Japanese B Encephalitis

Synonyms: it is often known as simply Japanese encephalitis or JE.

The infection is caused by a flavivirus, a single-stranded RNA virus. It is transmitted by the bite of the Culex tritaeniorhynchus mosquito. The virus multiplies at the site of the bite and in regional lymph nodes before viraemia develops. Viraemia can lead to inflammatory changes in the heart, lungs, liver, and reticuloendothelial system.

The immune system usually overwhelms the virus before it can invade the central nervous system and so most disease is subclinical. Neurological infection is thought to occur in only about 1 case in 300.¹ The virus can spread across vascular endothelial cells, with involvement of large areas of the brain, including the thalamus, basal ganglia, brain stem, cerebellum, hippocampus and cerebral cortex.

• The endemic area for Japanese encephalitis spreads across Asia from Pakistan to the coast of Siberia and includes Japan. Around 3 billion people live in this endemic area.
• In temperate parts it is a seasonal disease, from June to September but further south in subtropical areas, transmission begins as early as March and extends until October. In some tropical areas such as Indonesia, Malaysia and the Philippines, infection occurs all year round.
• It may be spreading as far as Australasia.²
• It tends to occur in wet areas where mosquitoes thrive. Other hosts include pigs and wading birds.
• The World Health Organisation estimates that there are between 35,000 and 50,000 symptomatic cases per year worldwide with 10,000 deaths, mostly in children.
• Local incidence varies from 1 to 10 cases per 100,000 population but can reach more than 100 cases per 100,000 during outbreaks.
• In endemic areas, most adults show antibody evidence of past infection. Symptomatic disease is more common in males in a ratio of 1.5:1. It tends to affect children aged 2 to 10 but may affect older people too.
• This age distribution applies to the indigenous population. Visitors may be affected at any age.
• The risk to travellers to rural areas is thought to be between 1 in 5,000 and 1 in 20,000 per week.³ Japanese encephalitis is rare in the United Kingdom and invariably contracted abroad.

• The incubation period is 6 to 16 days.
• There is a prodrome of fever, headache, nausea, diarrhoea, vomiting and myalgia, which may last for several days.
• This may be followed by a spectrum of neurological disease ranging from mild confusion, to agitation, to overt coma.
• Two-thirds of patients have seizures. It is more common in children, while headache and meningism are more common in adults.
• Tremor or other involuntary movements are common.
• Mutism has been described as a presenting symptom. So has a syndrome of acute flaccid paralysis.
• Fever resolves by the second week, and choreoathetosis or extrapyramidal symptoms develop as the other neurological symptoms disappear.

Neurological features

These are varied and include:

• Generalised weakness, hypertonia and hyperreflexia, which are common.
• Papilloedema is seen in less than 10% of patients.
• A third has cranial nerve findings such as disconjugate gaze and cranial nerve palsies.
• Extrapyramidal signs are often seen. They include a mask-like face, tremor, rigidity, and choreoathetoid movements, producing a Parkinson's-like syndrome.⁴
• There may be central hyperpnoeic breathing.

• Meningitis
• Dengue fever and other flaviviruses
• Malaria
• Herpes simplex encephalitis

• FBC shows a mild, non-specific leukocytosis in the first week. Mild anaemia is also common.
• Inappropriate ADH secretion often leads to a low serum Na⁺.
• CT or MRI scan may show bilateral thalamic lesions with haemorrhage. The basal ganglia, putamen, pons, spinal cord and cerebellum may also be abnormal.
• EEG often shows diffuse continuous delta slowing or diffuse delta pattern with spikes. The severity of EEG changes does not correlate with clinical outcome.
• Lumbar puncture may be undertaken.
• Virus can be isolated from the blood during the first week of illness. The CSF rarely will yield virus, except in severe or fatal cases.

Lumbar puncture

• The procedure is often undertaken to exclude meningitis or other causes of encephalitis.
• The opening pressure is usually normal.
• CSF protein is mildly elevated in most cases.
• White cells are usually between 10 and 500 mononuclear cells per cubic millimetre.

Antibody tests

• IgM capture enzyme-linked immunosorbent assay (ELISA) of serum or CSF is the standard diagnostic test. Sensitivity is nearly 100% when both serum and CSF are tested. False-negatives may result if the samples are tested too early, as in the first week of illness.
• There is some cross-reactivity with other flaviviruses and from Japanese encephalitis and yellow fever vaccinations.
• New IgM dot ELISA for CSF and serum are portable and simple tests that can be used in the field. Compared with IgM capture ELISA as the gold standard, the sensitivity and specificity are around 98% and 99% respectively.

• There is no specific treatment for the disease and management is purely supportive. A double blind RCT of interferon alpha-2a in 112 Vietnamese children showed no significant benefit.⁵
• Support often includes feeding, airway management, and anticonvulsants.
• If there is raised intracranial pressure, mannitol is given, especially if the Glasgow Coma Score is less than 8.⁶ Steroids do not appear to be beneficial.⁷
• Outcome appears to be improved by adequate sedation and fluids and sodium intake tailored to their needs.⁶

• As well as problems such as pneumonia and urinary tract infection, there are potential complications of convulsions.
• Neurological complications may not resolve when the disease subsides.
• If the disease strikes in pregnancy it may cause fetal death in the first or second trimester but does not seem to be such a problem in the third trimester.

• The prognosis is highly variable and neurological deficits are common.
• Mortality can range from 20% to 50% but is usually around 33%.^4,8 It tends to be lower in areas with more sophisticated medical care. Death usually occurs in the first 5 days with deepening coma and respiratory arrest.
• Disabilities may range from subtle changes in behaviour to blindness, ataxia, weakness and movement disorders.
• As many as 25% to 30% may have serious residual neurological problems at 1 year.

The pivots of prevention are vector control and immunisation. For those visiting endemic areas, avoidance of mosquito bites is also important.

Avoidance of mosquito bites

Mosquitoes tend to bite at night and for visitors to endemic areas the usual precautions are recommended. This may mean using insect repellant after dark, wearing long sleeves and covering legs and avoiding sitting near lights unless behind mosquito screens. An insect repellent soap has been found to be very acceptable and highly effective.⁹ The use of mosquito nets at night should be considered as for malaria. Nets impregnated with insecticide or repellent are more effective.

Vector control

Vector control may include spraying insecticide, draining swamps and the introduction of fish that eat the larvae of the mosquito.¹⁰ In a substantial part of the area affected, the staple diet is rice, and paddy fields are an essential part of the economy.

Vaccination

The vaccine used for Japanese B Encephalitis Vaccination (see our dedicated record) has been produced since 1992. The vaccine is effective but not without risks and the substantial risks of the disease and the risks of the vaccine have to be balanced,⁸ especially for stays of brief duration. Ixiaro® is a newly-licensed Japanese B encephalitis vaccine and is now available in the United Kingdom.¹¹ These are both discussed more fully in the article on that subject.

As with malaria, prophylaxis must be supplemented by techniques to avoid being bitten by mosquitoes.