Sepsis-like Disease in Infants Due to Human Parechovirus Type 3 During an Outbreak in Australia

Abstract

We report the largest series of HPeV-3 infection in infants, and the first outbreak in Australia. Infants presented with a severe sepsis-like syndrome with a high rate of ICU admissions, but all recovered from the acute infection without complications. Long-term sequelae are unknown.

Parechovirus Encephalitis and Neurodevelopmental Outcomes

“…However, we think it is likely that all these cases are HPeV3 associated because they have a similar phenotype, they all occurred within a 6-month period, they are all from the east coast of Australia, and HPeV3 was identified among other specimens in state reference laboratories during the period. 34,39 Our study confirms features described in a similarly sized, retrospective series reported by Verboon-Maciolek et al, 3,40 and shows that young age and premature birth are possible risk factors for encephalitis in HPeV infection, that female gender is overrepresented, and that cranial ultrasound is an inadequately sensitive imaging modality in this disease. We also show that, although short-term outcomes may be reassuring, a high proportion of infants experience neurodevelopmental sequelae.…”

“…34 In this report, most (75/118) cases had CNS infection confirmed by the presence of HPeV RNA on polymerase chain reaction (PCR); however, infants with mild CNS HPeV infection were not differentiated from those with more serious disease, due to the lack of application of formal clinical definitions of encephalitis. When compared with this retrospective series, our prospectively collected HPeV encephalitis cases were younger (median 13 days compared with median 39 days 34 ) and more likely to be girls (7/9 compared with 53/118 [45%] 34 ). This, and the high proportion of prematurity in our series suggests that young age may be a risk factor for encephalitis from HPeV infection, and that there may be a gender difference in susceptibility.…”

“…We confirmed cases to be HPeV-related following review by a cross-disciplinary expert panel (pediatric infectious diseases, microbiology, neurology, and epidemiology) who also categorized cases as confirmed encephalitis or "not encephalitis" by using the International Encephalitis Consortium definition and Brighton criteria. 31,32 Parechovirus molecular testing was performed by using in-house assays: NSW and Victorian cases at the Victorian Infectious Diseases Reference Laboratory, as previously described 34,35 ; Queensland cases at Royal Children's Hospital, Brisbane, according to the protocol described by Benschop et al 36 Suspected encephalitis was defined as encephalopathy (altered level of consciousness, lethargy, or behavior and/or personality change) lasting ≥24 hours with ≥1 of the following: fever, seizures, focal neurologic findings, at least 1 abnormality of CSF (age determined pleocytosis, or elevated protein ≥40 mg/dL), or EEG/neuroimaging findings consistent with encephalitis.…”

Human picornaviruses associated with neurological diseases and their neutralization by antibodies

“…The fraction of symptomatic HPeV-3-infected infants that develop sepsis-like illness can exceed 80 %; most such patients require hospitalization and up to one-third of them are admitted to the ICU [104][105][106]. The CNS symptoms of HPeV-3 infection can include meningitis, meningoencephalitis, encephalitis or cerebral haemorrhage, with occasional white-matter alterations [107,108]. Whereas HPeV-3 meningitis typically has a good prognosis, meningoencephalitis entailing white-matter alterations may have long-term sequelae, such as cerebral palsy, learning disabilities, epilepsy or visual impairment [34].…”

Parechovirus Sepsis and Meningitis in a Neonatal Intensive Care Unit

“…HPeV is a small RNA virus belonging to the Picornaviridae family of enteroviruses [1]. The genus contains six members, with HPeV 3 associated with neonatal infections presenting with symptoms in the central nervous system (CNS) [2].…”