Japanese encephalitis

 Japanese encephalitis

What is Japanese encephalitis?

• Japanese encephalitis is a virus in the flavivirus family. The Culex mosquito passes it on.
• The virus can infect horses and pigs, as well as humans. This can lead to encephalitis in horses and miscarriage in pigs.
• A host is the source of a virus, and the vector passes it on. Wild birds are likely to be the natural hosts of JEV, and mosquitoes are the vectors. A vector does not cause disease but passes it on.
• When mosquitoes infect an animal, the animal might become a carrier of the virus. When other mosquitos feed on these animals that have newly acquired the virus, they take it on board and infect other animals.
• People are at the highest risk in rural areas where the virus is common. Japanese encephalitis is common around towns and cities.
• It is more likely to affect children because adults in areas where the virus is endemic generally become immune as they get older.

Structure of Japanese Encephalitis (JE) Virus

•     Japanese encephalitis (JE) virus falls under the family Flaviviridae.
•     The particles appear to be spherical, 50 nm in diameter, containing an electron dense core (about 30 nm diameter) surrounded by a lipid bilayer.
•     Mature virions sediment between 170 and 210S, have a buoyant density of 1.19 to 1.23 g/mL.
•     It has a small lipoprotein envelope surrounding a nucleocapsid comprising of the core protein.
•     The nucleocapsid also encloses the single stranded RNA genome with positive polarity which is 11kb in length.

Genome of Japanese Encephalitis (JE) Virus

•     Surrounding the ORF are 5′ and 3′ noncoding regions (NCRs) of around 100 nucleotides (nt) and 400 to 700 nt, respectively.
•     The genome is translated as a large polyprotein that is processed co- and posttranslationally by cellular proteases and a virally encoded serine protease into at least 10 discrete products.
•     The N-terminal one quarter of the polyprotein encodes the structural proteins, and the remainder contains the nonstructural (NS) proteins, in the following order: C-prM-E-NS1-NS2A-NS3-NS4A-NS4B-NS5.
•     Three viral proteins are associated with virions: the E (envelope), M (membrane), and C (capsid) proteins.
•     The E protein (50kd) is the major surface protein of the viral particle, probably interacts with viral receptors, and mediates virus–cell membrane fusion.
•     M protein is a small proteolytic fragment of prM protein (26kd), which is important for maturation of the virus into an infectious form.
•     C protein (about 11 kd) is highly basic, consistent with its proposed role in forming a ribonucleoprotein complex with packaged genomic RNA.

Pathogenesis of Japanese Encephalitis (JE) Virus

•     The portal of entry for the JE virus is through the bite of mosquito which contain virus.
•     After the bite on skin the virus enter the Reticuloendothelial system (RES) and follows transient phase of viremia.
•     After the transient viremia the virus invades the central nervous system.
•     The virus enters the neuroparenchyma by crossing the capillary walls of brain and distributes itself in hypothalamus, hippocampus, substantia nigra and medulla oblongata regions of brain via vascular endothelial cells by the mechanism of endocytosis.
•     The mechanism of endocytosis is either cholesterol or clathrin mediated pathway.
•     Virus then replicates in neurons and matures in the neuronal secretory system.
•     JE typically develops in patients after an incubation period of 5–15 days.
•     It is possible that during this time, the virus resides and multiplies within host leukocytes, which act as carriers to the CNS.
•     T lymphocytes and IgM play a major role in the recovery and clearance of the virus after infection.
•     Besides neuronal cells, researchers have shown that astrocytes are also infected by JEV.
•     Crossing the blood brain barrier is an important factor in the increased pathogenesis and clinical outcome of the neurotropic viral infection.
•     Astrocytes, being a component of the blood–brain barrier, may help in the transmission of JEV from peripheral tissues to the cerebrospinal fluid.
•     It is known that JEV causes neuronal cell death in two ways: direct neuronal killing , wherein viral multiplication within neuronal cells leads to cell death, and the indirect mode of killing, wherein massive inflammatory response causes an up-regulation of reactive oxygen species and cytokines such as tumor necrosis factor α (TNFα), which, in turn, causes neuronal death. 

Laboratory Diagnosis of Japanese Encephalitis (JE) Virus

•     Specimens: CSF, Blood, Plasma, Serum, Tissue(rare)
•     Detection of JE virus–specific IgM by using a JE virus–specific IgM-capture ELISA on CSF or serum.
•     JE virus–specific IgM can be measured in the CSF of most patients by 4 days after onset of symptoms and in serum by 7 days after onset.
•     Plaque reduction neutralization tests can be performed to confirm the presence of JE virus–specific neutralizing antibodies and discriminate between cross-reacting antibodies from closely related flaviviruses.
•     A greater 4-fold rise in JE virus– specific neutralizing antibodies between acute-and convalescent-phase serum specimens may be used to confirm recent infection.
•     Detection of JE antigen in tissue by immunofluorescence or immunohistochemistry.
•     Detection of JE virus genome in serum, plasma, blood, CSF or tissue by RT-PCR.

Treatment of Japanese Encephalitis (JE) Virus

•     There is no specific antiviral treatment for JE.
•     Therapy consists of supportive care and management of complications.

Prevention and Control of Japanese Encephalitis (JE) Virus

Vaccination

•     One JE vaccine is licensed and available in the United States which is an inactivated Vero cell culture derived vaccine, Ixiaro.
•     Other inactivated and live attenuated JE vaccines are manufactured and used in other countries.
•     The vaccine is given as a 2-dose series, with the doses spaced 28 days apart and administered intramuscularly.
•     The second dose should be given at least a week before travel.
•     Children younger than 3 years of age get a smaller dose than patients who are 3 or older.
•     A booster dose might be recommended for anyone 17 or older who was vaccinated more than a year ago and is still at risk of exposure. 
•     The Advisory Committee on Immunization Practices recommends JE vaccine for travelers who plan to spend ≥1 month in endemic areas during the JE virus transmission season which includes long-term travelers, recurrent travelers, or expatriates who will be based in urban areas but are likely to visit endemic rural or agricultural areas during a high-risk period of JE virus transmission.
•     Early case detection and treatment.
•     Use of Larvicides, insecticides, and ecofriendly methods such as using neem cakes and growing larvivorous fish in controlling mosquitoes in paddy fields.
•     Vector control by reduction of breeding source for larvae, reduction of man-mosquito contact by wearing proper clothing to reduce mosquito bites and control of adult mosquitoes.