Dynamics of endemic virus re-emergence in children in the USA following the COVID-19 pandemic (2022-23): a prospective, multicentre, longitudinal, immunoepidemiological surveillance study.

Background: The Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) programme was established to translate knowledge gained from global immunoepidemiological surveillance into a better understanding of population-level dynamics of emerging and re-emerging infections, as well as into the discovery and development of biomedical countermeasures against potential pandemic threats. As proof of principle for this approach, we conducted a longitudinal immunoepidemiological study in children in the USA, focusing on enterovirus D68 (EV-D68) infection dynamics but also capturing surveillance of a broad array of other endemic respiratory pathogens. Serendipitously, our sampling spanned the lifting of widespread COVID-19 non-pharmaceutical interventions (NPIs) in 2022-23, following a unique period during which virus exposure markedly diminished.

Using COVID-19 pandemic perturbation to model RSV-hMPV interactions and potential implications under RSV interventions.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are closely related pathogens responsible for a significant burden of acute respiratory infections. Interactions between RSV and hMPV have been hypothesized, but the mechanisms of interaction are largely unknown. Here, we use a mathematical model to quantify the likelihood of interactions from population-level surveillance data and investigate whether interactions could lead to increases in hMPV burden under RSV medical interventions, including active and passive immunization.

Return of the Biennial Circulation of Enterovirus D68 in Colorado Children in 2024 Following the Large 2022 Outbreak.

Enterovirus D68 (EV-D68) caused large biennial cyclical outbreaks of respiratory disease and cases of acute flaccid myelitis from 2014 to 2018 in the USA. An anticipated outbreak did not occur in 2020, likely due to non-pharmaceutical interventions targeting the COVID-19 pandemic. A large respiratory disease outbreak occurred again in 2022, but uncertainty remained regarding if circulation of EV-D68 would return to the pre-pandemic patterns.

Opportunities for collaboration: the synergy between antimicrobial and diagnostic stewardship in pediatrics.

Advancement of antimicrobial stewardship (AS) programs requires partnership with clinicians, quality assurance teams, and laboratorians. Inevitably, AS programs also practice diagnostic stewardship (DS), as stewards are aptly placed to connect key stakeholders and help steer processes toward higher value care for pediatric patients. In this review, we illustrate five moments of collaboration between stakeholders in the interplay between AS and DS in pediatrics.

Enterovirus and Parechovirus Neurologic Infections in Children: Clinical Presentations and Neuropathogenesis.

Enteroviruses (EVs) and parechoviruses (PeVs) are common pathogens of childhood. Enteroviral infections cause a range of clinical syndromes from mild illness to neurologic manifestations of meningitis, encephalitis, and acute flaccid myelitis. Disease manifestations are driven by a combination of viral replication and host immune response.

Recruitment and retention of pediatric participants for pandemic preparedness research: Experience from the PREMISE EV-D68 Pilot Study.

Recruitment and retention are challenges for prospective pediatric cohort studies, particularly those involving serial venipunctures. We investigated factors underlying enrollment and retention in the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) Enterovirus D68 (EV-D68) Pilot Study, a multicenter prospective longitudinal cohort study assessing the utility of immunologic surveillance for pandemic preparedness. This study enrolls children ≤10 years for two blood draws, pre- and post-EV-D68 season, separated by 6-18 months.

Enterovirus-D68 - A Reemerging Non-Polio Enterovirus that Causes Severe Respiratory and Neurological Disease in Children.

The past decade has seen the global reemergence and rapid spread of enterovirus D68 (EV-D68), a respiratory pathogen that causes severe respiratory illness and paralysis in children. EV-D68 was first isolated in 1962 from children with pneumonia. Sporadic cases and small outbreaks have been reported since then with a major respiratory disease outbreak in 2014 associated with an increased number of children diagnosed with polio-like paralysis.

Clinical Impact of Pleural Fluid Streptococcus pneumoniae Polymerase Chain Reaction Testing in Children With Complicated Pneumonia.

Background: While Streptococcus pneumoniae (Spn) is the leading cause of pediatric complicated community-acquired pneumonia (cCAP), it is infrequently recovered by culture-based methods. We studied the real-world clinical impact of an Spn polymerase chain reaction (PCR) assay for pleural fluid.

Methods: This pre-post quasi-experimental cohort study compared pathogen detection, antibiotic usage, and outcomes in children hospitalized with cCAP requiring pleural effusion or empyema drainage at Children's Hospital Colorado between 2016 and 2023.

Multimodal Surveillance Model for Enterovirus D68 Respiratory Disease and Acute Flaccid Myelitis among Children in Colorado, USA, 2022.

Surveillance for emerging pathogens is critical for developing early warning systems to guide preparedness efforts for future outbreaks of associated disease. To better define the epidemiology and burden of associated respiratory disease and acute flaccid myelitis (AFM), as well as to provide actionable data for public health interventions, we developed a multimodal surveillance program in Colorado, USA, for enterovirus D68 (EV-D68). Timely local, state, and national public health outreach was possible because prospective syndromic surveillance for AFM and asthma-like respiratory illness, prospective clinical laboratory surveillance for EV-D68 among children hospitalized with respiratory illness, and retrospective wastewater surveillance led to early detection of the 2022 outbreak of EV-D68 among Colorado children.

Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US.

Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions.

Gaps in diagnosing suspected infection in immunocompromised children with cancer: A systematic review.

While the survival of children with cancer has improved over time, infection remains a major morbidity and mortality risk. We conducted a systematic literature review to determine the unmet needs in diagnosing infection in immunocompromised children with cancer. The comprehensive search strategy followed the guidelines established by the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement, and spanned multiple bibliographic databases and other public sources from January 1, 2012 to June 23, 2022.

Duration of Enterovirus D68 RNA Shedding in the Upper Respiratory Tract and Transmission among Household Contacts, Colorado, USA.

Enterovirus D68 (EV-D68) causes cyclical outbreaks of respiratory disease and acute flaccid myelitis. EV-D68 is primarily transmitted through the respiratory route, but the duration of shedding in the respiratory tract is unknown. We prospectively enrolled 9 hospitalized children with EV-D68 respiratory infection and 16 household contacts to determine EV-D68 RNA shedding dynamics in the upper respiratory tract through serial midturbinate specimen collections and daily symptom diaries.

Improving antimicrobial use through better diagnosis: The relationship between diagnostic stewardship and antimicrobial stewardship.

Antimicrobial stewardship programs (ASPs) exist to optimize antibiotic use, reduce selection for antimicrobial-resistant microorganisms, and improve patient outcomes. Rapid and accurate diagnosis is essential to optimal antibiotic use. Because diagnostic testing plays a significant role in diagnosing patients, it has one of the strongest influences on clinician antibiotic prescribing behaviors.

Plasma Microbial Cell-Free DNA Sequencing from over 15,000 Patients Identified a Broad Spectrum of Pathogens.

Microbial cell-free DNA (mcfDNA) sequencing is an emerging infectious disease diagnostic tool which enables unbiased pathogen detection and quantification from plasma. The Karius Test, a commercial mcfDNA sequencing assay developed by and available since 2017 from Karius, Inc. (Redwood City, CA), detects and quantifies mcfDNA as molecules/μL in plasma.

Qualitative detection of enterovirus D68 from PrimeStore® molecular transport medium: implications for home- and self-collection.

To ensure proper specimen handling for detecting pathogens, like Enterovirus D68 (EV-D68), from home- and self-collection, alternative techniques are needed to ensure safe transport and reliable testing. PrimeStore® Molecular Transport Medium (MTM) may be an option since it does not require cold storage and inactivates virus while preserving RNA for detection. The purpose of this validation study was to demonstrate the ability to detect EV-D68 via rRT-PCR in MTM.

Perspectives on Diagnosis and Management of All-Cause Encephalitis: A National Survey of Adult Infectious Diseases Physicians.

Background: Encephalitis is widely recognized as a challenging condition to diagnose and manage. The care of patients with encephalitis typically involves multiple disciplines, including neurologists and infectious disease (ID) physicians. Our objective was to describe the perspectives and needs of ID physicians regarding encephalitis, using a cross-sectional questionnaire survey.

Acute Liver Failure in a Child With Adenovirus Detected by PCR in the Explanted Liver.

As of June 15, 2022, the Centers for Disease Control and Prevention has reported 296 pediatric patients under investigation for hepatitis of unknown etiology in the United States; the World Health Organization has reported 650 probable cases worldwide. One of the leading hypotheses for this cluster of cases is adenovirus, a virus that commonly causes respiratory or gastrointestinal symptoms in healthy children but rarely causes severe hepatitis or acute liver failure in immunocompetent children. The other leading hypothesis is that prior infection with SARS-CoV-2 may predispose children to developing liver injury from a normally innocuous agent.

Clinical and Financial Impact of a Diagnostic Stewardship Program for Children with Suspected Central Nervous System Infection.

Objective: To investigate the optimal implementation and clinical and financial impacts of the FilmArray Meningitis Encephalitis Panel (MEP) multiplex polymerase chain reaction testing of cerebrospinal fluid (CSF) in children with suspected central nervous system infection.

Study Design: A pre-post quasiexperimental cohort study to investigate the impact of implementing MEP using a rapid CSF diagnostic stewardship program was conducted at Children's Hospital Colorado (CHCO). MEP was implemented with electronic medical record indication selection to guide testing to children meeting approved use criteria: infants <2 months, immunocompromised, encephalitis, and ≥5 white blood cells/μL of CSF.

Metagenomic Next-Generation Sequencing for Diagnosis of Pediatric Meningitis and Encephalitis: A Review.

Metagenomic next-generation sequencing is a novel diagnostic test with the potential to revolutionize the diagnosis of pediatric meningitis and encephalitis through unbiased detection of bacteria, viruses, parasites, and fungi in cerebrospinal fluid. Current literature is mostly observational with variable indications, populations, and timing of testing with resulting variability in diagnostic yield and clinical impact. Diagnostic stewardship strategies are needed to direct testing toward high-impact pediatric populations, to optimize timing of testing, to ensure appropriate interpretation of results, and to guide prompt optimization of antimicrobials.