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Japanese encephalitis virus (JEV) is a major cause of neurological disability in Asia and causes thousands of severe encephalitis cases and deaths each year. Although Japanese encephalitis (JE) is a WHO reportable disease, cases and deaths are significantly underreported and the true burden of the disease is not well understood in most endemic countries. Here, we first conducted a spatial analysis of the risk factors associated with JE to identify the areas suitable for sustained JEV transmission and the size of the population living in at-risk areas. We then estimated the force of infection (FOI) for JE-endemic countries from age-specific incidence data. Estimates of the susceptible population size and the current FOI were then used to estimate the JE burden from 2010 to 2019, as well as the impact of vaccination. Overall, 1,543.1 million (range: 1,292.6-2,019.9 million) people were estimated to live in areas suitable for endemic JEV transmission, which represents only 37.7% (range: 31.6-53.5%) of the over four billion people living in countries with endemic JEV transmission. Based on the baseline number of people at risk of infection, there were an estimated 56,847 (95% CI: 18,003-184,525) JE cases and 20,642 (95% CI: 2,252-77,204) deaths in 2019. Estimated incidence declined from 81,258 (95% CI: 25,437-273,640) cases and 29,520 (95% CI: 3,334-112,498) deaths in 2010, largely due to increases in vaccination coverage which have prevented an estimated 314,793 (95% CI: 94,566-1,049,645) cases and 114,946 (95% CI: 11,421-431,224) deaths over the past decade. India had the largest estimated JE burden in 2019, followed by Bangladesh and China. From 2010-2019, we estimate that vaccination had the largest absolute impact in China, with 204,734 (95% CI: 74,419-664,871) cases and 74,893 (95% CI: 8,989-286,239) deaths prevented, while Taiwan (91.2%) and Malaysia (80.1%) had the largest percent reductions in JE burden due to vaccination. Our estimates of the size of at-risk populations and current JE incidence highlight countries where increasing vaccination coverage could have the largest impact on reducing their JE burden.

Japanese encephalitis virus (JEV) is a zoonotic pathogen mainly found in East and Southeast Asia and transmitted by mosquitoes. The objective of this review is to summarize the knowledge on the diversity of JEV mosquito vector species. Therefore, we systematically analyzed reports of JEV found in field-caught mosquitoes as well as experimental vector competence studies. Based on the investigated publications, we classified 14 species as confirmed vectors for JEV due to their documented experimental vector competence and evidence of JEV found in wild mosquitoes. Additionally, we identified 11 mosquito species, belonging to five genera, with an experimentally confirmed vector competence for JEV but lacking evidence on their JEV transmission capacity from field-caught mosquitoes. Our study highlights the diversity of confirmed and potential JEV vector species. We also emphasize the variety in the study design of vector competence investigations. To account for the diversity of the vector species and regional circumstances, JEV vector competence should be studied in the local context, using local mosquitoes with local virus strains under local climate conditions to achieve reliable data. In addition, harmonization of the design of vector competence experiments would lead to better comparable data, informing vector and disease control measures.

The flaviviruses dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors ( Aedes and Culex spp.), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses.

Japanese encephalitis virus (JEV) is maintained in an enzootic cycle between swine, water birds, and mosquitoes. JEV has circulated indigenously in Asia, with Culex tritaeniorhynchus as the primary vector. In some areas where the primary vector is scarce or absent, sporadic cases of Japanese encephalitis have been reported, with Aedes japonicus japonicus presumed to have the potential as a secondary vector. As one of the world’s most invasive culicid species, Ae . j . japonicus carries a considerable health risk for spreading diseases to wider areas, including Europe and North America. Thus, evaluation of its competency as a JEV vector, particularly in a native population, will be essential in preventing potential disease spread. In this study, the two mosquito species’ vector competence in transmitting three JEV genotypes (I, III, and V) was assessed, with Cx . tritaeniorhynchus serving as a point of reference. The mosquitoes were virus-fed and the infection rate (IR), dissemination rate (DR), and transmission rate (TR) evaluated individually by either RT-qPCR or focus forming assay. Results showed striking differences between the two species, with IR of 95% (261/274) and 9% (16/177) in Cx . tritaeniorhynchus and Ae . j . japonicus , respectively. Both mosquitoes were susceptible to all three JEV genotypes with significant differences in IR and mean viral titer. Results confirm the primary vector’s competence, but the fact that JEV was able to establish in Ae . j . japonicus is of public health significance, and with 2%–16% transmission rate it has the potential to successfully transmit JEV to the next host. This may explain the human cases and infrequent detection in primary vector-free areas. Importantly, Ae . j . japonicus could be a relevant vector spreading the disease into new areas, indicating the need for security measures in areas where the mosquito is distributed or where it may be introduced.

The Japanese encephalitis virus (JEV) is transmitted by mosquitoes and circulates in Asia, the western Pacific, and other parts of the world. It is classified into five genotypes (GI-GV) based on the nucleotide sequence of the envelope (E) gene. Despite extensive surveillance, shifts in genotype distribution and mosquito species remain underreported, particularly in the Republic of Korea. We conducted a nationwide mosquito collection from 2017 to 2022, capturing 1,102,031 mosquitoes from 32 sites nationwide. The predominant species were Aedes vexans (34.2%), Culex pipiens (17.9%), Cx. tritaeniorhynchus (13.4%), Ae. albopictus (4.0%), and Cx. orientalis (0.6%). JEV was detected in 49 pools, with the majority from Cx. pipiens and Cx. tritaeniorhynchus. Genetic analyses identified genotypes I, III, and V, with genotype V becoming dominant from 2020 onwards. The emergence of genotype V as the dominant strain of the JEV, along with its detection in mosquito species other than the previously known Cx. tritaeniorhynchus, highlights the need for ongoing surveillance. These findings underscore the importance of developing vaccines effective against all JEV genotypes to mitigate public health risks.

Japanese encephalitis (JE) is a viral disease predominantly located in South East Asia and commonly associated with transmission between amplifying hosts, such as pigs, and the mosquito Culex tritaeniorhynchus, where human infection represents a dead end in the life cycle of the virus. The expansion of JE beyond an Asiatic confine is dependent on a multitude of complex factors that stem back to genetic subtype variation. A complex interplay of the genetic variation and vector competencies combine with variables such as geography, climate change and urbanization. Our understanding of JE is still at an early stage with long-term longitudinal vector surveillance necessary to better understand the dynamics of JE transmission and to characterize the role of potential secondary vectors such as Cx. pipiens and Cx. bitaeniorhynchus. The authors review the vectors indicated in transmission and the ecological, genetic and anthropological factors that affect the disease's range and epidemiology. Monitoring for the presence of JE virus in mosquitoes in general can be used to estimate levels of potential JE exposure, intensity of viral activity and genetic variation of JEV throughout surveyed areas. Increased surveillance and diagnosis of viral encephalitis caused by genotype 5 JE virus is required in particular, with the expansion in epidemiology and disease prevalence in new geographic areas an issue of great concern. Additional studies that measure the impact of vectors (e.g. bionomics and vector competence) in the transmission of JEV and that incorporate environmental factors (e.g. weekly rainfall) are needed to define the roles of Culex species in the viral pathogenesis during outbreak and non-outbreak years.

Japanese encephalitis virus (JEV), a main cause of severe viral encephalitis in humans, has a complex ecology, composed of a cycle involving primarily waterbirds and mosquitoes, as well as a cycle involving pigs as amplifying hosts. To date, JEV transmission has been exclusively described as being mosquito-mediated. Here we demonstrate that JEV can be transmitted between pigs in the absence of arthropod vectors. Pigs shed virus in oronasal secretions and are highly susceptible to oronasal infection. Clinical symptoms, virus tropism and central nervous system histological lesions are similar in pigs infected through needle, contact or oronasal inoculation. In all cases, a particularly important site of replication are the tonsils, in which JEV is found to persist for at least 25 days despite the presence of high levels of neutralizing antibodies. Our findings could have a major impact on the ecology of JEV in temperate regions with short mosquito seasons. Japanese encephalitis virus (JEV) is primarily transmitted between mosquitoes and birds but can also infect pigs. Here the authors demonstrate that JEV, which was thought to be spread exclusively by mosquitoes, can be transmitted between pigs through a direct contact.

Japanese encephalitis (JE), a mosquito-borne viral disease caused by the Japanese encephalitis virus (JEV), remains a significant public health threat in Asia. Although vaccination programs have successfully reduced the incidence of JE, challenges persist in the adult population, and the emergence of rare JEV genotypes poses additional risks. In this study, a phylogenetic analysis of the whole JEV genome sequence, along with a temporal–spatial analysis of isolates and a host–vector analysis, was used to examine the changes in JEV transmission dynamics before and after 2012. The results revealed persistent differences between the dominant G1 and G3 genotypes, as well as the re-emergence of G4 and G5 genotypes. Although JEV has been detected in non-traditional vectors and atypical mammalian hosts, Culex tritaeniorhynchus and pigs remain the primary vector and amplifying host, respectively. These findings underscore the need to enhance existing JEV genotype surveillance while addressing emerging threats from genotype diversity, host expansion, and geographic spread.

Japanese encephalitis virus (JEV) is a multi-vector, multi-host pathogen maintained in circulation between Culex mosquitoes and waterbirds, with occasional spillover to humans. In Australia, sporadic local transmission of JEV was historically confined to northern Australia until 2021 after which outbreaks occurred for the first time in temperate southern regions in 2022 and 2023, respectively. Following this outbreak, there have been concerns that JEV has potentially become endemic in Australia, posing an ongoing public health risk exacerbated by shifting climatic and environmental factors. We developed and applied a spatially explicit spillover modelling framework which focuses on estimating i) an ecological suitability index for JEV in Australia and, ii) the spillover potential to human populations if endemic transmission is established. To calculate ecological suitability and the potential number of humans that could be exposed, we integrated the ecological and epidemiological conditions that would allow JEV to circulate in Australia and spillover to human populations. An ecological suitability index was calculated by combining the presence of hosts ( Ardeidae birds, domestic piggeries, feral pigs) and vectors ( Culex annulirostris and Culex quinquefasciatus ), host-vector contact rates, and vector infection and transmission potential for JEV at a 1km resolution. JEV spillover potential was estimated by multiplying the ecological suitability index with human population density. We used this estimate to calculate the total population that could be exposed to JEV at the Local Government Area (LGA) level and State/Territory level. We validated our estimates by calculating a population-weighted mean value for each LGA and compared the values between LGAs with confirmed JEV clinical cases to those without. We found an elevated ecological suitability along the east coast and south-western coast of Australia, inland from the northern centre of the country, and surrounding the Murray River Basin (along the border of New South Wales and Victoria). If JEV becomes established in ecologically suitable areas, high spillover potential to humans would exist along Australia’s eastern coast. This exposure potential extends inland to areas like the Murray River Basin, which provide ample habitat for enzootic hosts and vector species. High spillover potential also exists in the Northern Territory, along the southwestern coast of Western Australia, and in South Australia. LGAs with historically confirmed clinical cases in humans had a statistically higher population-weighted mean value compared to those without confirmed cases, supporting the model’s capability to differentiate highly suitable areas. By integrating vector-host dynamics and human population density into a spatially explicit framework, we identified areas with high JEV ecological suitability and the potential for spillover into human populations if transmission of JEV were to become established. The results were driven by interactions between vectors, hosts and vector competence. These findings provide insights for targeted surveillance and vector control strategies in Australia. Proactive and sustained interventions are essential to mitigate JEV’s growing threat and to protect vulnerable populations in the face of ongoing environmental changes.

Background Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen, primarily transmitted by Culex tritaeniorhynchus in rural regions. In the Republic of Korea (ROK), genotype V (GV) has become the dominant JEV strain since 2010, raising suspicion about the vector competence of urban mosquitoes like Culex pipiens pallens . Methods This study evaluated the vector competence of Cx. tritaeniorhynchus and Cx. pipiens pallens for JEV GIII and GV under laboratory conditions. Mosquitoes were orally infected, and the infection rate (IR), dissemination rate (DR), and transmission rate (TR) were assessed at days 7 and 14 post-infection. Results Culex tritaeniorhynchus showed consistently high IR, DR, and TR for both genotypes, with over 95% of mosquitoes infected and actively transmitting the virus. In contrast, Cx. pipiens pallens exhibited a markedly lower IR, ranging from 23.1 to 39.2%; however, among infected mosquitoes, DR and TR were comparatively high. Viral load and titers were also markedly higher in Cx. tritaeniorhynchus than in Cx. pipiens pallens , particularly in the head-thorax and salivation samples. Conclusions These findings confirm that Cx. tritaeniorhynchus is a highly competent vector for JEV GIII and GV and suggest that Cx. pipiens pallens may play a notable role in the transmission of Japanese encephalitis virus in urban areas. This study emphasizes the importance of targeted vector surveillance and control strategies for multiple mosquito species, especially given the recent urbanization of JE cases in the ROK. Graphical Abstract