Specific Association of Human Parechovirus Type 3 with Sepsis and Fever in Young Infants, as Identified by Direct Typing of Cerebrospinal Fluid Samples

Background. Human parechoviruses (HPeVs), along with human enteroviruses (HEVs), are associated with neonatal sepsis and meningitis. We determined the relative importance of these viruses and the specific HPeV types involved in the development of central nervous system-associated disease. Methods. A total of 1575 cerebrospinal fluid (CSF) samples obtained during 2006-2008 were screened for HPeV by means of nested polymerase chain reaction. All samples for which results were positive were typed by sequencing of viral protein (VP) 3/VP1. Screening for HEV was performed in parallel, as was detection of HPeV in respiratory and fecal surveillance samples, to identify virus types circulating in the general population. Results. HPeV was detected in 14 CSF samples obtained exclusively from young infants (age, <3 months) with sepsis or pyrexia. The frequency of detection of HPeVs varied greatly by year, with the highest frequency (7.2%) noted in 2008 exceeding that of HEVs. Direct typing of CSF samples revealed that all infections were caused by HPeV type 3, a finding that is in contrast to the predominant circulation of HPeV1 in contemporary respiratory and fecal surveillance samples. Conclusion. HPeV was a significant cause of severe sepsis and fever with central nervous system involvement in young infants, rivaling enteroviruses. The specific targeting of young infants by HPeV type 3 may reflect a difference in tissue tropism between virus types or a lack of protection of young infants by maternal antibody consequent to the recent emergence of HPeV.