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Viruses Feb 2023Japanese encephalitis virus (JEV), which uses a mosquito primary vector and swine as a reservoir host, poses a significant risk to human and animal health. JEV can be...
Japanese encephalitis virus (JEV), which uses a mosquito primary vector and swine as a reservoir host, poses a significant risk to human and animal health. JEV can be detected in cattle, goats and dogs. A molecular epidemiological survey of JEV was conducted in 3105 mammals from five species, swine, fox, racoon dog, yak and goat, and 17,300 mosquitoes from 11 Chinese provinces. JEV was detected in pigs from Heilongjiang (12/328, 3.66%), Jilin (17/642, 2.65%), Shandong (14/832, 1.68%), Guangxi (8/278, 2.88%) and Inner Mongolia (9/952, 0.94%); in goats (1/51, 1.96%) from Tibet; and mosquitoes (6/131, 4.58%) from Yunnan. A total of 13 JEV envelope (E) gene sequences were amplified in pigs from Heilongjiang (5/13), Jilin (2/13) and Guangxi (6/13). Swine had the highest JEV infection rate of any animal species, and the highest infection rates were found in Heilongjiang. Phylogenetic analysis indicated that the predominant strain in Northern China was genotype I. Mutations were found at residues 76, 95, 123, 138, 244, 474 and 475 of E protein but all sequences had predicted glycosylation sites at 'N154. Three strains lacked the threonine 76 phosphorylation site from non-specific (unsp) and protein kinase G (PKG) site predictions; one lacked the threonine 186 phosphorylation site from protein kinase II (CKII) prediction; and one lacked the tyrosine 90 phosphorylation site from epidermal growth factor receptor (EGFR) prediction. The aim of the current study was to contribute to JEV prevention and control through the characterization of its molecular epidemiology and prediction of functional changes due to E-protein mutations.
Topics: Cattle; Animals; Humans; Swine; Dogs; Encephalitis Virus, Japanese; Phylogeny; China; Genotype; Encephalitis Viruses, Japanese; Encephalitis, Japanese; Culicidae; Threonine; Mammals
PubMed: 36992334
DOI: 10.3390/v15030625 -
Viruses Dec 2023Japanese encephalitis virus is a mosquito-borne member of the family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high...
Japanese encephalitis virus is a mosquito-borne member of the family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality, and neurological sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for the spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO) has been approved by the US Food and Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of the introduction of JEV into the US, the need to integrate planning for such an event in public health policy, and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.
Topics: Humans; United States; Animals; Horses; Swine; Encephalitis, Japanese; Encephalitis Virus, Japanese; Encephalitis, Viral; Agriculture; Chiroptera; Culicidae; Vaccines; Zika Virus; Zika Virus Infection
PubMed: 38257754
DOI: 10.3390/v16010054 -
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 -
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 -
Viruses Jan 2024Japanese encephalitis virus (JEV) belongs to the family and is a representative mosquito-borne flavivirus responsible for acute encephalitis and meningitis in humans.... (Review)
Review
Japanese encephalitis virus (JEV) belongs to the family and is a representative mosquito-borne flavivirus responsible for acute encephalitis and meningitis in humans. Despite the availability of vaccines, JEV remains a major public health threat with the potential to spread globally. According to the World Health Organization (WHO), there are an estimated 69,000 cases of JE each year, and this figure is probably an underestimate. The majority of JE victims are children in endemic areas, and almost half of the surviving patients have motor or cognitive sequelae. Thus, the absence of a clinically approved drug for the treatment of JE defines an urgent medical need. Recently, several promising and potential drug candidates were reported through drug repurposing studies, high-throughput drug library screening, and de novo design. This review focuses on the historical aspects of JEV, the biology of JEV replication, targets for therapeutic strategies, a target product profile, and drug development initiatives.
Topics: Child; Animals; Humans; Encephalitis Virus, Japanese; Encephalitis, Japanese; Encephalitis, Viral; High-Throughput Screening Assays; Drug Development
PubMed: 38399978
DOI: 10.3390/v16020202 -
Journal of the Chinese Medical... May 2015Japanese encephalitis (JE) is a mosquito-borne flavivirus infection and an important cause of encephalitis in most of Asia and parts of the western Pacific. Most people... (Review)
Review
Japanese encephalitis (JE) is a mosquito-borne flavivirus infection and an important cause of encephalitis in most of Asia and parts of the western Pacific. Most people infected with the JE virus (JEV) are asymptomatic or seemingly suffer from a nonspecific, flu-like illness; in others, JE can cause illness ranging from fever and headache to severe encephalitis. Although it can cause significant morbidity and mortality, JE is a vaccine-preventable disease, and vaccination programs have proven most effective in preventing and diminishing the burden of disease. Such JE vaccines have been available for decades with four types of JE vaccines-live attenuated SA14-14-2 vaccine, inactivated mouse brain-derived vaccine (JE-MB), inactivated Vero cell culture vaccine (JE-VC), and live attenuated chimeric vaccine (IMOJEV)-and are currently used in most countries. In some Asian countries such as Japan, China, Taiwan, Korea, and Thailand, immunization programs have been conducted for children and so the ongoing incidence of JE has declined considerably in recent decades. Until quite recently, the primary JE vaccine in use internationally has been the JE-MB, which is now commonly replaced by cell culture-based vaccines.
Topics: Animals; Chlorocebus aethiops; Cost-Benefit Analysis; Encephalitis, Japanese; Humans; Immunization Schedule; Japanese Encephalitis Vaccines; Mice; Vero Cells
PubMed: 25841620
DOI: 10.1016/j.jcma.2014.12.009 -
The spatial-temporal pattern of Japanese encephalitis and its influencing factors in Guangxi, China.Infection, Genetics and Evolution :... Jul 2023Japanese encephalitis (JE) is a major global public health threat. Using Japanese encephalitis incidence data from 2004 to 2010 in Guangxi Province, China, this study...
Japanese encephalitis (JE) is a major global public health threat. Using Japanese encephalitis incidence data from 2004 to 2010 in Guangxi Province, China, this study comprehensively explored the driving forces and the interactive effects between environmental and social factors of Japanese encephalitis using the Geo-detector method. The results indicated that the incidence of Japanese encephalitis showed a fluctuating downward trend from 2004 to 2010. The onset of JE was seasonal, mainly concentrated in June-July, and highly aggregated in northwestern Guangxi. Among the factors associated with Japanese encephalitis, days with temperatures >30 °C, accumulated temperatures >25 °C, slope, the normalized difference vegetation index, the gross domestic product of tertiary industries, the gross domestic product of primary industries and the number of pigs slaughtered showed higher contributions to Japanese encephalitis incidence. An enhanced interactive effect was found between environmental and social factors, and the interaction between days with humidity levels >80% and the gross domestic product of tertiary industries had the greatest combined effect on JE. These findings enhanced the understanding of the combined effect of social and environmental factors on the incidence of Japanese encephalitis and could help improve Japanese encephalitis transmission control and prevention strategies.
Topics: Animals; Swine; Encephalitis, Japanese; China; Incidence; Temperature; Gross Domestic Product
PubMed: 37037290
DOI: 10.1016/j.meegid.2023.105433 -
Emerging Infectious Diseases Dec 2023Japanese encephalitis (JE) is associated with an immense social and economic burden. Published cost-of-illness data come primarily from decades-old studies. To determine...
Japanese encephalitis (JE) is associated with an immense social and economic burden. Published cost-of-illness data come primarily from decades-old studies. To determine the cost of care for patients with acute JE and initial and long-term sequelae from the societal perspective, we recruited patients with laboratory-confirmed JE from the past 10 years of JE surveillance in Bangladesh and categorized them as acute care, initial sequalae, and long-term sequelae patients. Among 157 patients, we categorized 55 as acute, 65 as initial sequelae (53 as both categories), and 90 as long-term sequelae. The average (median) societal cost of an acute JE episode was US $929 ($909), of initial sequelae US $75 ($33), and of long-term sequelae US $47 ($14). Most families perceived the effect of JE on their well-being to be extreme and had sustained debt for JE expenses. Our data about the high cost of JE can be used by decision makers in Bangladesh.
Topics: Humans; Encephalitis, Japanese; Bangladesh; Critical Care; Japanese Encephalitis Vaccines; Encephalitis Virus, Japanese
PubMed: 37987586
DOI: 10.3201/eid2912.230594 -
Cell Reports Sep 2023Japanese encephalitis (JE) is a vector-borne viral disease that causes acute encephalitis in children. Although vaccines have been developed against the JE virus (JEV),...
Japanese encephalitis (JE) is a vector-borne viral disease that causes acute encephalitis in children. Although vaccines have been developed against the JE virus (JEV), no effective antiviral therapy exists. Our study shows that inhibition of poly(ADP-ribose) polymerase 1 (PARP1), an NAD-dependent (poly-ADP) ribosyl transferase, protects against JEV infection. Interestingly, PARP1 is critical for JEV pathogenesis in Neuro-2a cells and mice. Small molecular inhibitors of PARP1, olaparib, and 3-aminobenzamide (3-AB) significantly reduce clinical signs and viral load in the serum and brains of mice and improve survival. PARP1 inhibition confers protection against JEV infection by inhibiting autophagy. Mechanistically, upon JEV infection, PARP1 PARylates AKT and negatively affects its phosphorylation. In addition, PARP1 transcriptionally upregulates PTEN, the PIP3 phosphatase, negatively regulating AKT. PARP1-mediated AKT inactivation promotes autophagy and JEV pathogenesis by increasing the FoxO activity. Thus, our findings demonstrate PARP1 as a potential mediator of JEV pathogenesis that can be effectively targeted for treating JE.
Topics: Child; Humans; Encephalitis, Japanese; Encephalitis Virus, Japanese; Proto-Oncogene Proteins c-akt; Brain; Poly (ADP-Ribose) Polymerase-1
PubMed: 37676769
DOI: 10.1016/j.celrep.2023.113103