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Laboratory diagnosis of CNS infections in children due to emerging and re-emerging neurotropic viruses

Pediatric Research volume 95, pages 543–550 (2024)Cite this article

Abstract

Recent decades have witnessed the emergence and re-emergence of numerous medically important viruses that cause central nervous system (CNS) infections in children, e.g., Zika, West Nile, and enterovirus/parechovirus. Children with immature immune defenses and blood–brain barrier are more vulnerable to viral CNS infections and meningitis than adults. Viral invasion into the CNS causes meningitis, encephalitis, brain imaging abnormalities, and long-term neurodevelopmental sequelae. Rapid and accurate detection of neurotropic viral infections is essential for diagnosing CNS diseases and setting up an appropriate patient management plan. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis/encephalitis. However, the expansion of test menu has led to new challenges in selecting appropriate tests and making accurate interpretation of test results. There are unmet gaps in development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses. Herein we will discuss the advances and challenges in the laboratory diagnosis of viral CNS infections in children. This review not only sheds light on selection and interpretation of a suitable diagnostic test for emerging/re-emerging neurotropic viruses, but also calls for more research on development and clinical utility study of novel molecular assays.

Impact

  • Children with immature immune defenses and blood–brain barrier, especially neonates and infants, are more vulnerable to viral central nervous system infections and meningitis than adults.

  • The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis and encephalitis.

  • There are unmet gaps in the development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses.

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Fig. 1: Timeline of emerging and re-emerging viral diseases that have caused central nervous system infections in the past two decades.
Fig. 2: Children, especially neonates and infants, are more vulnerable to viral CNS infections and meningitis than adults.
Fig. 3: Commonly used clinical diagnostic testing methods for emerging and re-emerging viral diseases.
Fig. 4: Classification of molecular methods for infectious diseases diagnostics based on number of targets.

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Funding

Funding

B.M.L. was supported by the William L. Roberts Memorial Fund (553-Liu-11.20.20 and 553-Mehta-08.31.20), ARUP Institute for Experimental Pathology. This publication resulted, in part, from research supported by the District of Columbia Center for AIDS Research, an NIH funded program (P30AI117970), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NIDDK, NIMHD, NIDCR, NINR, FIC, and OAR. Research reported in this work was also supported by the National Center for Advancing Translational Sciences and the NIAID of the NIH under award number U54AI150225. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Authors and Affiliations

  1. Division of Pathology and Laboratory Medicine, Children’s National Hospital, Washington, DC, USA

    Benjamin M. Liu & Joseph M. Campos

  2. Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Benjamin M. Liu, Sarah B. Mulkey, Joseph M. Campos & Roberta L. DeBiasi

  3. Department of Pathology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Benjamin M. Liu & Joseph M. Campos

  4. Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Benjamin M. Liu, Joseph M. Campos & Roberta L. DeBiasi

  5. Children’s National Research Institute, Washington, DC, USA

    Benjamin M. Liu, Sarah B. Mulkey & Roberta L. DeBiasi

  6. The District of Columbia Center for AIDS Research, Washington, DC, USA

    Benjamin M. Liu

  7. Prenatal Pediatrics Institute, Children’s National Hospital, Washington, DC, USA

    Sarah B. Mulkey

  8. Division of Neurology, Children’s National Hospital, Washington, DC, USA

    Sarah B. Mulkey

  9. Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Sarah B. Mulkey

  10. Division of Pediatric Infectious Diseases, Children’s National Hospital, Washington, DC, USA

    Roberta L. DeBiasi

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B.M.L. drafted the article, Figs. 1–4, and Table 1. S.B.M., J.M.C. and R.L.D. revised the manuscript.

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Correspondence to Benjamin M. Liu or Roberta L. DeBiasi.

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Liu, B.M., Mulkey, S.B., Campos, J.M. et al. Laboratory diagnosis of CNS infections in children due to emerging and re-emerging neurotropic viruses. Pediatr Res 95, 543–550 (2024). https://doi.org/10.1038/s41390-023-02930-6

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