Encephalitis in US Children

Messacar, Kevin; Fischer, Marc; Dominguez, Samuel R.; Tyler, Kenneth L.; Abzug, Mark J.

doi:10.1016/j.idc.2017.10.007

Cited by 73 publications

(83 citation statements)

References 73 publications

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“…Management of CNS disease caused by unknown agent poses a challenge to clinicians. It is recommended that patients diagnosed with infectious encephalitis should receive empiric acyclovir and antibacterial agents until bacterial and viral study results are available [36]. Therefore, prompt identification of a specific pathogen reduces the inappropriate use of antibiotics and antivirals and hospital admission costs [1,2,5,20].…”

Section: Discussionmentioning

confidence: 99%

Etiology, Clinical Presentation and Incidence of Infectious Meningitis and Encephalitis in Polish Children

Toczyłowski

Bojkiewicz

Barszcz

et al. 2020

JCM

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Little is known about the causes and the frequency of meningitis and encephalitis in Poland. We did a retrospective single-center cohort study of children under 18 years old hospitalized with infectious meningitis or encephalitis. Incidence rates were calculated using collected data from patients from the North-East Poland only. A total of 374 children hospitalized between 1 January 2015 and 31 December 2019 were included in the study. A total of 332 (89%) children had meningitis, and 42 (11%) had encephalitis. The etiology of the infection was established in 331 (89%) cases. Enteroviruses accounted for 224 (60%) of all patients. A total of 68 (18%) cases were tick-borne infections. Bacterial pathogens were detected in 26 (7%) children. The median length of hospital stay for children with enteroviral meningitis was 7 days (IQR 7–9), increasing to 11 days (8–13) in those treated with antibiotics. The incidence of meningitis was estimated to be 32.22 (95% CI, 25.33–40.98) per 100,000 and that of encephalitis to be 4.08 (95% CI, 2.07–8.02) per 100,000. By the broad use of molecular diagnostic methods, we managed to identify etiology of the infection in the majority of children. Our data suggest that thorough diagnostics of central nervous system infections are needed to rationalize treatment.

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Section: Discussionmentioning

confidence: 99%

Etiology, Clinical Presentation and Incidence of Infectious Meningitis and Encephalitis in Polish Children

Toczyłowski

Bojkiewicz

Barszcz

et al. 2020

JCM

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“…Herpes simplex virus 1 (HSV-1) causes lifelong latent infections, periodic reactivation of which may result in recurrent disease ( 1 ). The annual incidence of herpes simplex encephalitis (HSE) worldwide is 2 to 4 per 1,000,000, with rates of neonatal encephalitis rising in the United States ( 2 – 4 ). While such cases can be treated by antiviral acyclovir therapy, which dramatically reduces the mortality to approximately 25%, over 60% of survivors experience severe long-term neurologic deficits.…”

Section: Introductionmentioning

confidence: 99%

Patterns of Herpes Simplex Virus 1 Infection in Neural Progenitor Cells

Zheng

Klammer

Naciri

et al. 2020

J Virol

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HSV-1 can induce damage in brain regions that include the hippocampus and associated limbic structures. These neurogenic niches are important because they are associated with memory formation and are highly enriched with neural progenitor cells (NPCs). The susceptibility and fate of HSV-1 infected NPCs is largely unexplored. We differentiated human induced pluripotent stem cells (iPSCs) into NPCs to generate two-dimensional (2D) and three-dimensional (3D) culture models to examine the interaction of HSV-1 with NPCs. Here, we show that: i) NPCs can be efficiently infected by HSV-1, but infection does not result in cell death of most NPCs, even at high multiplicity of infections (MOIs); ii) limited HSV-1 replication and gene expression can be detected in the infected NPCs; iii) a viral silencing mechanism is established in NPCs exposed to antivirals (E)-5-(2-bromovinyl)-2′-deoxyuridine (5BVdU) and interferon-α (IFN-α). When the antivirals are removed, spontaneous reactivation can occur at low frequency; iv) HSV-1 impairs the ability of NPCs to migrate in a dose-dependent fashion in the presence of 5BVdU + IFN-α; and v) 3D cultures of NPCs are less susceptible to HSV-1 infection than 2D cultures, yet still retain latent genomes. These results suggest that NPC pools could be sites of HSV-1 reactivation in the CNS. Finally, our results highlight the potential value of iPSC 3D cultures to model HSV-1-NPCs interaction. IMPORTANCE This study employed human induced pluripotent stem cells (hiPSCs) to model the interaction of HSV-1 with NPCs, which reside in the neurogenic niches of the CNS and play a fundamental role in adult neurogenesis. Herein, we provide evidence that in NPCs infected at an MOI as low as 0.001 HSV-1 can establish a latent state, suggesting that i) HSV-1 latency is not only restricted to mature neurons, but it can be established during earlier stages of neuronal differentiation; ii) neurogenic niches in the brain may constitute additional HSV-1 latent reservoirs. Lytic HSV-1 infections impaired NPCs migration, which represents a critical step in neurogenesis. Difference in susceptibility to HSV-1 infection between two-dimensional (2D) and three-dimensional (3D) NPC cultures was observed, highlighting the potential value of 3D cultures for modeling host-pathogen interactions. Together, our results are relevant in light of observations relating HSV-1 infection to post-encephalitic cognitive dysfunction.

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“…Both of these viruses represent parental sequences to the HCoV-HUK1, MHV-JHM, HCoV-OC43, and PHEV viruses, and descendant sequences of the MERS-CoV virus. Figure 1B represents a circular phylogram demonstrating the evolutionary relationship between SARS-CoV-2 and 23 non-segmented neuroinvasive and neurotropic RNA viruses known to infect humans (Messacar et al, 2018). Nineteen of these RNA viruses (red-labelled) are also known to infect infants and children (Messacar et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

“…Figure 1B represents a circular phylogram demonstrating the evolutionary relationship between SARS-CoV-2 and 23 non-segmented neuroinvasive and neurotropic RNA viruses known to infect humans (Messacar et al, 2018). Nineteen of these RNA viruses (red-labelled) are also known to infect infants and children (Messacar et al, 2018). This phylogram demonstrates that CoVs alone are one of the three major clades.…”

Section: Resultsmentioning

confidence: 99%

Potential neuroinvasive and neurotrophic properties of SARS-CoV-2 in pediatric patients: Comparison of SARS-CoV-2 with non-segmented RNA viruses

Chen

2020

Preprint

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The emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is causing global health and economic crises. Infants and children can be infected, but are less likely to develop severe abnormalities including neurological disorders compared with adults. However, whether SARS-CoV-2 can directly cause neurological impairments in pediatric patients is not known. The possible evolutionary and molecular relationship between SARS-CoV-2 and non-segmented RNA viruses were examined with reference to neurological disorders in pediatric patients. SARS-CoV-2 appears to share similar functional domains and protein sequences with neuroinvasive and neurotropic RNA viruses and thus has the potential to cause neurological diseases in pediatric patients.

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Encephalitis in US Children

Cited by 73 publications

References 73 publications

Etiology, Clinical Presentation and Incidence of Infectious Meningitis and Encephalitis in Polish Children

Etiology, Clinical Presentation and Incidence of Infectious Meningitis and Encephalitis in Polish Children

Patterns of Herpes Simplex Virus 1 Infection in Neural Progenitor Cells

Potential neuroinvasive and neurotrophic properties of SARS-CoV-2 in pediatric patients: Comparison of SARS-CoV-2 with non-segmented RNA viruses

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