Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases, symptoms may include headache, vomiting, fever, confusion and seizures. This occurs about 5 to 15 days after infection. JEV is generally spread by mosquitoes, specifically those of the Culex type. Pigs and wild birds serve as a reservoir for the virus. The disease occurs mostly outside of cities. Diagnosis is based on blood or cerebrospinal fluid testing. Prevention is generally with the Japanese encephalitis vaccine, which is both safe and effective. Other measures include avoiding mosquito bites. Once infected, there is no specific treatment, with care being supportive. This is generally carried out in a hospital. Permanent problems occur in up to half of people who recover from JE. The disease primarily occurs in East and Southeast Asia as well as the Western Pacific. About 3 billion people live in areas where the disease occurs. About 68,000 symptomatic cases occur a year, with about 17,000 deaths. Often, cases occur in outbreaks. The disease was first described in Japan in 1871. Signs and symptoms The Japanese encephalitis virus (JEV) has an incubation period of 2 to 26 days. The vast majority of infections are asymptomatic: only 1 in 250 infections develop into encephalitis. 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 which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised body temperature between . 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. 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,