Introduction 

Japanese encephalitis disease is caused by the virus known as Japanese encephalitis virus (JEV). The virus can lead to infection which then has the possibility to develop into the disease Japanese encephalitis. The virus is mainly transmitted by mosquitoes which explain the major regional areas that are affected by the virus. The virus can also infect other types of animals like pigs and birds, which are then able to pass on the infection to humans.²

However it's important to note that humans can then not subsequently pass it on to other humans.

Currently, the disease is a significant issue in parts of Asia and the western pacific and is endemic in many of these areas, particularly affecting children under the age of 15.¹

It is an issue of significance because of its severity, as it is known to cause severe symptoms with a fatality rate of up to 30% in those who are infected in the brain. Currently vaccination programs have been recommended to avoid contraction but in the case of this already happening, there are several ways in which the disease can be diagnosed and differentially diagnosed from other viruses which present similarly.³

Clinical presentation

In the majority of these cases, it takes from 5 to 15 days for the virus to manifest into symptoms that a person will experience. 

This is known as the incubation period of the virus.²

For the vast majority of people who contract japanese encephalitis virus, they will not experience any symptoms and therefore are asymptomatic. For those who do manifest symptoms, this can mean the development of non-encephalitic disease. When neurological symptoms begin to present however, this is often a sign of encephalitic disease, meaning there is inflammation of the brain.⁷

Initial symptoms (non-encephalitic disease)

These symptoms are often non specific to japanese encephalitis and usually not as drastic when compared to the more severe cases.

• Fever
• Headache
• Vomiting 
• Stomach pain
• Muscle pain

Symptoms like vomiting and gastrointestinal pain are more prominently seen in children.

Severe symptoms (encephalitis)

More severe symptoms are less common in infection but around 1 in 250 people infected with the virus will experience some form of these symptoms.¹ These types of symptoms often tend to have a faster onset after infection, especially when the disease is more severe.

Neurological symptoms can also present, and these can certainly be rapid and abrupt. These symptoms can mean inflammation in the brain as a result of viral infection.⁷

• Fever and headache 
• Neck stiffness
• Disorentration
• Seizures
• Coma

Disorientation, seizures and possibility of a coma are all neurological symptoms that point to a more severe case of the disease.^1,2

Seizures particularly are seen in young children with japanese encephalitis.

Diagnostic approach in a clinical setting 

It's important to acknowledge that diagnosing japanese encephalitis can be difficult because of the lack of symptoms in many of those who are infected.

So when approaching a diagnosis, it's important for clinicians to consider several factors, including travel history, any symptoms that are present and finally, laboratory testing. 

Combining serological testing and clinical information is key to the most accurate and definitive diagnosis of japanese encephalitis.

Assessing travel history 

When people first come in to get diagnosed in a clinical setting, it is most important for a clinician to explore travel history, in order to investigate whether a person has recently visited areas where there are current japanese encephalitis endemics.

This is often a strong indicator to whether japanese encephalitis should be initially suspected, or another possible disease should be considered instead.

In the situation where a person has recently been to these regions, for example in Asia or the Western pacific, a clinical examination can be done to observe the presentation of symptoms.

Clinical examination 

Most symptoms for the initial infection of japanese encephalitis virus are non specific. Consequently encephalitis caused by viral infection are known as clinically non-specific.

This means that these symptoms are present in many types of illness, but particularly in contraction of many different viruses. 

The flu, for example, is a virus which would result in many of the very same symptoms as those seen in the initial infection of japanese encephalitis. 

In the case where more severe neurological symptoms are observed by a clinician, along with confirmation of recent travel to an endemic country, a laboratory test is likely to be done for a final and definitive diagnosis.^6,4

Laboratory testing

Several laboratory tests can be conducted to definitively confirm if a person has japanese encephalitis as a result of JEV infection.

A lumbar puncture examination can be done to draw and collect cerebrospinal fluid from a patient with suspected japanese encephalitis.

Cerebrospinal fluid is useful as the virus can be isolated and examined from the fluid. Cerebrospinal fluid is used because japanese encephalitis is a virus which infects the central nervous system. This makes it a great source to isolate the virus from.

A lab can then carry out investigations which use this sample to test for antibodies which are specific to japanese encephalitis virus. When your body contracts a virus, there is a usual process where your immune system develops antibodies which are specific to the virus you have contracted. This is so that the virus can be fought efficiently by the immune system.

If a person does have japanese encephalitis virus, this testing will confirm if the person is positive for JEV antibodies and does in fact have the virus. 

This type of testing is known as an ELISA technique.

A PCR test is also commonly done, using cerebral spinal fluid. This can identify if a sample is positive for DNA of the japanese encephalitis virus and subsequently determine if a person does have JEV or not.⁴ More thorough testing can also be carried out through molecular testing, similar to PCR, to identify the particular geographical origin of the virus strain. This can be helpful when deciding how to manage the infection.

These types of molecular testing furthermore have the ability to accurately differentiate between viruses, for a specific and accurate diagnosis. This is very helpful, as japanese encephalitis virus presents with the same symptoms as some other viruses which belong to the same family.⁴

Neuroimaging

Brain scans can be performed in order to support a laboratory diagnosis or a clinical examination diagnosis. They can also additionally serve a purpose in aiding management of the disease once it has been definitively diagnosed.

A common feature which is seen from scans is damage to the thalamus part of the brain or lesion in the midbrain.

Though these brain scans support laboratory investigations, they often are not able to differentiate between the flaviviruses that have caused the lesions. This means that though an encephalitis infection can be seen, the information presented by brain imaging is simply not enough to differentiate between the possible causative viruses. For example dengue virus and japanese encephalitis virus cannot be differentiated depending on the brain imaging alone. Therefore brain imaging is used as a supportive diagnosis tool rather than being solely relied on for an accurate diagnosis.

MRI scans can often be better in identifying these brain lesions in comparison to CT scans. This is because of the improved soft tissue contrast seen through MRI scans.^7,6

Differential diagnosis 

These conditions can initially present very similar to other viruses which can be contracted in those same endemic regions. These include viruses like west nile and dengue virus. 

Japanese encephalitis virus belongs to a virus family called Flaviviridae. In this Flaviviridae family, there are other viruses like west nile virus, zika and dengue virus. These viruses belong to the same family because of their shared characteristics. And because of these, many of the viruses cause similar symptoms and presentation.^3,5

As discussed before however, some types of molecular testing which isolate the virus DNA can be helpful in distinguishing which viral infection a person has.

Summary

Japanese encephalitis is a viral infection, caused by the japanese encephalitis virus. As previously discussed, diagnosis of this disease can sometimes be challenging. A combination of various factors including clinical information, laboratory findings and neuroimaging are all essential for the most accurate diagnosis.

Early diagnosis is crucial because it is the greatest way of managing the disease as efficiently as possible, determining the best possible outcome for the patient.  While initial symptoms may be mild and non specific to the disease, more severe symptoms can prove more identifiable to the disease and ultimately help identify the disease. 

Although diagnostic methods, which include various laboratory tests, are both specific and accurate, vaccination remains the most effective way to prevent infection. The current diagnostic criteria are essential for rapid and accurate detection, facilitating prompt treatment to manage the disease effectively.