Neurological and neurodevelopmental outcomes after human parechovirus CNS infection in neonates and young children: a systematic review and meta-analysis

Hinsbergh, Ted M. T. van; Elbers, Roy G.; Ket, Hans; Furth, A. Marceline van; Obihara, Charlie C.

doi:10.1016/s2352-4642(20)30181-4

Cited by 31 publications

(39 citation statements)

References 93 publications

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“…Infections were more common in infants under one year of age, regardless of sex, and these had more severe symptoms in infections that could be related to the symptoms reported for PeV-A and are similar to the results obtained in Missouri in 2019 [26]. Only a 1-day-old female patient with CSF could be associated with PeV-A3 and that he had some symptoms previously reported by [27].…”

Section: Discussionsupporting

confidence: 84%

Detection of Human Parechovirus a in Respiratory, Gastrointestinal, and Neurological Clinical Samples of Hospitalized Patients in Panama

Saenz¹,

Gutierrez²,

Franco³

et al. 2022

Preprint

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Human parechoviruses, officially known as Parechovirus A (PeV-A), from the family Picornaviri-dae, genus Parechovirus, are non-enveloped, icosahedral, positive-sense RNA viruses associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of HPeVs in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to characterize PeV-A circulating in the Republic of Panama. Respiratory, gastrointestinal and neurological samples were collected from 200 Panamanian pe-diatric patients hospitalized between 2014 and 2015 and were analyzed for the presence of PeV-A by real-time RT-PCR. PeV-A positive samples were sequenced for genetic characterization. These samples followed predetermined inclusion criteria and were negative for viral/bacterial examinations that were requested by the patient's physician when the specimen was sent to the ICGES. Eight positive PeV-A infections (4%) were detected for the 200 subjects, in gastrointestinal samples. Human Parechovirus PeV-A was detected and genetically characterized for the first time in the Republic of Panama in samples from 2014 and 2015.

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Section: Discussionsupporting

confidence: 84%

Detection of Human Parechovirus a in Respiratory, Gastrointestinal, and Neurological Clinical Samples of Hospitalized Patients in Panama

Saenz¹,

Gutierrez²,

Franco³

et al. 2022

Preprint

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“…Neonates have increased risk of PeV-A3 infection due probably to reduced neutralization antibody protection ( 15 ). After PeV CNS infections, some of the neonates and young children exhibited neurological sequelae and neurodevelopmental delay ( 16 ). Different from PeV-A1, PeV-A3 lacks the Arginyl-Glycyl-Aspartic acid (RGD) motif in VP1 to bind integrin receptors to the cell membrane for entering cells ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis

Jan

Chang

et al. 2021

Front. Immunol.

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Human parechovirus type 3 (PeV-A3) infection has been recognized as an emerging etiologic factor causing severe nerve disease or sepsis in infants and young children. But the neuropathogenic mechanisms of PeV-A3 remain unknown. To understand the pathogenesis of PeV-A3 infection in the neuronal system, PeV-A3-mediated cytopathic effects were analyzed in human glioblastoma cells and neuroblastoma cells. PeV-A3 induced interferons and inflammatory cytokine expression in these neuronal cells. The pronounced cytopathic effects accompanied with activation of death signaling pathways of apoptosis, autophagy, and pyroptosis were detected. A new experimental disease model of parechovirus encephalitis was established. In the disease model, intracranial inoculation with PeV-A3 in C57BL/6 neonatal mice showed body weight loss, hindlimb paralysis, and approximately 20% mortality. PeV-A3 infection in the hippocampus and cortex regions of the neonatal mouse brain was revealed. Mechanistic assay supported the in vitro results, indicating detection of PeV-A3 replication, inflammatory cytokine expression, and death signaling transduction in mouse brain tissues. These in vitro and in vivo studies revealed that the activation of death signaling and inflammation responses is involved in PeV-A3-mediated neurological disorders. The present results might account for some of the PeV-A3-associated clinical manifestations.

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“…Our findings are consistent with those described by Hinsbergh et al since children showed a suspect gross motor function delay at 6 months that was normalized during 24 months follow-up, but no longitudinal association was found between HPeV CNS infection and gross motor function ( 32 ). Hinsbergh et al ( 33 ) conducted a systematic review and meta-analysis of neurological and neurodevelopmental outcomes in newborns and young children after HPeV CNS infections, including encephalitis. The authors found an increasing proportion of children with neurological sequelae over time, in 5% of cases during short-term follow-up, and increased to 27% during long-term follow-up.…”

Section: Discussionmentioning

confidence: 99%

Neurodevelopmental Outcomes of Infants Younger Than 90 Days Old Following Enterovirus and Parechovirus Infections of the Central Nervous System

et al. 2021

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Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of central nervous system (CNS) infection in young infants. They have been implicated in neurodevelopmental delay, however limited data are available. The aim of this study is to describe the clinical outcome of young infants and to assess and compare the medium-term neurodevelopment following CNS infections caused by EV and HPeV. A multicentre observational ambispective study was conducted between May 2013 and March 2018. Children under 3 months of age with EV or HPeV CNS infection excluding encephalitis were included. Infants were contacted 1 year after the acute infection and their neurological development was evaluated using the Ages and Stages Questionnaire-3 (ASQ-3). If any area assessed was abnormal during the first round of tests, a second round was completed 6 to 12 months later. Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) were positive for EV and 15 (31.3%) for HPeV. At first assessment 14 out of 29 EV (48.3%) and 3 out of 15 HPeV (20%) positive cases presented some developmental concern in the ASQ-3 test. EV-positive infants showed mild and moderate alteration in all domains analyzed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (31 vs. 0%, p = 0.016). At second assessment 4 out of 13 EV-positive patients (30.8%) showed mild to moderate concerns in communication and gross motor function domains and 3 out of 13 (23.1%) showed significant concern in fine motor function. Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months almost half of the EV-infected infants (48.3%) and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3 test. We recommend monitor the neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation of psychomotor development if necessary.

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Neurological and neurodevelopmental outcomes after human parechovirus CNS infection in neonates and young children: a systematic review and meta-analysis

Cited by 31 publications

References 93 publications

Detection of Human Parechovirus a in Respiratory, Gastrointestinal, and Neurological Clinical Samples of Hospitalized Patients in Panama

Detection of Human Parechovirus a in Respiratory, Gastrointestinal, and Neurological Clinical Samples of Hospitalized Patients in Panama

Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis

Neurodevelopmental Outcomes of Infants Younger Than 90 Days Old Following Enterovirus and Parechovirus Infections of the Central Nervous System

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