川田 潤一

BACKGROUND: Rotavirus vaccination effectively prevents severe rotavirus gastroenteritis; however, administration during neonatal hospitalization is often avoided because of theoretical concerns regarding vaccine-virus transmission. Data on the safety of in-hospital rotavirus vaccination in neonatal step-down care settings remain limited. METHODS: We conducted a 1-year prospective cohort study in a Japanese growing care unit, a step-down neonatal unit comparable to Level II-III neonatal intensive care units in the United States. Hospitalized infants were monitored for adverse events and vaccine-strain shedding after administration of monovalent rotavirus vaccine (RV1). Stool samples were collected weekly and analyzed using RV1 strain-specific real-time quantitative reverse transcription polymerase chain reaction targeting the NSP2 gene. Routine contact precautions, including gown and glove use for all patient care activities and environmental cleaning, were consistently implemented. RESULTS: Among 237 infants included in the analysis, 15 received a total of 19 doses of RV1 during hospitalization. RV1 vaccine-strain RNA was detected in 26 of 38 postvaccination stool samples (68.4%). No RV1 strain RNA was detected in unvaccinated infants or in samples collected before vaccination. No serious adverse events were observed, and no evidence of horizontal transmission was identified. Six vaccinated infants exceeded the upper age limit for vaccine initiation at discharge and would have missed vaccination opportunities without in-hospital vaccination. CONCLUSIONS: RV1 vaccination was not associated with detectable transmission or serious adverse events in a neonatal step-down care setting under routine contact precautions, supporting its potential safety and role in preventing missed vaccination opportunities among high-risk infants.

Severe acute encephalopathy/encephalitis (AE) associated with SARS-CoV-2 has been increasingly reported since the emergence of the Omicron variant. Several pediatric cases have shown the development of acute fulminant cerebral edema (AFCE) or hemorrhagic shock encephalopathy syndrome (HSES), which are linked to high morbidity and mortality. However, the underlying pathogenic mechanisms remain unclear. We performed single-cell RNA sequencing of peripheral blood mononuclear cells from a pediatric patient with SARS-CoV-2-associated AE presenting with AFCE/HSES and compared the data with those from two patients with mild AE, one patient with febrile seizures due to non-SARS-CoV-2 pathogens, and publicly available pediatric COVID-19 datasets without neurological complications. During the acute phase, we observed a prominent expansion of B-cell populations, including distinct activated B-cell clusters. Cell-cell communication analysis identified macrophage migration inhibitory factor signaling, although it was not specific to SARS-CoV-2-associated AE. Notably, heat shock protein genes, particularly HSPA1A and HSPB1, were selectively upregulated across multiple immune cell types only in severe SARS-CoV-2-associated AE. Enzyme-linked immunosorbent assay confirmed significantly elevated plasma and serum protein levels of HSPA1A and HSPB1 during the acute phase. These findings highlight HSPA1A and HSPB1 as potential biomarkers of severe SARS-CoV-2-associated AE and suggest a pathogenic possible role for stress-response pathways.

BACKGROUND: Exanthem subitum (ES), a benign febrile exanthematous disease, is caused by primary human betaherpesvirus 6B (HHV-6B) infection. It may cause neurological complications, including complex febrile seizures (cFS), acute encephalopathy with biphasic seizures, and late reduced diffusion (AESD). cFS resolves spontaneously; however, AESD can pose severe sequelae. We aimed to elucidate AESD pathogenesis using a proteomic analysis. METHODS: Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), serum and cerebrospinal fluid (CSF) protein profiles were compared between patients with AESD and those with cFS (n = 3 or 4 per group). Metascape was used for enrichment analysis, and the selected proteins were validated using a large sample via enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 698 proteins were identified across all serum and CSF samples using LC-MS/MS. Nineteen serum proteins were differentially expressed in AESD and cFS during the acute phase. The glycolytic pathway was upregulated in AESD. Myristoylated alanine-rich C kinase substrate (MARCKS) and Golgi membrane protein 1 (GOLM1) were selected for validation using ELISA. Both proteins were upregulated during the acute phase (n = 11) compared with the convalescent phase (n = 21) in AESD (MARCKS, P = .016; GOLM1, P < .001). MARCKS during the acute phase was also upregulated in AESD compared with that in uncomplicated ES (n = 15) (P = .015). In CSF, 38 proteins were differentially expressed between AESD and cFS during the acute phase. Cholesteryl ester transfer protein in the CSF of patients with AESD was upregulated; however, this could not be validated using ELISA. CONCLUSIONS: Glycolysis and MARCKS pathways might be involved in HHV-6B-associated AESD pathogenesis.

ABSTRACT Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is an intractable form of epilepsy involving the hippocampus, and temporal lobectomy remains an effective treatment. Human herpesvirus 6B (HHV‐6B) establishes latency in the hippocampus and may contribute to MTLE‐HS pathogenesis by altering host gene expression; however, transcriptomic data from healthy controls remain limited. This study investigated the role of HHV‐6B to MTLE‐HS pathogenesis by analyzing gene expression in resected hippocampal tissues. Samples were collected from 12 to 43 HHV‐6 DNA‐positive and ‐negative patients, respectively, and three controls. RNA sequencing was performed on eight representative samples, followed by RT‐qPCR validation of nine selected genes in 58 samples. RNA sequencing identified 600 differentially expressed genes (210 upregulated, 390 downregulated) between HHV‐6B‐positive MTLE‐HS and controls. Pathway enrichment analysis revealed involvement of synaptic signaling and inflammatory responses, with prostaglandin biosynthesis specifically upregulated in HHV‐6B‐positive tissues. Two genes were significantly upregulated in HHV‐6B‐positive compared with HHV‐6B‐negative samples. RT‐qPCR confirmed elevated cholesterol 25‐hydroxylase and interleukin 1 beta expression in HHV‐6 DNA‐positive samples (both p  = 0.031). These findings suggest that HHV‐6B may contribute to MTLE‐HS pathogenesis by modulating the expression of host inflammatory genes, supporting a role for neuroinflammation and the potential benefits of anti‐inflammatory therapies.