Japanese encephalitis

Definition:
Japanese encephalitis  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.

It was first recognised in Japan in the late 1800s (hence the name) and has since been found throughout most countries of east and South East Asia where it is the leading cause of viral encephalitis. Approximately 30,000 to 50,000 cases are reported every year, and there are about 10,000 deaths, mostly in children. In fact it’s now thought that many more people have the infection (research shows that by the age of 15 most people in South East Asia have had it) but symptoms are usually minimal so it doesn’t get reported.

Symptoms:
Most people who are infected show only mild symptoms or no symptoms at all. However, in severe cases the disease may be fatal.

Japanese encephalitis begins like flu with headache, fever, and weakness. As it progresses to inflammation of the brain there may be confusion and delirium. Gastrointestinal problems, including vomiting, may also be present. About one third of these patients will die, and 25-30 per cent have neurological damage including paralysis, speech difficulties, Parkinson’s-like syndrome or psychological problems. Children are most vulnerable.

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.

Increased microglial activation following JEV infection has been found to influence the outcome of viral pathogenesis. Microglia are the resident immune cells of the central nervous system (CNS) and have a critical role in host defense against invading microorganisms. Activated microglia secrete cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-?), which can cause toxic effects in the brain. Additionally, other soluble factors such as neurotoxins, excitatory neurotransmitters, prostaglandin, reactive oxygen, and nitrogen species are secreted by activated microglia.

In a murine model of JE, it was found that in the hippocampus and the striatum, the number of activated microglia was more than anywhere else in the brain closely followed by that in the thalamus. In the cortex, number of activated microglia was significantly less when compared with other regions of the mouse brain. An overall induction of differential expression of proinflammatory cytokines and chemokines from different brain regions during a progressive JEV infection was also observed.

Although the net effect of the proinflammatory mediators is to kill infectious organisms and infected cells as well as to stimulate the production of molecules that amplify the mounting response to damage, it is also evident that in a nonregenerating organ such as brain, a dysregulated innate immune response would be deleterious. In JE the tight regulation of microglial activation appears to be disturbed, resulting in an autotoxic loop of microglial activation that possibly leads to bystander neuronal damage

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

Treatment ;
At present, there is no medical ‘cure’ for Japanese encephalitis once infection has occurred although supportive care in hospital can help.There is no transmission from person to person and therefore patients do not need to be isolated.

A breakthrough in the field of Japanese encephalitis therapeutics is the identification of macrophage receptor involvement in the disease severity. A recent report of an Indian group demonstrates the involvement of monocyte and macrophage receptor CLEC5A in severe inflammatory response in JEV infection of brain. This transcriptomic study provides a hypothesis of neuroinflammation and a new lead in development of appropriate therapeutic against Japanese encephalitis.

Prevention:
As with any disease transmitted by mosquitoes, you can prevent exposure to JE virus by:

•remaining in wellscreened areas,

•wearing clothes that cover most of the body, and

•using an effective insect repellent, such as those containing up to 30% N,N-diethyl metatoluamide (DEET) on skin and clothing. Use of permethrin on clothing will also help prevent mosquito bites.

Japanese encephalitis vaccine can prevent JE, however, JE vaccine is not 100% effective and is not a substitute for mosquito precautions. It is licensed for use in the UK and the USA for people who plan to travel to South East Asia. Allergic reactions can occur in up to one in 100 people vaccinated but are mostly minor.

Who should get Japanese encephalitis vaccine and when?
Who should get vaccinated?

•People who live or travel in certain rural parts of Asia should get the vaccine.

•Laboratory workers at risk of exposure to JE virus should also be vaccinated.

When to get the vaccine?

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•Three doses of vaccine are given, with the 2nd dose given 7 days after the 1st and the 3rd dose given 30 days after the 1st.

•The third dose should be given at least 10 days before travel, to be sure the vaccine begins to protect and to allow for medical care if there are delayed side effects.

•A booster dose may be needed after 2 years.

Children 1-3 years of age get a smaller dose than older children and adults. Children younger than 1 year of age should not normally get the vaccine.

JE vaccine may be given at the same time as other vaccines.

Who should NOT get Japanese encephalitis vaccine?Return to top .
Anyone who has ever had a life-threatening reaction to mouse protein, thimerosal, or to a previous dose of JE vaccine. Tell your doctor if you:

•have severe allergies, especially a history of allergic rash (hives) or wheezing after a wasp sting or taking medications,

•are pregnant, or are a nursing mother,

•will be traveling for fewer than 30 days, especially if you will be in major urban areas. (You may be at lower risk for Japanese encephalitis and not need the vaccine.)

Risks of Japanese encephalitis vaccine
A vaccine, like any medicine, is capable of causing serious problems, such as severe allergic reactions. The risk of a vaccine causing serious harm, or death, is extremely small.

Mild problems:

•soreness, redness, or swelling where the shot was given (about 1 person in 5)

•fever, headache, muscle pain, abdominal pain, rash, chills, nausea/vomiting, dizziness (about 1 person in 10)

•If these problems occur, they usually begin soon after the shot and last for a couple of days.

Moderate or Severe Problems:
•Serious allergic reactions including rash; swelling of the hands and feet, face, or lips; and breathing difficulty. These have occurred within minutes to as long as 10 to 17 days after receiving the vaccine, usually about 48 hours after the vaccination. (About 60 per 10,000 people vaccinated have had allergic reactions to JE vaccine.)

•Other severe problems, such as seizures or nervous system problems, have been reported. These are rare (probably less than 1 per 50,000 people vaccinated).

What is to be done if there is a moderate or severe reaction.
•Look for any unusual conditions, such as high fever, allergic symptoms or neurologic problems that occur 1-30 days after vaccination. Signs of an allergic reaction can include difficulty breathing, hoarseness or wheezing, hives, swelling of extremities, face, or lips, paleness, weakness, a fast heartbeat, or dizziness within a few minutes up to two weeks after the shot.

•Call a doctor, or get the person to a doctor right away.

•Tell your doctor what happened, the date and time it happened, and when the vaccination was given.

•Ask your health care provider to file a Vaccine Adverse Event Reporting System (VAERS) form if you have any reaction to the vaccine. Or call VAERS yourself at 1-800-822-7967 begin_of_the_skype_highlighting 1-800-822-7967 end_of_the_skype_highlighting, or visit their website at http://vaers.hhs.gov.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose

Resources:
http://en.wikipedia.org/wiki/Japanese_encephalitis
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a607019.html
http://www.bbc.co.uk/health/physical_health/conditions/japanese-encephalitis.shtml

http://ocw.jhsph.edu/imagelibrary/index.cfm/go/il.viewimagedetails/resourceid/439d2d83-d8de-7364-797f08dccfbde10c/

http://www.cdc.gov/ncidod/dvbid/westnile/culex-image.htm

http://modernmedicalguide.com/wp-content/uploads/2011/03/Japanese-encephalitis.jpg

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