Japanese B Encephalitis An Overview of the Diseas

Authors: Ruth Chin Joseph Torresi

Publish Date: 2013/11/19

Volume: 2, Issue: 2, Pages: 145-158

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Abstract

The Japanese encephalitis virus JEV is endemic in many countries in southern Asia and the western Pacific Rim with new spread to previously unrecognized countries It is an important cause of childhood neurological disease associated with permanent neurological sequelae and death Fortunately JE is a vaccinepreventable disease The ChimeriVax™JE Sanofi Pasteur Lyon France is a liveattenuated chimeric vaccine derived from the liveattenuated yellow fever virus YF17D which expresses the envelope proteins of the attenuated JEV vaccine strain SA14142 It is a safe welltolerated vaccine that is highly immunogenic in adults and children The average geometric mean neutralizing antibody titer GMT in adults is 1392 and over 90 of adults remain seroprotected 5 years after vaccination In children and toddlers more than 80 remain seroprotected 2 years after primary vaccination and demonstrate a robust and durable anamnestic response 500fold rise in GMT with 991 seroprotection rates 1 year after a booster vaccine dose The ChimeriVax™JE is effective in children living in endemic regions where the vaccine could possibly be integrated into existing childhood vaccination programs ChimeriVax™JE is also indicated for travelers at risk of JE infectionJapanese encephalitis virus JEV causes a serious and potentially lifethreatening infection of the central nervous system of which children are the most affected Although the majority of infections are asymptomatic the case fatality is estimated at 20–30 in those who develop clinical disease and up to 50 of survivors experience lifelong neuropsychiatric sequelae 1 2 There is no specific antiviral treatment for JE infection but with the availability of safe effective vaccines that can be integrated into existing childhood vaccination programs in endemic countries there is an opportunity to reduce the adverse health and economic burden of JEV diseaseCurrently there are three commercial vaccines licensed for use in several regions of the world 3 4 5 This review will focus on the liveattenuated JEchimeric vaccine ChimeriVax™JE also known as IMOJEV and JECV Sanofi Pasteur Lyon France It is a safe and effective prophylactic vaccine against JE for adults and children over 12 months of age and represents a significant advance from the mouse brainderived inactivated JE vaccine that had been available since 1955 There is emerging evidence that ChimeriVax™JE is capable of eliciting longlasting immunity even after a single dose of vaccine making this vaccine an attractive option for use in JE endemic regions of the worldThe analysis in this article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors This review was conducted through a MEDLINE search limited to the English language from 1980 to June 2013 using the following search terms and filters Japanese encephalitis natural history virology and vaccine Manualsearch of reference list of relevant studies clinical trials and reviews was also conductedJEV belongs to the family of Flaviviridae genus Flavivirus and shares antigenic crossreactivity with other members of the Flavivirus genus including dengue virus Murray Valley encephalitis virus Kunjin virus West Nile Virus and St Louis encephalitis virus It is an enveloped spherical virus that contains an 11kb single stranded positivesense RNA genome The viral genome encodes a single polyprotein that is cleaved into three structural proteins capsid membrane and envelope and seven nonstructural proteins NS1 NS2A NS2B NS3 NS4A NS4B and NS5 The envelope E protein is involved in host receptor binding and entry neurovirulence and tissue tropism and is the major antigenic determinant of the host immune response 6 7There are four major genotypes of JEV based on the envelope gene and each genotype has been shown to have a relatively specific regional geographic distribution Genotypes I and III predominate in the more temperate regions of Korea Japan China Taiwan Philippines northern Thailand and Cambodia These viruses are often associated with epidemics of JE In contrast genotypes II and IV are associated with endemic infection in southern Thailand Malaysia and Indonesia 8 Genotype V was identified in association with an epidemic of encephalitis in Malaysia in 1952 8 and has been isolated in the mosquito vector Culex tritaeniorhynchus in China 9JEV is transmitted in a zoonotic cycle between mosquitoes water birds and pigs The principal mosquito vector is the Culex mosquito in particular C tritaeniorhynchus an evening and nighttime biting mosquito 10 Mosquitoes are zoophilic feeding on wading birds herons and egrets and pigs which are the primary hosts in the infection cycle JEV infection causes hightiter viremia in pigs which are increasingly recognized as the most important ecological reservoir for JE in the amplification and spread of JEV 7 Humans are incidental endhosts in the lifecycle of JEV and not necessary for the maintenance of the viral transmission due to lowtiter viremia in humans that is insufficient to infect the biting mosquito vectors

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