title: Severe Enterovirus Infections in Hospitalized Children in the South of England: Clinical Phenotypes and Causative Genotypes.
abstract: Most enterovirus surveillance studies lack detailed clinical data, which limits their clinical usefulness. This study aimed to describe the clinical spectrum and outcome of severe enterovirus infections in children, and to determine whether there are associations between causative enterovirus genotypes and clinical phenotypes.
  
  
  
  Retrospective analysis of microbiological and clinical data from a tertiary children's hospital in the South of England over a 17-month period (2012-2013).
  
  
  
  In total, 30 patients were identified, comprising sepsis (n = 9), myocarditis (n = 8), meningitis (n = 8) and encephalitis (n = 5). Cases with sepsis or myocarditis were significantly younger than those with central nervous system disease (median age 21 and 15 days vs. 79 days; P = 0.0244 and P = 0.0310, respectively). There was considerable diversity in the causative genotypes in each of the clinical phenotypes, with some predominance of echoviruses in the meningitis group, and coxsackie B viruses in the myocarditis group. Thirteen cases required mechanical ventilation, 11 cases inotropic support, 3 cases dialysis and 3 cases extracorporal membrane oxygenation. The overall mortality was 10% (sepsis group, n = 1; myocarditis group, n = 2). Of the survivors, 5 (19%) had long-term sequelae (myocardial dysfunction, n = 2; neurological sequelae, n = 3). Patients with encephalitis had the longest hospital stay (median: 16 days), compared with 9, 6 and 3 days in patients with myocarditis, sepsis and meningitis, respectively (P = 0.005).
  
  
  
  Enterovirus infections, particularly enteroviral myocarditis and encephalitis, can cause significant morbidity and mortality. The results show that there are currently no strong associations between clinical phenotypes and particular causative enterovirus genotypes in the South of England.
authors.affiliation: From the *Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; †Southampton NIHR Wellcome Trust Clinical Research Facility, ‡Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; §Public Health England Microbiology Services, Southampton, United Kingdom; ¶Department of Paediatric Intensive Care, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; ‖Institute for Life Sciences, University of Southampton, Southampton, United Kingdom; **Department of Paediatric Immunology & Infectious Diseases, ††NIHR Southampton Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; ‡‡Global Health Research Institute, University of Southampton, Southampton, United Kingdom; and §§Department of Paediatrics, The University of Melbourne, Parkville, Australia.
authors.forename: Hans
authors.initials: H
authors.lastname: de Graaf
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pelosi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cooper
authors.forename: John
authors.initials: J
authors.lastname: Pappachan
authors.forename: Kim
authors.initials: K
authors.lastname: Sykes
authors.forename: Iain
authors.initials: I
authors.lastname: MacIntosh
authors.forename: Diane
authors.initials: D
authors.lastname: Gbesemete
authors.forename: Tristan W
authors.initials: TW
authors.lastname: Clark
authors.forename: Sanjay V
authors.initials: SV
authors.lastname: Patel
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.forename: Marc
authors.initials: M
authors.lastname: Tebruegge
mesh_terms: D000293:Adolescent; D002493:Central Nervous System Diseases / Q000453:epidemiology / Q000628:therapy / Q000821:virology; D002648:Child; D002673:Child, Hospitalized / Q000706:statistics & numerical data*; D002675:Child, Preschool; D004739:England / Q000453:epidemiology; D004770:Enterovirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D029822:Enterovirus B, Human / Q000302:isolation & purification; D004769:Enterovirus Infections / Q000453:epidemiology* / Q000628:therapy / Q000821:virology; D015199:Extracorporeal Membrane Oxygenation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D012189:Retrospective Studies; D015996:Survival Rate