Characteristics and outcomes of human parechovirus infection in infants (2008–2012)

Human parechoviruses (HPeVs) are members of the family Picornaviridae and are classified into 3 known serotypes: HPeV1, HPeV2, and the recently identified HPeV3. HPeV1 and HPeV2 infections are most commonly associated with mild respiratory or gastrointestinal symptoms and occasionally with severe disease conditions, such as flaccid paralysis and encephalitis. HPeV3 infection has been associated with transient paralysis and neonatal infection and has until now only been reported in Japan and Canada. Culture isolates considered to be enterovirus on the basis of cell culture but that were found to be enterovirus negative by 5' untranslated region reverse-transcriptase polymerase chain reaction (5'UTR RT-PCR) during the period December 2000 through January 2005 were selected. Isolates were tested by HPeV 5'UTR RT-PCR and were genotyped by sequencing the VP1 region. Phylogenetic analysis was performed, and the association with clinical symptoms was established. Thirty-seven (12%) of the 303 isolates that tested positive for enterovirus by cell culture were in fact HPeV. The majority of the HPeV-positive isolates (n = 27) could be identified as HPeV1. The remaining 10 isolates, which were grown from samples obtained in 2001, 2002, and 2004, could be typed as the recently identified HPeV3. HPeV was exclusively detected in children aged < 3 years. Children infected with HPeV3 were significantly younger than children infected with HPeV1, and sepsis-like illness and central nervous system involvement were more frequently reported in children infected with HPeV3. We report HPeV infections in young children during the period of 2000-2005 and show an association between HPeV3 infection and sepsis-like illness and central nervous system involvement in neonates.

To assess the role of human parechoviruses (HPeVs) as a cause of neonatal cerebral infection and to report neuroimaging findings of newborn infants with encephalitis caused by HPeVs. Clinical presentation, cranial ultrasonography, magnetic resonance imaging (MRI) findings, and neurodevelopmental outcome of 10 infants admitted to a neonatal intensive care unit and diagnosed with encephalitis caused by HPeVs are reported. Nine of 10 infants, with a gestational age of 29 to 41 weeks, presented at 36 to 41 weeks postmenstrual age with clinical seizures. Seven had a fever and six had a rash. Clinical presentation was similar to that of infants with enterovirus infection. Cranial ultrasonography showed increased echogenicity in the periventricular white matter in all infants. Neonatal MRI confirmed white matter changes in nine infants, which changed to gliosis on later MRI. Outcome was variable with cerebral palsy in one, a suspect outcome at 18 months in one, learning disabilities at 7 years of age in one, epilepsy in one, and normal neurodevelopmental outcome in five children. Follow-up of one infant was only 9 months. HPeVs should be added to the list of neurotropic viruses that may cause severe central nervous system infection in the neonatal period. White matter injury can be visualized with cranial ultrasonography, but more detailed information is obtained with MRI and especially diffusion-weighted imaging. Because clinical presentation of HPeV encephalitis is similar to that of enterovirus, real-time polymerase chain reaction for both viruses should be performed in atypical presentation of neonatal seizures.

Human parechoviruses (HPeVs) are members of the large and growing family of Picornaviridae. Although originally described as echovirus 22 and 23 within human enteroviruses because of their clinical and morphological properties, they have since been shown to be distinct from this and other picornavirus groups in several features of their genome organisation, structure and replication. Human parechoviruses show genetic and antigenic heterogeneity and a number of distinct HPeV types are known to circulate widely in human populations throughout the world. Although the majority of HPeV infections occur early in life without specific symptoms, disease manifestations associated with many of the currently described types have been described, ranging from gastroenteritis and respiratory infections to neurological disease, particularly in neonates. Although HPeV diagnosis has historically been made by virus isolation, a new generation of sensitive and specific molecular tests for HPeV RNA promises to greatly improve the effectiveness of HPeV detection and type identification, as well as providing a greater understanding its molecular epidemiology. By this means, we will learn much more about the clinical relevance of HPeVs and the association of different HPeV types with specific disease presentations.