Introduction

Every year there are about 100,000 cases of Japanese encephalitis globally.¹ Japanese encephalitis is a viral infection caused by mosquito bites carrying the Japanese encephalitis virus (JEV). It is a rare yet serious condition and most commonly affects unvaccinated visitors to agricultural areas like farms or rice paddies in countries such as Japan, India, South Korea, Taiwan, Indonesia, Thailand, Malaysia, Vietnam, and China (NHS).^{1, 2}

Around 3 billion people are susceptible to Japanese encephalitis since twenty-four countries in Asia and Western Pacific regions were identified for JEV transmission risk (WHO). This article aims to explain what Japanese encephalitis is and how this infection could impact the brain. 

What is japanese encephalitis?

The first case of Japanese encephalitis was identified in Japan in 1871 (WHO). It is a viral infection caused by the Japanese encephalitis virus (JEV). JEV is part of the genus Flavivirus, which is related to the West Nile virus (Klarity). It is transmitted through the bite of the Culex mosquito species infected with JEV and act as hosts or carriers of the virus. The most common host is the Culex tritaeniorhynchus (WHO). Other common hosts of the JEV include water birds and pigs, so the transmission of the virus exists in an enzootic cycle (cycle of transmission within animals only).²

 When the JEV enters the human body, infected humans do not produce enough viraemia (replication of the virus in the human bloodstream for further transmission), so they cannot pass on the JEV to the feeding mosquitoes. Thus, common hosts of the JEV are found in agricultural areas like rice paddies and farms, and infection rates peak in rural areas with flood irrigation during the monsoon season and pre-harvest period during summer in the tropical and subtropical regions of Asia, known to cultivate rice (CDC). ² Although rural areas are common sites of infection, there have been increasing cases in suburban areas of China, South Korea, Taiwan and Singapore.²

Japanese encephalitis commonly affects children, and most adults develop natural immunity after infection in their childhood, but routine childhood vaccination has greatly reduced the number of cases (ECDC). However, infection can occur at any age, especially in unvaccinated travellers and those who do not take any precautionary measures while visiting rice fields or areas with stagnant water in any of the countries stated above.²

Symptoms and progression

The incubation period for the symptoms of the infection to appear ranges between 5 to 15 days (CDC, ECDC). Most cases of Japanese encephalitis are asymptomatic, which means that infected individuals may not present any visible symptoms (NHS). 

Symptomatic individuals usually present mild symptoms such as:

• Fever 
• Headache
• Nausea or vomiting
• A general feeling of discomfort and illness (malaise)
• Gastrointestinal or stomach pain in children

Severe symptoms in affected individuals are caused by a case of encephalitis, where the infection spreads to the brain ² 

• Severe headache
• High fever
• Diarrhoea
• Neck stiffness or myalgia
• Disorientation, confusion and agitation
• Psychosis
• Seizures or fits
• Paralysis
• Coma
• In very serious cases, death

Up to 30% of cases that present severe symptoms can result in death, and of those that survive, 20 to 30% of individuals experience neurological, behavioural and cognitive issues like seizures, paralysis, loss of hearing or vision, difficulties in memory, language, speech and communication, and the inability to carry out daily activities independently (WHO).² Approximately 25,000 deaths are recorded globally due to Japanese encephalitis every year (WHO).

Impact of japanese encephalitis on the brain

The JEV is a single-stranded RNA virus, which means that it can enter host cells and produce proteins that promote the survival of the virus in the human body. ³ When the JEV enters the human bloodstream, it starts replicating copies of itself (viraemia). Still, this process does not produce enough copies to allow for human-to-human transmission of the JEV, so humans are dead-end hosts of Japanese encephalitis.^{2, 3} 

The JEV then progresses toward the central nervous system, which triggers inflammation of the nerve cells, damage to blood vessels, and the degeneration of nerve cells.³ This process represents the initial stage of the infection. The JEV then invades the blood-brain barrier, which usually protects the lining of the brain’s blood vessels and filters out harmful molecules from entering the brain. The invasion of the blood-brain barrier by the JEV is a characteristic pathway in the case of a Japanese encephalitis infection.³

This leads to an increase in the activity of pro-inflammatory cytokines that are released by the immune system to fight against the virus. The activation of pro-inflammatory cytokines leads to an inflammation of the brain or encephalitis.³

Encephalitis is associated with the appearance of mild symptoms like headaches, fever, stiffness of the neck and nausea (Mayo Clinic). As the disease progresses, more severe symptoms appear that induce impairment of cognitive functions, dysfunction in movement, and seizures. Less than 1% of infected individuals develop encephalitis, of which 1 in 4 cases lead to death (CDC). 

Of those who survive serious infection, up to 30% experience long-term neurological effects such as memory loss, impairment of speech, vision or hearing, behavioural changes like personality, trouble sleeping, agitation, hallucinations, psychosis, and difficulty in movement such as trouble walking and recurrent seizures.²

Summary

Japanese encephalitis is a preventable viral infection caused by the Japanese encephalitis virus, commonly transmitted through the bite of the Culex mosquito species. Japanese encephalitis occurs in countries of Asia and the Western Pacific regions. Agricultural areas like rice fields and farms or areas with flooded irrigation and stagnant water are common sites for infection if individuals are unvaccinated and do not take preventative measures. Children are commonly affected by Japanese encephalitis, after which most adults would have developed natural immunity against the infection, but Japanese encephalitis can affect individuals at any age. Mild symptoms include fever, headache, nausea, and stomach pain in children. Severe symptoms include severe headache, high fever, myalgia, psychosis, seizures, coma and ultimately death.

The JEV invades the blood-brain barrier, which causes encephalitis and is associated with cognitive, neurological, and behavioural effects that can persist even after recovery from serious infection. Since Japanese encephalitis has no cure, aside from vaccination, travellers and residents should use mosquito repellants, mosquito nets or screens during sleep and wear clothing that covers any exposed skin.