Enterovirus D68 (EV-D68) causes respiratory tract infections and neurologic manifestations. We compared the clinical manifestations from 2 EV-D68 outbreaks in 2014 and 2018 and a low-activity period in 2016 among hospitalized children in central Ohio, USA, and used PCR and sequencing to enable phylogenetic comparisons. During both outbreak periods, infected children had respiratory manifestations that led to an increase in hospital admissions for asthma. The 2018 EV-D68 outbreak appeared to be milder in terms of respiratory illness, as shown by lower rates of pediatric intensive care unit admission. However, the frequency of severe neurologic manifestations was higher in 2018 than in 2014. During the same period in 2016, we noted neither an increase in EV-D68 nor a significant increase in asthma-related admissions. Phylogenetic analyses showed that EV-D68 isolates from 2018 clustered differently within clade B than did isolates from 2014 and are perhaps associated with a different EV-D68 subclade.

BackgroundAn outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014.MethodsMay through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time.ResultsIn 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011–13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B.ConclusionsThis is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68 circulated before 2014, the outbreak isolates clustered differently than those from prior years.

Abstract Background Most U.S. children with perinatal hepatitis C virus (HCV) exposure fail to receive the recommended anti-HCV antibody test at age ≥18 months. Earlier testing for viral RNA might facilitate increased screening, but sensitivity of this approach has not been established. We hypothesized that modern HCV-RNA RT-PCR platforms would adequately detect infected infants. Methods Nationwide Children’s Hospital electronic health records from 1/1/2008 to 6/30/2018 were reviewed to identify perinatally-exposed infants tested by HCV-RNA RT-PCR at age 2-6 months. Diagnostic performance was determined using a composite case definition: 1) infected children had positive repeat HCV-RNA testing or positive anti-HCV at age ≥24 months; 2) uninfected children lacked these criteria and had negative anti-HCV at age ≥18 months. Results During the study period, 770 perinatally-exposed infants underwent HCV-RNA testing at age 2-6 months. Of these, 28 (3.6%) tested positive, and viremia was confirmed in all who underwent repeat testing (n=27). Among 742 infants with negative HCV-RNA results, 226 received follow-up anti-HCV testing at age ≥18 months, of whom 223 tested negative. Three children had low-positive anti-HCV results at age 18-24 months that were negative upon re-testing after age 24 months, possibly indicating waning maternal antibodies. Using the composite case definitions, early HCV-RNA screening demonstrated sensitivity of 100% (87.5%-100%, Wilson-Brown 95% confidence interval) and specificity of 100% (98.3-100%). Conclusion Modern HCV-RNA RT-PCR assays have excellent sensitivity for diagnosis of perinatally-acquired infection at age 2-6 months and could aid HCV surveillance given the substantial loss to follow-up at ≥18 months of age.

The role of rhinoviruses (RVs) in children with clinical syndromes not classically associated with RV infections is not well understood. We analyzed a cohort of children ≤21 years old who were PCR+ for RV at a large Pediatric Hospital from 2011 to 2013. Using univariate and multivariable logistic regression, we analyzed the associations between demographic, clinical characteristics, microbiology data, and clinical outcomes in children with compatible symptoms and incidental RV detection. Of the 2473 children (inpatients and outpatients) with an RV+ PCR, 2382 (96%) had compatible symptoms, and 91 (4%) did not. The overall median age was 14 months and 78% had underlying comorbidities. No differences in RV viral loads were found according to the presence of compatible symptoms, while in children with classic RV symptoms, RV viral loads were higher in single RV infections versus RV viral co-infections. Bacterial co-infections were more common in RV incidental detection (7.6%) than in children with compatible symptoms (1.9%, p < 0.001). The presence of compatible symptoms independently increased the odds ratio (OR, 95% CI) of hospitalization 4.8 (3.1–7.4)), prolonged hospital stays 1.9 (1.1–3.1), need for oxygen 12 (5.8–25.0) and pediatric intensive care unit (PICU) admission 4.13 (2.0–8.2). Thus, despite comparable RV loads, disease severity was significantly worse in children with compatible symptoms.

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In schizophrenia, the years before psychosis are morbid, not premorbid. Widespread, low-grade corruption of circuitry (brain damage) occurs, resulting in enduring deficits in cognitive, social, and motor functioning and motivation. These deficits persist during patients’ lifetime and do not respond to medication or talking. Expectations of patients’ functioning must be modified (reduced); interactions and environments must be accommodated to support best residual functioning, and prostheses (mechanical or actions of others) must replace functions no longer available. One of the deficits—anosognosia—interferes with treatment efforts. When the circuits managing dopamine neurons in the ventral tegmental area are corrupted, storms of dopamine imbue random items of sensory experience and intrapsychic life with salience—psychosis appears. Early and uninterrupted dopamine antagonist medication results in sustained remission of psychosis but is rarely achieved because of the inadequacies of standard care. Enduring engagement by multi-disciplinary teams is the necessary response to the neurobiology of schizophrenia.

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