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Human parechovirus encephalitis in infants: a retrospective single-center study (2017–2022)

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Abstract

Parechoviruses cause a spectrum of clinical presentations ranging from self-limited to severe encephalitis. In July 2022, state health departments across the USA received an increase in reports of PeV infections among infants. A retrospective cohort study describing the clinical characteristics and outcomes of PeV encephalitis in infants aged < 90 days. Rates of PeV encephalitis were determined based on the number of PeV encephalitis cases out of all meningoencephalitis multiplex polymerase chain reaction panel (MEP) obtained among infants aged < 90 days per year. Out of 2115 infants evaluated for meningoencephalitis, 32 (1.5%) cases of PeV encephalitis were identified. All cases had an absence of pleocytosis and normal protein and glucose levels on CSF analysis. Half of the cases presented with a symptomatic triad (fever, rash, and fussiness). More than one-third of cases (39%) presented with a sepsis-like syndrome, 13% presented with seizures, and 25% were admitted to the pediatric intensive care unit (PICU). MRI of the brain was obtained in four of the cases presented with seizure, all of which demonstrated characteristic radiological findings of the periventricular white matter with frontoparietal predominance and involving the corpus callosum, thalami, and internal and external capsules. Rates of PeV encephalitis varied from year to year, with the highest rates in 2018 and 2022. PeV was the second most detected pathogen in MEP in both 2018 and 2022, and the fifth most detected pathogen in all positive MEP during the study period 2017–2022.

Conclusion: PeV can cause encephalitis and sepsis-like syndrome in infants, and it should be considered even with normal CSF parameters. Prospective studies are needed to better understand PeV epidemiology and to monitor outbreaks.

What is Known:

• PeV is a frequent cause of encephalitis and clinical sepsis in infants in the first 90 days.

• Normal CSF parameters in PeV encephalitis and diagnostic importance of MEP to avoid unnecessary prolonged antibiotics and hospitalization..

• Centers for Disease Control and Prevention (CDC) issued a Health Advisory alert in Summer 2022 of uptick PeV encephalitis cases in the USA likely secondary of COVID-19 mitigation measures relaxation, but no comparison with previous years..

What is New:

• Knowledge of radiological MRI brain characteristics in PeV encephalitis can be a clue diagnosis.

• Knowledge of the biennial seasonality pattern in PeV infection.

• PeV was the second most detected pathogen in BIOFIRE ME panel in both 2018 and 2022 in our cohort sample.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

PeV:

Parechovirus encephalitis

CSF:

Cerebrospinal fluid

PICU:

Pediatric intensive care unit

PCR:

Polymerase chain reaction

CDC:

Control and Prevention

MEP:

Meningitis/Encephalitis Panel

COVID-19:

Coronavirus disease 2019

CT:

Computed tomography

MRI:

Magnetic resonance imaging

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

ALC:

Absolute lymphocyte count

ANC:

Absolute neutrophil count

References

  1. Aizawa Y, Izumita R, Saitoh A (2017) Human parechovirus type 3 infection: an emerging infection in neonates and young infants. J Infect Chemother 23(7):419–426

    Article  PubMed  Google Scholar 

  2. Black S et al (2019) Comparing the clinical severity of disease caused by enteroviruses and human parechoviruses in neonates and infants. Pediatr Infect Dis J 38(2):e36–e38

    Article  PubMed  Google Scholar 

  3. Gupta S et al (2010) Extensive white matter abnormalities associated with neonatal parechovirus (PeV) infection. Eur J Paediatr Neurol 14(6):531–534

    Article  PubMed  Google Scholar 

  4. Harvala H, Wolthers KC, Simmonds P (2010) Parechoviruses in children: understanding a new infection. Curr Opin Infect Dis 23(3):224–230

    Article  PubMed  Google Scholar 

  5. Renaud C, Harrison CJ (2015) Human parechovirus 3: the most common viral cause of meningoencephalitis in young infants. Infect Dis Clin North Am 29(3):415–428

    Article  PubMed  Google Scholar 

  6. de Crom SC et al (2016) Enterovirus and parechovirus infection in children: a brief overview. Eur J Pediatr 175(8):1023–1029

    Article  PubMed  PubMed Central  Google Scholar 

  7. Olijve L, Jennings L, Walls T (2018) Human parechovirus: an increasingly recognized cause of sepsis-like illness in young infants. Clin Microbiol Rev 31(1)

  8. Shoji K et al (2013) Dermatologic manifestations of human parechovirus type 3 infection in neonates and infants. Pediatr Infect Dis J 32(3):233–236

    Article  PubMed  Google Scholar 

  9. Karsch K et al (2015) Human parechovirus infections associated with seizures and rash in infants and toddlers. Pediatr Infect Dis J 34(10):1049–1055

    Article  PubMed  Google Scholar 

  10. Britton PN et al (2016) Parechovirus encephalitis and neurodevelopmental outcomes. Pediatrics 137(2):e20152848

    Article  PubMed  Google Scholar 

  11. Verboon-Maciolek MA et al (2008) Human parechovirus causes encephalitis with white matter injury in neonates. Ann Neurol 64(3):266–273

    Article  PubMed  Google Scholar 

  12. Esposito S et al (2014) Pediatric parechovirus infections. J Clin Virol 60(2):84–89

    Article  PubMed  Google Scholar 

  13. Tao L et al (2022) Notes from the field: cluster of parechovirus central nervous system infections in young infants - Tennessee, 2022. MMWR Morb Mortal Wkly Rep 71(30):977–978

    Article  PubMed  PubMed Central  Google Scholar 

  14. Thomson J et al (2018) Cerebrospinal fluid reference values for young infants undergoing lumbar puncture. Pediatrics 141(3)

  15. Molloy TJHHKKLMM (2022) The Harriet Lane handbook, 22nd edn

    Google Scholar 

  16. Yum S et al (2021) Trends in viral respiratory infections during COVID-19 pandemic. South Korea Emerg Infect Dis 27(6):1685–1688

    Article  CAS  PubMed  Google Scholar 

  17. Mosscrop LG, Williams TC, Tregoning JS (2022) Respiratory syncytial virus after the SARS-CoV-2 pandemic - what next? Nat Rev Immunol 22(10):589–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Escuret A et al (2013) Epidemiology of parechovirus infections of the central nervous system in a French pediatric unit. Arch Pediatr 20(5):470–475

    Article  CAS  PubMed  Google Scholar 

  19. Fischer TK et al (2014) Human parechovirus infection. Denmark Emerg Infect Dis 20(1):83–87

    Article  PubMed  Google Scholar 

  20. Selvarangan R et al (2011) Human parechovirus 3 causing sepsis-like illness in children from midwestern United States. Pediatr Infect Dis J 30(3):238–242

    Article  PubMed  Google Scholar 

  21. van der Sanden SM, Koopmans MP, van der Avoort HG (2013) Detection of human enteroviruses and parechoviruses as part of the national enterovirus surveillance in the Netherlands, 1996–2011. Eur J Clin Microbiol Infect Dis 32(12):1525–1531

    Article  PubMed  Google Scholar 

  22. Holmes CW et al (2017) Human parechovirus cluster in the UK, 8 May-2 August 2016-sequence analysis. J Clin Virol 93:37–39

    Article  CAS  PubMed  Google Scholar 

  23. Calvert J et al (2010) Recombination dynamics of human parechoviruses: investigation of type-specific differences in frequency and epidemiological correlates. J Gen Virol 91(Pt 5):1229–1238

    Article  CAS  PubMed  Google Scholar 

  24. Watanabe K, Hirokawa C, Tazawa T (2016) Seropositivity and epidemiology of human parechovirus types 1, 3, and 6 in Japan. Epidemiol Infect 144(16):3451–3460

    Article  CAS  PubMed  Google Scholar 

  25. Seo JH et al (2015) Prevalence of human parechovirus and enterovirus in cerebrospinal fluid samples in children in Jinju. Korea Korean J Pediatr 58(3):102–107

    Article  PubMed  Google Scholar 

  26. Khatami A et al (2020) Epidemic and inter-epidemic burden of pediatric human parechovirus infection in New South Wales, Australia, 2017–2018. Pediatr Infect Dis J 39(6):507–511

    Article  PubMed  Google Scholar 

  27. Obermeier PE et al (2016) Acute disseminated encephalomyelitis after human parechovirus infection. Pediatr Infect Dis J 35(1):35–38

    Article  PubMed  Google Scholar 

  28. van Zwol AL et al (2009) Fatal neonatal parechovirus encephalitis. BMJ Case Rep 2009

  29. Volpe JJ (2008) Neonatal encephalitis and white matter injury: more than just inflammation? Ann Neurol 64(3):232–236

    Article  PubMed  PubMed Central  Google Scholar 

  30. Harvala H et al (2009) Specific association of human parechovirus type 3 with sepsis and fever in young infants, as identified by direct typing of cerebrospinal fluid samples. J Infect Dis 199(12):1753–1760

    Article  CAS  PubMed  Google Scholar 

  31. Felsenstein S et al (2014) Human parechovirus central nervous system infections in southern California children. Pediatr Infect Dis J 33(4):e87-91

    Article  PubMed  Google Scholar 

  32. Sharp J et al (2013) Characteristics of young infants in whom human parechovirus, enterovirus or neither were detected in cerebrospinal fluid during sepsis evaluations. Pediatr Infect Dis J 32(3):213–216

    Article  PubMed  PubMed Central  Google Scholar 

  33. Nielsen NM et al (2016) Severe human parechovirus infections in infants and the role of older siblings. Am J Epidemiol 183(7):664–670

    Article  PubMed  Google Scholar 

  34. Tierradentro-Garcia LO et al (2022) Neuroimaging findings in parechovirus encephalitis: a case series of pediatric patients. Pediatr Neurol 130:41–45

    Article  PubMed  Google Scholar 

  35. Sarma A et al (2019) Human parechovirus meningoencephalitis: neuroimaging in the era of polymerase chain reaction-based testing. AJNR Am J Neuroradiol 40(8):1418–1421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Aldriweesh MA et al (2020) Viruses causing aseptic meningitis: a tertiary medical center experience with a multiplex PCR assay. Front Neurol 11:602267

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, 705 Riley Hospital Drive, Indianapolis, IN, 46202, USA

    Muayad Alali, Shannon Hamilton & James G. Carlucci

  2. Indiana University School of Medicine, Indianapolis, IN, USA

    Kiet Tat

  3. Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA

    Drew A. Streicher

Authors
  1. Muayad Alali
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  2. Kiet Tat
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  3. Shannon Hamilton
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  4. Drew A. Streicher
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  5. James G. Carlucci
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Contributions

Dr. Muayad Alali and Dr. Kiet Tat drafted the initial manuscript and conducted data collection. Dr. Streicher created the figure MRI brain imaging, with caption, and critically reviewed and revised the manuscript. Dr. Hamilton reviewed and revised the manuscript and helped with tables and figures formatting. Dr. Carlucci and Dr. Alali critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree for all content of the work.

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Correspondence to Muayad Alali.

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The authors declare no conflict of conflicts.

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Communicated by Tobias Tenenbaum

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Article Summary

This is a description of an uptick infantile parechovirus encephalitis (PeV) cases in the summer of 2022 and highlighting important clinical characteristics and outcomes of PeV encephalitis. 

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Alali, M., Tat, K., Hamilton, S. et al. Human parechovirus encephalitis in infants: a retrospective single-center study (2017–2022). Eur J Pediatr 182, 4457–4465 (2023). https://doi.org/10.1007/s00431-023-05117-7

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  • DOI: https://doi.org/10.1007/s00431-023-05117-7

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