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Vaccine May 2024Tick-borne encephalitis (TBE) virus infects the central nervous system and may lead to severe neurological complications or death. This study assessed immunogenicity,...
BACKGROUND
Tick-borne encephalitis (TBE) virus infects the central nervous system and may lead to severe neurological complications or death. This study assessed immunogenicity, safety, and tolerability of TBE vaccine in Japanese participants 1 year of age and older.
METHODS
This phase 3, multicenter, single-arm, open-label study was conducted in Japanese adult (≥ 16 years) and pediatric (1-< 16 years) populations. Participants received a single 0.5-mL (adult) or 0.25-mL (pediatric) dose of TBE vaccine at each of 3 visits. The primary endpoint was the proportion of participants who were seropositive (neutralization test [NT] titer ≥ 1:10) 4 weeks after Dose 3. Secondary and exploratory endpoints included NT seropositivity rates 4 weeks after Dose 2, immunoglobulin G (IgG) seropositivity 4 weeks after Doses 2 and 3, NT geometric mean titers (GMTs), IgG geometric mean concentrations (GMCs), and geometric mean fold rises. Primary safety endpoints were frequencies of local reactions, systemic events, adverse events (AEs), and serious AEs.
RESULTS
Among 100 adult and 65 pediatric participants, 99.0 % and 100.0 % completed the study, respectively. NT seropositivity was achieved in 98.0 % adult and 100.0 % pediatric participants after Dose 3; seropositivity after Dose 2 was 93.0 % and 92.3 %, respectively. In both age groups, IgG seropositivity was ≥ 90.0 % and ≥ 96.0 % after Doses 2 and 3, respectively; GMTs and GMCs were highest 4 weeks after Dose 3. Reactogenicity events were generally mild to moderate in severity and short-lived. AEs were reported by 15.0 % (adult) and 43.1 % (pediatric) of participants. No life-threatening AEs, AEs leading to discontinuation, immediate AEs, related AEs, or deaths were reported. No serious AEs were considered related to TBE vaccine.
CONCLUSIONS
TBE vaccine elicited robust immune responses in Japanese participants 1 year of age and older. The 3-dose regimen was safe and well tolerated, and findings were consistent with the known safety profile of this TBE vaccine.
CLINICALTRIALS
gov: NCT04648241.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Young Adult; Antibodies, Neutralizing; Antibodies, Viral; East Asian People; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Healthy Volunteers; Immunogenicity, Vaccine; Immunoglobulin G; Japan; Neutralization Tests; Viral Vaccines; Aged, 80 and over
PubMed: 38614954
DOI: 10.1016/j.vaccine.2024.03.071 -
Cureus Mar 2024Background Instant infections in children due to acute encephalitis syndrome (AES) were reported in a tribal district of Bastar in Chattisgarh, India, between August...
Background Instant infections in children due to acute encephalitis syndrome (AES) were reported in a tribal district of Bastar in Chattisgarh, India, between August 2018 and August 2019. Objective The study was conducted to explore the possibility of a viral cause indicating an outbreak. Methods Clinical surveys and serological investigation tests were conducted to identify the viral etiology. The Bastar area in Chhattisgarh reported factors such as paddy fields near homes, a high pig-to-cattle ratio, a significant presence of mosquitoes, low socioeconomic status, and a lack of health awareness among the tribal people. Result This study, conducted at the Late Baliram Kashyap Memorial Government Medical College in Jagdalpur, Bastar, Chhattisgarh, India, analyzed 128 samples from fever cases out of 213 patients visiting the Japanese encephalitis virus (JEV) testing center. Among these samples, 71 cases exhibited AES, and subsequent JEV IgM ELISA testing identified 18 cases as JEV-positive, signifying recent JEV infections. Notably, the overwhelming majority (94.44%) of JEV-positive patients were under 16 years old, highlighting the heightened vulnerability of children to JEV illness in the Bastar region. Although male patients accounted for 61.11% of the JEV-positive cases compared to 38.88% of female patients, statistical analysis revealed that this gender disparity was not statistically significant (p-value = 0.18). Conclusion The study emphasizes the significance of identifying the etiology and delivering evidence-based care to patients with AES. Improved diagnosis and management of AES may result from a greater comprehension of the advantages and disadvantages associated with the application and administration of common laboratory and diagnostic algorithms.
PubMed: 38601378
DOI: 10.7759/cureus.55939 -
Acta Parasitologica Jun 2024Mosquitoes are important vectors of pathogens that can affect humans and animals. Culex tritaeniorhynchus is an important vector of arboviruses such as Japanese...
PURPOSE
Mosquitoes are important vectors of pathogens that can affect humans and animals. Culex tritaeniorhynchus is an important vector of arboviruses such as Japanese encephalitis virus, West Nile virus among various human and animal communities. These diseases are of major public health concern and can have huge economic and health burdens in prevalent countries. Although populations of this important mosquito species have been detected in the Mediterranean and Aegean regions of Türkiye; little is known about its population structure. Our study is to examine the population genetics and genetic composition of Cx. tritaeniorhynchus mosquitoes collected from several localities using cytochrome oxidase subunit I (COI) and the NADH dehydrogenase subunit 5 genes (ND5). This is the first extensive study of Cx. tritaeniorhynchus in the mainland Türkiye with sampling spanning many of provinces.
METHODS
In this study, DNA extraction, amplification of mitochondrial COI and ND5 genes and population genetic analyses were performed on ten geographic populations of Culex tritaeniorhynchus in the Aegean and Mediterranean region of Türkiye.
RESULTS
Between 2019 and 2020, 96 samples were collected from 10 geographic populations in the Aegean and Mediterranean regions; they were molecularly analyzed and 139 sequences (50 sequence for COI and 89 sequence for ND5) were used to determine the population structure and genetic diversity. For ND5 gene region, the samples produced 24 haplotypes derived from 15 variable sites and for COI gene region, 43 haplotypes were derived from 17 variable sites. The haplotype for both gene regions was higher than nucleotide diversity. Haplotype phylogeny revealed two groups present in all populations. AMOVA test results show that the geographical populations were the same for all gene regions. Results suggest that Cx. tritaeniorhynchus is a native population in Türkiye, the species is progressing towards speciation and there is no genetic differentiation between provinces and regions.
CONCLUSION
This study provides useful information on the molecular identifcation and genetic diversity of Cx. tritaeniorhynchus; these results are important to improve mosquito control programs.
Topics: Animals; Culex; Electron Transport Complex IV; Mosquito Vectors; Turkey; Genetics, Population; Genetic Variation; NADH Dehydrogenase; Phylogeny; Haplotypes
PubMed: 38592372
DOI: 10.1007/s11686-024-00844-9 -
Journal of Virology May 2024Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases....
Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE.
Topics: Animals; Humans; Mice; Autophagy; Blood-Brain Barrier; Brain; Encephalitis Virus, Japanese; Encephalitis, Japanese; Endothelial Cells; Macrophage Migration-Inhibitory Factors; NF-kappa B; Viral Nonstructural Proteins
PubMed: 38591880
DOI: 10.1128/jvi.00116-24 -
Brain and Nerve = Shinkei Kenkyu No... Apr 2024Herein, the author summarize the basic findings on the neuropathology of inflammatory and autoimmune central nervous system (CNS) diseases. Current knowledge on...
Herein, the author summarize the basic findings on the neuropathology of inflammatory and autoimmune central nervous system (CNS) diseases. Current knowledge on infectious, demyelinating, and autoimmune diseases have also been reported. Further, I emphasize the importance of considering the neuropathology of meningitis, encephalitis, and abscesses as infectious diseases; multiple sclerosis and neuromyelitis optica as demyelinating diseases; and vasculitis, paraneoplastic neurological syndrome, and collagen diseases as autoimmune diseases.
Topics: Humans; Autoimmune Diseases; Multiple Sclerosis; Neuromyelitis Optica; Autoimmune Diseases of the Nervous System; Central Nervous System Diseases
PubMed: 38589280
DOI: 10.11477/mf.1416202612 -
Journal of Virus Eradication Mar 2024To explore epidemiological changes of Japanese encephalitis (JE) in a long-time span and evaluate the impact of mass immunisation.
OBJECTIVES
To explore epidemiological changes of Japanese encephalitis (JE) in a long-time span and evaluate the impact of mass immunisation.
METHOD
Data on JE cases from hospitals and the county Centers for Disease Control and Prevention in Guizhou Province was collected between 2005 and 2021. Epidemiological changes were analyzed according to a series of policy implementations and the coronavirus disease 2019 (COVID-19) pandemic.
RESULTS
A total of 5138 JE cases and 152 deaths were reported in Guizhou Province during 2005-2021. The average incidence and case fatality rates were 0.83/100,000 and 2.96%, respectively. The JE prevalence showed a declining trend over the years with the reduced incidence gap between age groups and narrowing of the high-epidemic regions. During the COVID-19 pandemic, the JE activity reached its nadir in 2020. The inclusion in the Expanded Program on Immunization of the JE vaccine and catch-up immunisations showed a significant impact on the JE declining incidence rate.
CONCLUSIONS
The implementation of JE immunisation programs has played a crucial role in controlling its spread. Continued efforts should be made to maintain high coverage of the JE vaccine and strengthen disease surveillance systems, ensuring JE effective control and eventual elimination.
PubMed: 38586471
DOI: 10.1016/j.jve.2024.100366 -
ACS Chemical Neuroscience Apr 2024Short-chain fatty acids (SCFAs) are gut microbial metabolic derivatives produced during the fermentation of ingested complex carbohydrates. SCFAs have been widely...
Prophylactic Administration of Gut Microbiome Metabolites Abrogated Microglial Activation and Subsequent Neuroinflammation in an Experimental Model of Japanese Encephalitis.
Short-chain fatty acids (SCFAs) are gut microbial metabolic derivatives produced during the fermentation of ingested complex carbohydrates. SCFAs have been widely regarded to have a potent anti-inflammatory and neuro-protective role and have implications in several disease conditions, such as, inflammatory bowel disease, type-2 diabetes, and neurodegenerative disorders. Japanese encephalitis virus (JEV), a neurotropic flavivirus, is associated with life threatening neuro-inflammation and neurological sequelae in infected hosts. In this study, we hypothesize that SCFAs have potential in mitigating JEV pathogenesis. Postnatal day 10 BALB/c mice were intraperitoneally injected with either a SCFA mixture (acetate, propionate, and butyrate) or PBS for a period of 7 days, followed by JEV infection. All mice were observed for onset and progression of symptoms. The brain tissue was collected upon reaching terminal illness for further analysis. SCFA-supplemented JEV-infected mice (SCFA + JEV) showed a delayed onset of symptoms, lower hindlimb clasping score, and decreased weight loss and increased survival by 3 days ( < 0.0001) upon infection as opposed to the PBS-treated JEV-infected animals (JEV). Significant downregulation of inflammatory cytokines TNF-α, MCP-1, IL-6, and IFN-Υ in the SCFA + JEV group relative to the JEV-infected control group was observed. Inflammatory mediators, phospho-NF-kB (P-NF-kB) and iba1, showed 2.08 ± 0.1 and 3.132 ± 0.43-fold upregulation in JEV versus 1.19 ± 0.11 and 1.31 ± 0.11-fold in the SCFA + JEV group, respectively. Tissue section analysis exhibited reduced glial activation (JEV group─42 ± 2.15 microglia/ROI; SCFA + JEV group─27.07 ± 1.8 microglia/ROI) in animals that received SCFA supplementation prior to infection as seen from the astrocytic and microglial morphometric analysis. Caspase-3 immunoblotting showed 4.08 ± 1.3-fold upregulation in JEV as compared to 1.03 ± 0.14-fold in the SCFA + JEV group and TUNEL assay showed a reduced cellular death post-JEV infection (JEV-6.4 ± 1.5 cells/ROI and SCFA + JEV-3.7 ± 0.73 cells/ROI). Our study critically contributes to the increasing evidence in support of SCFAs as an anti-inflammatory and neuro-protective agent, we further expand its scope as a potential supplementary intervention in JEV-mediated neuroinflammation.
Topics: Gastrointestinal Microbiome; Neuroinflammatory Diseases; Microglia; Encephalitis, Japanese; Fatty Acids, Volatile; Encephalitis Viruses, Japanese; Survival Analysis; Chemokines; Inflammation Mediators; Cytokine Release Syndrome; Humans; Female; Animals; Mice; Apoptosis; Brain; Viral Load; Time Factors
PubMed: 38581382
DOI: 10.1021/acschemneuro.4c00028 -
Emerging Microbes & Infections Dec 2024Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV)...
Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.
PubMed: 38578315
DOI: 10.1080/22221751.2024.2337677 -
European Journal of Immunology May 2024Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark... (Review)
Review
Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single-dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS-CoV-2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D-based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D-based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.
Topics: Humans; Yellow Fever Vaccine; Yellow fever virus; Vaccines, Attenuated; Animals; Yellow Fever; Vaccination
PubMed: 38571392
DOI: 10.1002/eji.202250133 -
European Journal of Clinical... Jun 2024Acute encephalitis syndrome (AES) outbreaks in children of Eastern Uttar Pradesh (E-UP) region of India have been a longstanding public health issue, with a significant...
Molecular and serological evidence of chikungunya virus infection with high case fatality among pediatric population with acute encephalitis syndrome: first report from Eastern Uttar Pradesh, India.
Acute encephalitis syndrome (AES) outbreaks in children of Eastern Uttar Pradesh (E-UP) region of India have been a longstanding public health issue, with a significant case fatality rate of 20-25%. Since past decade, a rise in chikungunya (CHIK) cases has been occurring, which is a reported etiology of AES. However, the burden of chikungunya virus (CHIKV) among pediatric AES (pAES) is unknown from E-UP. We included 238 hospitalized pAES cases. The presence of IgM antibodies for CHIKV, and Dengue virus (DENV) was tested, and RT-PCR was performed for CHIKV and DENV in serologically confirmed CHIKV and DENV pAES cases. Positive samples were sequenced using Sangers sequencing. Further, to check for co-infection, IgM antibodies for other AES etiologies including Japanese encephalitis virus (JEV), Leptospira and Orientia tsutsugamushi (OT) in serum were also investigated. IgM ELISA demonstrated 5.04% (12) positivity for CHIKV. Among CHIKV IgM positive, 3 (25%, 3/12) pAES patients died. CHIKV genome was detected in 3 pAES specimens. Among which, 2 CHIKV cases were also positive for OT DNA. Partially sequenced CHIKV were genotyped as ECSA. The overall finding indicates evidence of CHIKV infection with high case fatality among pAES patients from E-UP. This study advocates constant serological and molecular surveillance of CHIKV in AES endemic regions of India.
Topics: Humans; India; Chikungunya Fever; Child; Male; Female; Child, Preschool; Chikungunya virus; Antibodies, Viral; Immunoglobulin M; Acute Febrile Encephalopathy; Infant; Adolescent; Coinfection; Dengue Virus; Phylogeny; Disease Outbreaks
PubMed: 38557925
DOI: 10.1007/s10096-024-04817-8