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Human Vaccines & Immunotherapeutics 2015Japanese encephalitis virus, as the most important vaccine-preventable cause of viral encephalitis in Asia, is estimated to cause over 68,000 clinical cases yearly. In... (Review)
Review
Japanese encephalitis virus, as the most important vaccine-preventable cause of viral encephalitis in Asia, is estimated to cause over 68,000 clinical cases yearly. In endemic areas, most Japanese encephalitis infections occur in children younger than 10 y and clinical manifestation of this disease is critical, because there is no effective treatment available. As JEV infections are regarded as one of the most serious viral causes of encephalitis and mass immunization programmes are generally recommended for residents in endemic areas, a safe and effective JEV vaccine was needed to protect them as well as others at risk. Due to the safety concerns with the mouse brain derived vaccine, second generation vaccines against JE produced in cell culture like Vero cells were developed. IXIARO® is a purified, inactivated aluminum-adjuvanted JE vaccine, based on the SA14-14-2 virus strain, and is available in North America, Europe, Canada, Switzerland, Singapore, Hong Kong and Israel as well as in Australia & New Zealand (as JESPECT®).The safety, tolerability and immunogenicity profile of IXIARO® is well established through a number of clinical studies comparing IXIARO® with placebo as well as mouse brain derived vaccine. Recent data show that the global incidence of JE remains substantial, especially young children in endemic areas are most susceptible. As vaccination is the most feasible, reliable and cost effective tool for JE control, IXIARO® with confirmed excellent safety profile is highly recommendable, in particular for vaccination of children at risk. The European Commission as well as the FDA approved the extension of indication of IXIARO® to the pediatric segment (2 months of age and older) based on these data.
Topics: Adjuvants, Immunologic; Alum Compounds; Clinical Trials as Topic; Drug Approval; Drug-Related Side Effects and Adverse Reactions; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Vaccines, Inactivated
PubMed: 25621812
DOI: 10.4161/21645515.2014.983412 -
PLoS Neglected Tropical Diseases May 2022Japanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Over the years, efforts in JE treatment and control might...
BACKGROUND
Japanese Encephalitis (JE) is known for its high case fatality ratio (CFR) and long-term neurological sequelae. Over the years, efforts in JE treatment and control might change the JE fatality risk. However, previous estimates were from 10 years ago, using data from cases in the 10 years before this. Estimating JE disease severity is challenging because data come from countries with different JE surveillance systems, diagnostic methods, and study designs. Without precise and timely JE disease severity estimates, there is continued uncertainty about the JE disease burden and the effect of JE vaccination.
METHODOLOGY
We performed a systematic review to collate age-stratified JE fatality and morbidity data. We used a stepwise model selection with BIC as the selection criteria to identify JE CFR drivers. We used stacked regression, to predict country-specific JE CFR from 1961 to 2030. JE morbidity estimates were grouped from similar study designs to estimate the proportion of JE survivors with long-term neurological sequelae.
PRINCIPAL FINDINGS
We included 82 and 50 peer-reviewed journal articles published as of March 06 2021 for JE fatality and morbidity with 22 articles in both analyses. Results suggested overall JE CFR estimates of 26% (95% CI 22, 30) in 1961-1979, 20% (95% CI 17, 24) in 1980-1999, 14% (95% CI 11, 17) in 2000-2018, and 14% (95% CI 11, 17) in 2019-2030. Holding other variables constant, we found that JE fatality risk decreased over time (OR: 0.965; 95% CI: 0.947-0.983). Younger JE cases had a slightly higher JE fatality risk (OR: 1.012; 95% CI: 1.003-1.021). The odds of JE fatality in countries with JE vaccination is 0.802 (90% CI: 0.653-0.994; 95% CI: 0.62-1.033) times lower than the odds in countries without JE vaccination. Ten percentage increase in the percentage of rural population to the total population was associated with 15.35% (95% CI: 7.71, 22.57) decrease in JE fatality odds. Ten percentage increase in population growth rate is associated with 3.71% (90% CI: 0.23, 7.18; 95% CI: -0.4, 8.15) increase in JE fatality odds. Adjusting for the effect of year, rural population percent, age of JE cases, and population growth rate, we estimated that there was a higher odds of JE fatality in India compared to China. (OR: 5.46, 95% CI: 3.61-8.31). Using the prediction model we found that, in 2000-2018, Brunei, Pakistan, and Timor-Leste were predicted to have the highest JE CFR of 20%. Bangladesh, Guam, Pakistan, Philippines, and Vietnam had projected JE CFR over 20% for after 2018, whereas the projected JE CFRs were below 10% in China, Indonesia, Cambodia, Myanmar, Malaysia, and Thailand. For disability, we estimated that 36% (min-max 0-85) JE patients recovered fully at hospital discharge. One year after hospital discharge, 46% (min-max 0%-97%) JE survivors were estimated to live normally but 49% (min-max 3% - 86%)till had neurological sequelae.
CONCLUSION
JE CFR estimates were lower than 20% after 2000. Our study provides an updated estimation of CFR and proportion of JE cases with long-term neurological sequelae that could help to refine cost-benefit assessment for JE control and elimination programs.
Topics: China; Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Morbidity; Philippines; Thailand
PubMed: 35613183
DOI: 10.1371/journal.pntd.0010361 -
Brain and Behavior Feb 2022Japanese encephalitis (JE) is a potentially fatal viral infection with a wide range of manifestations and can also present with a variety of movement disorders (MD)... (Review)
Review
BACKGROUND
Japanese encephalitis (JE) is a potentially fatal viral infection with a wide range of manifestations and can also present with a variety of movement disorders (MD) including dystonia. Dystonic features in JE are uncommon. Here, we have tried to summarize the clinical features and management of dystonia among JE patients with a comprehensive literature search.
METHODS
Various databases, including PubMed, Embase, and Google Scholar, were searched against the predefined criteria using suitable keywords combination and boolean operations. Relevant information from observational and case studies was extracted according to the author, dystonic features, radiological changes in the brain scans, treatment options, and outcome wherever provided.
RESULT
We identified 19 studies with a total of 1547 JE patients, the diagnosis of which was confirmed by IgM detection in serum and/or cerebrospinal fluid in the majority of the patients (88.62%). 234 (15.13%) of JE patients had dystonia with several types of focal dystonia being present in 131 (55.98%) either alone or in combination. Neuroimaging showed predominant involvement of thalami, basal ganglia, and brainstem. Oral medications including anticholinergics, GABA agonists, and benzodiazepines followed by botulinum toxin were the most common treatment modalities.
CONCLUSION
Dystonia can be a disabling consequence of JE, and various available medical therapies can significantly improve the quality of life. Owing to insufficient studies on the assessment of dystonia associated with JE, longitudinal studies with a larger number of patients are warranted to further clarify the clinical course, treatment, and outcome of dystonia.
Topics: Dystonia; Dystonic Disorders; Encephalitis, Japanese; Humans; Movement Disorders; Quality of Life
PubMed: 35025122
DOI: 10.1002/brb3.2496 -
Vector Borne and Zoonotic Diseases... Nov 2022Japanese encephalitis virus (JEV) continues to cause significant numbers of human infections and fatalities despite the availability of efficacious vaccines. It is... (Review)
Review
Japanese encephalitis virus (JEV) continues to cause significant numbers of human infections and fatalities despite the availability of efficacious vaccines. It is regarded as an emerging mosquito-borne pathogen with the potential of introduction into many countries. In 2022, JEV was detected in Australia on a hitherto unprecedented scale, with local transmission by indigenous mosquitoes to amplifying swine hosts and to humans. In this study, we review this recent disease activity, propose possible routes of virus movement, ecological drivers of activity, and consider possible future transmission scenarios. Measures to enhance current surveillance systems and potential strategies for health authorities to minimize future risks are discussed.
Topics: Animals; Humans; Australia; Culex; Culicidae; Encephalitis Virus, Japanese; Encephalitis, Japanese; Public Health; Swine; Swine Diseases
PubMed: 36354964
DOI: 10.1089/vbz.2022.0037 -
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 -
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 -
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 Infection in Developing... Sep 2015Japanese encephalitis (JE) is a serious arboviral disease caused by a virus of the genus Flavivirus. Japanese encephalitis is the most common vaccine-preventable virus... (Review)
Review
Japanese encephalitis (JE) is a serious arboviral disease caused by a virus of the genus Flavivirus. Japanese encephalitis is the most common vaccine-preventable virus causing encephalitis in Asia, affecting more than 50,000 persons and leading to 15,000 fatalities per year in endemic countries. For most travelers to Asia, the risk of Japanese encephalitis infection is extremely low and depends on destination, duration of travel, season, and activities. This article reviews travel-acquired Japanese encephalitis with a focus on epidemiology and prevention in the light of the newly available options for active immunization against Japanese encephalitis which have become available, and of the increasing popularity of travels to Japanese encephalitis endemic countries.
Topics: Asia; Encephalitis, Japanese; Endemic Diseases; Humans; Japanese Encephalitis Vaccines; Travel; Vaccination
PubMed: 26409731
DOI: 10.3855/jidc.5108 -
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 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