Japanese encephalitis#Virology

The Japanese encephalitis virus (JEV) has an incubation period of 2 to 26 days.{{cite journal |last1=Moloney |first1=Rachael M. |last2=Kmush |first2=Brittany |last3=Rudolph |first3=Kara E. |last4=Cummings |first4=Derek A. T. |last5=Lessler |first5=Justin |title=Incubation Periods of Mosquito-Borne Viral Infections: A Systematic Review |journal=The American Journal of Tropical Medicine and Hygiene |date=7 May 2014 |volume=90 |issue=5 |pages=882–891 |doi=10.4269/ajtmh.13-0403 |pmid=24639305 |pmc=4015582}} The vast majority of infections are asymptomatic.{{cite book |first=Johnie A.|last=Yates|editor1-last=Jong |editor1-first=Elaine C. |editor2-last=Stevens |editor2-first=Dennis L. |title=Netter's Infectious Diseases |date=2022 |publisher=Elsevier |location=Philadelphia |isbn=978-0-323-71159-3 |page=419|edition=2nd |chapter-url=https://books.google.com/books?id=l8skEAAAQBAJ&pg=PA419|language=en |chapter=70. Arboviruses of medical importance}} Only 1 in 250 infections develop into encephalitis.{{cite book |last1=Simon |first1=LV |last2=Kruse |first2=B |title=Encephalitis, Japanese |chapter=Japanese Encephalitis |date=January 2018 |pmid=29262148 |url=https://www.ncbi.nlm.nih.gov/books/NBK470423/|publisher=StatPearls }}

Severe rigors may mark the onset of this disease in humans. Fever, headache, and malaise are other non-specific symptoms of this disease which may last for a period of between 1 and 6 days. Signs that develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions, and a raised body temperature between {{convert|38|–|41|C|F|1}}. The mortality rate of the disease is around 25% and is generally higher in children under five, the immuno-suppressed, and the elderly. Transplacental spread has been noted. Neurological disorders develop in 40% of those who survive with lifelong neurological defects such as deafness, emotional lability and hemiparesis occurring in those who had central nervous system involvement.

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Increased microglial activation following Japanese encephalitis infection has been found to influence the outcome of viral pathogenesis. Microglia are the resident immune cells of the central nervous system (CNS) and have a critical role in host defense against invading microorganisms. Activated microglia secrete cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), which can cause toxic effects in the brain. Additionally, other soluble factors such as neurotoxins, excitatory neurotransmitters, prostaglandin, reactive oxygen, and nitrogen species are secreted by activated microglia.{{cite journal| journal=Cytokine | title=Japanese Encephalitis virus infection in astrocytes modulate microglial function: Correlation with inflammation and oxidative stress | url= https://pubmed.ncbi.nlm.nih.gov/37567102/ |date= October 2023 | vauthors=Mohapatra S, Chakraborty T, Basu A| volume=170 | doi=10.1016/j.cyto.2023.156328 | pmid=37567102 }}

In a murine model of JE, it was found that in the hippocampus and the striatum, the number of activated microglia was more than anywhere else in the brain, closely followed by that in the thalamus. In the cortex, the number of activated microglia was significantly less when compared to other regions of the mouse brain. An overall induction of differential expression of proinflammatory cytokines and chemokines from different brain regions during a progressive Japanese encephalitis infection was also observed.{{cite journal | journal=Virol. J. | vauthors=Shukla M, Garg A, Dhole TN, Chaturvedi R | date=2023 | title=Exaggerated levels of some specific TLRs, cytokines and chemokines in Japanese encephalitis infected BV2 and neuro 2A cell lines associated with worst outcome| volume=20 | issue=1 | page=16 | doi=10.1186/s12985-023-01966-8 | doi-access=free | pmid=36707891 | pmc=9881527 }}

Although the net effect of the proinflammatory mediators is to kill infectious organisms and infected cells as well as to stimulate the production of molecules that amplify the mounting response to damage, it is also evident that in a non-regenerating organ such as the brain, a dysregulated innate immune response would be deleterious. In JE the tight regulation of microglial activation appears to be disturbed, resulting in an autotoxic loop of microglial activation that possibly leads to bystander neuronal damage.{{cite journal | last1 = Ghoshal | first1 = A | last2 = Das | first2 = S | last3 = Ghosh | first3 = S | last4 = Mishra | first4 = MK | last5 = Sharma | first5 = V | last6 = Koli | first6 = P | last7 = Sen | first7 = E | last8 = Basu | first8 = A. | year = 2007 | title = Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis | journal = Glia | volume = 55 | issue = 5| pages = 483–96 | doi = 10.1002/glia.20474 | pmid = 17203475 | s2cid = 13192982 | doi-access = free }} In animals, key signs include infertility and abortion in pigs, neurological disease in horses, and systemic signs including fever, lethargy and anorexia.[http://en.wikivet.net/Japanese_Encephalitis_Virus Japanese Encephalitis Virus] {{webarchive|url=https://web.archive.org/web/20130718134013/http://en.wikivet.net/Japanese_Encephalitis_Virus |date=18 July 2013 }} reviewed and published by WikiVet, accessed 11 October 2011.

It is a disease caused by the mosquito-borne Japanese encephalitis virus (JEV).{{cite journal | last1 = Solomon| first1 = T. | year = 2006 | title = Control of Japanese encephalitis – within our grasp? | journal = New England Journal of Medicine| volume = 355 | issue = 9| pages = 869–71 | doi = 10.1056/NEJMp058263 | pmid = 16943399 }}

{{virusbox

| name = Japanese encephalitis virus

| image = Ijms-20-04657-g002.webp

| image_alt =

| image_caption = Flavivirus structure and genome

| parent = Flavivirus

| species = Orthoflavivirus japonicum

}}

JEV is a virus from the family Flaviviridae, part of the Japanese encephalitis serocomplex of nine genetically and antigenically related viruses, some of which are particularly severe in horses, and four of which, including West Nile virus, are known to infect humans.{{cite journal | pmc=3337329 | pmid=22309667 | doi=10.1586/erv.11.180 | volume=11 | issue=2 | title=Feasibility of cross-protective vaccination against flaviviruses of the Japanese encephalitis serocomplex | year=2012 | journal=Expert Rev Vaccines | pages=177–87 |vauthors=Lobigs M, Diamond MS }} The enveloped virus is closely related to the West Nile virus and the St. Louis encephalitis virus. The positive sense single-stranded RNA genome is packaged in the capsid which is formed by the capsid protein. The outer envelope is formed by envelope protein and is the protective antigen. It aids in the entry of the virus into the cell. The genome also encodes several nonstructural proteins (NS1, NS2a, NS2b, NS3, N4a, NS4b, NS5). NS1 is also produced as a secretory form. NS3 is a putative helicase, and NS5 is the viral polymerase. It has been noted that Japanese encephalitis infects the lumen of the endoplasmic reticulum (ER){{cite journal |author=He B |title=Viruses, endoplasmic reticulum stress, and interferon responses |journal=Cell Death Differ. |volume=13 |issue=3 |pages=393–403 |date=March 2006 |pmid=16397582 |doi=10.1038/sj.cdd.4401833 |df=dmy-all |doi-access=free }}{{cite journal |vauthors=Su HL, Liao CL, Lin YL |title=Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response |journal=J. Virol. |volume=76 |issue=9 |pages=4162–71 |date=May 2002 |pmid=11932381 |pmc=155064 |doi=10.1128/JVI.76.9.4162-4171.2002 |df=dmy-all }} and rapidly accumulates substantial amounts of viral proteins.

Based on the envelope gene, there are five genotypes (I–V). The Muar strain, isolated from a patient in Malaya in 1952, is the prototype strain of genotype V. Genotype V is the earliest recognized ancestral strain.{{cite journal | doi=10.1186/s12985-015-0270-z | doi-access=free | title=Insights into the evolutionary history of Japanese encephalitis virus (JEV) based on whole-genome sequences comprising the five genotypes | date=2015 | last1=Gao | first1=Xiaoyan | last2=Liu | first2=Hong | last3=Li | first3=Minghua | last4=Fu | first4=Shihong | last5=Liang | first5=Guodong | journal=Virology Journal | volume=12 | page=43 | pmid=25884184 | pmc=4369081 }} The first clinical reports date from 1870, but the virus appears to have evolved in the mid-16th century. Complete genomes of 372 strains of this virus have been sequenced as of 2024.{{cite web | url=https://www.ncbi.nlm.nih.gov/nuccore/?term=txid11072%5Borganism%3Aexp%5D+AND+genome | date=2024 | title=Japanese encephalitis virus complete genome}}

Japanese encephalitis is diagnosed by commercially available tests detecting JE virus-specific IgM antibodies in serum and/or cerebrospinal fluid, for example by IgM capture ELISA.{{cite journal |vauthors=Shrivastva A, Tripathi NK, Parida M, Dash PK, Jana AM, Lakshmana Rao PV |title=Comparison of a dipstick enzyme-linked immunosorbent assay with commercial assays for detection of Japanese encephalitis virus-specific IgM antibodies |journal=J Postgrad Med |volume=54 |issue=3 |pages=181–5 |year=2008 |pmid=18626163 |doi=10.4103/0022-3859.40959 |df=dmy-all |doi-access=free |hdl=1807/52179 |hdl-access=free }}

JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented. Therefore, positive IgM antibodies occasionally may reflect a past infection or vaccination. Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample. Patients with JE virus IgM antibodies should have confirmatory neutralizing antibody testing.{{Cite journal |last1=Pham |first1=David |last2=Howard-Jones |first2=Annaleise R. |last3=Hueston |first3=Linda |last4=Jeoffreys |first4=Neisha |last5=Doggett |first5=Stephen |last6=Rockett |first6=Rebecca J. |last7=Eden |first7=John-Sebastian |last8=Sintchenko |first8=Vitali |last9=C-A. Chen |first9=Sharon |last10=O'Sullivan |first10=Matthew V. |last11=Maddocks |first11=Susan |last12=Dwyer |first12=Dominic E. |last13=Kok |first13=Jen |date=October 2022 |title=Emergence of Japanese encephalitis in Australia: a diagnostic perspective |journal=Pathology |language=en |volume=54 |issue=6 |pages=669–677 |doi=10.1016/j.pathol.2022.07.001|pmid=35995617 |s2cid=251422417 |doi-access=free }}

Confirmatory testing in the US is available only at the CDC and a few specialized reference laboratories. In fatal cases, nucleic acid amplification and virus culture of autopsy tissues can be useful. Viral antigens can be shown in tissues by indirect fluorescent antibody staining.

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{{Main|Japanese encephalitis vaccine}}

Infection with Japanese encephalitis confers lifelong immunity. There are currently three vaccines available: SA14-14-2, IXIARO (IC51, also marketed in Australia, New Zealand as JESPECT and India as JEEV{{cite web |url=http://pharmabiz.com/NewsDetails.aspx?aid=71186&sid=1 |title=Jeev an inactivated Japanese Encephalitis vaccine launched in Hyderabad |publisher=pharmabiz.com |date=15 September 2012 |access-date=11 January 2013 |url-status=live |archive-url=https://web.archive.org/web/20121023150048/http://pharmabiz.com/NewsDetails.aspx?aid=71186&sid=1 |archive-date=23 October 2012 |df=dmy-all }}) and ChimeriVax-JE (marketed as IMOJEV).{{cite journal |vauthors=Schiøler KL, Samuel M, Wai KL |title=Vaccines for preventing Japanese encephalitis |journal=Cochrane Database Syst Rev |issue=3 |pages=CD004263 |year=2007 |volume=2007 |doi=10.1002/14651858.CD004263.pub2 |pmid=17636750|pmc=6532601 }} All current vaccines are based on the genotype III virus.{{citation needed|date=May 2021}}

A formalin-inactivated mouse-brain-derived vaccine was first produced in Japan in the 1930s and validated for use in Taiwan in the 1960s and Thailand in the 1980s. The widespread use of vaccines and urbanization has led to control of the disease in Japan and Singapore. The high cost of this vaccine, which is grown in live mice, means that poorer countries could not afford to give it as part of a routine immunization program.

The most common adverse effects are redness and pain at the injection site. Uncommonly, an urticarial reaction can develop about four days after injection. Vaccines produced from mouse brain have a risk of autoimmune neurological complications of around 1 per million vaccinations.{{cite journal |author=Jelinek T |s2cid=34671998 |title=Japanese encephalitis vaccine in travelers |journal=Expert Rev Vaccines |volume=7 |issue=5 |pages=689–93 |date=July 2008 |pmid=18564023 |doi=10.1586/14760584.7.5.689}} However where the vaccine is not produced in mouse brains but in vitro using cell culture there are few adverse effects compared to placebo, the main side effects being headache and myalgia.[https://wayback.archive-it.org/all/20120215160622/http://www.emea.europa.eu/pdfs/human/opinion/Ixiaro_66231608en.pdf EMEA Approval of Vaccine]

The neutralizing antibody persists in the circulation for at least two to three years, and perhaps longer.{{cite journal |vauthors=Gambel JM, DeFraites R, Hoke C, et al | year=1995 | title=Japanese encephalitis vaccine: persistence of antibody up to 3 years after a three-dose primary series (letter) | journal=J Infect Dis | volume=171 | issue=4 | page=1074 |pmid=7706798 | doi=10.1093/infdis/171.4.1074| doi-access=free }}{{cite journal |vauthors=Kurane I, Takashi T | year=2000 | title=Immunogenicity and protective efficacy of the current inactivated Japanese encephalitis vaccine against different Japanese encephalitis virus strains | journal=Vaccine | volume=18 |issue=Suppl | pages=33–5 |pmid=10821971 | doi=10.1016/S0264-410X(00)00041-4 }} The total duration of protection is unknown, but because there is no firm evidence for protection beyond three years, boosters are recommended every 11 months for people who remain at risk.{{cite web | url=https://www.mayoclinic.org/drugs-supplements/japanese-encephalitis-virus-vaccine-intramuscular-route/proper-use/drg-20072758 | publisher=Mayo Clinic |title=Japanese Encephalitis Virus Vaccine (Intramuscular Route) | date=2024}} Some data are available regarding the interchangeability of other JE vaccines and IXIARO.{{cite web |date=January 13, 2020 | title=Are Japanese Encephalitis Vaccines Interchangeable? | author=Grant M. Gallagher| url=https://www.contagionlive.com/view/are-japanese-encephalitis-vaccines-interchangeable}}

There is no specific treatment for Japanese encephalitis and treatment is supportive,{{cite journal |vauthors=Solomon T, Dung NM, Kneen R, Gainsborough M, Vaughn DW, Khanh VT | year = 2000 | title = Japanese encephalitis | journal = Journal of Neurology, Neurosurgery, and Psychiatry| volume = 68| issue = 9| pages = 405–15 | doi = 10.1136/jnnp.68.4.405 | pmc = 1736874 | pmid=10727474}} with assistance given for feeding, breathing or seizure control as required. Raised intracranial pressure may be managed with mannitol.{{eMedicine|article|233802|Japanese encephalitis|treatment}} There is no transmission from person to person and therefore patients do not need to be isolated.{{citation needed|date=June 2021}}

A breakthrough in the field of Japanese encephalitis therapeutics is the identification of macrophage receptor involvement in the disease severity. A recent report of an Indian group demonstrates the involvement of monocyte and macrophage receptor CLEC5A in severe inflammatory response in Japanese encephalitis infection of the brain. This transcriptomic study provides a hypothesis of neuroinflammation and a new lead in development of appropriate therapies for Japanese encephalitis.{{cite journal |author1=Nimesh Gupta |author2=Vinay Lomash |author3=P.V. Lakshmana Rao |title=Expression profile of Japanese encephalitis virus-induced neuroinflammation and its implication in disease severity |journal=Journal of Clinical Virology|volume= 49|issue= 1|pages= 04–10|date=September 2010 |pmid=20637688 |doi=10.1016/j.jcv.2010.06.009 }}{{cite journal |author1=Nimesh Gupta |author2=P.V. Lakshmana Rao |title=Transcriptomic profile of host response in Japanese encephalitis virus infection |journal= Virology Journal|volume= 8|issue= 92|date=March 2011 |pmid=21371334|doi=10.1186/1743-422X-8-92 |page=92 |pmc=3058095 |doi-access=free }}

The effectiveness of intravenous immunoglobulin for Japanese encephalitis is unclear due to a paucity of evidence.{{Cite journal|last1=Iro|first1=Mildred A.|last2=Martin|first2=Natalie G.|last3=Absoud|first3=Michael|last4=Pollard|first4=Andrew J.|date=2017-10-02|title=Intravenous immunoglobulin for the treatment of childhood encephalitis|journal=The Cochrane Database of Systematic Reviews|volume=2017|issue=10 |pages=CD011367|doi=10.1002/14651858.CD011367.pub2|issn=1469-493X|pmc=6485509|pmid=28967695}} Intravenous immunoglobulin for Japanese encephalitis appeared to have no benefit.

File:Japanese encephalitis world map - DALY - WHO2002.svg for Japanese encephalitis per 100,000 inhabitants in 2002{{Div col|small=yes|colwidth=10em}}

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Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, with up to 70,000 cases reported annually.{{cite journal |vauthors=Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, Marfin AA, Solomon T, Tsai TF, Tsu VD, Ginsburg AS |title=Estimmated global incidence of Japanese encephalitis: a systematic review |journal=Bull World Health Organ |volume=89 |issue=10 |pages=766–74 |date=November 2011 |pmid=22084515 |pmc=3209971 |doi=10.2471/BLT.10.085233}} Of those with symptoms case-fatality rates range from 20% to 30%.{{cite web |date=2024 |title=Japanese Encephalitis - Chapter 4 - 2024 Yellow Book {{!}} Travelers' Health {{!}} CDC |url=https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/japanese-encephalitis |archive-url=https://web.archive.org/web/20250320143845/https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/japanese-encephalitis |archive-date=20 March 2025 |access-date=20 March 2025 |website=wwwnc.cdc.gov |language=en-us}} Rare outbreaks in U.S. territories in the Western Pacific have also occurred. Residents of rural areas in endemic locations are at highest risk; Japanese encephalitis does not usually occur in urban areas.

Countries that have had major epidemics in the past, but which have controlled the disease primarily by vaccination, include China, South Korea, Singapore, Japan, Taiwan and Thailand. Other countries that still have periodic epidemics include Vietnam, Cambodia, Myanmar, India, Nepal, and Malaysia. Japanese encephalitis has been reported in the Torres Strait Islands, and two fatal cases were reported in mainland northern Australia in 1998. There were reported cases in Kachin State, Myanmar in 2013. There were 116 deaths reported in Odisha's Malkangiri district of India in 2016.{{citation needed|date=June 2022}}

In 2022, the notable increase in the distribution of the virus in Australia due to climate change became a concern to health officials as the population has limited immunity to the disease and the presence of large numbers of farmed and feral pigs could act as reservoirs for the virus.{{cite news |last1=Davey |first1=Melissa |title=What is Japanese encephalitis and why is it spreading in Australia? |url=https://www.theguardian.com/australia-news/2022/mar/08/what-is-japanese-encephalitis-and-why-is-it-spreading-in-australia |access-date=20 October 2022 |agency=The Guardian Australia |date=8 March 2022}} In February 2022, Japanese encephalitis was detected and confirmed in piggeries in Victoria, Queensland and New South Wales. On 4 March, cases were detected in South Australia. By October 2022, the outbreak in eastern mainland Australia had caused 42 symptomatic human cases of the disease, resulting in seven deaths. In 2025, further cases and a fatality were recorded in south-eastern Australia.{{cite web |vauthors=((Australian Government Department of National pest & disease outbreaks)) |title=Japanese encephalitis |url=https://www.outbreak.gov.au/current-responses-to-outbreaks/japanese-encephalitis |date=March 2022 }}{{cite web |title=Japanese encephalitis virus |url=https://www.health.gov.au/health-alerts/japanese-encephalitis-virus-jev/about |publisher=Australian Government Department of Health and Aged Care |access-date=20 October 2022}}{{cite news |title=Sydney man dies after contracting Japanese encephalitis in Murrumbidgee region |url=https://www.abc.net.au/news/2025-02-25/sydney-man-dies-japanese-encephalitis-mosquito/104979634 |access-date=25 February 2025 |agency=ABC News |date=25 February 2025}}

Humans, cattle, and horses are dead-end hosts as the disease manifests as fatal encephalitis. Pigs act as amplifying hosts and have a vital role in the epidemiology of the disease. Infection in swine is asymptomatic, except in pregnant sows when abortion and fetal abnormalities are common sequelae. The most important vector is Culex tritaeniorhynchus, which feeds on cattle in preference to humans. The natural hosts of the Japanese encephalitis virus are birds, not humans, and many believe the virus will never be eliminated.{{cite journal |vauthors=Ghosh D, Basu A |title=Japanese encephalitis-a pathological and clinical perspective |journal=PLOS Negl Trop Dis |volume=3 |issue=9 |pages=e437 |date=September 2009 |pmid=19787040 |pmc=2745699 |doi=10.1371/journal.pntd.0000437 |editor1-last=Brooker |editor1-first=Simon |doi-access=free }} In November 2011, the Japanese encephalitis virus was reported in Culex bitaeniorhynchus in South Korea.{{cite journal | author = Kim, Heung Chul | author2 = Terry A. Klein | author3 = Ratree Takhampunya | author4 = Brian P. Evans | author5 = Sirima Mingmongkolchai | author6 = Ampornpan Kengluecha | author7 = John Grieco | author8 = Penny Masuoka | author9 = Myung-Soon Kim | author10 = Sung-Tae Chong | author11 = Jong-Koo Lee | author12 = Won-Ja Lee | name-list-style = amp | year = 2011 | title = Japanese Encephalitis Virus in Culicine Mosquitoes (Diptera: Culicidae) Collected at Daeseongdong, a Village in the Demilitarized Zone of the Republic of Korea | journal = Journal of Medical Entomology | volume = 48 | issue = 6| pages = 1250–1256 | doi=10.1603/me11091| pmid = 22238887 | s2cid = 23321660 | doi-access = }}

Recently, whole genome microarray research of neurons infected with the Japanese encephalitis virus has shown that neurons play an important role in their own defense against Japanese encephalitis infection. Although this challenges the long-held belief that neurons are immunologically quiescent, an improved understanding of the proinflammatory effects responsible for immune-mediated control of viral infection and neuronal injury during Japanese encephalitis infection is an essential step for developing strategies for limiting the severity of CNS disease.{{cite journal |author1=Nimesh Gupta |author2=S.R. Santhosh |author3=J. Pradeep Babu |author4=M.M. Parida |author5=P.V. Lakshmana Rao |title=Chemokine profiling of Japanese encephalitis virus-infected mouse neuroblastoma cells by microarray and real-time RT-PCR: Implication in neuropathogenesis |journal=Virus Research|volume= 147|issue= 1|pages= 107–12|date=January 2010 |pmid=19896511 |doi=10.1016/j.virusres.2009.10.018 |pmc=7126115 }}

A number of drugs have been investigated to either reduce viral replication or provide neuroprotection in cell lines or studies in mice. None are currently advocated in treating human patients.

• The use of rosmarinic acid,{{cite journal |vauthors=Swarup V, Ghosh J, Ghosh S, Saxena A, Basu A |title=Antiviral and anti-inflammatory effects of rosmarinic acid in an experimental murine model of Japanese encephalitis |journal=Antimicrob. Agents Chemother. |volume=51 |issue=9 |pages=3367–70 |date=September 2007 |pmid=17576830 |pmc=2043228 |doi=10.1128/AAC.00041-07 }} arctigenin,{{cite journal |vauthors=Swarup V, Ghosh J, Mishra MK, Basu A |title=Novel strategy for treatment of Japanese encephalitis using arctigenin, a plant lignan |journal=J. Antimicrob. Chemother. |volume=61 |issue=3 |pages=679–88 |date=March 2008 |pmid=18230688 |doi=10.1093/jac/dkm503 |df=dmy-all |doi-access=free }} and oligosaccharides with degree of polymerization 6 from Gracilaria sp. or Monostroma nitidum{{cite journal |vauthors=Kazłowski B, Chiu YH, Kazłowska K, Pan CL, Wu CJ |title=Prevention of Japanese encephalitis virus infections by low-degree-polymerisation sulfated saccharides from Gracilaria sp. and Monostroma nitidum |journal=Food Chem |volume=133 |issue=3 |pages=866–74 |date=August 2012 |doi=10.1016/j.foodchem.2012.01.106 }} is effective in a mouse model of Japanese encephalitis.
• Curcumin has been shown to impart neuroprotection against Japanese encephalitis infection in an in vitro study. Curcumin possibly acts by decreasing cellular reactive oxygen species levels, restoration of cellular membrane integrity, decreasing pro-apoptotic signaling molecules, and modulating cellular levels of stress-related proteins. It has also been shown that the production of infective viral particles from previously infected neuroblastoma cells is reduced, which is achieved by inhibition of the ubiquitin-proteasome system.{{cite journal |vauthors=Dutta K, Ghosh D, Basu A |s2cid=24691000 |title=Curcumin Protects Neuronal Cells from Japanese Encephalitis Virus-Mediated Cell Death and also Inhibits Infective Viral Particle Formation by Dysregulation of Ubiquitin-Proteasome System |journal=J Neuroimmune Pharmacol |volume= 4|issue= 3|pages= 328–37|date=May 2009 |pmid=19434500 |doi=10.1007/s11481-009-9158-2 }}
• Minocycline in mice resulted in marked decreases in the levels of several markers, viral titer, and the level of proinflammatory mediators{{cite journal |vauthors=Mishra MK, Basu A |title=Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis |journal=J. Neurochem. |volume=105 |issue=5 |pages=1582–95 |date=June 2008 |pmid=18208541 |doi=10.1111/j.1471-4159.2008.05238.x |s2cid=205618838 |doi-access=free }} and also prevented blood–brain barrier damage.{{cite journal |vauthors=Mishra MK, Dutta K, Saheb SK, Basu A |s2cid=26964251 |title=Understanding the molecular mechanism of blood–brain barrier damage in an experimental model of Japanese encephalitis: correlation with minocycline administration as a therapeutic agent |journal=Neurochem Int |volume=55 |issue=8 |pages=717–23 |date=December 2009 |pmid=19628016 |doi=10.1016/j.neuint.2009.07.006 }}

It is theorized that the virus may have originated from an ancestral virus in the mid-1500s in the Malay Archipelago region and evolved there into five different genotypes that spread across Asia.{{cite journal |vauthors=Mohammed MA, Galbraith SE, Radford AD, Dove W, Takasaki T, Kurane I, Solomon T |title=Molecular phylogenetic and evolutionary analyses of Muar strain of Japanese encephalitis virus reveal it is the missing fifth genotype |journal=Infect Genet Evol |volume=11 |issue=5 |pages=855–62 |date=July 2011 |doi=10.1016/j.meegid.2011.01.020 |pmid=21352956|bibcode=2011InfGE..11..855M }} The mean evolutionary rate has been estimated to be 4.35{{e|−4}} (range: 3.49{{e|−4}} to 5.30{{e|−4}}) nucleotide substitutions per site per year.

The clinical recognition and recording of Japanese encephalitis (JE) trace back to the 19th century when recurring encephalitis outbreaks were noted during Japan’s summer months. The first clinical case of JE was documented in 1871 in Japan. However, it wasn’t until 1924, during a major outbreak involving over 6,000 cases, that JE’s severity and potential for widespread impact became apparent. Subsequent outbreaks in Japan were recorded in 1927, 1934, and 1935, each contributing to a deeper understanding of the disease and its transmission patterns. The spread of JE extended beyond Japan over the following decades, impacting numerous countries across Asia. On the Korean Peninsula, the first JE cases were reported in 1933, and mainland China documented its initial cases in 1940. The virus reached the Philippines in the early 1950s and continued its westward spread, with Pakistan recording cases in 1983, marking JE’s furthest westward extension. By 1995, JE cases had reached Papua New Guinea and northern Australia (specifically the Torres Strait), representing the virus's southernmost range. According to the World Health Organization (WHO), JE is also endemic to the Western Pacific Islands, but cases are rare, possibly due to an enzootic cycle that does not sustain continuous viral transmission. Epidemics in these islands likely occur only when the virus is introduced from other JE-endemic regions. In the early 2020s, JE had become endemic in the southern parts of Australia with locally contracted human fatalities from the disease being recorded in these areas for the first time.{{Cite journal |last1=Erlanger |first1=Tobias E. |last2=Weiss |first2=Svenja |last3=Keiser |first3=Jennifer |last4=Utzinger |first4=Jürg |last5=Wiedenmayer |first5=Karin |date=January 2009 |title=Past, Present, and Future of Japanese Encephalitis |url=http://wwwnc.cdc.gov/eid/article/15/1/08-0311_article.htm |journal=Emerging Infectious Diseases |volume=15 |issue=1 |pages=1–7 |doi=10.3201/eid1501.080311 |issn=1080-6040 |pmc=2660690 |pmid=19116041}}{{cite news |last1=Fernando |first1=Manisha |title=Japanese encephalitis virus spreads to new areas |url=https://www1.racgp.org.au/newsgp/clinical/japanese-encephalitis-virus-spreads-to-new-areas |access-date=25 February 2025 |agency=newsGP |publisher=RACGP |date=10 January 2025}}

{{reflist}}

{{Portal|Japan|Viruses}}

{{refbegin}}

• {{cite web |title=Questions and Answers About Japanese Encephalitis |date=8 February 2019 |publisher=Centers for Disease Control and Prevention |url=https://www.cdc.gov/japaneseencephalitis/}}
• {{cite web |title=Japanese Encephalitis |date=2012 |publisher=Australian government Department of Health and Aging |url=http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-surveil-nndss-casedefs-cd_je.htm }}
• {{cite book |chapter=20. Japanese encephalitis |chapter-url=https://www.gov.uk/government/publications/japanese-encephalitis-the-green-book-chapter-20 |editor-first=Mary |editor-last=Ramsay |title=Immunisation against infectious disease |publisher=Public Health England |date=2020 |url=https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book |series=Green Book}}
• {{cite web |title=Japanese encephalitis resource library |date= |publisher= |url=http://www.path.org/vaccineresources/japanese-encephalitis.php}}
• {{cite journal |vauthors=Heffelfinger JD, Li X, Batmunkh N, Grabovac V, Diorditsa S, Liyanage JB, Pattamadilok S, Bahl S, Vannice KS, Hyde TB, Chu SY, Fox KK, Hills SL, Marfin AA |title=Japanese Encephalitis Surveillance and Immunization — Asia and Western Pacific Regions, 2016 |journal=MMWR Morb Mortal Wkly Rep |volume=66 |issue=22 |pages=579–583 |date=9 June 2017 |doi=10.15585/mmwr.mm6622a3 |pmid=28594790 |pmc=5720240 }} Erratum in: MMWR Morb Mortal Wkly Rep. 2017 Jun 23;66(24):653.
• {{cite book |last1=Simon |first1=LV |last2=Kruse |first2=B |title=Encephalitis, Japanese |chapter=Japanese Encephalitis |date=January 2018 |pmid=29262148 |url=https://www.ncbi.nlm.nih.gov/books/NBK470423/ |publisher=StatPearls Publishing |location=FL |id=NBK470423}}

{{refend}}

{{Medical resources

| DiseasesDB = 7036

| ICD11 = {{ICD11|1C85}}

| ICD10 = {{ICD10|A|83|0|a|80}}

| ICD9 = {{ICD9|062.0}}

| ICDO =

| OMIM =

| MedlinePlus =

| eMedicineSubj = med

| eMedicineTopic = 3158

| MeshID = D004672

| Orphanet = 79139

}}

{{Taxonbar|from1=Q738292|from2=Q19838331}}

{{Zoonotic viral diseases}}

{{Use dmy dates|date=April 2017}}

{{DEFAULTSORT:Japanese Encephalitis}}

Category:Swine diseases

Category:Tropical diseases

Category:Viral encephalitis

Category:Wikipedia medicine articles ready to translate

Category:Vaccine-preventable diseases