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
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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.
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The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis and encephalitis.
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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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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.
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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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DOI: https://doi.org/10.1038/s41390-023-02930-6
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