Introduction

Encephalitis is a condition that causes brain inflammation, resulting in changes in behaviour, personality, cognitive function, and consciousness.¹ A variety of different causes are responsible for the development of this condition, including viral infections and autoimmune diseases. This article focuses on one of the most common forms of encephalitis, Japanese encephalitis (JE) and its relationship with other types such as herpes simplex virus, tick and anti-NMDAR encephalitis.² These comparisons can help to widen the understanding of how vast encephalitis is and the different ways to prevent and treat it.

What is Japanese encephalitis?

Japanese encephalitis virus (JE virus), belonging to the flavivirus class, is a common cause of viral encephalitis.³ It spreads via an insect, known as the Culex mosquito.²

Many animal species, including pigs, wild wading birds, and Culex mosquitoes, are involved in the natural cycle of JE virus circulation.²

How does it spread?

Mosquitoes acquire the JE virus by feeding on infected animals and transfer it to people. It can result in encephalitis as the infection travels to the brain.³

People do not pass on the virus to other humans as efficiently as other mosquitoes, effectively ending the cycle. They are known as “dead-end hosts” as a result. They are not able to continue the cycle as there is not a high enough concentration of the JE virus in a person's bloodstream to infect a mosquito.²

What are the associated complications?

JE mainly affects children below 14, although adults are also at risk in regions with high transmission rates. Those with the virus can either experience no symptoms at all or symptoms similar to the flu that can last from 5 to 15 days.²

Seizures, unusual behaviours, headaches and fever can be common symptoms that occur from 2 to 4 days after infection, when the infection leads to encephalitis.²

Severe brain inflammation might result in paralysis and a stiff neck. Mortality rates can reach 30%, and those who survive may suffer from long-term mental and physical problems, such as difficulties speaking or moving.²

Which regions are affected? 

The virus is prominent in Southeast Asia, Western Pacific regions and has now spread to parts of Australia.⁴

New transmission sites have been discovered in numerous Asian and Western Pacific locations. From 2021 to 2022, more than 40 cases of Japanese encephalitis were identified on the Australian mainland.⁴

Further expansion of JE virus transmission in Asia could be caused by the increased growth in rice, pig farming, changing environmental circumstances, migratory birds, or windblown mosquitoes.⁴

How to prevent JE? 

Countries where the JE virus poses a risk have designed and implemented vaccination programmes where a weakened strain of the virus is injected. This is given two or three doses during childhood to stimulate long-term immunity.²

JE vaccine strategies include campaigns mainly targeted at children and routine vaccination programmes. These programs are helping to control the JE virus, but greater surveillance is needed to increase estimates of the disease's prevalence, as many cases go unreported.²

How to treat JE?

Currently, there are no specific treatments, so new therapies are needed. The aim when treating JE is to try to manage symptoms.⁵ Positive outcomes have been observed with a certain kind of medicine called minocycline, but further research is needed.⁵

Other types of encephalitis

Herpes simplex virus encephalitis

Two different types of viruses cause herpes simplex virus encephalitis (HSVE)

Herpes simplex virus encephalitis type 1 (HSV-1) or type 2 (HSV-2)⁶ 

HSV-1, the most common cause of infectious encephalitis, as HSV-1 induce encephalitis in adults and children. On the contrary, HSV-2-induced encephalitis can typically occur in newborns and people with weaker immune systems.⁶

One of the prominent signs of an HSV-1 infection is the appearance of sores around the mouth, such as cold sores.⁶ Relapses are common but decrease in severity over time as the host's immunity gradually recovers.⁶ 

Symptoms

Common symptoms associated with HSVE include:⁸

• Fever
• Confusion
• Changes in personality
• Impaired mental state
• Seizures
• Nausea and vomiting
• Altered speech

Treatments

Antiviral drugs are the primary therapy options. Aciclovir is the most common medication used to prevent the virus from multiplying. For the best results, antiviral medication should begin as soon as symptoms appear.⁷ If someone is resistant to aciclovir, other antiviral medications can be prescribed. 

Differences from JE

• HSVE spreads through direct contact, whilst JE spreads by mosquito bites
• JE is more common in the Western Pacific and Asia; however, HSVE is a disease that affects people all over the world
• JE can be prevented by vaccination, but this is not available for HSVE
• Specific antiviral medications are available to treat HSVE, whilst treatment for JE relies on providing supportive care

Anti-NMDA receptor encephalitis

A rare type of autoimmune encephalitis is Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. It results from the production of autoantibodies to the neuronal NMDAR NR1 subunit. These autoantibodies are thought to disrupt the receptor’s function.⁹

People with this disorder experience a decline in normal functioning, which is frequently accompanied by seizures, movement disorders, disturbed sleep and brain dysfunction. It was formerly classified as a paraneoplastic syndrome (an illness that can arise when the immune system reacts to a cancerous tumour), occurring in young females in conjunction with an ovarian teratoma.⁹

Symptoms

People initially experience headaches and fever, followed by mental and behavioural symptoms, which are as follows

• Seizures
• Speech difficulty
• Involuntary movements
• Decreased attentiveness
• Issues with memory 

Overheating, hypersalivation, and urinary incontinence are all involuntary signs of the illness. Young children are more likely than teenagers and adults to experience neurological problems.⁹

Treatments

Early initiation of immunotherapies (steroids and plasma exchanges) has demonstrated an improvement in outcomes and reduced relapse rates. Once diagnosed, the treatment plan usually consists of escalating immunotherapy and removing the teratoma if necessary.⁹

The second line of treatment consists of the medication rituximab.⁹

Differences from JE 

• Anti-NMDAR encephalitis does not spread, it is an autoimmune illness, so you can’t be infected by a mosquito like with JE
• Immunotherapy is used to treat anti-NMDAR encephalitis, but no particular antiviral medication is used to treat JE
• When comparing mortality rates, JE has a higher rate than anti-NMDAR encephalitis

Tick-borne encephalitis

Tick-borne encephalitis (TBE) is caused by a flavivirus, similar to the one that causes JE. It is a viral infection of the central nervous system (CNS) and occurs through the bite of an infected tick or by unpasteurised dairy products. TBE virus (TBEV) circulates naturally among ticks and wild hosts, including rodents, hedgehogs, and moles.¹⁰

The TBEV has three subtypes: European, Siberian and Far Eastern.¹⁰ TBE is prominent in Europe and several regions of Asia.¹¹

Vector activity affects TBE seasonality; human infections are most common in Europe during the tick feeding season, which ranges from late spring to early autumn.¹⁰

Male adults aged between 45 and 64 years are the most affected by TBE, due to recreational or occupational exposure or outdoor sports activities.¹⁰

Symptoms

The majority of TBEV infections are asymptomatic. Approximately 75% of people with TBE undergo the typical two-phase clinical course. This starts with flu-like symptoms such as fever, body pain, nausea, and potentially progresses to meningitis or encephalitis.¹¹

The CNS is involved in the rest of the cases, whose disease progresses in a one-phase manner.¹¹

Treatment

There are no particular antiviral treatments for TBE. People with TBE need to be hospitalised and receive care based on their symptoms. This includes analgesics and antiemetics.¹¹

To prevent the disease, it is important to get vaccinated against it.¹⁰ Further precautions include wearing protective clothing (such as long-sleeved items), regularly inspecting clothing for ticks, avoiding unpasteurised dairy products and minimising tick populations by cutting the grass.¹¹

Differences from JE

• Although both viruses are part of the Flavivirus family, they are transmitted by different vectors (JE through mosquitoes and TBE through ticks)
• TBE is found in Europe and Asia, whilst JE is dominant in Asia
• TBE consists of a biphasic course, whereas JE tends to lead to severe neurological symptoms more rapidly
• Unpasteurised milk is also a cause for TBE, which is not the case for JE

Summary

Below is a table summarising JE and other types of encephalitis: