Japanese encephalitis virus

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that circulates between Culex mosquitoes, wading birds, and pigs, and is the leading cause of vaccine-preventable viral encephalitis in Asia. Most human infections are mild or symptomless, but in the small fraction that reach the brain the disease is severe: up to 30% of people with encephalitis die, and 30–50% of survivors are left with lasting neurological, cognitive, or behavioral problems.

The World Health Organization estimates about 100,000 clinical cases each year, mostly in children under 15 in endemic areas. Transmission occurs across much of South and Southeast Asia, East Asia, and the western Pacific, and is closely tied to rural rice farming and pig rearing.

JEV is a member of the genus Orthoflavivirus in the family Flaviviridae, closely related to West Nile virus and St. Louis encephalitis virus and more distantly to dengue virus, Zika virus, and yellow fever virus.

Like other flaviviruses, it is an enveloped, positive-sense single-stranded RNA virus with a genome of about 11,000 nucleotides. The genome is translated as one long polyprotein, which is cut into three structural proteins (capsid, prM/M, and the envelope protein E, which binds cells and is the main target of protective antibodies) and seven non-structural proteins that copy the genome and suppress the host's interferon response. Five genotypes are recognized; genotype III dominated historically, and genotype I has become common across much of Asia in recent decades.

JEV is maintained in an enzootic cycle that does not depend on humans:

• Vectors: The main vector is Culex tritaeniorhynchus, which breeds in flooded rice paddies and irrigation water. Other Culex species, including members of the Culex pipiens complex, also transmit the virus in some regions.
• Reservoir hosts: Ardeid wading birds such as herons and egrets maintain the virus in nature.
• Amplifying hosts: Domestic pigs develop high levels of virus in the blood without usually becoming seriously ill, so they multiply the virus and infect many feeding mosquitoes. Pig farming near rice fields therefore greatly raises the risk to people.
• Dead-end hosts: Humans and horses can become ill, but they develop too little virus in the blood to infect mosquitoes, so they do not pass the virus on.

In temperate parts of Asia transmission peaks in summer and autumn. In the tropics it can occur year-round, often rising during the rainy season and irrigation periods. Like other arboviruses, JEV's spread depends on temperature through the extrinsic incubation period in the mosquito. Its appearance in new areas is watched closely: in 2022 Australia recorded its first large outbreak in the southeastern mainland states, linked to piggeries after heavy rains and flooding.

Fewer than 1% of infections cause clinical illness. After an incubation period of about 5–15 days, symptomatic patients develop fever, headache, and vomiting, which can progress over a few days to confusion, seizures (especially in children), paralysis, and coma. Damage to the thalamus, basal ganglia, and brainstem can produce movement disorders resembling parkinsonism.

There is no antiviral treatment; care is supportive, focused on managing seizures, brain swelling, and breathing. Diagnosis usually relies on detecting JEV-specific IgM antibodies in cerebrospinal fluid or blood, although cross-reaction with related flaviviruses can complicate interpretation.

Because treatment is limited and human infection does not feed transmission, vaccines are the cornerstone of control. The WHO recommends including JE vaccination in national immunization programs wherever the disease is a recognized public health problem. Several types are in use:

• Live attenuated vaccines based on the SA 14-14-2 strain, widely used in Asia and effective after a single dose.
• Live recombinant (chimeric) vaccines, which place JEV's surface genes on a yellow fever vaccine backbone.
• Inactivated Vero cell-derived vaccines, used for travelers and in some national programs.

Large childhood vaccination campaigns have sharply reduced the disease in countries such as Japan, South Korea, and China. Personal protection against mosquito bites, mosquito control around rice fields, and relocating pig housing away from homes add further protection. Vaccinating pigs has been tried but is hard to sustain because of the high turnover of pig herds.

JEV is one of the most important mosquito-borne diseases of Asia. Its close kinship with West Nile virus, a Culex-borne flavivirus of the Americas, Europe, and Africa, makes the two a useful comparison in epidemiology and vector control research.