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Sensors (Basel, Switzerland) Aug 2020A highly effective way to improve prognosis of viral infectious diseases and to determine the outcome of infection is early, fast, simple, and efficient diagnosis of... (Review)
Review
A highly effective way to improve prognosis of viral infectious diseases and to determine the outcome of infection is early, fast, simple, and efficient diagnosis of viral pathogens in biological fluids. Among a wide range of viral pathogens, attract a special attention. genus includes more than 70 viruses, the most familiar being dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV). Haemorrhagic and encephalitis diseases are the most common severe consequences of flaviviral infection. Currently, increasing attention is being paid to the development of electrochemical immunological methods for the determination of . This review critically compares and evaluates recent research progress in electrochemical biosensing of DENV, ZIKV, and JEV without labelling. Specific attention is paid to comparison of detection strategies, electrode materials, and analytical characteristics. The potential of so far developed biosensors is discussed together with an outlook for further development in this field.
Topics: Biosensing Techniques; Dengue; Encephalitis, Japanese; Flavivirus; Humans; Zika Virus; Zika Virus Infection
PubMed: 32824351
DOI: 10.3390/s20164600 -
PLoS Neglected Tropical Diseases Jul 2022Japanese encephalitis virus (JEV) is the emerging and geographically expanding flavivirus and the major causative agent of encephalitis in humans in Asia. There are...
Japanese encephalitis virus (JEV) is the emerging and geographically expanding flavivirus and the major causative agent of encephalitis in humans in Asia. There are risks of JEV introduction into the Americas given a large population of amplifying hosts-pigs and wild boars, and insect vectors-Culex mosquitoes. There are emerging concerns about vector-free ways of flavivirus transmission, for example sexual and transplacental Zika virus transmissions, which may change flavivirus epidemiology and expand the geographical range to territories with no insect vectors. It is unknown whether JEV has tropism in the female lower reproductive tract and the potential for sexual transmission in humans. While clinical outcomes of transplacental JEV infection are described in humans and pigs, cellular targets and tissue tropism in the upper reproductive tract are also unknown. Here, we studied JEV infection phenotypes and host transcriptional responses in human reproductive epithelial cells. We found that JEV caused persistent infection and cytopathology in the vaginal epithelium, endometrial epithelium, and trophoblast. Human vaginal epithelial cells infected with JEV had altered transcriptional responses associated with inflammation and disruption of epithelial barrier function. Also, using pigs-the native amplifying host for JEV, we confirmed JEV tropism in the female lower and upper reproductive tracts. We discovered that JEV persists in the vaginal mucosa for at least 28 days and pigs shed the virus in vaginal secretions. We also found JEV persistence in the endometrium and placenta with transplacental and fetal infections. Altogether, we discovered that JEV targets the vaginal epithelium and has the potential for sexual transmission in humans. We also contributed to a better understanding of JEV pathogenesis during transplacental infection. Further studies are needed to better understand the interactions of JEV with reproductive tissues, how persistent infection affects female reproductive functions, and the risks for non-vector transmission.
Topics: Animals; Culex; Encephalitis Virus, Japanese; Encephalitis, Japanese; Epithelium; Female; Humans; Mosquito Vectors; Swine; Zika Virus; Zika Virus Infection
PubMed: 35905074
DOI: 10.1371/journal.pntd.0010656 -
Journal of Epidemiology and Global... Jun 2023We estimated the incidence of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) following routine immunization with the live-attenuated SA 14-14-2 JE...
BACKGROUND
We estimated the incidence of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) following routine immunization with the live-attenuated SA 14-14-2 JE vaccine.
METHODS
We implemented enhanced surveillance of AES and JE hospitalizations in endemic districts in Maharashtra and Telangana States during 2015-2016 and 2018-2020. We estimated incidence and compared differences in the incidence of JE and AES between two states, and vaccinated and unvaccinated districts during two study periods. We also considered secondary data from public health services to understand long-term trends from 2007 to 2020.
RESULTS
The annual AES incidence rate of 2.25 cases per 100,000 children in Maharashtra during 2018-2020 was significantly lower than 3.36 cases per 100,000 children during 2015-2016. The six JE-vaccinated districts in Maharashtra had significantly lower incidence rates during 2018-2020 (2.03, 95% CI 1.73-2.37) than in 2015-16 (3.26, 2.86-3.70). In addition, the incidence of both JE and AES in two unvaccinated districts was higher than in the vaccinated districts in Maharashtra. Telangana had a lower incidence of both JE and AES than Maharashtra. The AES incidence rate of 0.95 (0.77-1.17) during 2018-2020 in Telangana was significantly lower than 1.67 (1.41-1.97) during 2015-2016.
CONCLUSIONS
The annual incidence rate of Japanese encephalitis was < 1 case per 100,000 children. It indicated accelerated control of Japanese encephalitis after routine immunization. However, the annual incidence of acute encephalitis syndrome was still > 1 case per 100,000 children. It highlights the need for improving surveillance and evaluating the impacts of vaccination.
Topics: Child; Humans; Encephalitis, Japanese; Incidence; Acute Febrile Encephalopathy; India; Hospitalization
PubMed: 37162636
DOI: 10.1007/s44197-023-00110-7 -
Frontiers in Bioscience (Landmark... Jun 2020Japanese Encephalitis Virus (JEV) is the most common Flavivirus based mosquito borne viral encephalitis in the world, especially in countries of South-East Asia. The... (Review)
Review
Japanese Encephalitis Virus (JEV) is the most common Flavivirus based mosquito borne viral encephalitis in the world, especially in countries of South-East Asia. The conventional methods such as Enzyme-Linked Immunosorbent Assays (ELISA), Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), Plaque Reduction Neutralization Test and virus isolation are still in use today but new advances are being made to develop more efficient, inexpensive, quicker, sensitive and time-saving techniques to detect JEV. Some of these include the use of immunosensors, both lateral flow based assays and electrochemical, as well as the incorporation of nanotechnology into biosensors to develop highly sensitive detection tools. This review focuses on the recent advances that have been made to diagnose Japanese Encephalitis Virus which are critical in breaking the link to zoonotic transmission into the human population where humans are dead-end hosts.
Topics: Animals; Antibodies, Viral; Biosensing Techniques; Encephalitis Virus, Japanese; Encephalitis, Japanese; Enzyme-Linked Immunosorbent Assay; Humans; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Viral Zoonoses
PubMed: 32472762
DOI: 10.2741/4882 -
Journal of Virology Sep 2019Accumulated evidence demonstrates that Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor...
Accumulated evidence demonstrates that Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, the precise role of PERK in JEV-induced apoptosis and encephalitis remains unknown. Here, we report that JEV infection activates the PERK-ATF4-CHOP apoptosis pathway both and PERK activation also promotes the formation of stress granule, which in turn represses JEV-induced apoptosis. However, PERK inhibitor reduces apoptosis, indicating that JEV-activated PERK predominantly induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway. Among JEV proteins that have been reported to induce ER stress, only JEV NS4B can induce PERK activation. PERK has been reported to form an active molecule by dimerization. The coimmunoprecipitation assay shows that NS4B interacts with PERK. Moreover, glycerol gradient centrifugation shows that NS4B induces PERK dimerization. Both the LIG-FHA and the LIG-WD40 domains within NS4B are required to induce PERK dimerization, suggesting that JEV NS4B pulls two PERK molecules together by simultaneously interacting with them via different motifs. PERK deactivation reduces brain cell damage and encephalitis during JEV infection. Furthermore, expression of JEV NS4B is sufficient to induce encephalitis via PERK in mice, indicating that JEV activates PERK primarily via its NS4B to cause encephalitis. Taken together, our findings provide a novel insight into JEV-caused encephalitis. Japanese encephalitis virus (JEV) infection triggers endoplasmic reticulum (ER) stress and neuron apoptosis. ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, whether the PERK pathway of ER stress response plays important roles in JEV-induced apoptosis and encephalitis remains unknown. Here, we found that JEV infection activates ER stress sensor PERK in neuronal cells and mouse brains. PERK activation induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway upon JEV infection. Among the JEV proteins prM, E, NS1, NS2A, NS2B, and NS4B, only NS4B activates PERK. Moreover, activated PERK participates in apoptosis and encephalitis induced by JEV and NS4B. These findings provide a novel therapeutic approach for JEV-caused encephalitis.
Topics: Activating Transcription Factor 4; Adenine; Animals; Apoptosis; Binding Sites; Cell Line; Disease Models, Animal; Encephalitis Virus, Japanese; Encephalitis, Japanese; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Indoles; Mice; Neurons; Protein Multimerization; Signal Transduction; Transcription Factor CHOP; Viral Nonstructural Proteins; eIF-2 Kinase
PubMed: 31189710
DOI: 10.1128/JVI.00887-19 -
Veterinary Sciences May 2024The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has a wide host range, extending from pigs and ardeid birds to opportunistic dead-end hosts, such as...
The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has a wide host range, extending from pigs and ardeid birds to opportunistic dead-end hosts, such as humans and horses. However, JEV encephalitis infections in aquatic mammals are rare, with only two cases in seals reported to date. Here, we report a lethal case of JEV and co-infection in an aquarium-housed harbor seal in Japan. We isolated JEV from the brain of the dead seal and characterized its phylogeny and pathogenicity in mice. The virus isolate from the seal was classified as genotype GIb, which aligns with recent Japanese human and mosquito isolates as well as other seal viruses detected in China and Korea, and does not exhibit a unique sequence trait distinct from that of human and mosquito strains. We demonstrated that the seal isolate is pathogenic to mice and causes neuronal symptoms. These data suggest that seals should be considered a susceptible dead-end host for circulating JEV in natural settings.
PubMed: 38787188
DOI: 10.3390/vetsci11050215 -
The Lancet. Infectious Diseases Oct 2023Zika virus infection is a threat to at-risk populations, causing major birth defects and serious neurological complications. Development of a safe and efficacious Zika... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of a purified inactivated Zika virus vaccine candidate in adults primed with a Japanese encephalitis virus or yellow fever virus vaccine in the USA: a phase 1, randomised, double-blind, placebo-controlled clinical trial.
BACKGROUND
Zika virus infection is a threat to at-risk populations, causing major birth defects and serious neurological complications. Development of a safe and efficacious Zika virus vaccine is, therefore, a global health priority. Assessment of heterologous flavivirus vaccination is important given co-circulation of Japanese encephalitis virus and yellow fever virus with Zika virus. We investigated the effect of priming flavivirus naive participants with a licensed flavivirus vaccine on the safety and immunogenicity of a purified inactivated Zika vaccine (ZPIV).
METHODS
This phase 1, placebo-controlled, double-blind trial was done at the Walter Reed Army Institute of Research Clinical Trials Center in Silver Spring, MD, USA. Eligible participants were healthy adults aged 18-49 years, with no detectable evidence of previous flavivirus exposure (by infection or vaccination), as measured by a microneutralisation assay. Individuals with serological evidence of HIV, hepatitis B, or hepatitis C infection were excluded, as were pregnant or breastfeeding women. Participants were recruited sequentially into one of three groups (1:1:1) to receive no primer, two doses of intramuscular Japanese encephalitis virus vaccine (IXIARO), or a single dose of subcutaneous yellow fever virus vaccine (YF-VAX). Within each group, participants were randomly assigned (4:1) to receive intramuscular ZPIV or placebo. Priming vaccinations were given 72-96 days before ZPIV. ZPIV was administered either two or three times, at days 0, 28, and 196-234. The primary outcome was occurrence of solicited systemic and local adverse events along with serious adverse events and adverse events of special interest. These data were analysed in all participants receiving at least one dose of ZPIV or placebo. Secondary outcomes included measurement of neutralizing antibody responses following ZPIV vaccination in all volunteers with available post-vaccination data. This trial is registered at ClinicalTrials.gov, NCT02963909.
FINDINGS
Between Nov 7, 2016, and Oct 30, 2018, 134 participants were assessed for eligibility. 21 did not meet inclusion criteria, 29 met exclusion criteria, and ten declined to participate. 75 participants were recruited and randomly assigned. 35 (47%) of 75 participants were male and 40 (53%) were female. 25 (33%) of 75 participants identified as Black or African American and 42 (56%) identified as White. These proportions and other baseline characteristics were similar between groups. There were no statistically significant differences in age, gender, race, or BMI between those who did and did not opt into the third dose. All participants received the planned priming IXIARO and YF-VAX vaccinations, but one participant who received YF-VAX dropped out before receipt of the first dose of ZPIV. 50 participants received a third dose of ZPIV or placebo, including 14 flavivirus-naive people, 17 people primed with Japanese encephalitis virus vaccine, and 19 participants primed with yellow fever vaccine. Vaccinations were well tolerated across groups. Pain at the injection site was the only adverse event reported more frequently in participants who received ZPIV than in those who received placebo (39 [65%] of 60 participants, 95% CI 51·6-76·9 who received ZPIV vs three [21·4%] of 14 who received placebo; 4·7-50·8; p=0·006). No patients had an adverse event of special interest or serious adverse event related to study treatment. At day 57, the flavivirus-naive volunteers had an 88% (63·6-98·5, 15 of 17) seroconversion rate (neutralising antibody titre ≥1:10) and geometric mean neutralising antibody titre (GMT) against Zika virus of 100·8 (39·7-255·7). In the Japanese encephalitis vaccine-primed group, the day 57 seroconversion rate was 31·6% (95% CI 12·6-56·6, six of 19) and GMT was 11·8 (6·1-22·8). Participants primed with YF-VAX had a seroconversion rate of 25% (95% CI 8·7-49·1, five of 20) and GMT of 6·6 (5·2-8·4). Humoral immune responses rose substantially following a third dose of ZPIV, with seroconversion rates of 100% (69·2-100; ten of ten), 92·9% (66·1-99·8; 13 of 14), and 60% (32·2-83·7, nine of 15) and GMTs of 511·5 (177·6-1473·6), 174·2 (51·6-587·6), and 79 (19·0-326·8) in the flavivirus naive, Japanese encephalitis vaccine-primed, and yellow fever vaccine-primed groups, respectively.
INTERPRETATION
We found ZPIV to be well tolerated in flavivirus naive and primed adults but that immunogenicity varied significantly according to antecedent flavivirus vaccination status. Immune bias towards the flavivirus antigen of initial exposure and the timing of vaccination may have impacted responses. A third ZPIV dose overcame much, but not all, of the discrepancy in immunogenicity. The results of this phase 1 clinical trial have implications for further evaluation of ZPIV's immunisation schedule and use of concomitant vaccinations.
FUNDING
Department of Defense, Defense Health Agency; National Institute of Allergy and Infectious Diseases; and Division of Microbiology and Infectious Disease.
Topics: Adult; Female; Humans; Male; Antibodies, Neutralizing; Antibodies, Viral; Double-Blind Method; Encephalitis Virus, Japanese; Immunogenicity, Vaccine; Japanese Encephalitis Vaccines; Vaccines, Inactivated; Viral Vaccines; Yellow Fever Vaccine; Yellow fever virus; Zika Virus; Zika Virus Infection; Yellow Fever
PubMed: 37390836
DOI: 10.1016/S1473-3099(23)00192-5 -
PLoS Neglected Tropical Diseases Jul 2022Japanese encephalitis (JE) is a vector-borne zoonosis and the leading cause of human viral encephalitis in Asia. Its transmission cycle is usually described as involving...
Japanese encephalitis (JE) is a vector-borne zoonosis and the leading cause of human viral encephalitis in Asia. Its transmission cycle is usually described as involving wild birds as reservoirs and pigs as amplifying hosts. JE is endemic in Cambodia, where it circulates in areas with low pig densities (<70 pigs per km2), and could be maintained in a multi-host system composed of pigs, but also poultry as competent hosts, and dogs, cattle and humans as non-competent hosts. We used a mathematical model representing Japanese encephalitis virus (JEV) transmission in a traditional Cambodian village that we calibrated with field data collected in 3 districts of Kandal province, Cambodia. First, R0 calculations allowed us to assess the capacity of the epidemiological system to be invaded by JEV and sustain virus transmission in villages in the 3 districts, and we predicted human exposure at the epidemiological equilibrium, based on simulations. Changes in spatial density of livestock, in agricultural practices, and epizootics (e.g., African swine fever), can profoundly alter the composition of host communities, which could affect JEV transmission and its impact on human health. In a second step, we then used the model to analyse how host community composition affected R0 and the predicted human exposure. Lastly, we evaluated the potential use of dog JE seroprevalence as an indicator of human exposure to JEV. In the modeled villages, the calculated R0 ranged from 1.07 to 1.38. Once the equilibrium reached, predicted annual probability of human exposure ranged from 9% to 47%, and predicted average age at infection was low, between 2 and 11 years old, highlighting the risk of severe forms of JEV infection and the need to intensify child immunization. According to the model, increasing the proportion of competent hosts induced a decrease in age at infection. The simulations also showed that JEV could invade a multi-host system with no pigs, reinforcing the assumption of poultry acting as reservoirs. Finally, the annual human exposure probability appeared linearly correlated with dog seroprevalence, suggesting that in our specific study area, dog seroprevalence would be a good proxy for human exposure.
Topics: African Swine Fever; Animals; Asian People; Cattle; Child; Child, Preschool; Dogs; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Seroepidemiologic Studies; Swine
PubMed: 35816555
DOI: 10.1371/journal.pntd.0010572 -
PLoS Neglected Tropical Diseases Jun 2021Japanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this...
BACKGROUND
Japanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this study estimated the economic burden and the disability-adjusted life years (DALYs) due to JE in Zhejiang Province, China during 2013-2018, to increase disease awareness and provide evidence for effective health policy.
METHODOLOGY/PRINCIPLE FINDINGS
We merged multiple data sources, including National Notifiable Disease Registry System (NNDRS), patient interviews and medical records from corresponding hospitals for JE cases which occurred during 2013-2018 in Zhejiang Province. Direct costs were extracted from hospitals' billing systems and patient interviews. Indirect costs and disease burden were calculated based on questionnaire survey from patient interviews and follow-up assessment by general practitioners. Given under-reporting, an expansion factor (EF) was applied to extrapolate the JE burden to the provincial level. The total economic burden of JE during 2013-2018 was estimated at US $12.01 million with an EF = 3. Of this, $8.32 million was due to direct economic cost and $3.69 million to indirect cost. The disease burden of JE was 42.75 DALYs per million population (28.44 YLD, 14.28 YLL) according to the 1990 Global Burden of Disease (GBD 1990) methodology and 80.01 DALYs (53.67YLD, 26.34YLL) according to the GBD 2010 methodology. Sensitivity analysis demonstrated that the overall economic burden varied from US$ 1.73-36.42 million. The greatest variation was due to the prognosis of illness (-85.57%-203.17%), followed by occupation (-34.07%-134.12%) and age (-72.97%-47.69%).
CONCLUSIONS/SIGNIFICANCE
JE imposes a heavy burden for families and society in Zhejiang Province. This study provides comprehensive empirical estimates of JE burden to increase awareness and strengthen knowledge of the public. These data may support provincial level public health decision making for prevention and control of JE. Ongoing surveillance for acute meningitis and encephalitis syndrome (AEMS) in sentinel hospitals, is needed to further refine estimates of JE burden.
Topics: Adolescent; Adult; Child; Child, Preschool; China; Cost of Illness; Encephalitis Virus, Japanese; Encephalitis, Japanese; Female; Health Care Costs; Humans; Infant; Male; Middle Aged; Quality-Adjusted Life Years
PubMed: 34153039
DOI: 10.1371/journal.pntd.0009505 -
Virologica Sinica Aug 2021Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, which causes the most commonly diagnosed viral encephalitis named Japanese encephalitis (JE) in the...
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, which causes the most commonly diagnosed viral encephalitis named Japanese encephalitis (JE) in the world with an unclear pathogenesis. Axl, a receptor tyrosine kinase from TAM family, plays crucial role in many inflammatory diseases. We have previously discovered that Axl deficiency resulted in more severe body weight loss in mice during JEV infection, which we speculate is due to the anti-inflammatory effect of Axl during JE. Currently, the role of Axl in regulating the neuroinflammation and brain damage during JE has not been investigated yet. In this study, by using Axl deficient and heterozygous control mice, we discovered that Axl deficient mice displayed accelerated JE progression and exacerbated brain damage characterized by increased neural cell death, extended infiltration of inflammatory cells, and enhanced production of pro-inflammatory cytokines, in comparison to control mice. Additionally, consistent with our previous report, Axl deficiency had no impact on the infection and target cell tropism of JEV in brain. Taken together, our results suggest that Axl plays an anti-inflammatory and neuroprotective role during the pathogenesis of JE.
Topics: Animals; Brain; Cytokines; Disease Models, Animal; Encephalitis Virus, Japanese; Encephalitis, Japanese; Mice
PubMed: 33534086
DOI: 10.1007/s12250-020-00342-y