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Expert Opinion on Biological Therapy Aug 2018Japanese encephalitis is the most common vaccine-preventable encephalitis in the Asia-Pacific region. (Review)
Review
INTRODUCTION
Japanese encephalitis is the most common vaccine-preventable encephalitis in the Asia-Pacific region.
AREAS COVERED
We provide an overview on Japanese encephalitis virus and associated disease, review the results of studies on the immunogenicity and efficacy of the licensed vaccines, and describe the new vaccines that are under development. We also discuss data on candidate anti-Japanese encephalitis drugs that have shown promising results in experimental models.
EXPERT OPINION
The global burden of the Japanese encephalitis and associated mortality is still high, thus emphasizing the need to achieve the highest vaccination coverage in endemic areas. Clinical trials exhaustively demonstrated the safety and efficacy of current Japanese encephalitis vaccines. In addition, several new vaccine candidates, characterized by high immunogenicity and broad cross-protection, have been developed and evaluated in experimental models, warranting further clinical testing. No licensed anti-Japanese encephalitis drugs are available, notwithstanding intense research efforts. Some candidate antiviral agents that inhibit viral entry and replication have been identified, including compounds with broad-spectrum antiviral activity. Further research is needed to refine candidate compounds into drugs suitable for clinical evaluation, characterized by low toxicity, ability to penetrate the blood-brain barrier, activity during the late phase of infection, and high genetic barrier to resistance.
Topics: Antiviral Agents; Asia; Biological Therapy; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines
PubMed: 29991325
DOI: 10.1080/14712598.2018.1499721 -
Medical and Veterinary Entomology Dec 2023In Southeast Asia, despite the use of Japanese encephalitis vaccines and vaccination coverage, Japanese encephalitis (JE) transmission is still a major public health...
In Southeast Asia, despite the use of Japanese encephalitis vaccines and vaccination coverage, Japanese encephalitis (JE) transmission is still a major public health issue. The main vectors of this virus are mosquitoes from the genus Culex, which diversity and density are important in Southeast Asia. The main vector species of Japanese encephalitis virus (JEV) in Cambodia belong to the Vishnui subgroup. However, their morphological identification solely based on the adult stage remains challenging, making their segregation and detection difficult. In order to identify and describe the distribution of the three main JEV vector species in Cambodia, namely Culex vishnui, Cx. pseudovishnui and Cx. tritaeniorhynchus, mosquito samplings were carried out throughout the country in different environments. Phylogenetic analysis of the cytochrome c oxidase subunit I (coI) gene using maximum-likelihood tree with ultrafast bootstrap and phylogeographic analysis were performed. The three main Culex species are phylogenetically separated, and represent two distinct clades, one with Cx. tritaeniorhynchus and the second with Cx. vishnui and Cx. pseudovishnui, the latter appearing as a subgroup of Cx. vishnui. The phylogeographic analysis shows a distribution of the Vishnui subgroup on the entire Cambodian territory with an overlapped distribution areas leading to a sympatric distribution of these species. The three JEV vector species are geographically well-defined with a strong presence of Cx. pseudovishnui in the forest. Combined with the presence of Cx. tritaeniorhynchus and Cx. vishnui in rural, peri-urban, and urban areas, the presence of JEV-competent vectors is widespread in Cambodia.
Topics: Animals; Encephalitis Virus, Japanese; Phylogeny; Cambodia; Encephalitis, Japanese; Culicidae; Culex; Mosquito Vectors
PubMed: 37404158
DOI: 10.1111/mve.12678 -
Nature Reviews. Neurology Apr 2018Japanese encephalitis is a mosquito-borne disease that occurs in Asia and is caused by Japanese encephalitis virus (JEV), a member of the genus Flavivirus. Although many... (Review)
Review
Japanese encephalitis is a mosquito-borne disease that occurs in Asia and is caused by Japanese encephalitis virus (JEV), a member of the genus Flavivirus. Although many flaviviruses can cause encephalitis, JEV causes particularly severe neurological manifestations. The virus causes loss of more disability-adjusted life years than any other arthropod-borne virus owing to the frequent neurological sequelae of the condition. Despite substantial advances in our understanding of Japanese encephalitis from in vitro studies and animal models, studies of pathogenesis and treatment in humans are lagging behind. Few mechanistic studies have been conducted in humans, and only four clinical trials of therapies for Japanese encephalitis have taken place in the past 10 years despite an estimated incidence of 69,000 cases per year. Previous trials for Japanese encephalitis might have been too small to detect important benefits of potential treatments. Many potential treatment targets exist for Japanese encephalitis, and pathogenesis and virological studies have uncovered mechanisms by which these drugs could work. In this Review, we summarize the epidemiology, clinical features, prevention and treatment of Japanese encephalitis and focus on potential new therapeutic strategies, based on repurposing existing compounds that are already suitable for human use and could be trialled without delay. We use our newly improved understanding of Japanese encephalitis pathogenesis to posit potential treatments and outline some of the many challenges that remain in tackling the disease in humans.
Topics: Animals; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans
PubMed: 29697099
DOI: 10.1038/nrneurol.2018.30 -
Pharmacological Reports : PR Apr 2022Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV) is one of Asia's most common viral encephalitis. JEV is a flavivirus, common in rural and... (Review)
Review
Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV) is one of Asia's most common viral encephalitis. JEV is a flavivirus, common in rural and sub-urban regions of Asian countries. Although only 1% of JEV-infected individuals develop JE, there is a 20-30% chance of death among these individuals and possible neurological sequelae post-infection. No licensed anti-JE drugs are currently available, despite extensive efforts to develop them. Literature search was performed using databases such as PubMed Central, Google Scholar, Wiley Online Library, etc. using keywords such as Japanese encephalitis virus, antiviral drugs, antiviral drug screening, antiviral drug targets, etc. From around 230 papers/abstracts and research reviews retrieved and reviewed for this study, approximately 180 most relevant and important ones have been cited. Different approaches in drug testing and various antiviral drug targets explored so far have been thoroughly searched from the literature and compiled, besides addressing the future perspectives of the antiviral drug development strategies. Although the development of effective anti-JE drugs is an urgent issue, only supportive care is currently available. Recent advancements in understanding the biology of infection and new drug targets have been promising improvements. Despite hindrances such as the unavailability of a proper drug delivery system or a treatment regimen irrespective of the stage of infection, several promising anti-JE candidate molecules are in different phases of clinical trials. Nonetheless, efficient therapy against JEV is expected to be achieved with drug combinations and a highly targeted drug delivery system soon.
Topics: Antiviral Agents; Drug Evaluation, Preclinical; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans
PubMed: 35182390
DOI: 10.1007/s43440-022-00355-2 -
Viruses Oct 2022In the last three decades, several flaviviruses of concern that belong to different antigenic groups have expanded geographically. This has resulted in the presence of... (Review)
Review
In the last three decades, several flaviviruses of concern that belong to different antigenic groups have expanded geographically. This has resulted in the presence of often more than one virus from a single antigenic group in some areas, while in Europe, Africa and Australia, additionally, multiple viruses belonging to the Japanese encephalitis (JE) serogroup co-circulate. Morphological heterogeneity of flaviviruses dictates antibody recognition and affects virus neutralization, which influences infection control. The latter is further impacted by sequential infections involving diverse flaviviruses co-circulating within a region and their cross-reactivity. The ensuing complex molecular virus-host interplay leads to either cross-protection or disease enhancement; however, the molecular determinants and mechanisms driving these outcomes are unclear. In this review, we provide an overview of the epidemiology of four JE serocomplex viruses, parameters affecting flaviviral heterogeneity and antibody recognition, host immune responses and the current knowledge of the cross-reactivity involving JE serocomplex flaviviruses that leads to differential clinical outcomes, which may inform future preventative and therapeutic interventions.
Topics: Humans; Encephalitis Viruses, Japanese; Encephalitis, Japanese; Flavivirus; Cross Reactions; Europe; Encephalitis Virus, Japanese; Antibodies, Viral; West Nile virus
PubMed: 36298768
DOI: 10.3390/v14102213 -
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 -
Journal of Vector Borne Diseases 2022Japanese encephalitis (JE) is a very serious public health problem in India and the conducive environment permit its emergence in non-endemic areas in the country. There... (Review)
Review
Japanese encephalitis (JE) is a very serious public health problem in India and the conducive environment permit its emergence in non-endemic areas in the country. There are constant changes taking place in the pattern of current agricultural practices and vector breeding habitats which had far-reaching consequences on the epidemiology of JE and the severity of epidemic outbreaks today. Due to the continuous ecological changes taking place, vectors changed in their breeding dynamics, feeding, and resting behavior and started invading previously non-endemic areas. JE has recently spread to new territories due to land-use changes, including forest fragmentation and concentrated livestock production. Changes in the livestock population decreased the cattle pig ratio which enhanced the Japanese encephalitis virus (JEV) infection. This review brings forth the present widespread changes encountered that grossly impact the risk of infection in many places for the emergence of Japanese encephalitis and to address the implications for its control.
Topics: Animals; Swine; Cattle; Encephalitis, Japanese; Seasons; Encephalitis Virus, Japanese; India; Disease Outbreaks
PubMed: 36751762
DOI: 10.4103/0972-9062.345180 -
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 -
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 -
Viruses Feb 2021Japanese encephalitis (JE) is a vaccine-preventable disease caused by the Japanese encephalitis virus (JEV), which is primarily prevalent in Asia. JEV is a Flavivirus,... (Review)
Review
Japanese encephalitis (JE) is a vaccine-preventable disease caused by the Japanese encephalitis virus (JEV), which is primarily prevalent in Asia. JEV is a Flavivirus, classified into a single serotype with five genetically distinct genotypes (I, II, III, IV, and V). JEV genotype III (GIII) had been the most dominant strain and caused numerous outbreaks in the JEV endemic countries until 1990. However, recent data shows the emergence of JEV genotype I (GI) as a dominant genotype and it is gradually displacing GIII. The exact mechanism of this genotype displacement is still unclear. The virus can replicate in mosquito vectors and vertebrate hosts to maintain its zoonotic life cycle; pigs and aquatic wading birds act as an amplifying/reservoir hosts, and the humans and equines are dead-end hosts. The important role of pigs as an amplifying host for the JEV is well known. However, the influence of other domestic animals, especially birds, that live in high abundance and close proximity to the human is not well studied. Here, we strive to briefly highlight the role of birds in the JEV zoonotic transmission, discovery of birds as a natural reservoirs and amplifying host for JEV, species of birds susceptible to the JEV infection, and the proposed effect of JEV on the poultry industry in the future, a perspective that has been neglected for a long time. We also discuss the recent in vitro and in vivo studies that show that the newly emerged GI viruses replicated more efficiently in bird-derived cells and ducklings/chicks than GIII, and an important role of birds in the JEV genotype shift from GIII to GI.
Topics: Animals; Birds; Encephalitis Virus, Japanese; Encephalitis, Japanese; Genotype; Humans; Mosquito Vectors
PubMed: 33668224
DOI: 10.3390/v13030357