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. Human, cattle, and horses are dead-end hosts as the disease manifests as fatal encephalitis. Pigs act as an amplifying host and have a very important 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 therefore never be eliminated. In November 2011, the Japanese encephalitis virus was reported in Culex bitaeniorhynchus in South Korea. 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. A number of drugs have been investigated to either reduce viral replication or provide neuroprotection in cell lines or studies upon mice. None are currently advocated in treating human patients. The use of rosmarinic acid, arctigenin, and oligosaccharides with degree of polymerization 6 from Gracilaria sp. or Monostroma nitidum has been shown to be 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 level, 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. Minocycline in mice resulted in marked decreases in the levels of several markers, viral titer, and the level of proinflammatory mediators and also prevented blood–brain barrier damage. Evolution It is theorized that the virus may have originated from an ancestral virus in the mid-1500s in the Malay Archipelago region