Introduction

Japanese encephalitis (JE) is a viral infection transmitted between animals and humans by the Culex mosquitoes. The virus belongs to the Flavivirus species, the same group as dengue, yellow fever, Zika virus, and tick-borne encephalitis viruses. JE originated from Southeast Asia (like Japan, Malaysia, Myanmar) but has since spread to the East and West, and the Pacific Rim, with an affected population of over 3 billion. Approximately 20,000 cases are reported annually, of which 6,000 cases have resulted in death. Only one-third of the surviving patients are in complete recovery, while almost half of the surviving patients have residual neurological impairment, such as aphasia. The peak transmission period of the infection is during the rainy season from May to October, when the mosquitoes proliferate more actively. Although JE is not found in the UK and Europe, there have been reports of travellers suffering from JE upon their return from Asia, particularly after extended stays in rural areas.^1,2 

Following a mosquito bite, the virus invades the central nervous system and, in severe cases, causes irreversible neurological damage. Most often, people infected with JE do not present any symptoms. The first sign of symptoms, however, usually only appears between one week to two weeks of the incubation period. The manifestation of the infection also depends on which part of the central nervous system is affected. Some symptoms include high fever, chills, headache, abdominal pain and vomiting. In more severe cases, patients may lose consciousness, experience seizures, photophobia, and movement disorders. All age groups are affected by JE, but children and young adults of less than 10 years of age are at a higher risk of infection.^3,4 

The diagnosis of JE is usually confirmed by laboratory testing. It involves a blood test to detect the antibody to JE virus, and a cerebrospinal fluid (CSF) analysis. Antibodies are detectable between days 3 and 8 after the onset of infection. If early testing indicates a negative result, a repeated lumbar puncture is necessary to confirm the diagnosis. Imaging studies such as a CT scan may also be used to confirm the diagnosis. Patients’ travel history is crucial during the medical examination to rule out differential diagnoses such as dengue fever, or other similar viral encephalitis.⁵ 

Treatment options for JE

Currently, there is no specific antiviral treatment for Japanese encephalitis (JE); management is limited to supportive and symptomatic care. Interferon-α (INF-α) is currently the most promising antiviral agent against JE. Patients have shown positive responses to IFN-α, likely due to its role as a naturally occurring component of the immune system’s response to JE infection. However, further research is needed to validate its efficacy and establish standardised treatment protocols. Besides that, intravenous immunoglobulin (IVIG) with virus-specific neutralising antibodies also shows promising results in in-vitro studies and animal models, and could be one of the treatment options for JE in the future. Other possible treatment options include minocycline, N-methylisatin-β-thiosemicarbazone derivative, and N-nonyl-deoxynojirimycin.^6,7,8

Supportive care

Supportive care is given as primary treatment to prevent further complications that could arise from JE. While most patients do not show symptoms, patients with symptoms are recommended to seek medical help as soon as possible given that JE can progress rapidly. Hospitalisation may be required to ensure patients’ vital functions are closely monitored. For example, patients with symptoms of seizures may be sedated to improve overall outcome and prevent further possible damage to the brain. Patients who experience a reduced gag reflex due to JE are at risk of complications like aspiration pneumonia and therefore should be monitored for these symptoms. Supportive care also includes management of fluids and electrolytes to prevent dehydration, as one of the common symptoms of JE is vomiting.⁶

Symptomatic treatment

Symptomatic treatment is individualised for each patient and is dependent on the symptoms they experience. Some medications for the common symptom management of JE include:^9,10 

• Antipyretics like paracetamol for fever management 
• Anticonvulsants like diazepam and phenytoin to control seizures
• NSAIDs like ibuprofen, or other pain relievers for pain management
• Haloperidol to treat abnormal movements

Effective management of intracranial pressure (ICP) is crucial in Japanese Encephalitis (JE), as controlling risk factors that elevate ICP significantly reduces both mortality and morbidity. An increase in ICP causes intracranial hypertension, which aggravates cerebral ischaemia. A prolonged cerebral ischaemia that is not promptly treated or effectively prevented could cause irreversible cerebral damage. Therefore, management of ICP in JE is mainly to prevent cerebral damage and to preserve neurological function.  Corticosteroids have long been used to reduce ICP, although recent studies have proven no benefits. Diuretics, like furosemide, can be used to reduce ICP. Additionally, since pain can elevate ICP by increasing cerebral blood flow, sedation is often administered to prevent further intracranial hypertension.^9,10  

Rehabilitation post-infection

There are long-term effects of JE, such as cognitive impairment, motor dysfunction, and speech issues. Since JE usually affects children and young adults, it is important for the survivors to undergo early rehabilitation post-infection to regain daily living skills and work towards independence.¹¹

There are different types of rehabilitation available depending on the impairment, such as:

• Physical therapy to regain motor skills and strength
• Occupational therapy for daily function and self-care
• Speech therapy for communication difficulties

Patients and caregivers should also seek psychological support and counselling. This helps to reduce the psychological burden experienced by both patients and caregivers, as the rehabilitation process requires time and patience, and can be frustrating with the slow or minor improvements.

Prevention of JE

Vaccination is the primary prevention tool in JE. There are two types of vaccines available, which are the inactivated (e.g., JE-VAX) and live-attenuated (e.g., SA 14-14-2) vaccines. The vaccine is recommended for all residents in the endemic regions of JE, as well as individuals travelling to the parts of the world where the virus is prevalent. Currently, two doses of live-attenuated JE vaccine are shown to be effective with more than 95% protection.¹²

To avoid JE altogether is to prevent mosquito bites. The use of mosquito nets and mosquito repellent is recommended. Wearing protective clothing that covers exposed skin while outside, especially at nighttime, is helpful to reduce the risk of getting bitten. 

Summary

JE is rare but can be life-threatening. While it is a disease of children, adults are also at risk of JE infection. Currently, there is no cure for JE, and the absence of specific treatment makes supportive care and symptomatic treatment, as well as rehabilitation, important to improve outcomes. JE can be prevented via vaccination and taking precautionary measures to prevent mosquito bites.