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Journal of Translational Medicine Nov 2023Viral and autoimmune encephalitis may present with similar symptoms, but require different treatments. Thus, there is a need for biomarkers to improve diagnosis and...
BACKGROUND
Viral and autoimmune encephalitis may present with similar symptoms, but require different treatments. Thus, there is a need for biomarkers to improve diagnosis and understanding of pathogenesis. We hypothesized that virus-host cell interactions lead to different changes in central nervous system (CNS) metabolism than autoimmune processes and searched for metabolite biomarkers in cerebrospinal fluid (CSF) to distinguish between the two conditions.
METHODS
We applied a targeted metabolomic/lipidomic analysis to CSF samples from patients with viral CNS infections (n = 34; due to herpes simplex virus [n = 9], varicella zoster virus [n = 15], enteroviruses [n = 10]), autoimmune neuroinflammation (n = 25; autoimmune anti-NMDA-receptor encephalitis [n = 8], multiple sclerosis [n = 17), and non-inflamed controls (n = 31; Gilles de la Tourette syndrome [n = 20], Bell's palsy with normal CSF cell count [n = 11]). 85 metabolites passed quality screening and were evaluated as biomarkers. Standard diagnostic CSF parameters were assessed for comparison.
RESULTS
Of the standard CSF parameters, the best biomarkers were: CSF cell count for viral infections vs. controls (area under the ROC curve, AUC = 0.93), Q-albumin for viral infections vs. autoimmune neuroinflammation (AUC = 0.86), and IgG index for autoimmune neuroinflammation vs. controls (AUC = 0.90). Concentrations of 2 metabolites differed significantly (p < 0.05) between autoimmune neuroinflammation and controls, with proline being the best biomarker (AUC = 0.77). In contrast, concentrations of 67 metabolites were significantly higher in viral infections than controls, with SM.C16.0 being the best biomarker (AUC = 0.94). Concentrations of 68 metabolites were significantly higher in viral infections than in autoimmune neuroinflammation, and the 10 most accurate metabolite biomarkers (AUC = 0.89-0.93) were substantially better than Q-albumin (AUC = 0.86). These biomarkers comprised six phosphatidylcholines (AUC = 0.89-0.92), two sphingomyelins (AUC = 0.89, 0.91), and acylcarnitines isobutyrylcarnitine (C4, AUC = 0.92) and isovalerylcarnitine (C5, AUC = 0.93). Elevated C4 and C5 concentrations suggested dysfunctional mitochondrial β-oxidation and correlated only moderately with CSF cell count (Spearman ρ = 0.41 and 0.44), indicating that their increase is not primarily driven by inflammation.
CONCLUSIONS
Changes in CNS metabolism differ substantially between viral CNS infections and autoimmune neuroinflammation and reveal CSF metabolites as pathophysiologically relevant diagnostic biomarkers for the differentiation between the two conditions. In viral CNS infections, the observed higher concentrations of free phospholipids are consistent with disruption of host cell membranes, whereas the elevated short-chain acylcarnitines likely reflect compromised mitochondrial homeostasis and energy generation.
Topics: Humans; Neuroinflammatory Diseases; Phospholipids; Central Nervous System Viral Diseases; Biomarkers; Albumins
PubMed: 37919735
DOI: 10.1186/s12967-023-04637-y -
Heliyon May 2024Acute meningitis is a disease with case fatality and disability rate that is dependent on the causative agent.
BACKGROUND
Acute meningitis is a disease with case fatality and disability rate that is dependent on the causative agent.
OBJECTIVE
Determine the meningitis trend in Iraq from 2007 to 2023 using a joinpoint regression at national and sub-national levels and describe the epidemiology.
METHODS
Joinpoint regression model was used on surveillance data from Jan 2007 until May 2023, to calculate annual and average annual percent changes to determine the trend. Meningitis total count was modelled by year of reporting and province using the log transformation and Poisson variance. Best-fit model was chosen based on the weighted BIC criteria as the final point.
RESULTS
Bacterial meningitis was higher than viral meningitis from 2007 to 2018, then viral meningitis started to exceed till 2023. Meningococcal meningitis was lower than other bacterial and viral meningitis from 2007 to 2023. Most meningitis cases across the years were lower than 15 years, at almost 80 %, while 20 %-40 % were lower than one year. Across all years, 55 % of the cases were males; apart from 2019, 70 % were females.
CONCLUSION
In Iraq, viral meningitis has been the predominant type since 2018. Most meningitis patients were lower than 15-year-old males. The meningitis trend in Iraq was stable from 2007 till 2023.
PubMed: 38707473
DOI: 10.1016/j.heliyon.2024.e30088 -
Journal of Neuroinflammation Sep 2023Viral rewiring of host bioenergetics and immunometabolism may provide novel targets for therapeutic interventions against viral infections. Here, we have explored the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Viral rewiring of host bioenergetics and immunometabolism may provide novel targets for therapeutic interventions against viral infections. Here, we have explored the effect on bioenergetics during the infection with the mosquito-borne flavivirus West Nile virus (WNV), a medically relevant neurotropic pathogen causing outbreaks of meningitis and encephalitis worldwide.
RESULTS
A systematic literature search and meta-analysis pointed to a misbalance of glucose homeostasis in the central nervous system of WNV patients. Real-time bioenergetic analyses confirmed upregulation of aerobic glycolysis and a reduction of mitochondrial oxidative phosphorylation during viral replication in cultured cells. Transcriptomics analyses in neural tissues from experimentally infected mice unveiled a glycolytic shift including the upregulation of hexokinases 2 and 3 (Hk2 and Hk3) and pyruvate dehydrogenase kinase 4 (Pdk4). Treatment of infected mice with the Hk inhibitor, 2-deoxy-D-glucose, or the Pdk4 inhibitor, dichloroacetate, alleviated WNV-induced neuroinflammation.
CONCLUSIONS
These results highlight the importance of host energetic metabolism and specifically glycolysis in WNV infection in vivo. This study provides proof of concept for the druggability of the glycolytic pathway for the future development of therapies to combat WNV pathology.
Topics: Humans; Animals; Mice; West Nile Fever; Glycolysis; Central Nervous System; Disease Outbreaks; Gene Expression Profiling
PubMed: 37759218
DOI: 10.1186/s12974-023-02899-3 -
Eastern Mediterranean Health Journal =... May 2024Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200...
BACKGROUND
Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200 children with suspected meningitis were admitted to hospital in Halabja Governorate, Iraq. No outbreak of meningitis had been reported previously in that region.
AIMS
To investigate the aetiology and epidemiology of meningitis among children in Halabja Governorate, Iraq, and expedite clinical management and prevention.
METHODOLOGY
Blood and cerebrospinal fluid specimens were collected from 197 children admitted to Halabja Paediatric and Maternity Teaching Hospital from 1 March to 1 July 2023 and analysed. The sample t-test was used to compare the haematological, serological and biochemical characteristics of the samples.
RESULTS
The majority (76.6%) of the children were aged 2-9 years and 54% were males. The clinical manifestations of the disease were fever (100.0%), headache (89.0%), vomiting (85.7%), and photophobia (72.4%); none of the children had convulsions. The mean values for both neutrophil count and C-reactive protein were statistically significantly raised (P < 0.05) and the red blood cells, white blood cells and neutrophil counts, and lactate dehydrogenase values were statistically significantly raised (P < 0.05). The causative organism was enterovirus (98.5%), with sporadic cases of streptococcal meningitis (1.5%). All the patients recovered fully.
CONCLUSION
The rapid diagnosis of the disease was crucial to the therapeutic and prevention control measures for the outbreak. Although it is still unclear how and where this outbreak started, contaminated drinking water and transmission among children in nurseries and schools are suspected. Further investigations are recommended to determine the source of the enterovirus and identify the virus species and serotypes.
Topics: Humans; Iraq; Child; Child, Preschool; Male; Disease Outbreaks; Female; Meningitis, Viral; Adolescent; Infant; Meningitis, Bacterial
PubMed: 38874294
DOI: 10.26719/2024.30.5.350 -
Journal of Neurology, Neurosurgery, and... Aug 2023To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. (Observational Study)
Observational Study
UNLABELLED
To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses.
METHODS
A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B).
RESULTS
Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], =0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031).
CONCLUSIONS
Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.
Topics: Male; Humans; Female; Autoimmunity; Retrospective Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Autoantibodies; Encephalitis; Immunoglobulin G
PubMed: 37225405
DOI: 10.1136/jnnp-2022-330626 -
Journal of Medical Virology Dec 2023Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of...
Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of patients with RHS and concurrent VZV meningitis (henceforth RHS meningitis) are limited. Thus, we conducted a nationwide population-based cohort study of all adults hospitalized for RHS meningitis at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with VZV meningitis without cranial nerve palsies were included for comparison. In total, 37 patients with RHS meningitis (mean annual incidence: 1.6/1 000 000 adults) and 162 with VZV meningitis without cranial nerve palsies were included. In RHS meningitis, the median age was 52 years (interquartile range: 35-64), and in addition to peripheral facial nerve palsy (100%), dizziness (46%), and hearing loss (35%) were common symptoms. The triad of headache, neck stiffness, and photophobia/hyperacusis was less common in RHS meningitis than in VZV meningitis without cranial nerve palsies (0/27 [0%] vs. 24/143 [17%]; p = 0.02). At 30 days after discharge, 18/36 (50%) patients with RHS meningitis had persistent peripheral facial nerve palsy, with no statistically significant difference between those treated with and without adjuvant glucocorticoids (6/16 [38%] vs. 12/20 [60%]; p = 0.18). Additional sequelae of RHS meningitis included dizziness (29%), neuralgia (14%), tinnitus/hyperacusis (11%), hearing loss (9%), headache (9%), fatigue (6%), and concentration difficulties (3%). In conclusion, clinical features and outcomes of RHS meningitis were primarily related to cranial neuropathies.
Topics: Adult; Humans; Middle Aged; Herpes Zoster Oticus; Herpesvirus 3, Human; Cohort Studies; Dizziness; Hyperacusis; Facial Paralysis; Chickenpox; Hearing Loss; Headache; Denmark
PubMed: 38058258
DOI: 10.1002/jmv.29291 -
Microbial Genomics Aug 2023Encephalitis and meningitis are notable global public health concerns, especially among infants or children. Metagenomic next-generation sequencing (mNGS) has greatly...
Encephalitis and meningitis are notable global public health concerns, especially among infants or children. Metagenomic next-generation sequencing (mNGS) has greatly advanced our understanding of the viruses responsible for these diseases. However, the detection rate of the aetiology remains low. We conducted RNA sequencing and virome analysis on cerebrospinal fluid (CSF) and serum samples commonly used in the clinical diagnosis to detect viral pathogens. In total, 226 paired CSF and serum samples from 113 children with encephalitis and meningitis were enrolled. The results showed that the diversity of viruses was higher in CSF, with a total of 12 viral taxa detected, including one case each of herpesvirus, coronavirus and enterovirus, and six cases of adenovirus related to human diseases. In contrast, the was the most abundant viral family detected in serum, and only a few samples contained human viral pathogens, including one case of enterovirus and two cases of adenovirus. The detection rate for human viral pathogens increases to 10.6 %(12/113) when both types of samples are used simultaneously, compared to CSF along 7.9 % (9/113) or serum alone 2.6 % (3/113). However, we did not detect these viruses simultaneously in paired samples from the same case. These results suggest that CSF samples still have irreplaceable advantages for using mNGS to detect viruses in patients with meningitis and encephalitis, and serum can supplement to improve the detection rate of viral encephalitis and meningitis. The findings of this study could help improve the etiological diagnosis, clinical management and prognosis of patients with meningitis and encephalitis in children.
Topics: Infant; Humans; Child; Meningitis; Encephalitis; Viruses; Enterovirus; Sequence Analysis, RNA; RNA
PubMed: 37531160
DOI: 10.1099/mgen.0.001079 -
Nature Communications Dec 2023Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the...
Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. We found that BA.2.86 does not have significantly more escape relative to Omicron XBB.1.5 from neutralizing immunity elicited by either Omicron XBB-family subvariant infection or from residual neutralizing immunity of recently collected sera from the South African population. BA.2.86 does have extensive escape relative to ancestral virus with the D614G substitution (B.1 lineage) when neutralized by sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 when neutralized by sera from Omicron BA.1 infected individuals. BA.2.86 and XBB.1.5 show similar viral infection dynamics in the VeroE6-TMPRSS2 and H1299-ACE2 cell lines. We also investigate the relationship of BA.2.86 to BA.2 sequences. The closest BA.2 sequences are BA.2 samples from Southern Africa circulating in early 2022. Similarly, many basal BA.2.86 sequences were sampled in Southern Africa. This suggests that BA.2.86 potentially evolved in this region, and that unobserved evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2.
Topics: Humans; Africa, Southern; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; SARS-CoV-2
PubMed: 38057313
DOI: 10.1038/s41467-023-43703-3 -
Frontiers in Microbiology 2023Viruses invade susceptible cells through a complex mechanism before injecting their genetic material into them. This causes direct damage to the host cell, as well as... (Review)
Review
Viruses invade susceptible cells through a complex mechanism before injecting their genetic material into them. This causes direct damage to the host cell, as well as resulting in disease in the corresponding system. Echovirus type 30 (E30) is a member of the Enterovirus B group and has recently been reported to cause central nervous system (CNS) disorders, leading to viral encephalitis and viral meningitis in children. In this review, we aim to help in improving the understanding of the mechanisms of CNS diseases caused by E30 for the subsequent development of relevant drugs and vaccines.
PubMed: 37485505
DOI: 10.3389/fmicb.2023.1174410