which no virus was detected. Conclusions PIV is frequently associated with ARI requiring hospitalization in young Jordanian children. Substantial overlap in clinical features may preclude distinguishing PIV infections from other viral infections at presentation.

Background Streptococcus pneumoniae coinfection with influenza results in synergistic lethality, but there are limited data on pneumococcal coinfection with SARS-CoV-2. Methods Public Health England conducts invasive pneumococcal disease (IPD) and SARS-CoV-2 surveillance in England. IPD trends during 2000/01-2019/20 were analysed and cases between during February-June 2020 were linked with laboratory-confirmed SARS-CoV-2 infections. Multivariable logistic regression was used to assess risk factors for death. Results IPD incidence in 2019/20 (7.6/100,000; n=3,964) was 30% (IRR 0.70, 95%CI, 0.18-2.67) lower compared to 2018/19 (10.9/100,000; n=5,666) with large reductions observed across all age-groups during March-June 2020. The serotypes responsible for IPD during 2019/20 were similar to previous years. There were 160,886 SARS-CoV-2 and 1,137 IPD cases during February-June 2020, including 40 IPD/COVID-19 (0.025% [95%sCI, 0.018-0.034] of SARS-CoV-2 infections; 3.5% [95%CI, 2.5-4.8] of IPD cases), 21 with COVID-19 diagnosed 3-27 days after IPD and 27 who developed COVID-19 ≥28 days after IPD. Case-fatality rates (CFR) were 63.2% (25/40), 47.6% (10/21) and 33.3% (9/27), respectively (p

Background Antibiotic use is common for acute respiratory infections (ARIs) in children, but much of this use is inappropriate. Few studies have examined whether rurality of residence is associated with inappropriate antibiotic use. We examined whether rates of ARI-related inappropriate antibiotic use among children vary by rurality of residence. Methods We conducted a retrospective cohort study of children aged 2 months–5 years enrolled in Tennessee Medicaid between 2007 and 2017 and diagnosed with ARI in the outpatient setting. Study outcomes included ARI, ARI-related antibiotic use, and ARI-related inappropriate antibiotic use. Multivariable Poisson regression was used to measure associations between rurality of residence, defined by the US Census Bureau, and the rate of study outcomes, while accounting for other factors including demographics and underling comorbidities. Results A total of 805 332 children met selection criteria and contributed 1 840 048 person-years (p-y) of observation. Children residing in completely rural, mostly rural, and mostly urban counties contributed 70 369 (4%) p-y, 479 121 (26%) p-y, and 1 290 558 p-y (70%), respectively. Compared with children in mostly urban counties (238 per 1000 p-y), children in mostly rural (450 per 1000 p-y) and completely rural counties (468 per 1000 p-y) had higher rates of inappropriate antibiotic use (adjusted incidence rate ratio [aIRR] = 1.34, 95% confidence interval [CI] = 1.33–1.35 and aIRR = 1.33, 95% CI = 1.32–1.35, respectively). Conclusions Inappropriate antibiotic use is common among young children with ARI, with higher rates in rural compared with urban counties. These differences should inform targeted outpatient antibiotic stewardship efforts., The rate of inappropriate antibiotic use is over 30% higher among children living in rural counties compared with those living in urban counties. Factors associated with rural residence can be incorporated into targeted outpatient antibiotic stewardship programs.

Background Human coronaviruses (HCoVs) are a significant cause of acute respiratory illness (ARI) in children; however, the role of HCoVs in ARI among hospitalized children in the Middle East is not well defined. Methods Children under 2 years admitted with fever and/or respiratory symptoms were enrolled from 2010 to 2013 in Amman, Jordan. Nasal/throat swabs were collected and stored for testing. Demographic and clinical characteristics were collected through parent/guardian interviews and medical chart abstractions. Prior stored specimens were tested for HCoVs (HKU1, OC43, 229E and NL63) by qRT-PCR. Results Of the 3168 children enrolled, 6.7% were HCoVs-positive. Among HCoV-positive children, the median age was 3.8 (1.9-8.4) months, 59% were male, 14% were premature, 11% had underlying medical conditions and 76% had viral-codetection. The most common presenting symptoms were cough, fever, wheezing and shortness of breath. HCoVs were detected year-round, peaking in winter-spring months. Overall, 56%, 22%, 13% and 6% were OC43, NL63, HKU1 and 229E, respectively. There was no difference in disease severity between the species, except higher intensive care unit admission frequency in NL63-positive subjects. Conclusions HCoVs were detected in around 7% of children enrolled in our study. Despite HCoV detection in children with ARI with highest peaks in respiratory seasons, the actual burden and pathogenic role of HCoVs in ARI merits further evaluation given the high frequency of viral codetection.

BackgroundLittle is known regarding the full spectrum of illness among children with SARS-CoV-2 infection across ambulatory and inpatient settings.MethodsActive surveillance was performed for SARS-CoV-2 by polymerase chain reaction among asymptomatic and symptomatic individuals in a quaternary care academic hospital laboratory in Tennessee from March 12-July 17, 2020. For symptomatic patients ≤18 years of age, we performed phone follow-up and medical record review to obtain sociodemographic and clinical data on days 2, 7, and 30 after diagnosis and on day 30 for asymptomatic patients ≤18 years. Daily and 7-day average test positivity frequencies were calculated for children and adults beginning April 26, 2020.ResultsSARS-CoV-2 was detected in 531/10327 (5.1%) specimens from patients ≤18 years, including 46/5752 (0.8%) asymptomatic and 485/4575 (10.6%) specimens from 459 unique symptomatic children. Cough (51%), fever (42%), and headache (41%) were the most common symptoms associated with SARS-CoV-2 infection. SARS-CoV-2-related hospitalization was uncommon (18/459 children; 4%); no children with SARS-CoV-2 infection during the study period required intensive care unit admission. Symptom resolution occurred by follow-up day 2 in 192/459 (42%), by day 7 in 332/459 (72%), and by day 30 in 373/396 (94%). The number of cases and percent positivity rose in late June and July in all ages.ConclusionsIn an integrated healthcare network, most pediatric SARS-CoV-2 infections were mild, brief, and rarely required hospital admission, despite increasing cases as community response measures were relaxed.Key pointsIn an integrated healthcare network in the Southeastern United States, symptomatic SARS-CoV-2 infection in children was generally mild, resolved rapidly, and rarely required hospitalization. Cases increased in children and adults as community mitigation measures became less restrictive.

Background Despite increasing recognition of the importance of optimal antibiotic selection and expansion of antimicrobial stewardship activities to ambulatory settings, few studies have examined the frequency of parenteral antibiotic use among ambulatory children. We assessed the prevalence and patterns of parenteral antibiotic administration among ambulatory children in pediatric emergency departments (EDs). Methods We conducted a cross-sectional assessment of parenteral antibiotic use among ambulatory children aged 0–18 years in 49 US children’s hospital EDs in 2018. We assessed the prevalence rates of parenteral antibiotic use and stratified these by patient-, clinic-, and hospital-level characteristics. We also assessed the prevalence of use of specific antibiotics by age and diagnosis category. Among encounters associated with an infection diagnosis, we identified factors associated with parenteral antibiotic use using multivariable logistic regression. Results Among 3 452 011 ambulatory ED encounters in 2018, parenteral antibiotics were administered in 62 648 (1.8%). The highest proportion of parenteral antibiotic use occurred in the 15–18-year age group (3.3%) and among encounters in children with complex chronic conditions (8.9%) and with primary diagnoses of neoplasms (36%). Ceftriaxone was the most commonly administered parenteral antibiotic (61%). In multivariable analysis, several factors including age ≤2 months, White race, private insurance, complex chronic conditions, digestive and genitourinary system diseases, and encounters attributed to emergency medicine providers were significantly associated with higher odds of parenteral antibiotic use. Conclusions This study demonstrates substantial variability in the frequency of parenteral antibiotic administration by age and diagnosis in the ambulatory ED setting and highlights potential opportunities to target stewardship activities.

Purpose The purpose of the study was to increase the proportion of youth living with HIV (YLWH) aged ≥11 years who undergo developmentally appropriate disclosure about their HIV status. Methods A quality improvement project was initiated at an urban pediatric HIV clinic between July 2018 and March 2020. The primary outcome measure was the proportion of YLWH aged ≥11 years who were disclosed to about their HIV status. The proportion of undisclosed YLWH who had documented nondisclosure status was also assessed as a process measure. Plan-Do-Study-Act (PDSA) cycles for change included monthly clinic staff check-ins to discuss new disclosures, quarterly team meetings to discuss strategies to improve disclosure, and modifying a clinic note template to prompt providers to document disclosure status. Annotated run charts were used to analyze the data. Results Before the first PDSA cycle, 26/46 (57%) of the target population of YLWH aged ≥11 years had their HIV status disclosed to them, and none of the undisclosed youth had disclosure status documented in their medical record. After 20 months and six PDSA cycles, the proportion of YLWH aged ≥11 years disclosed to about their HIV status increased to 80% and the proportion of undisclosed YLWH with documentation of their disclosure status increased to 100%. Conclusions Several interventions integrated throughout the pediatric HIV care process were associated with an increase in the proportion of YLWH with developmentally appropriate HIV disclosure and documentation of disclosure status, an important psychosocial aspect of care in these individuals.

BackgroundParainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia.MethodsWe conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in 8 US hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression.ResultsPIV was more commonly detected in children (155/2354; 6.6%) than in adults (66/2297; 2.9%) (P < .001). Other pathogens were commonly co-detected among PIV cases (110/221; 50%). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other nonbacterial pneumonia, whereas children with bacterial pneumonia exhibited increased severity (odds ratio, 8.42; 95% confidence interval, 1.88–37.80). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens.ConclusionsClinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community-acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia.

Objective:To characterize the prevalence of and seasonal and regional variation in inpatient antibiotic use among hospitalized US children in 2017–2018.Design:We conducted a cross-sectional examination of hospitalized children. The assessments were conducted on a single day in spring (May 3, 2017), summer (August 2, 2017), fall (October 25, 2017), and winter (January 31, 2018). The main outcome of interest was receipt of an antibiotic on the study day.Setting:The study included 51 freestanding US children’s hospitals that participate in the Pediatric Health Information System (PHIS).Patients:This study included all patients Results:Of 52,769 total hospitalized children, 19,174 (36.3%) received antibiotics on the study day and 6,575 of these (12.5%) received broad-spectrum antibiotics. The overall prevalence of antibiotic use varied across hospitals from 22.3% to 51.9%. Antibiotic use prevalence was 29.2% among medical patients and 47.7% among surgical patients. Although there was no significant seasonal variation in antibiotic use prevalence, regional prevalence varied, ranging from 32.7% in the Midwest to 40.2% in the West (P< .001). Among units, pediatric intensive care unit patients had the highest prevalence of both overall and broad-spectrum antibiotic use at 58.3% and 26.6%, respectively (P< .001).Conclusions:On any given day in a national network of children’s hospitals, more than one-third of hospitalized children received an antibiotic, and 1 in 8 received a broad-spectrum antibiotic. Variation across hospitals, setting and regions identifies potential opportunities for enhanced antibiotic stewardship activities.

Objective To determine the frequency of neurologic complications associated with influenza in hospitalized children. Stud design We performed a cross-sectional study of children (2 months through 17 years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression. Results Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2). Conclusions Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations.

Background Influenza C virus (ICV) is associated with acute respiratory illness. Yet ICV remains under recognized, with most previous studies using only culture to identify cases. Objectives To develop a sensitive and specific real-time RT-PCR assay for ICV that allows for rapid and accurate detection in a clinical or research setting. Study design Multiple ICV sequences obtained from GenBank were analyzed, including 141 hemagglutinin-esterase (HE), 106 matrix (M), and 97 nucleoprotein (NP) sequences. Primers and probes were designed based on conserved regions. Multiple primer-probe sets were tested against multiple ICV strains. Results The ICV M and NP genes offered the most conserved sequence regions. Primers and probes based on newer sequence data offered enhanced detection of ICV, especially for low titer specimens. An NP-targeted assay yielded the best performance and was capable of detecting 10–100 RNA copies per reaction. The NP assay detected multiple clinical isolates of ICV collected in a field epidemiology study conducted in Peru. Conclusions We report a new real-time RT-PCR assay for ICV with high sensitivity and specificity.

Background The Centers for Disease Control and Prevention (CDC) defines inappropriate antibiotic use as prescribing antibiotics not in accordance with national and local evidence-based guidelines, wrong selection of antibiotics, wrong dosing of antibiotics, or wrong duration of antibiotic use. Inappropriate antibiotic use has been associated with the development and transmission of antibiotic-resistant organisms. Acute respiratory illnesses (ARI) are the leading causes of antibiotic use among children with rates of antibiotic use in Tennessee children among the highest in the United States. The reasons for this have not been adequately assessed, particularly in children enrolled in the Tennessee Medicaid (TennCare) program, who tend to live in low-income households and rural locales and are disproportionately underrepresented in database studies conducted in large managed care organizations. We sought to examine whether the rates of ARI-related overall antibiotic use and inappropriate antibiotic use among young children enrolled in TennCare vary by the rurality of their county of residence. Methods This was a retrospective cohort study of children aged 2 months–5 years enrolled in TennCare from July 1, 2007, to June 30, 2017. We used pharmacy and healthcare claims data to calculate the incidence of ARI and ARI-related antibiotic use. Each eligible child entered into the cohort at the earliest time when selection criteria were met, and follow-up continued from cohort entry until the earliest of loss of enrollment, death, end of study, or meeting exclusion criteria. ARI was identified using International Classification of Diseases, Ninth and Tenth Revisions (ICD-9 and ICD-10) and ARI-related antibiotic use was defined as an antibiotic prescription filled within 72 hours of an ARI. ARI-related antibiotic use was classified as potentially appropriate or inappropriate using a previously published CDC classification system. The rurality of children’s county of residence was defined as either mostly urban, mostly rural, or completely rural based upon the United States Census Bureau definitions. We calculated incidence rates for ARI, ARI-related antibiotic use, and ARI-related inappropriate antibiotic use. To assess the effect of rurality of residence on these outcomes, we used multivariable mixed-effects Poisson regression. These analyses accounted for other factors including child age, gender, race, underlying comorbidities, calendar year and month, and history of antibiotic exposure. Results In total, 813,432 children met enrollment criteria and contributed a total of 2,057,272 person-years for the cohort. Overall, the rate of ARIs, antibiotic use associated with ARIs, and inappropriate antibiotic use associated with ARIs has trended down over time (Figure 1A). There were higher rates of these three outcomes in children who live in mostly rural and completely rural counties compared with those who live in mostly urban counties (Figure 1B–D). Conclusions Children who live in rural counties in Tennessee are disproportionately affected by higher rates of ARIs, antibiotic use, and inappropriate antibiotic use compared with those who live in urban counties. These findings can inform targeted stewardship interventions to reduce inappropriate antibiotic prescribing and to decrease the rates of antibiotic-resistant infections.

Background On March 11, 2020, a pandemic due to SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), was declared. The disease spectrum varies from asymptomatic detection to severe disease. Data on community versus hospitalized cases are limited. We aim to evaluate and compare the epidemiological and clinical characteristics associated with SARS-CoV-2 infection among suspected and confirmed COVID-19 cases primarily diagnosed in the ambulatory setting and compare their illness presentation. Methods We are prospectively enrolling a longitudinal cohort of laboratory-confirmed or suspected COVID-19 subjects and their close contacts. Suspect cases are defined as anyone who developed fever and/or Covid-19 like-symptoms in the post-Covid-19 era without proven SARS-CoV-2 detection. We consented and interviewed subjects over the phone to capture detailed sociodemographic data, medical and social histories, and clinical characteristics of the illness. Results From March 20 to June 16, 2020, 463 subjects were enrolled (Figure 1). Of those, 178 were SARS-CoV-2 positive [164 adults and 13 pediatric (< 18 years) cases] and 192 were COVID-19 suspected (111 adults and 78 pediatric cases). Adult confirmed cases were more likely to be Hispanic and have an underlying medical condition but less likely to be white compared to suspected cases (Table 1). Pediatric confirmed cases were more likely to be Hispanic and have smoke exposure, but less likely to have a travel history compared to suspected cases (Table 1). Both adult and pediatric confirmed subjects had fatigue, headache and cough as the most common symptoms reported. Cough, muscle aches and chest tightness were more likely to be reported in pediatric confirmed than suspected cases; whereas loss of taste, smell and appetite, diarrhea and fever ≥ 100.4 were documented more often in adult confirmed than suspected cases (Figure 2). Figure 1. Cumulative enrollment of subjects by day Table 1. Sociodemographic characteristics among confirmed and suspected COVID-19 cases Figure 2. Adults and pediatrics, confirmed and suspected cases, by clinical presentation Conclusion We observed differences of clinical presentation between confirmed and suspected cases among both pediatric and adult participants. Further research is needed to determine whether these differences are due to disease severity or absence of proven COVID-19. We are collecting serial nasal swabs, blood and stool specimens, on which future testing will confirm SARS-CoV-2 infection in suspected subjects. Disclosures Danielle A. Rankin, MPH, CIC, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) 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)

We detected human metapneumovirus (HMPV) in 54 (5%) of 1055 children aged 5 to 13 years with acute respiratory illness (ARI) identified by outpatient and emergency department surveillance between November and May 2003-2009. Its clinical features were similar to those of HMPV-negative ARI, except a diagnosis of pneumonia was more likely (13% vs 4%, respectively; P = .005) and a diagnosis of pharyngitis (7% vs 24%, respectively; P = .005) was less likely in patients with HMPV- positive ARI than those with HMPV-negative ARI.

Background One day after the pandemic was announced, Tennessee declared a state of emergency on March 12, 2020 with implementation of a stay-at-home order on March 23, 2020. Data regarding the routes and patterns of community transmission of SARS-CoV-2 are limited. We initiated an investigation after clusters of confirmed COVID-19 cases attended a large social gathering. Methods We were notified of clinical providers who attended a “Silent School Auction” on March 7, 2020, of which several confirmed-cases were identified as targeted participants. To derive a standardized REDCap web-survey, we conducted a hypothesis-generating interview with three confirmed attendees to collect event details. Once finalized, enrollment included collecting sociodemographic, epidemiologic, and clinical data. Attendees were classified as: 1) confirmed if they had a positive SARS-CoV-2 test; 2) suspected if they developed symptoms 21-days before or after the auction; and 3) asymptomatic if no symptoms were noted. Results From March 20-June 16, 100/166 (60%) of attendees were enrolled, with a median age of 41 years, 54% female, and 99% white. Of those, 34 and 32 were confirmed- and suspect-cases, respectively. Table 1 compares sociodemographic behaviors of all attendees, with the majority of confirmed-cases eating late in the evening. From March 6 to March 8, 58 participants reported attending other social events, of which three (i.e., church service, women’s retreat, and a birthday party) were common among 43 attendees and five individuals reported onset of mild respiratory symptoms prior to the event (Figure 1). Confirmed-cases were more likely to report having shortness of breath, chest tightness, loss of taste, loss of smell, and fever compared to suspect-cases (Figure 2) and no one required hospitalization. Dining tables from the school auction depicted a clustering of cases occurring at each table, with some individuals visiting more than one table during the event (Figure 3). Conclusion We identified several COVID-19 cases from a single event that occurred prior to social mitigation strategies. Our investigation highlights the importance of staying home when sick and the significance of social distancing to halt transmission of COVID-19. Disclosures Danielle A. Rankin, MPH, CIC, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Zaid Haddadin, MD, CDC (Grant/Research Support, Research Grant or Support)Quidel Corporation (Grant/Research Support, Research Grant or Support)sanofi pasteur (Grant/Research Support, Research Grant or Support) 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)

Background Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens. Methods Active, population-based surveillance was previously conducted for radiographically confirmed, community-acquired pneumonia hospitalizations among children and adults in 8 United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia and, after excluding codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and severe) and length of stay using multivariable proportional odds regression. Results HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly codetected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43–9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI, .59–.99) and atypical (OR, 0.39; 95% CI, .19–.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI, .55–1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87–7.47) and RSV pneumonia (OR, 1.82; 95% CI, 1.32–2.50) were more severe than HMPV (reference), but all other pathogens had similar severity. Conclusions Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia, but was otherwise as or more severe than other common pathogens.

The role of health literacy on HIV outcomes has not been evaluated widely in Africa, in part because few appropriate literacy measures exist. We developed a 16-item scale, the HIV Literacy Test (HIV-LT) to assess literacy-related tasks needed to participate in HIV care. Items were scored as correct or incorrect; higher scores indicated higher literacy skill (range 0–100 %). We tested internal reliability (Kuder–Richardson coefficient) of the HIV-LT in a convenience sample of 319 Portuguese-speaking, HIV infected adults on antiretroviral treatment in Maputo, Mozambique. Construct validity was assessed by a hypothetical model developed a priori. The HIV-LT was reliable and valid to measure participants’ literacy skills. The mean HIV-LT score was 42 %; literacy skills applicable to HIV care were challenging for many participants. The HIV-LT could be used to assess the relationship of literacy and HIV-related outcomes in diverse settings, and evaluate interventions to improve health communication for those in HIV care. Electronic supplementary material The online version of this article (doi:10.1007/s10461-016-1348-3) contains supplementary material, which is available to authorized users.

Background Understanding patterns of inpatient antibiotic use is necessary to enhance appropriate use and minimize preventable harm at hospitals. Few studies have characterized antibiotic use in the inpatient setting in children. Methods We conducted a cross-sectional study in children admitted to 51 freestanding US children’s hospitals included in the Pediatric Health Information System (PHIS). Overall and broad-spectrum antibiotic use (see Table) were measured using charge data, and prevalence of use was assessed on a single day of each 2017–2018 season over one year. Comparisons were made based on clinical setting (medical vs. surgical), clinical unit (PICU, NICU, and all others), hospital, and region. We assessed the relationship between antibiotic use and median hospital case-mix index (CMI), a surrogate for clinical complexity. Results Of 52769 hospitalized children assessed on a study day, 19174 (36%) received antibiotics, and 6575 (12%) received broad-spectrum antibiotics (table). Overall antibiotic use prevalence varied across hospitals from 22% to 52% (Figure 1). Median hospital CMI had no significant relationship with overall antibiotic use and only a weak correlation (ρ=0.29) with broad-spectrum antibiotic use (Figure 2). Antibiotic use prevalence varied minimally by season, ranging from 36% in fall to 37% in summer. Antibiotic use prevalence was 29% (9470/32436) among medical patients and 48% (9704/20333) among surgical patients. The antibiotics most commonly administered in medical patients were ceftriaxone and ampicillin, while surgical patients most commonly received cefazolin and vancomycin. Regional prevalence ranged from 33% (Midwest) to 40% (West). By unit, PICU patients had the highest prevalence of overall [58% (4006/6874)] and broad-spectrum [27% (1830/6874)] antibiotic use. Children with complex chronic conditions accounted for 63% of hospitalized children but represented 72% of children receiving any antibiotic and 85% of those receiving broad-spectrum antibiotics. Conclusion We observed large and apparently unexplained variability in antibiotic use prevalence among children’s hospitals, clinical settings, and regions. This indicates potential opportunities for enhanced antibiotic stewardship activities. Disclosures Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant

Background Increased density of nasopharyngeal (NP) pneumococcal colonization has been associated with invasive pneumococcal disease in children. However, factors that lead to increased pneumococcal density are poorly understood. We sought to determine whether viral detection during asymptomatic periods in young children was associated with increased NP pneumococcal density and the subsequent development of acute respiratory illness (ARI). Methods Using NP samples obtained during asymptomatic periods from children less than 3 years of age in the rural Peruvian Andes, we determined NP pneumococcal colonization density by quantitative polymerase chain reaction (qPCR) and identified respiratory viruses by RT–PCR. We examined the association between viral detection and pneumococcal density adjusting for relevant covariates using a multivariable quantile mixed effects regression model. We also assessed the association of pneumococcal density during asymptomatic periods in these children on the time to the next ARI using survival analysis. Results During asymptomatic periods, the presence of NP pneumococcal colonization was more common when respiratory viruses were detected. In addition, in the multivariable model, log10-transformed pneumococcal densities were significantly higher during asymptomatic periods when viruses were detected [median 4.52 (4.14, 5.01) P < 0.001], specifically human rhinovirus (HRV) [median 4.58 (4.27, 5.12), P < 0.001] and adenovirus (AdV) [median 4.21 (3.79, 4.91), P = 0.014], compared with when no virus was detected [median 3.16 (2.92, 3.73), Figure 1]. Increased pneumococcal density was also significantly associated with a higher rate of subsequent ARI (p = 0.008, Figure 2). Conclusion Among young children, detection of respiratory viruses during asymptomatic periods was associated with increased pneumococcal colonization density, which, in turn, was associated with higher rate of subsequent ARI. Disclosures All authors: No reported disclosures.

Background Although antibiotics are often indicated to treat early-life infections, such exposure may lead to serious adverse outcomes. Few studies have characterized patterns of antibiotic use among neonatal intensive care units (NICUs). Methods We performed a cross-sectional study of antibiotic use in 51 NICUs participating in the Pediatric Health Information System (PHIS), a database that includes clinical and resource utilization data for standalone children’s hospitals in the United States. Assessments were conducted on a single mid-week day of 2017. We examined the use of any antibiotic and broad-spectrum antibiotics using charge data in children admitted in each NICU on the study day. We compared antibiotic use among NICUs and geographical regions, and assessed its association with the NICU median case mix index (CMI) (as a surrogate for clinical complexity). Results 2813 infants were hospitalized in NICUs on the study day; the median number of patients at each study site was 47 (IQR = 34 – 62). 90% were Conclusion There is substantial variability in antibiotic use among US NICUs, which seems partially explained by patient case-mix. Additional studies are needed to identify drivers of unwarranted variability in antibiotic use among NICUs. Disclosures Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant.

Background Influenza A/H5N1 vaccines have been poorly immunogenic. Addition of Adjuvant System 03 (AS03) markedly enhances immune responses, but the mechanisms of this enhancement are unclear. Methods We compared gene expression in peripheral blood mononuclear cells (PBMCs) between recipients of AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 vaccine on days 1, 3, 7, and 28 postvaccination. We used a systems vaccinology approach to assess functional classifications of differentially expressed (DE) genes between the two vaccine groups, identify DE genes that correlate with serologic responses, and compare these findings with previous cell-specific assessments. Results AS03-adjuvanted vaccine induced the strongest differential gene expression signals on day 1 after vaccination (Figure 1). Multiple innate immune signaling pathways were activated, including the interferon, JAK-STAT, and TNF pathways, and FC gamma receptor (Fc_R) mediated phagocytosis. Immune pathways specific for antigen processing and presentation and influenza A responses were also enriched. Early differential expression of several signal transduction (day 1) and immunoglobulin (day 7) genes were predictive of peak HAI titer (Figure 2). Compared with cell-specific responses, DE gene, and immunologic pathways of PBMCs were most similar to innate immune cell subsets. However, several pathways were unique to PBMCs, and several cell-type-specific pathways, particularly from neutrophils, were absent in PBMCs (Figure 3). Conclusion Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early differential regulation of multiple innate immune signaling pathways and enrichment of pathways involved in antigen presentation and influenza immune responses. Early expression of several genes was associated with peak HAI responses, suggesting a potential role for application of these signatures in earlier determination of vaccine responses. While PBMC and immune cell-specific results shared key innate immune signals, unique signals were identified by either approach. Disclosures L. Howard, Pfizer: Grant Investigator, Grant recipient. C. B. Creech, Pfizer: Grant Investigator, Research grant. Novartis: Grant Investigator, Research grant. K. Edwards, Novartis: Grant Investigator, Research grant. Novartis: Scientific Advisor, Consulting fee.

BACKGROUND Viruses are commonly detected in children with acute respiratory illnesses (ARIs) and in asymptomatic children. Longitudinal studies of viral detections during asymptomatic periods surrounding ARI could facilitate interpretation of viral detections but are currently scant. METHODS We used reverse transcription polymerase chain reaction to analyze respiratory samples from young Andean children for viruses during asymptomatic periods within 8-120 days of index ARI (cough or fever). We compared viral detections over time within children and explored reverse transcription polymerase chain reaction cycle thresholds (CTs) as surrogates for viral loads. RESULTS At least 1 respiratory virus was detected in 367 (43%) of 859 samples collected during asymptomatic periods, with more frequent detections in periods with rhinorrhea (49%) than those without (34%, P < 0.001). Relative to index ARI with human rhinovirus (HRV), adenovirus (AdV), respiratory syncytial virus (RSV) and parainfluenza virus detected, the same viruses were also detected during 32, 22, 10 and 3% of asymptomatic periods, respectively. RSV was only detected 8-30 days after index RSV ARI, whereas HRV and AdV were detected throughout asymptomatic periods. Human metapneumovirus and influenza were rarely detected during asymptomatic periods (