Comparison of human parechovirus and enterovirus detection frequencies in cerebrospinal fluid samples collected over a 5‐year period in edinburgh: HPeV type 3 identified as the most common picornavirus type

Abstract

Human enteroviruses (EVs) and more recently parechoviruses (HPeVs) have been identified as the principal viral causes of neonatal sepsis-like disease and meningitis. The relative frequencies of specific EV and HPeV types were determined over a 5-year surveillance period using highly sensitive EV and HPeV PCR assays for screening 4,168 cerebrospinal fluid (CSF) specimens collected from hospitalized individuals between 2005 and 2010 in Edinburgh. Positive CSF samples were typed by sequencing of VP1. From the 201 EV and 31 HPeV positive (uncultured) CSF samples on screening, a high proportion of available samples could be directly typed (176/182, 97%). Highest frequencies of EV infections occurred in young adults (n = 43; 8.6%) although a remarkably high proportion of positive samples (n = 98; 46%) were obtained from young infants (<3 months). HPeV infections were seen exclusively in children under the age of 3 months (31/1,105; 2.8%), and confined to spring on even-numbered years (22% in March 2006, 25% in April 2008, and 22% in March 2010). In contrast, EV infections were distributed widely across the years. Twenty different EV serotypes were detected; E9, E6, and CAV9 being found most frequently, whereas all but one HPeVs were type 3. Over this period, HPeV3 was identified as the most prevalent picornavirus type in CNS-related infections with similarly high incidences of EV infection frequencies in very young children. The highly sensitive virus typing methods applied in this study will assist further EV and HPeV screening of sepsis and meningitis cases as well as in future molecular epidemiological studies and population surveillance.

Human picornaviruses associated with neurological diseases and their neutralization by antibodies

“…HPeV-3 was first isolated in 1999 from an infant with severe CNS disease [94], and since then different studies have recognized it as the most or second most prevalent virus causing CNS infections in infants under three months old [7,[95][96][97][98]. Outbreaks of HPeV-3 usually occur in the summer/autumn seasons and have a distinct biennial pattern [96,98].…”

“…HPeV-3 was first isolated in 1999 from an infant with severe CNS disease [94], and since then different studies have recognized it as the most or second most prevalent virus causing CNS infections in infants under three months old [7,[95][96][97][98]. Outbreaks of HPeV-3 usually occur in the summer/autumn seasons and have a distinct biennial pattern [96,98]. They have been documented in Europe [99], North America [100], Asia [101] and Australia [102], and are regularly associated with a variety of clinical presentations, from mild gastrointestinal or respiratory illness to life-threatening conditions in neonates [36,96,103].…”

“…Outbreaks of HPeV-3 usually occur in the summer/autumn seasons and have a distinct biennial pattern [96,98]. They have been documented in Europe [99], North America [100], Asia [101] and Australia [102], and are regularly associated with a variety of clinical presentations, from mild gastrointestinal or respiratory illness to life-threatening conditions in neonates [36,96,103]. It can cause systemic infections with possible neurological involvement in infants, which are collectively described as 'sepsis-like illnesses' [98,99,104].…”

“…The incidence of HPeV-3 infections and the increasing number of CNS disease cases [96] with no treatment options available necessitate a search for antivirals and better understanding of HPeV neutralization by antibodies [114].…”

Human Parechoviruses, New Players in the Pathogenesis of Viral Meningitis

“…Screening of CSF samples show HPeV3 to be the dominant type found in children, in particular neonates (Benschop et al, 2008c;Harvala et al, 2009Harvala et al, , 2011Pineiro et al, 2010;Renaud et al, 2011;Selvarangan et al, 2011;Verboon-Maciolek et al, 2008aWatanabe et al, 2007;Wolthers et al, 2008). These infections account for approximately 3-17% of CNS infections reported as meningitis or encephalitis (Harvala et al, 2009;Pineiro et al, 2010;Watanabe et al, 2007;Wolthers et al, 2008;Yamamoto et al, 2009), far exceeding the percentage of herpes simplex virus infections.…”