Editing Japanese encephalitis (section)

==Signs and symptoms==

The Japanese encephalitis virus (JEV) has an [[incubation period]] of 2 to 26 days.<ref>{{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}}</ref> The vast majority of infections are [[asymptomatic]].<ref name=Jong2022>{{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}}</ref> Only 1 in 250 infections develop into encephalitis.<ref name=Simon2018>{{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 }}</ref>

Severe rigors may mark the onset of this disease in humans. Fever, headache, and [[malaise]] are other [[non-specific symptom]]s 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 disorder]]s 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.<ref name="davey" />
[[File:Pathogens-08-00111-g003.png|thumb|Japanese encephalitis virus enters the brain through two ways and leads to infection of neurons and encephalitis.]]
Increased [[Microglial cell|microglial]] activation following Japanese encephalitis infection has been found to influence the outcome of viral pathogenesis. Microglia are the resident [[immune cell]]s 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 family|interleukin-1 (IL-1)]] and [[Tumor necrosis factor alpha|tumor necrosis factor-alpha (TNF-α)]], which can cause toxic effects in the brain. Additionally, other soluble factors such as [[neurotoxins]], [[excitatory neurotransmitter]]s, [[prostaglandin]], [[Reactive oxygen species|reactive oxygen]], and nitrogen species are secreted by activated microglia.<ref>{{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 }}</ref>

In a [[murinae|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 [[Autotoxicity|autotoxic]] loop of microglial activation that possibly leads to bystander neuronal damage.<ref>{{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 }}</ref> In animals, key signs include infertility and abortion in pigs, neurological disease in horses, and systemic signs including fever, lethargy and anorexia.<ref name="WikiVet">[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.</ref>