Japanese Encephalitis

Japanese encephalitis (Japanese: 日本脳炎, Nihon-nōen; previously known as Japanese B encephalitis to distinguish it from von Economo's A encephalitis) is a disease caused by the mosquito-borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus from the family Flaviviridae. Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may cause severe symptoms. One of the most important vectors of this disease is the mosquito Culex tritaeniorhynchus. This disease is most prevalent in Southeast Asia and the Far East.

Epidemiology
Japanese encephalitis is the leading cause of viral encephalitis in Asia, with 30,000–50,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and depends on the population and on age. Rare outbreaks in U.S. territories in Western Pacific have occurred. Residents of rural areas in endemic locations are at highest risk; Japanese encephalitis does not usually occur in urban areas. Countries which have had major epidemics in the past, but which have controlled the disease primarily by vaccination, include China, Korea, Japan, Taiwan and Thailand. Other countries that still have periodic epidemics include Vietnam, Cambodia, Myanmar, India, Nepal, and Malaysia. Japanese encephalitis has been reported on the Torres Strait Islands and two fatal cases were reported in mainland northern Australia in 1998. The spread of the virus in Australia is of particular concern to Australian health officials due to the unplanned introduction of Culex gelidus, a potential vector of the virus, from Asia.

Human, cattle and horses are dead-end hosts and disease manifests as fatal encephalitis. Swine acts as amplifying host and has very important role in epidemiology of the disease. Infection in swine is asymptomatic, except in pregnant sows, when abortion and fetal abnormalities are common sequelae. The most important vector is C. tritaeniorhynchus, which feeds on cattle in preference to humans, it has been proposed that moving swine away from human habitation, and that cattle be used to divert the mosquito away from humans and swine. The natural host of the Japanese encephalitis virus is bird, not human, and the virus will therefore never be completely eliminated.

Clinical features
Japanese encephalitis has an incubation period of 5 to 15 days and the vast majority of infections are asymptomatic: only 1 in 250 infections develop into encephalitis.

Severe rigors mark the onset of this disease in humans. Fever, headache and malaise are other non-specific symptoms of this disease which may last for a period of between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised body temperature between 38 and 41 degrees Celsius. Mental retardation developed from this disease usually leads to coma. Mortality of this disease varies but is generally much higher in children. Transplacental spread has been noted. Life-long neurological defects such as deafness, emotional lability and hemiparesis may occur in those who have had central nervous system involvement. In known cases some effects also include, nausea, headache, fever,vomiting and sometimes swelling of the testicles.

Virology
The causative agent Japanese encephalitis virus is an enveloped virus of the genus flavivirus; it is closely related to the West Nile virus and St. Louis encephalitis virus. Positive sense single stranded RNA genome is packaged in the capsid, formed by the capsid protein. The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The genome also encodes several nonstructural proteins also (NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5). NS1 is produced as secretory form also. NS3 is a putative helicase, and NS5 is the viral polymerase. It has been noted that the Japanese encephalitis virus (JEV) infects the lumen of the endoplasmic reticulum (ER) and rapidly accumulates substantial amounts of viral proteins for the JEV.

Japanese Encephalitis is diagnosed by detection of antibodies in serum and CSF (cerebrospinal fluid) by IgM capture ELISA.

Prevention
Infection with JEV confers life-long immunity. All current vaccines are based on the genotype III virus. A formalin-inactivated mouse-brain derived vaccine was first produced in Japan in the 1930s and was validated for use in Taiwan in the 1960s and in Thailand in the 1980s. The widespread use of vaccine and urbanisation has led to control of the disease in Japan, Korea, Taiwan and Singapore. The high cost of the vaccine, which is grown in live mice, means that poorer countries have not been able to afford to give it as part of a routine immunisation programme.

In the UK, the two vaccines used (but which are unlicensed) are JE-Vax&reg; and Green Cross. Three doses are given at 0, 7–14 and 28–30 days. The dose is 1ml for children and adult, and 0.5ml for infants under 36 months of age.

The most common adverse effects are redness and pain at the injection site. Uncommonly, an urticarial reaction can develop about four days after injection. Because the vaccine is produced from mouse brain, there is a risk of autoimmune neurological complications of around 1 per million vaccinations.

Neutralising antibody persists in the circulation for at least two to three years, and perhaps longer. The total duration of protection is unknown, but because there is no firm evidence for protection beyond three years, boosters are recommended every two years for people who remain at risk.

There are a number of new vaccines under development. The mouse-brain derived vaccine is likely to be replaced by a cell-culture derived vaccine that is both safer and cheaper to produce. China licensed a live attenuated vaccine in 1988 and more than 200 million doses have been given; this vaccine is available in Nepal, Sri Lanka, South Korea and India. There is also a new chimeric vaccine based on the yellow fever 17D vaccine that is currently under development.

Treatment
There is no specific treatment for Japanese encephalitis and treatment is supportive. There is no transmission from person to person and therefore patients do not need to be isolated.

External links and general references

 * Clinical medicine, fifth edition by Kumar and Clark, 2002 published by W.B Saunders
 * Centers for Disease Control and Prevention Questions and Answers About Japanese Encephalitis
 * Australian government Department of Health and Aging, Japanese Encephalitis, 2004
 * Monath, TP, Pathobiology of the flaviviruses. In: The Togaviridae and flaviviridae (Eds Schlesinger, S. and Schlesinger, M.J.) Plenum Press, New York/London,, pp. 375-440, 1986
 * UK Department of Health. (2006) Immunisation against Infectious Disease Chapter 20: Japanese Encephalitis
 * WHO.
 * PATH's Japanese encephalitis project
 * Japanese encephalitis resource library