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WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination. We conducted a cluster randomised controlled trial (TyVAC; ISRCTN11643110) in Dhaka, Bangladesh, between 2018 and 2021. Children aged 9 months to 15 years were invited to receive a single dose of TCV or Japanese encephalitis vaccine between April 15, 2018, and November 16, 2019, based on the randomisation of their clusters of residence. Children who received the Japanese encephalitis vaccine were invited to receive TCV at the final visit between Jan 6, and Aug 31, 2021, according to the protocol. This follow-on study extended the follow-up of the original trial until Aug 14, 2023. The primary endpoint of this study was to compare the incidence of blood culture-confirmed typhoid between children who received TCV in 2018–19 (the previous-TCV group) and those who received the vaccine in 2021 (the recent-TCV group), to evaluate the relative decline in vaccine protection. We also did a nested study using the test-negative design comparing the recent-TCV and previous-TCV groups with unvaccinated individuals, as well as an immunogenicity study in a subset of 1500 children. Compared with the recent-TCV group, the previous-TCV group had an increased risk of typhoid fever between 2021–23, with an adjusted incidence rate ratio of 3·10 (95% CI 1·53 to 6·29; p<0·0001), indicating a decline in the protection of a single-dose of TCV 3–5 years after vaccination. The extrapolated vaccine effectiveness in years 3–5 was 50% (95% CI –13 to 78), and was validated using the test-negative design analysis, with a vaccine effectiveness of 84% (74 to 90) in the recent-TCV group and 55% (36 to 68) in the previous-TCV group, compared with unvaccinated individuals. Anti-Vi-IgG responses declined over the study period. The highest rate of decay was seen in children vaccinated at younger than 2 years in the original trial. The inverse correlation between age and the decay of antibodies was also seen in the subgroup analysis of vaccine effectiveness, where the youngest age group (<7 years at fever visits) exhibited the fastest waning, with vaccine effectiveness dropping to 24% (95% CI –29 to 55) at 3–5 years after vaccination. A decline in the protection conferred by a single-dose TCV was observed 3–5 years after vaccination, with the greatest decline in protection and immune responses observed in children vaccinated at younger ages. A booster dose of TCV around school entry age might be needed for children vaccinated while younger than 2 years to sustain protection against typhoid fever during the school years when the risk is the highest. The Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Introduction: Group B arbovirus is the cause of Japanese encephalitis (JE), with a 20–40% case fatality rate, is spread by the culicine mosquito.¹ Due to the rise in incidence reported in Karnataka, JE immunization campaign with inactivated JENVAC vaccine was conducted in December 2022 in 10 Karnataka districts including Kalaburagi, an undeveloped district vaccinating children aged 1-15 years.² Objectives: To evaluate vaccine coverage and the challenges faced among children in Kalaburagi city, following the campaign. Materials & Methods: 210 children were chosen using 30*7 cluster sample method.3 Eligible children residing at Kalaburagi city were included, although recently immigrated and immunized residents of surrounding talukas were not. This survey was conducted two months following the campaign. JE vaccination status was assessed using a pretested, semi-structured questionnaire from reliable informants.SPSS software version 16 was used for analysis after the data were entered into an Excel sheet. Statistical tests like Chisquare, frequency and percentage were used. Results: Of the 210 children, the majority were younger than five years old. Estimated vaccine coverage was 68.6% with the major reason being unawareness followed by hesitancy for vaccination with no significant association with sociodemographic factors. Conclusion: Raising awareness through the media and medical professionals contributes to the vaccination’s ability to lower the prevalence of JE and vaccinating nonvaccinators unless contraindicated. [ABSTRACT FROM AUTHOR]

Introduction: Group B arbovirus is the cause of Japanese encephalitis (JE), with a 20–40% case fatality rate, is spread by the culicine mosquito.1 Due to the rise in incidence reported in Karnataka, JE immunization campaign with inactivated JENVAC vaccine was conducted in December 2022 in 10 Karnataka districts including Kalaburagi, an undeveloped district vaccinating children aged 1-15 years.2 Objectives: To evaluate vaccine coverage and the challenges faced among children in Kalaburagi city, following the campaign. Materials & Methods: 210 children were chosen using 30*7 cluster sample method.3 Eligible children residing at Kalaburagi city were included, although recently immigrated and immunized residents of surrounding talukas were not. This survey was conducted two months following the campaign. JE vaccination status was assessed using a pretested, semi-structured questionnaire from reliable informants.SPSS software version 16 was used for analysis after the data were entered into an Excel sheet. Statistical tests like Chisquare, frequency and percentage were used. Results: Of the 210 children, the majority were younger than five years old. Estimated vaccine coverage was 68.6% with the major reason being unawareness followed by hesitancy for vaccination with no significant association with sociodemographic factors. Conclusion: Raising awareness through the media andmedical professionals contributes to the vaccination’s ability to lower the prevalence of JE and vaccinating nonvaccinators unless contraindicated. [ABSTRACT FROM AUTHOR]

Viral encephalitis is characterized by inflammation of the brain parenchyma caused by a variety of viruses, among which the Japanese encephalitis (JE) virus (JEV) is a typical representative arbovirus. Neuronal death, neuroinflammation, and breakdown of the blood brain barrier (BBB) constitute vicious circles of JE progression. Currently, there is no effective therapy to prevent this damage. Growth arrest specific gene 6 (GAS6) is a secreted growth factor that binds to the TYRO3, AXL, and MERTK (TAM) family of receptor tyrosine kinases and has been demonstrated to participate in neuroprotection and suppression of inflammation in many central nervous system (CNS) diseases which has great potential for JE intervention. In this study, we found that GAS6 expression in the brain was decreased and was reversely correlated with viral load and neuronal loss. Mice with GAS6/TAM signalling deficiency showed higher mortality and accelerated neuroinflammation during peripheral JEV infection, accompanied by BBB breakdown. GAS6 directly promoted the expression of tight junction proteins in bEnd.3 cells and strengthened BBB integrity, partly via AXL. Mice administered GAS6 were more resistant to JEV infection due to increased BBB integrity, as well as decreased viral load and neuroinflammation. Thus, targeted GAS6 delivery may represent a strategy for the prevention and treatment of JE especially in patients with impaired BBB. [ABSTRACT FROM AUTHOR]

Japanese encephalitis is an acute infectious disease of the central nervous system caused by neurotropic Japanese encephalitis virus (JEV). As a member of TAM (Tyro3, Axl and Mertk) family, Mertk has involved in multiple biological processes by engaging with its bridging ligands Gas6 and Protein S, including invasion of pathogens, phagocytosis of apoptotic cells, inflammatory response regulation, and the maintenance of blood brain barrier (BBB) integrity. However, its role in encephalitis caused by JEV infection has not been studied in detail. Here, we found that Mertk−/− mice exhibited higher mortality and more rapid disease progression than wild-type mice after JEV challenge. There were no significant differences in viral load and cytokines expression level in peripheral tissues between Wild type and Mertk−/− mice. Furthermore, the absence of Mertk had little effect on the inflammatory response and immunopathological damage while it can cause an increased viral load in the brain. For the in vitro model of BBB, Mertk was shown to maintain the integrity of the BBB. In vivo, Mertk−/− mice exhibited higher BBB permeability and lower BBB integrity. Taken together, our findings demonstrate that Mertk acts as a protective factor in the development of encephalitis induced by JEV infection, which is mainly associated with its beneficial effect on BBB integrity, rather than its regulation of inflammatory response. [ABSTRACT FROM AUTHOR]

Background: Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis and a significant cause of disability in Asia and the western Pacific. Many countries have introduced JE vaccination programs, including several low resource countries following WHO's prioritization of JE vaccination in 2006. We sought to characterize the public health impact of JE vaccination programs. Methodology/Principal findings: JE case data and vaccination coverage rates, were requested from country health officials in 23 JE endemic countries and Chinese Taipei. Additional data were extracted from meeting presentations and published literature. JE incidence was compared before and after vaccination using a minimum three year period pre and post program introduction or expansion. Data suitable for analysis were available for 13 JE-endemic countries and Chinese Taipei, for either all age groups or for children aged under 15 years only. Five countries and Chinese Taipei introduced vaccine prior to 2006 and the all-age JE incidence was reduced by 73–100% in about 5–20 years following introduction. Six countries have introduced JE vaccine since 2006, and JE incidence in children aged younger than 15 years has been reduced by 14–79% as of 2015–2021. JE-specific data were unavailable before introduction in Thailand and Vietnam, but vaccination programs reduced acute encephalitis incidence by 80% and 74%, respectively. Even in the programs with greatest impact, it took several years to achieve their results. Conclusions/Significance: JE vaccination has greatly reduced JE in 13 JE-endemic countries and Chinese Taipei. Highest impact has been observed in countries that introduced prior to 2006, but it often took roughly two decades and substantial resources to achieve that level of success. For greatest possible impact, more recently introducing countries and funding agencies should commit to continuous improvements in delivery systems to sustain coverage after initial vaccine introduction. Author summary: While JE has been controlled by vaccination in a handful of economically developed countries endemic for JE transmission with disease reductions of 73–100%, introduction of JE vaccines has ocurred later in low and low-middle income countries (LLMIC) endemic for JE. Since 2006 focused effort has been undertaken to assist with establishment of sustained vaccination efforts against JE in LLMIC. The outcome has been growing evidence of the impact of vaccination against JE in LLMIC endemic for JE transmission with disease reductions of 14–79% among children aged under 15 years. We describe the public health impact of JE vaccination programs in both economically developed and LLMIC JE endemic countries and discuss how time and sustained effort on JE vaccination in LLMIC has high potential to reach the level of control seen in earlier decades in economically developed countries. [ABSTRACT FROM AUTHOR]

High-throughput experiments often produce ranked gene outputs, with forward genetic screening being a notable example. While there are various tools for analyzing individual datasets, those that perform comparative and meta-analytical examination of such ranked gene lists remain scarce. Here, we introduce Gene Rank Meta Analyzer (GeneRaMeN), an R Shiny tool utilizing rank statistics to facilitate the identification of consensus, unique, and correlated genes across multiple hit lists. We focused on two key topics to showcase GeneRaMeN: virus host factors and cancer dependencies. Using GeneRaMeN 'Rank Aggregation', we integrated 24 published and new flavivirus genetic screening datasets, including dengue, Japanese encephalitis, and Zika viruses. This meta-analysis yielded a consensus list of flavivirus host factors, elucidating the significant influence of cell line selection on screening outcomes. Similar analysis on 13 SARS-CoV-2 CRISPR screening datasets highlighted the pivotal role of meta-analysis in revealing redundant biological pathways exploited by the virus to enter human cells. Such redundancy was further underscored using GeneRaMeN's 'Rank Correlation', where a strong negative correlation was observed for host factors implicated in one entry pathway versus the alternate route. Utilizing GeneRaMeN's 'Rank Uniqueness', we analyzed human coronaviruses 229E, OC43, and SARS-CoV-2 datasets, identifying host factors uniquely associated with a defined subset of the screening datasets. Similar analyses were performed on over 1000 Cancer Dependency Map (DepMap) datasets spanning 19 human cancer types to reveal unique cancer vulnerabilities for each organ/tissue. GeneRaMeN, an efficient tool to integrate and maximize the usability of genetic screening datasets, is freely accessible via https://ysolab.shinyapps.io/GeneRaMeN. [ABSTRACT FROM AUTHOR]

Acute encephalitis syndrome (AES) is a major public health concern in India as the aetiology remains unknown in the majority of cases with the current testing algorithm. We aimed to study the incidence of Japanese encephalitis (JE) and determine the aetiology of non‐JE AES cases to develop an evidence‐based testing algorithm. Cerebrospinal fluid (CSF) samples were tested for Japanese encephalitis virus by ELISA and polymerase chain reaction (PCR). Multiplex real‐time PCR was done for Dengue, Chikungunya, West Nile, Zika, Enterovirus, Epstein Barr Virus, Herpes Simplex Virus, Adenovirus, Cytomegalovirus, Herpesvirus 6, Parechovirus, Parvovirus B19, Varicella Zoster Virus, Scrub typhus, Rickettsia species, Leptospira, Salmonella species, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Plasmodium species and by ELISA for Mumps and Measles virus. Of the 3173 CSF samples, 461 (14.5%) were positive for JE. Of the 334 non‐JE AES cases, 66.2% viz. Scrub typhus (25.7%), Mumps (19.5%), Measles (4.2%), Parvovirus B19 (3.9%) Plasmodium (2.7%), HSV 1 and 2 (2.4%), EBV and Streptococcus pneumoniae (2.1% each), Salmonella and HHV 6 (1.2% each) were predominant. Hence, an improved surveillance system and our suggested expanded testing algorithm can improve the diagnosis of potentially treatable infectious agents of AES in India. [ABSTRACT FROM AUTHOR]

Background and Objective: Dengue is a major infectious disease with potential for outbreaks and epidemics. A specific and sensitive diagnosis is a prerequisite for clinical management of the disease. We designed our study to identify epitopes on the Dengue virus (DENV) envelope (E) and non-structural protein 1 (NS1) with potential for diagnosis. Methods: Serology and immunoinformatic approaches were employed. We collected DENV-positive, DENV-negative and Japanese encephalitis virus-positive samples from collaborating hospitals in 2019 and 2022–2023. Seropositive peptides in 15–18 mer peptide arrays of E and NS1 proteins of DENV2 were determined by an indirect enzyme-linked immunosorbent assay. B-cell linear and conformational epitopes were predicted using BepiPred2.0 and ElliPro, respectively. A consensus recombinant peptide was designed, synthesised and evaluated for its diagnostic potential using patient sera. Results: Eight peptides of E protein and six peptides of NS1 protein were identified to be the most frequently recognised by Dengue-positive patients. These peptide sequences were compared with B-cell epitope regions and found to be overlapped with predicted B-cell linear and conformational epitopes. EP11 and NSP15 showed a 100% amino acid sequence overlap with B-cell epitopes. EP1 and NSP15 had 14 whereas EP28, EP31, EP60 16, NSP12 and NSP32 had more than 15 interacting interface residues with a neutralising antibody, suggesting a strength of interaction. Interestingly, potential epitopes identified were localised on the surface of proteins as visualised by PyMOL. Validation with a recombined synthetic peptide yielded 92.3% sensitivity and 91.42% specificity. Conclusions: Immunodominant regions identified by serology and computationally predicted epitopes overlapped, thereby showing the robustness of the methodology and the peptide designed for diagnosis. [ABSTRACT FROM AUTHOR]

Japanese encephalitis virus (JEV) is a major threat to human health. Bangladesh is considering introducing a JEV vaccine; however, the investment case is hampered by a limited understanding of key aspects of JEV ecology. We conducted a seroprevalence study in a high-incidence region using an assay that limits cross-reactivity with dengue virus. We also trapped mosquitoes and collected information about potential host species. We used mathematical models to recover risk factors for infection and underlying probabilities of severe disease and death. We observed 19.0% [95% confidence interval (CI):17.1 to 21.1] of JEV antibodies. On average, 0.7% (95% CI: 0.2 to 2.0) of the susceptible population gets infected yearly, with pig proximity being the main human infection risk factor. Our traps captured 10 different mosquito species that have been linked with JEV transmission. We estimated that 1 in 1000 infections results in severe disease, 1 in 10,000 results in death, and 76% of severe cases are missed by surveillance. [ABSTRACT FROM AUTHOR]

Background and purpose: Culicidae plays a crucial role in the spread of diseases like Malaria and arboviral diseases such as Japanese Encephalitis, Zika virus, Chikungunya, Dengue fever, Yellow fever, and West Nile fever. Different mosquito species have different abundance and distribution due to a variety of factors, such as physicochemical factors, weather conditions, vegetation, and human activities. The characteristics of larval habitats are among the factors affecting the population, and diversity, and determining the preferred breeding places of the species. For this reason, a study was conducted to examine the species diversity of Culicidae and their larval habitats in Shushtar County. Materials and methods: This cross-sectional study was conducted in Shushtar County from the central, Mian Ab and Shuaibiya districts, 2021. Larvae were collected from the breeding places in the sampling areas including Noormohammadi, Konarpir, Saheli, Abu Gerva, and Pirdalu by using the dipping technique in spring and summer and kept in lactophenol solution. Then, a microscopic slide was prepared from the samples using licidophor, which were identified with valid diagnostic keys. Characteristics of larval habitat such as habitat type, water condition, vegetation, substrate type, water quality, and light condition were also recorded. To analyze the data and determine the relationship between the frequency and characteristics of larval habitats, SPSS version 16 software and a chi-square statistical test were used. Qualitative variables were also reported as numbers (percentages). Abundance and distribution maps of samples were prepared using ArcGIS software version 10.5. Results: In this study, a total of 527 larvae were identified, including five species of Anopheles stephensi, Culex pusillus, and Cx. sinaiticus, Cx. theileri and, Cx. Perexiguus. Anopheles stephensi with the lowest frequency (8.48%) was reported only from the Saheli area. This species was collected from temporary, stationary, without vegetation, mud substrate, cloudy water, sunny, and natural habitats. Culex theileri, one of the important vectors of arboviral diseases, was observed in temporary and natural habitats, stagnant waters without vegetation, and cloudy and sunny waters habitates. Culex pusillus was the only species observed in Pirdalo and Abu Gerva. By examining the larval habitats of Culicidae in Shushtar County, Cx. pusillus was the most abundant collected species, from temporary habitat (82.7%), stagnant waters (73.6%), mud substrate (100%), turbid waters (78.6%), natural (95%), and sunny (82.7%). Also, the abundance of collected larvae in temporary habitats, stagnant waters, in areas with vegetation, and mud substrate was high. Besides, it was more abundant in turbid waters and sunny areas, and these differences were statistically significant (P<0.0001). Conclusion: In this study, Cx.pusillus was the most common species, while An. stephensi was the least common abundance among collected species. It was observed significant difference between this species and the type of habitat, water flow, vegetation, water quality, and light conditions. Conducting more comprehensive studies in this field, especially regarding the possible role of different species of Culicidae, helped to solve the health and medical problems of humans and veterinary medicine in the future. [ABSTRACT FROM AUTHOR]

Pigs are the most common amplifying hosts of the Japanese encephalitis virus (JEV). In 2016, four residents on Tsushima Island who did not own pig farms were diagnosed with JE. Therefore, a serosurvey was conducted to estimate the risk and seroprevalence of JEV after the outbreak. Sera collected from 560 Tsushima Island residents between January and September 2017 were tested for neutralizing antibodies against JEV strains JaGAr01 (genotype 3) and Muar (genotype 5). Sera collected from six wild boars between June and July 2022 were tested. The seroprevalence rates of neutralizing antibodies against JaGAr01 and Muar were 38.8% and 24.6%, respectively. High anti-JEV neutralizing antibody titers of ≥320 were identified in 16 residents, including 3 younger than 6 years with prior JEV vaccination, 2 in their 40s, and 11 older than 70. However, no anti-JEV-specific IgM was detected. Residents who engaged in outdoor activities had higher anti-JEV antibody titers. Sera from wild boars were negative for JEV RNA, but four of six samples contained neutralizing antibodies against JEV. Therefore, JEV transmission continues on Tsushima Island, even in the absence of pig farms, and wild boars might serve as the amplifying hosts. [ABSTRACT FROM AUTHOR]

Many viruses have evolved structured RNA elements that can influence transcript abundance and translational efficiency, and help evade host immune factors by hijacking cellular machinery during replication. Here, we evaluated the functional impact of sub-genomic flaviviral RNAs (sfRNAs) known to stall exoribonuclease activity, by incorporating these elements into recombinant adeno-associated viral (AAV) genome cassettes. Specifically, sfRNAs from Dengue, Zika, Japanese Encephalitis, Yellow Fever, Murray Valley Encephalitis, and West Nile viruses increased transcript stability and transgene expression compared to a conventional woodchuck hepatitis virus element (WPRE). Further dissection of engineered transcripts revealed that sfRNA elements (i) require incorporation in cis within the 3′ untranslated region (UTR) of AAV genomes, (ii) require minimal dumbbell structures to exert the observed effects, and (iii) can stabilize AAV transcripts independent of 5′−3′ exoribonuclease 1 (XRN1)-mediated decay. Additionally, preliminary in vivo assessment of AAV vectors bearing sfRNA elements in mice achieved increased transcript abundance and expression in cardiac tissue. Leveraging the functional versatility of engineered viral RNA elements may help improve the potency of AAV vector-based gene therapies. IMPORTANCE Viral RNA elements can hijack host cell machinery to control stability of transcripts and consequently, infection. Studies that help better understand such viral elements can provide insights into antiviral strategies and also potentially leverage these features for therapeutic applications. In this study, by incorporating structured flaviviral RNA elements into recombinant adeno-associated viral (AAV) vector genomes, we show improved AAV transcript stability and transgene expression can be achieved, with implications for gene transfer. [ABSTRACT FROM AUTHOR]

Flaviviruses, including dengue (DENV), Zika (ZIKV), West Nile (WNV), Japanese encephalitis (JEV), yellow fever (YFV), and tick-borne encephalitis (TBEV) viruses, pose a significant global emerging threat. With their potential to cause widespread outbreaks and severe health complications, the development of effective vaccines and antiviral therapeutics is imperative. The flaviviral non-structural protein 5 (NS5) is a highly conserved and multifunctional protein that is crucial for viral replication, and the NS5 protein of many flaviviruses has been shown to be a potent inhibitor of interferon (IFN) signalling. In this review, we discuss the functions of NS5, diverse NS5-mediated strategies adopted by flaviviruses to evade the host antiviral response, and how NS5 can be a target for the development of vaccines and antiviral therapeutics. [ABSTRACT FROM AUTHOR]

Japanese encephalitis is a disease caused by the Japanese encephalitis virus (JEV) and is a concern for U.S. military personnel stationed in the Republic of Korea (ROK). The recent literature reports a potential shift from GI to GV as the dominant genotype circulating in east Asia. In the ROK, GV has been reported in a few Culex spp., but not in the main JEV vector, Cx. tritaeniorhynchus. The goal of this surveillance was to shed light on the current knowledge of the epidemiology of JEV in the ROK by analyzing mosquito collection data from three consecutive years, 2021–2023, and molecularly detecting and genotyping JEV in all Culex spp. collected in several military locations across the ROK. In this study, we detected only JEV GI in Cx. tritaeniorhynchus in 2021 samples. In contrast, all 2022 and 2023 positive samples were GV and detected in Cx. bitaeniorhynchus, Cx. orientalis, and Cx. pipiens. Results support a shift in JEV genotype in the ROK and suggest that for GV, Culex spp. other than Cx. tritaeniorhynchus may be playing an important role. [ABSTRACT FROM AUTHOR]

Background: The causative agents of Acute Encephalitis Syndrome remain unknown in 68–75% of the cases. In Nepal, the cases are tested only for Japanese encephalitis, which constitutes only about 15% of the cases. However, there could be several organisms, including vaccine-preventable etiologies that cause acute encephalitis, when identified could direct public health efforts for prevention, including addressing gaps in vaccine coverage. Objectives: This study employs metagenomic next-generation-sequencing in the investigation of underlying causative etiologies contributing to acute encephalitis syndrome in Nepal. Methods: In this study, we investigated 90, Japanese-encephalitis-negative, banked cerebrospinal fluid samples that were collected as part of a national surveillance network in 2016 and 2017. Randomization was done to include three age groups (< 5-years; 5-14-years; >15-years). Only some metadata (age and gender) were available. The investigation was performed in two batches which included total nucleic-acid extraction, followed by individual library preparation (DNA and RNA) and sequencing on Illumina iSeq100. The genomic data were interpreted using Chan Zuckerberg-ID and confirmed with polymerase-chain-reaction. Results: Human-alphaherpes-virus 2 and Enterovirus-B were seen in two samples. These hits were confirmed by qPCR and semi-nested PCR respectively. Most of the other samples were marred by low abundance of pathogen, possible freeze-thaw cycles, lack of process controls and associated clinical metadata. Conclusion: From this study, two documented causative agents were revealed through metagenomic next-generation-sequencing. Insufficiency of clinical metadata, process controls, low pathogen abundance and absence of standard procedures to collect and store samples in nucleic-acid protectants could have impeded the study and incorporated ambiguity while correlating the identified hits to infection. Therefore, there is need of standardized procedures for sample collection, inclusion of process controls and clinical metadata. Despite challenging conditions, this study highlights the usefulness of mNGS to investigate diseases with unknown etiologies and guide development of adequate clinical-management-algorithms and outbreak investigations in Nepal. [ABSTRACT FROM AUTHOR]

Background: Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. Results: In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P < 0.05), indicating many low-frequency mutations in the populations and that the populations might be in the process of expansion. Moreover, Wolbachia infection was detected only in SDJN (Jining) (2.24%), and all Wolbachia genotypes belonged to supergroup B. To understand the influence of environmental factors on mosquito-borne viruses, we examined the prevalence of Culex tritaeniorhynchus infection in three ecological environments in Shandong Province. We discovered that the incidence of JEV infection was notably greater in Culex tritaeniorhynchus from lotus ponds compared to those from irrigation canal regions. In this study, the overall JEV infection rate was 15.27 per 1000, suggesting the current risk of Japanese encephalitis outbreaks in Shandong Province. Conclusions: Tropical and subtropical populations of Culex tritaeniorhynchus showed higher genetic diversity and those climatic conditions provide great advantages for the establishment and expansion of Culex tritaeniorhynchus. There are differences in JEV infection rates in wild populations of Culex tritaeniorhynchus under different ecological conditions. Our results suggest a complex interplay of genetic differentiation, population structure, and environmental factors in shaping the dynamics of Culex tritaeniorhynchus. The low prevalence of Wolbachia in wild populations may reflect the recent presence of Wolbachia invasion in Culex tritaeniorhynchus. [ABSTRACT FROM AUTHOR]

Genotypes (G) 1, 3, and 5 of the Japanese encephalitis virus (JEV) have been isolated in China, but the dominant genotype circulating in Chinese coastal areas remains unknown. We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis (JE) in the coastal provinces of China. In this study, we collected serum specimens from patients with JE in three coastal provinces of China (Guangdong, Zhejiang, and Shandong) from 2018 to 2020 and conducted JEV cross-neutralization tests against G1, G3, and G5. Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong (92 patients), Zhejiang (192 patients), and Guangdong (77 patients), China, from 2018 to 2020. Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV. Two cases were confirmed to be infected with G1 JEV, 32 with G3 JEV, and two with G5 JEV. G3 was the primary infection genotype among JE cases with a definite infection genotype, and the infection caused by G5 JEV was confirmed serologically in China. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the distribution and prevalence of Japanese encephalitis virus (JEV) antibody (as evidence of past infection) in northern Victoria following the 2022 Japanese encephalitis outbreak, seeking to identify groups of people at particular risk of infection; to investigate the distribution and prevalence of antibodies to two related flaviviruses, Murray Valley encephalitis virus (MVEV) and West Nile virus Kunjin subtype (KUNV). Study design: Cross‐sectional serosurvey (part of a national JEV serosurveillance program). Setting: Three northern Victorian local public health units (Ovens Murray, Goulburn Valley, Loddon Mallee), 8 August – 1 December 2022. Participants: People opportunistically recruited at pathology collection centres and by targeted recruitment through community outreach and advertisements. People vaccinated against or who had been diagnosed with Japanese encephalitis were ineligible for participation, as were those born in countries where JEV is endemic. Main outcome measures: Seroprevalence of JEV IgG antibody, overall and by selected factors of interest (occupations, water body exposure, recreational activities and locations, exposure to animals, protective measures). Results: 813 participants were recruited (median age, 59 years [interquartile range, 42–69 years]; 496 female [61%]); 27 were JEV IgG‐seropositive (3.3%; 95% confidence interval [CI], 2.2–4.8%) (median age, 73 years [interquartile range, 63–78 years]; 13 female [48%]); none were IgM‐seropositive. JEV IgG‐seropositive participants were identified at all recruitment locations, including those without identified cases of Japanese encephalitis. The only risk factors associated with JEV IgG‐seropositivity were age (per year: prevalence odds ratio [POR], 1.07; 95% CI, 1.03–1.10) and exposure to feral pigs (POR, 21; 95% CI, 1.7–190). The seroprevalence of antibody to MVEV was 3.0% (95% CI, 1.9–4.5%; 23 of 760 participants), and of KUNV antibody 3.3% (95% CI, 2.1–4.8%; 25 of 761). Conclusions: People living in northern Victoria are vulnerable to future JEV infection, but few risk factors are consistently associated with infection. Additional prevention strategies, including expanding vaccine eligibility, may be required to protect people in this region from Japanese encephalitis. [ABSTRACT FROM AUTHOR]

Objectives: To determine the proportion of people in New South Wales towns at high risk of Japanese encephalitis virus (JEV) infections during the 2022 outbreak; to identify risk factors for JEV infection. Study design: Cross‐sectional serosurvey study of the seroprevalence of JEV‐specific antibodies in NSW. Setting, participants: Convenience sample of people (all ages) from five regional NSW towns deemed to be at high risk of JEV infections after first outbreak of Japanese encephalitis in southeastern Australia in early 2022 (Balranald, Corowa, Dubbo, Griffith, Temora), 21 June – 22 July 2022. Main outcome measures: Proportion of people seropositive for JEV total antibody, assayed by defined epitope‐blocking enzyme‐linked immunosorbent assay; prevalence odds ratios for exposure risk factors and protective behaviours. Results: Eighty of 917 eligible participants (559 girls or women, 61%; 42 Aboriginal and Torres Strait Islander people, 4.6%; median age, 52 years [IQR, 37–62 years]) were seropositive for JEV‐specific total antibody (8.7%); the median age of seropositive people was 61 years (IQR, 48–70 years). The seropositivity proportion was largest for people aged 65 years or more (30 of 192; weighted proportion, 13.7%) and larger for male than female participants (30 of 358, 10.6% v 50 of 559, 7.5%). Five of 42 samples from Aboriginal and Torres Strait Islander participants were seropositive (12%). We found mixed associations with a range of potential risk factors. Conclusion: We found evidence for a substantial number of JEV infections in five regional NSW towns during a single arbovirus season in 2022. Public health responses, including effective surveillance, vaccination against JEV, and mosquito management, are critical for controlling outbreaks. Promoting behaviours that reduce exposure to mosquitoes is a core component of prevention, particularly when the vaccine supply is limited. [ABSTRACT FROM AUTHOR]

Japanese Encephalitis remains a significant global health concern, contributing to millions of deaths annually worldwide. Microglial cells, as key innate immune cells within the central nervous system (CNS), exhibit intricate cellular structures and possess molecular phenotypic plasticity, playing pivotal roles in immune responses during CNS viral infections. Particularly under viral inflammatory conditions, microglial cells orchestrate innate and adaptive immune responses to mitigate viral invasion and dampen inflammatory reactions. This review article comprehensively summarizes the pathophysiology of viral invasion into the CNS and the cellular interactions involved, elucidating the roles of various immune mediators, including pro-inflammatory cytokines, in neuroinflammation. Leveraging this knowledge, strategies for modulating inflammatory responses and attenuating hyperactivation of glial cells to mitigate viral replication within the brain are discussed. Furthermore, current chemotherapeutic and antiviral drugs are examined, elucidating their mechanisms of action against viral replication. This review aims to provide insights into therapeutic interventions for Japanese Encephalitis and related viral infections, ultimately contributing to improved outcomes for affected individuals. [ABSTRACT FROM AUTHOR]

To evaluate the influence of ecological migration village construction on mosquito vector populations and mosquito-borne diseases in southern Yunnan Province. Two vicinal villages in Mengla County, the southern part of Yunnan Province, a native village, and a newly built village, were selected as study sites. Malaria and Japanese Encephalitis vector mosquito population divergence between the two villages were studied. Malaria and Japanese Encephalitis (JE) cases in the two villages were also compared. Anopheles minimus was the dominant population in houses in the newly built village, and An. jeyporiensis dominated the native village. Accordingly, there were nine malaria cases in the new village compared with zero cases in the native village. Culex tritaeniorhynchus, the chief JE vector in the study area, displayed no difference between the two villages; however, there was a higher density of the local secondary JE vector (Cx. pseudovishnui) in the native village than in the new one. The JE cases in the villages corresponded to zero. From the vector-borne disease perspective, our results suggest that local community should pay more attention to malaria and An. minimus during the construction of an ecological migration village in the new Chinese Western Developing Plan (CWDP) in southern Yunnan Province. [ABSTRACT FROM AUTHOR]

Aims: Japanese encephalitis (JE) is endemic in India. Although pigs are considered important hosts and sentinels for JE outbreaks in people, limited information is available on JE virus (JEV) surveillance in pigs. Methods and Results: We investigated the spatio‐temporal distribution of JEV seroprevalence and its association with climate variables in 4451 samples from pigs in 10 districts of eastern Uttar Pradesh, India, over 10 years from 2013 to 2022. The mean seroprevalence of IgG (2013–2022) and IgM (2017–2022) was 14% (95% CI 12.8–15.2) and 10.98% (95% CI 9.8–12.2), respectively. Throughout the region, higher seroprevalence from 2013 to 2017 was observed and was highly variable with no predictable spatio‐temporal pattern between districts. Seroprevalence of up to 60.8% in Sant Kabir Nagar in 2016 and 69.5% in Gorakhpur district in 2017 for IgG and IgM was observed, respectively. IgG seroprevalence did not increase with age. Monthly time‐series decomposition of IgG and IgM seroprevalence demonstrated annual cyclicity (3–4 peaks) with seasonality (higher, broader peaks in the summer and monsoon periods). However, most variance was due to the overall trend and the random components of the time series. Autoregressive time‐series modelling of pigs sampled from Gorakhpur was insufficiently predictive for forecasting; however, an inverse association between humidity (but not rainfall or temperature) was observed. Conclusions: Detection patterns confirm seasonal epidemic periods within year‐round endemicity in pigs in eastern Uttar Pradesh. Lack of increasing age‐associated seroprevalence indicates that JEV might not be immunizing in pigs which needs further investigation because models that inform public health interventions for JEV could be inaccurate if assuming long‐term immunity in pigs. Although pigs are considered sentinels for human outbreaks, sufficient timeliness using sero‐surveillance in pigs to inform public health interventions to prevent JEV in people will require more nuanced modelling than seroprevalence and broad climate variables alone. [ABSTRACT FROM AUTHOR]

Background: Japanese encephalitis virus (JEV) is an emerging mosquito-borne Orthoflavivirus that poses a significant public health risk in many temperate and tropical regions in Asia. Since the climate in some endemic countries is similar to temperate climates observed in Europe, understanding the role of specific mosquito species in the transmission of JEV is essential for predicting and effectively controlling the potential for the introduction and establishment of JEV in Europe. Methods: This study aimed to investigate the vector competence of colonized Culex pipiens biotype molestus mosquitoes for JEV. The mosquitoes were initially collected from the field in southern Sweden. The mosquitoes were offered a blood meal containing the Nakayama strain of JEV (genotype III), and infection rates, dissemination rates, and transmission rates were evaluated at 14, 21, and 28 days post-feeding. Results: The study revealed that colonized Swedish Cx. pipiens are susceptible to JEV infection, with a stable infection rate of around 10% at all timepoints. However, the virus was only detected in the legs of one mosquito at 21 days post-feeding, and no mosquito saliva contained JEV. Conclusions: Overall, this research shows that Swedish Cx. pipiens can become infected with JEV, and emphasizes the importance of further understanding of the thresholds and barriers for JEV dissemination in mosquitoes. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Thailand on the risk of Zika virus infection among international students. The study found that two out of eight students tested positive for Zika virus antibodies, indicating exposure to the virus. One of the students also showed symptoms of infection. The article emphasizes the importance of increased awareness of Zika risk and preventive measures, such as avoiding mosquito exposure and considering family planning. The study acknowledges limitations, such as the small sample size and potential for cross-reactions with other similar viruses. Overall, the study provides valuable insights into the epidemiology of Zika virus in the context of international travel. [Extracted from the article]

Japanese Encephalitis (JE) poses a significant public health threat across Asia and the Western Pacific, leading to considerable mortality and morbidity if not promptly diagnosed and treated. This flaviviral infection, transmitted by Culex mosquitoes, primarily affects children but can impact individuals of all ages. Prompt diagnosis relies on detecting Japanese Encephalitis Virus (JEV) IgM antibodies in serum or Cerebrospinal Fluid (CSF), alongside characteristic Magnetic Resonance Imaging (MRI) findings. In this MRI case series, three confirmed cases of JE are presented, showcasing the typical neuroimaging manifestations observed in affected individuals. All cases exhibited bilateral thalamic hyperintensities on T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) images, a hallmark feature of JE. Additionally, one patient demonstrated involvement of the substantia nigra and bilateral frontal cortex. The clinical implications of present study findings underscore the importance of considering JE as a differential diagnosis in patients presenting with symptoms of encephalitis, especially when MRI reveals bi-thalamic signal alterations. Early recognition and initiation of appropriate treatment, including antiviral agents, are crucial for improving outcomes and reducing mortality. This study contributes to the existing literature by reinforcing the importance of neuroimaging in diagnosing JE and highlighting the distinct MRI patterns associated with the disease. Recognising these characteristic imaging features can aid clinicians in promptly identifying and managing JE cases, thereby mitigating the associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background and objective: No autochthonous human cases of Japanese encephalitis (JE) have been reported to date in the European Union (EU). In this study, we assess the likelihood of Japanese encephalitis virus (JEV) introduction and transmission within the EU and propose outbreak response measures. Risk assessment: Given the global geographical distribution of JEV, the probability of virus introduction into the EU is currently very low, with viremic bird migration being the most plausible pathway of introduction. However, this likelihood would significantly increase if the virus were to become established in the Middle East, Caucasus, Central Asia or Africa. Considering the environmental conditions that are expected to be conducive for virus circulation, there is a high likelihood of virus transmission within the EU after its introduction in environmentally suitable areas. The spread of the virus within the EU would likely occur through the movement of wild birds, pigs and mosquitoes. Mitigation: To mitigate or potentially contain the emergence of JE in the EU, early detection of both human and animal cases will be crucial. [ABSTRACT FROM AUTHOR]

Objective We report the epidemiology of Japanese encephalitis (JE) disease after the implementation of routine immunization in medium-endemic districts in the states of Maharashtra and Telangana in Central India. Methods We investigated acute encephalitis syndrome (AES) patients hospitalized from October 2018 to September 2020. Field visits were also made to the residences of 262 AES cases, including 54 JE cases. Results The overall case fatality ratio was 31%. Maharashtra state contributed 72% of JE and 67% of AES cases. The rural localities had a significantly higher number of JE cases than the urban areas. The occurrence of JE was reported year round, with most JE cases reported during the rainy season. Both AES and JE cases were reported mostly among children, with JE in 66% and non-JE AES in 70% of children. Conclusion The JE disease continues to affect the population after routine immunization. Surveillance, prevention, and control need to be enhanced to achieve accelerated control. [ABSTRACT FROM AUTHOR]

Background: Macrophages play a pivotal role in the regulation of Japanese encephalitis (JE), a severe neuroinflammation in the central nervous system (CNS) following infection with JE virus (JEV). Macrophages are known for their heterogeneity, polarizing into M1 or M2 phenotypes in the context of various immunopathological diseases. A comprehensive understanding of macrophage polarization and its relevance to JE progression holds significant promise for advancing JE control and therapeutic strategies. Methods: To elucidate the role of NADPH oxidase-derived reactive oxygen species (ROS) in JE progression, we assessed viral load, M1 macrophage accumulation, and cytokine production in WT and NADPH oxidase 2 (NOX2)-deficient mice using murine JE model. Additionally, we employed bone marrow (BM) cell-derived macrophages to delineate ROS-mediated regulation of macrophage polarization by ROS following JEV infection. Results: NOX2-deficient mice exhibited increased resistance to JE progression rather than heightened susceptibility, driven by the regulation of macrophage polarization. These mice displayed reduced viral loads in peripheral lymphoid tissues and the CNS, along with diminished infiltration of inflammatory cells into the CNS, thereby resulting in attenuated neuroinflammation. Additionally, NOX2-deficient mice exhibited enhanced JEV-specific Th1 CD4 + and CD8 + T cell responses and increased accumulation of M1 macrophages producing IL-12p40 and iNOS in peripheral lymphoid and inflamed extraneural tissues. Mechanistic investigations revealed that NOX2-deficient macrophages displayed a more pronounced differentiation into M1 phenotypes in response to JEV infection, thereby leading to the suppression of viral replication. Importantly, the administration of H2O2 generated by NOX2 was shown to inhibit M1 macrophage polarization. Finally, oral administration of the ROS scavenger, butylated hydroxyanisole (BHA), bolstered resistance to JE progression and reduced viral loads in both extraneural tissues and the CNS, along with facilitated accumulation of M1 macrophages. Conclusion: In light of our results, it is suggested that ROS generated by NOX2 play a role in undermining the control of JEV replication within peripheral extraneural tissues, primarily by suppressing M1 macrophage polarization. Subsequently, this leads to an augmentation in the viral load invading the CNS, thereby facilitating JE progression. Hence, our findings ultimately underscore the significance of ROS-mediated macrophage polarization in the context of JE progression initiated JEV infection. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

The Immunization Agenda 2030 (IA2030) Impact Goal 1.1. aims to reduce the number of future deaths averted through immunization in the next decade. To estimate the potential impact of the aspirational coverage targets for IA2030, we developed an analytical framework and estimated the number of deaths averted due to an ambitious vaccination coverage scenario from 2021 to 2030 in 194 countries. A demographic model was used to determine annual age-specific mortality estimates associated with vaccine coverage rates. For ten pathogens (Hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, yellow fever), we derived single measures of country-, age-, and pathogen-specific relative risk of deaths conditional upon coverage rates, leveraging the data from 18 modeling groups as part of the Vaccine Impact Model Consortium (VIMC) for 110 countries. We used a logistic regression model to extrapolate the relative risk estimates to countries that were not modeled by VIMC. For four pathogens (diphtheria, tetanus, pertussis and tuberculosis), we used estimates from the Global Burden of Disease 2019 study and existing literature on vaccine efficacy. A future scenario defining years of vaccine introduction and scale-up needed to reach aspirational targets was developed as an input to estimate the long-term impact of vaccination taking place from 2021 to 2030. Overall, an estimated 51.5 million (95 % CI: 44.0–63.2) deaths are expected to be averted due to vaccinations administered between the years 2021 and 2030. With immunization coverage projected to increase over 2021–2030 an average of 5.2 million per year (4.4–6.3) deaths will be averted annually, with 4.4 million (3.9–5.1) deaths be averted for the year 2021, gradually rising to 5.8 million (4.9–7.5) deaths averted in 2030. The largest proportion of deaths is attributed to Measles and Hepatitis B accounting for 18.8 million (17.8–20.0) and 14.0 million (11.5–16.9) of total deaths averted respectively. The results from this global analysis demonstrate the substantial potential mortality reductions achievable if the IA2030 targets are met by 2030. Deaths caused by vaccine preventable diseases disproportionately affect LMICs in the African region. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 7-year-old child who presented with seizures and altered sensorium. The child had symptoms of a cold, fever, headache, and vomiting. Tests for dengue and Japanese B encephalitis were negative. CT and MRI scans revealed bilateral symmetric "owl eye" lesions in the thalami. The diagnosis was acute necrotizing encephalopathy (ANE), a rare disease that causes rapid neurological decline following a respiratory or gastrointestinal infection. The exact cause and pathogenesis of ANE are unknown, but it is believed to be related to immune and cytokine-related injury. Treatment includes supportive care, intravenous steroids, and immunoglobulins. The prognosis varies, with some patients experiencing minimal sequelae and others having high morbidity or mortality. [Extracted from the article]

Dengue vaccine candidates have been shown to improve vaccine safety and efficacy by altering the residues or accessibility of the fusion loop on the virus envelope protein domain II (DIIFL) in an ex vivo animal study. The current study aimed to comprehensively investigate the impact of DIIFL mutations on the antigenicity, immunogenicity, and protective efficacy of Japanese encephalitis virus (JEV) virus-like particles (VLPs) in mice. We found the DIIFL G106K/L107D (KD) and W101G/G106K/L107D (GKD) mutations altered the binding activity of JEV VLP to cross-reactive monoclonal antibodies but had no effect on their ability to elicit total IgG antibodies in mice. However, JEV VLPs with KD or GKD mutations induced significantly less neutralizing antibodies against JEV. Only 46% and 31% of the KD and GKD VLPs-immunized mice survived compared to 100% of the wild-type (WT) VLP-immunized mice after a lethal JEV challenge. In passive protection experiments, naïve mice that received sera from WT VLP-immunized mice exhibited a significantly higher survival rate of 46.7% compared to those receiving sera from KD VLP- and GKD VLP-immunized mice (6.7% and 0%, respectively). This study demonstrated that JEV DIIFL is crucial for eliciting potently neutralizing antibodies and protective immunity against JEV. IMPORTANCE Introduction of mutations into the fusion loop is one potential strategy for generating safe dengue and Zika vaccines by reducing the risk of severe dengue following subsequent infections, and for constructing live-attenuated vaccine candidates against newly emerging Japanese encephalitis virus (JEV) or Japanese encephalitis (JE) serocomplex virus. The monoclonal antibody studies indicated the fusion loop of JE serocomplex viruses primarily comprised non-neutralizing epitopes. However, the present study demonstrates that the JEV fusion loop plays a critical role in eliciting protective immunity in mice. Modifications to the fusion loop of JE serocomplex viruses might negatively affect vaccine efficacy compared to dengue and zika serocomplex viruses. Further studies are required to assess the impact of mutant fusion loop encoded by commonly used JEV vaccine strains on vaccine efficacy or safety after subsequent dengue virus infection. [ABSTRACT FROM AUTHOR]

On 12 September 2022, a 10-year-old female in Paracelis municipality, Mountain Province, the Philippines, without travel history outside the municipality, experienced acute onset of fever and a change in mental status with disorientation, an altered level of consciousness and new onset of seizures. She was hospitalized at the district hospital from 1 to 3 October 2022, before being transferred to the regional hospital. As diphtheria was originally suspected, the investigation team reviewed records and reports and interviewed key informants to gather additional information and organize case finding and contact tracing. The patient's condition was laboratory-confirmed for Japanese encephalitis virus infection. An environmental survey was carried out at the patient's residence to check for the presence of vectors and contributing factors. Exemplifying inadequate vaccination coverage for Japanese encephalitis virus in Mountain Province, the patient had not been vaccinated against the disease. It is recommended that vaccination campaigns be immediately implemented in the affected area and the surveillance system be strengthened for early detection and prompt response to the emergence of cases and outbreaks. Overall, the investigation highlighted the importance of strong surveillance and response systems for early detection and control of diseases, such as Japanese encephalitis virus. It also underscores the need for comprehensive vaccination programmes to prevent outbreaks and protect vulnerable populations. [ABSTRACT FROM AUTHOR]

Background: A significant public health issue in India is Japanese encephalitis (JE), which has a high fatality rate and causes residual neurological damage in survivors. The goal of the current study was to examine JE positive among patients who had been admitted with acute encephalitis syndrome (AES) and to analyse the differences in clinical profile, disease severity, neurological consequences, and mortality rate in Tezpur Medical College and Hospital. Methods: This study is a retrospective observational study in a patients who were diagnosed as Japanese encephalitis on the basis of JEV-specific IgM antibodies in blood and cerebrospinal fluid (CSF) samples. The study included 32 Japanese Encephalitis positive patients admitted in Tezpur Medical College and Hospital (who met the clinical case definition of AES) and thus, their clinical profile and outcome were analysed. Result: A total 32 JE cases were enrolled in the study diagnosed with CSF and Serum IgM ELISA antibody test. All of them were Serum IgM ELISA antibody positive, 9(28%) cases were both Serum and CSF IgM antibody positive. Most common age group affected was 12-20 years(31%). 59.37% cases recovered completely, 21.87% had neurological sequelae at the time of discharge and 18.75% died at ward. Conclusion: Japanese Encephalitis is one of the leading cause of AES in India. In our study it has been seen that GCS score on presentation and CSF cell counts has positive association with mortality and disease sequale. Adequate care and treatment should be provided in order to avoid subsequent complications/sequale. Proper vaccination and vector control can prevent or mitigate this disease. [ABSTRACT FROM AUTHOR]

Background: Anopheles vagus (subgenus Cellia) has been identified as a vector for malaria, filariasis, and Japanese encephalitis in Asia. Sporozoites of Plasmodium falciparum and Plasmodium vivax have been found in this zoophilic mosquito in Asia and Indonesia. This study systematically reviews publications regarding An. vagus species, variation, bio-ecology, and malaria transmission in various localities in Asia, especially Indonesia, to determine whether the current data support An. vagus as a species complex. Methods: The databases Pubmed, Scopus, Europe PMC, and Proquest were searched to identify information regarding the morphology, karyotypes, polytene chromosome, cross-mating, ecology, and molecular identification of An. vagus was then evaluated to determine whether there were possible species complexes. Results: Of the 1326 articles identified, 15 studies were considered for synthesis. The Anopheles spp. samples for this study came from Asia. Eleven studies used morphology to identify An. vagus, with singular studies using each of karyotype identification, chromosomal polytene identification, and cross-breeding experiments. Ten studies used molecular techniques to identify Anopheles spp., including An. vagus. Most studies discovered morphological variations of An. vagus either in the same or different areas and ecological settings. In this review, the members of An. vagus sensu lato grouped based on morphology (An. vagus, An. vagus vagus, An. vagus limosus, and An. limosus), karyotyping (form A and B), and molecular (An. vagus genotype A and B, An. vagus AN4 and AN5). Genetic analysis revealed a high conservation of the ITS2 fragment among members except for the An. vagus genotype B, which was, in fact, Anopheles sundaicus. This review also identified that An. vagus limosus and An. vagus vagus were nearly identical to the ITS2 sequence. Conclusion: Literature review studies revealed that An. vagus is conspecific despite the distinct morphological characteristic of An. vagus and An. limosus. Further information using another barcoding tool, such as mitochondrial COI and ND6 and experimental cross-mating between the An. vagus and An. limosus may provide additional evidence for the status of An. vagus as a species complex. [ABSTRACT FROM AUTHOR]

Vector-borne diseases pose a significant public health challenge in economically disadvantaged nations. Malaria, dengue fever, chikungunya, Zika, yellow fever, Japanese encephalitis, and lymphatic filariasis are spread by mosquitoes. Consequently, the most effective method of preventing these diseases is to eliminate the mosquito population. Historically, the majority of control programs have depended on chemical pesticides, including organochlorines, organophosphates, carbamates, and pyrethroids. Synthetic insecticides used to eradicate pests have the potential to contaminate groundwater, surface water, beneficial soil organisms, and non-target species. Nanotechnology is an innovative technology that has the potential to be used in insect control with great precision. The goal of this study was to test the in vitro anti-dengue potential and mosquitocidal activity of Chaetomorpha aerea and C. aerea–synthesized Mn-doped superparamagnetic iron oxide nanoparticles (CA-Mn-SPIONs). The synthesis of CA-Mn-SPIONs using C. aerea extract was verified by the observable alteration in the colour of the reaction mixture, transitioning from a pale green colour to a brown. The study of UV–Vis spectra revealed absorbance peaks at approximately 290 nm, which can be attributed to the surface Plasmon resonance of the CA-Mn-SPIONs. The SEM, TEM, EDX, FTIR, vibrating sample magnetometry, and XRD analyses provided evidence that confirmed the presence of CA-Mn-SPIONs. In the present study, results revealed that C. aerea aqueous extract LC50 values against Ae. aegypti ranged from 222.942 (first instar larvae) to 349.877 ppm in bioassays (pupae). CA-Mn-SPIONs had LC50 ranging from 20.199 (first instar larvae) to 26.918 ppm (pupae). After treatment with 40 ppm CA-Mn-SPIONs and 500 ppm C. aerea extract in ovicidal tests, egg hatchability was lowered by 100%. Oviposition deterrence experiments showed that in Ae. aegypti, oviposition rates were lowered by more than 66% by 100 ppm of green algal extract and by more than 71% by 10 ppm of CA-Mn-SPIONs (oviposition activity index values were 0.50 and 0.55, respectively). Moreover, in vitro anti-dengue activity of CA-Mn-SPIONs has good anti-viral property against dengue viral cell lines. In addition, GC–MS analysis showed that 21 intriguing chemicals were discovered. Two significant phytoconstituents in the methanol extract of C. aerea include butanoic acid and palmitic acid. These two substances were examined using an in silico methodology against the NS5 methyltransferase protein and demonstrated good glide scores and binding affinities. Finally, we looked into the morphological damage and fluorescent emission of third instar Ae. aegypti larvae treated with CA-Mn-SPIONs. Fluorescent emission is consistent with ROS formation of CA-Mn-SPIONs against Ae. aegypti larvae. The present study determines that the key variables for the successful development of new insecticidal agents are rooted in the eco-compatibility and the provision of alternative tool for the pesticide manufacturing sector. [ABSTRACT FROM AUTHOR]

Mosquitoes pose a severe threat to the environment as vectors of numerous harmful diseases affecting humans and animals. Mosquitoes transmit pathogens that cause dengue, chikungunya, malaria, zika, yellow fever, Japanese encephalitis, and filariasis. Today's mosquito control strategies heavily rely on the use of chemical insecticides such as N,N‐diethyl‐meta‐toluamide (DEET), N,N‐diethyl mandelic acid amide (DEM), and dimethyl phthalate (DMP). However, the widespread use of chemical insecticides has resulted in pollution, bio‐magnification, and other health and environmental issues. It has also become ineffective because of the mosquitoes' aptitude to develop resistance, emphasizing the urgent need for safe, effective, and long‐lasting strategies. An alternative and promising approach to circumventing these obstacles involves the implementation of insecticides made from natural compounds found in plants. Therefore, the scientific community has shifted its focus towards plant‐based phytochemicals, oils, and extracts, as these are eco‐friendly, safe, and cost‐effective alternatives to conventional chemical insecticides. This review aims to provide details on current advances in plant‐based products (plant compounds, extracts, and essential oils), which are used to control all the life cycle stages (egg, larva, pupa, and adult) of the mosquito genera Aedes, Anopheles, and Culex. Hopefully, this review will pave the way to devise control strategies against these challenging pests. [ABSTRACT FROM AUTHOR]

Background Travel to Southeast Asia increases the likelihood of acquiring mosquito-borne Flavivirus infections such as dengue (DENV), Japanese encephalitis (JEV) and Zika viruses (ZIKV). Expatriates are long-term travellers who have a higher risk of mosquito-borne illness at their destination country. The purpose of this study was to evaluate the seroprevalence of DENV, JEV and ZIKV infections and the determinants contributing to seropositivity among expatriates living in Thailand. Methods A cross-sectional study was performed from December 2017 to February 2020. Expatriates from non-Flavivirus endemic countries were recruited. 5 mL of blood was collected for DENV 1–4, JEV and ZIKV antibody testing by plaque reduction neutralization test (PRNT50). Individuals with vaccination histories or diagnoses for dengue, Japanese encephalitis, yellow fever and tick-borne encephalitis were excluded. Results Among 254 participants, most participants (83.1%) were male, the mean age was 65 years and the median duration of stay in Thailand was 6 years. Seroprevalence rate of any Flavivirus, non-specific DENV, DENV1–4, JEV and ZIKV were 34.3, 30.7, 20.5, 18.1, 18.9, 10.6, 4.7 and 2.8%, respectively. The presence of neutralizing antibodies against DENV1–4 positively correlates with the duration of stay in Thailand. DENV seropositivity was associated with living in urban areas (aOR 2.75, 95% CI 1.36–5.57). Expatriates were unlikely to have detectable anti-JEV antibodies regardless of time spent in a JEV-endemic area. No risk factors were identified that were significantly associated with JEV or ZIKV seropositivity. Only 48.4% received pre-travel counselling services, while only 18.9% visited a travel medicine specialist. Conclusions A high proportion (34.3%) of long-term expatriates living in Thailand were seropositive for flavivirus, mainly from dengue (30.7%). To minimize risk, travel medicine practitioners should provide adequate pre-travel health risk information on mosquito-borne flavivirus infection and offer advice on mosquito bite prevention strategies. Dengue vaccine might be considered in high-risk travellers such as long-term expatriate. [ABSTRACT FROM AUTHOR]

This document provides information on the risk of Japanese encephalitis (JE) infection for short-term travelers to endemic areas. It includes case studies of individuals who traveled to JE-endemic regions and discusses their activities, vaccination status, and outcomes. The document emphasizes that even brief exposure to mosquito bites can pose a substantial risk of infection for unvaccinated travelers. It also discusses the different types of JE vaccines available and suggests considering cost and vaccine type when making vaccination decisions. The document concludes by highlighting the importance of assessing individual itineraries and considering cumulative risks when making vaccination recommendations. [Extracted from the article]

Simple Summary: Mosquitoes, vectors of diseases like Japanese encephalitis, harbor complex microbial communities that influence their biology and disease transmission. The microbiome of Culex tritaeniorhynchus and Culex orientalis, key vectors of the Japanese encephalitis virus, remains poorly understood. Utilizing 16S rRNA Illumina sequencing, we investigated the microbiomes of these mosquitoes collected across diverse regions in the Republic of Korea. Our analysis revealed the presence of 36 prevalent bacterial families, with microbial composition variations predominantly influenced by geographic location. Moreover, the identification of species-specific biomarkers underscores the potential for ecological niche differentiation between Culex tritaeniorhynchus and Culex orientalis. This research sheds light on the intricate relationship between mosquito vectors, their microbiomes, and environmental factors, offering insights into vector ecology and disease transmission dynamics. Mosquitoes, the primary vectors of arboviruses, harbor a diverse microbiome that plays a crucial role in their development, immunity, and vector competence. The composition of the mosquito microbiome is heavily influenced by the environment and habitats. Therefore, identifying the relationship between the habitat and the mosquito's microbial community can improve the overall understanding of mosquito biology. However, The microbiome profiles of Culex tritaeniorhynchus and Culex orientalis, known as transmission vectors of the Japanese encephalitis virus, are poorly understood. Using 16S rRNA Illumina sequencing, we hereby investigated the microbial profiles in these two mosquito species collected in several areas in the Republic of Korea. Thirty-six prevalent bacterial families were identified from these mosquito species. The microbial composition variations were primarily influenced by the mosquito collecting sites. Moreover, species biomarkers were identified by utilizing the regional specificity of the mosquito microbiome. Based on the microbiome profiles representing high similarity, Culex orientalis may share an ecological niche with Culex tritaeniorhynchus. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the effectiveness of Pisonia alba Span commonly known as lettuce tree or bird catcher tree leaf extracts in controlling Aedes aegypti and Culex quinquefasciatus mosquitoes, which transmit several severe illnesses, such as dengue, Zika, chikungunya, yellow fever, West Nile virus, lymphatic filariasis and Japanese encephalitis. Methods: Sequential extraction of P. alba leaves was done using n-hexane, chloroform, and methanol. The larvicidal, pupicidal, and ovicidal activities of the extracts were evaluated against both mosquito species using standard bioassays. The concentrations of the extracts required to kill 50% of the mosquito larvae, pupae, and ova (LC50) were determined. Results: The results showed that the methanol extract of P. alba had significant potential in killing the larvae, pupae, and ova of both mosquito species, with LC50 values of 65.0 and 54.5 ppm for larvicidal activity, 73.7 and 69.7 ppm for pupicidal activity, and 78.4 and 80.0 ppm for ovicidal activity against Ae. aegypti and Cx. quinquefasciatus, respectively. The n-hexane extract demonstrated moderate larvicidal activity, while the n-hexane and chloroform extracts lacked ovicidal activity. Conclusion: The methanol extract from Pisonia alba could be a natural and eco-friendly alternative for controlling mosquito populations responsible for transmitting vector-borne diseases. Further research is warranted to determine their practical applications in controlling mosquito populations in the field. [ABSTRACT FROM AUTHOR]

Neurotropic viruses can infiltrate the CNS by crossing the blood–brain barrier (BBB) through various mechanisms including paracellular, transcellular, and "Trojan horse" mechanisms during leukocyte diapedesis. These viruses belong to several families, including retroviruses; human immunodeficiency virus type 1 (HIV-1), flaviviruses; Japanese encephalitis (JEV); and herpesviruses; herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), and mouse adenovirus 1 (MAV-1). For entering the brain, viral proteins act upon the tight junctions (TJs) between the brain microvascular endothelial cells (BMECs). For instance, HIV-1 proteins, such as glycoprotein 120, Nef, Vpr, and Tat, disrupt the BBB and generate a neurotoxic effect. Recombinant-Tat triggers amendments in the BBB by decreasing expression of the TJ proteins such as claudin-1, claudin-5, and zona occludens-1 (ZO-1). Thus, the breaching of BBB has been reported in myriad of neurological diseases including multiple sclerosis (MS). Neurotropic viruses also exhibit molecular mimicry with several myelin sheath proteins, i.e., antibodies against EBV nuclear antigen 1 (EBNA1) aa411–426 cross-react with MBP and EBNA1 aa385–420 was found to be associated with MS risk haplotype HLA-DRB1*150. Notably, myelin protein epitopes (PLP139-151, MOG35-55, and MBP87-99) are being used to generate model systems for MS such as experimental autoimmune encephalomyelitis (EAE) to understand the disease mechanism and therapeutics. Viruses like Theiler's murine encephalomyelitis virus (TMEV) are also commonly used to generate EAE. Altogether, this review provide insights into the viruses' association with BBB leakiness and MS along with possible mechanistic details which could potentially use for therapeutics. [ABSTRACT FROM AUTHOR]

Subglottic stenosis is narrowing of the area in between the vocal cords and the cricoid cartilage. It can cause respiratory problems which can be mild to severe. Study the management of paediatric airway in post-intubation subglottic stenosis associated with Japanese encephalitis. Case Setting and Design: Retrospective study of 18 patients presenting with encephalitis out of which 6 cases were of post-intubation subglottic stenosis associated with Japanese encephalitis between the study period of one year (September 2017–September 2018) in the, Department of Otolaryngology and Head and Neck Surgery, North Eastern Indira Gandhi Regional Institute Of Health And Medical Sciences, Shillong, Meghalaya, India. Fifteen patients were treated in the study period. Different approaches were used. Post-intubation subglottic stenosis depends on the duration of intubation and the quality of life post-tracheostomy depends on the type of tube used. Bronchoscopic assisted procedures during the tracheostomy or after an interval helps to decrease the morbidity. Management of paediatric airway in post-intubation subglottic stenosis associated with Japanese encephalitis needs proper strategy and dedicated and intensive post-operative care. Bivona® silicone tracheostomy tube is a better option. [ABSTRACT FROM AUTHOR]

In this paper, we developed a non-linear deterministic mathematical model of Japanese encephalitis (JE) and Dengue co-infection dynamics with the application of the impact of JE vaccine. We estimate a basic reproduction number of model to show the epidemiological state of infectious disease in a community. In this model, disease-free equilibrium points of Japanese encephalitis-Dengue fever as well as endemic equilibrium points are determined in the system, and stability has been studied by using specified approach. This model also exhibits a backward bifurcation phenomenon when the basic reproduction number is less than unity, as described by Center Manifold Theory. Sensitivity analysis has been discussed to observe which parameters are having a substantial impact on JE-dengue co-infection dynamics. A numerical simulation is used to study the existence of equilibrium points and justify model characteristics on disease with the effect of vaccination on co-infected class. According to our findings, vaccination against Japanese encephalitis improves co-infection control of JE with Dengue disease. Therefore, JE-Dengue co-infection could be treated with the use of JE vaccine, which also significantly reduces the spread of co-infection. [ABSTRACT FROM AUTHOR]

Background: Japanese encephalitis (JE) is a notifiable infectious disease in China. Information on every case of JE is reported to the superior health administration department. However, reported cases include both laboratoryconfirmed and clinically diagnosed cases. This study aimed to differentiate between clinical and laboratory-confirmed cases of Japanese encephalitis virus (JEV) infection, and improve the accuracy of reported JE cases by analyzing the acute-phase serum and cerebrospinal fluid of all reported JE cases in the Sichuan province from 2012 to 2022. Methods: All acute-phase serum and/or cerebrospinal fluid samples of the reported JE cases were screened for IgM(ImmunoglobulinM)to JEV using the enzyme-linked immunosorbent assay (ELISA), and the detection of the viral genes of JEV and 9 other pathogens including enterovirus (EV), using reverse transcription PCR was attempted. Epidemiological analyses of JE and non-JE cases based on sex, age, onset time, and geographical distribution were also performed. Results: From 2012 to 2022, 1558 JE cases were reported in the Sichuan province. The results of serological (JEV-specific IgM) and genetic testing for JEV showed that 81% (1262/1558) of the reported cases were confirmed as JEV infection cases (laboratory-confirmed cases). Among the 296 cases of non-JEV infection, 6 viruses were detected in the cerebrospinal fluid in 62 cases, including EV and the Epstein-Barr virus (EBV), constituting 21% (62/296) of all non-JE cases. Among the 62 non-JEV infection cases with confirmed pathogens, infections with EV and EBV included 17 cases each, herpes simplex virus (HSV-1/2) included 14 cases, varicella- zoster virus included 6 cases, mumps virus included 2 cases, and human herpes viruses-6 included 1 case. Additionally, there were five cases involving mixed infections (two cases of EV/EBV, one case of HSV-1/HSV-2, one case of EBV/HSV-1, and one case of EV/herpes viruses-6). The remaining 234 cases were classified as unknown viral encephalitis cases. Our analysis indicated that those aged 0–15 y were the majority of the patients among the 1558 reported JE cases. However, the incidence of laboratory-confirmed JE cases in the >40 y age group has increased in recent years. The temporal distribution of laboratory-confirmed cases of JE revealed that the majority of cases occurred from May to September each year, with the highest incidence in August. Conclusion: The results of this study indicate that there is a certain discrepancy between clinically diagnosed and laboratory-confirmed cases of JE. Each reported case should be based on laboratory detection results, which is of great importance in improving the accuracy of case diagnosis and reducing misreporting. Our results are not only important for addressing JE endemic to the Sichuan province, but also provide a valuable reference for the laboratory detection of various notifiable infectious diseases in China and other regions outside China. [ABSTRACT FROM AUTHOR]