Japanese Encephalitis
Encyclopedia
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 (herons) 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
.
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-α), 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.
In animals, key signs include infertility and abortion in pigs, neurological disease in horses and systemic signs including fever, lethargy and anorexia.
and is closely related to the West Nile virus
and St. Louis encephalitis
virus. The positive sense single stranded RNA
genome is packaged in the capsid
which is 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
.
Viral antigen can also be shown in tissues by indirect fluorescent antibody staining
.
Based on the envelope gene (E) there are five genotypes (I - V). The Muar strain, isolated from patient in Malaya
in 1952, is the prototype strain of genotype V. Genotype IV appears to be the ancestral strain and the virus appears to have evolved in the Indonesian-Malayasian region. The first clinical reports date from 1870 but the virus appears to have evolved in the mid 1500s.
Over 60 complete genomes of this virus have been sequenced as of 2010.
In the UK, the three vaccines used (two of which are unlicensed) which are JE-Vax, Green Cross and IXIARO (licensed). JE-Vax however has subsequentally been removed from market. JE-Vax and Green Cross require three doses 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.
IXIARO the new vaccine has been produced by Intercell Biomedical Ltd and requires only 2 doses, and is currently licensed in the U.S., Europe (inc UK), Canada and Australia.
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. However in the case of IXIARO where the vaccine is not produced in mouse brains but in vitro using cell culture there is little adverse effects compared to the Placebo, the main side effects are Headache and myalgia
.
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 three years for people who remain at risk http://www.dh.gov.uk/dr_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_112475.pdf. Furthermore there is also no data available regarding the interchangeability of other JE vaccines and IXIARO and recommended those previously immunised with other JE vaccines receive Green Cross or JE-Vax or a primary course of IXIARO.
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.
, breathing
or seizure
control as required. Raised intracranial pressure may be managed with mannitol
. 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.
Japanese encephalitis (JE) 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. However, the current presence on mainland Australia is minimal. 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 Culex tritaeniorhynchus
, which feeds on cattle in preference to humans, it has been proposed that moving swine away from human habitation can divert the mosquito away from humans and swine. The natural host of the Japanese encephalitis virus is bird, not human, and many believe the virus will therefore never be completely eliminated. In November 2011, Japanese encephalitis virus was reported in Culex bitaeniorhynchus in the Republic of Korea.
Recently whole genome microarray research of neuron in JE virus infection has shown that neurons play an important role in
their own defense against Japanese encephalitis viral infection. Although this challenges the long-held belief that neurons are immunologically quiescent,an improved understanding of the proinflammatory effects responsible for immune-mediated control of viral infection and neuronal injury during JEV infection is an essential step for developing strategies for limiting the severity of CNS disease.
A number of drugs have been investigated to either reduce viral replication or provide neuroprotection in cell lines or studies upon mice. None are currently advocated in treating human patients.
Constantin von Economo
Constantin Freiherr von Economo was a Romanian psychiatrist and neurologist of Greek origin. He is mostly known for his discovery of encephalitis lethargica and his atlas of cytoarchitectonics.- Youth and schooling :Constantin Freiherr Economo von San Serff was born in Brăila, Romania, to Greek...
's A encephalitis—is a disease caused by the mosquito
Mosquito
Mosquitoes are members of a family of nematocerid flies: the Culicidae . The word Mosquito is from the Spanish and Portuguese for little fly...
-borne Japanese encephalitis virus. The Japanese encephalitis virus is a virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
from the family Flaviviridae
Flaviviridae
The Flaviviridae are a family of viruses that are primarily spread through arthropod vectors . The family gets its name from Yellow Fever virus, a type virus of Flaviviridae; flavus means yellow in Latin...
. Domestic pigs
PIGS
PIGS is a four letter acronym that can stand for:* PIGS , Phosphatidylinositol glycan anchor biosynthesis, class S, a human gene* PIGS , the economies of Portugal, Italy , Greece and Spain...
and wild birds (herons) 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
Culex tritaeniorhynchus
Culex tritaeniorhynchus is a species of mosquitoes which transmits Japanese encephalitis. This mosquito is a native of northern Asia, and parts of Africa . The females target large animals for blood extraction, including cattle and swine.- External links :*...
. This disease is most prevalent in Southeast Asia
Southeast Asia
Southeast Asia, South-East Asia, South East Asia or Southeastern Asia is a subregion of Asia, consisting of the countries that are geographically south of China, east of India, west of New Guinea and north of Australia. The region lies on the intersection of geological plates, with heavy seismic...
and the Far East
Far East
The Far East is an English term mostly describing East Asia and Southeast Asia, with South Asia sometimes also included for economic and cultural reasons.The term came into use in European geopolitical discourse in the 19th century,...
.
Signs and symptoms
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
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
, hemiparesis
Hemiparesis
Hemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength....
, convulsions and a raised body temperature between 38 and 41 degrees Celsius. Mental retardation developed from this disease usually leads to coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
. 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
Hemiparesis
Hemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength....
may occur in those who have had central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
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-α), 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
Murinae
The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. This subfamily is larger than all mammal families except the Cricetidae and Muridae, and is larger than all mammal orders except the bats and the remainder of the...
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.
In animals, key signs include infertility and abortion in pigs, neurological disease in horses and systemic signs including fever, lethargy and anorexia.
Evolution
The virus appears to have originated from its ancestral virus in the mid 1500s in the Indonesia-Malaysia region and evolved there into five different genotypes and spread across Asia. The mean evolutionary rate has been estimated to be 4.35×10(-4) (range: 3.4906×10(-4) to 5.303×10(-4)) nucleotides substitutions per site per year.Virology
The causative agent Japanese encephalitis virus is an enveloped virus of the genus flavivirusFlavivirus
Flavivirus is a genus of the family Flaviviridae. This genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, and several other viruses which may cause encephalitis....
and is closely related to the West Nile virus
West Nile virus
West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...
and St. Louis encephalitis
St. Louis Encephalitis
St. Louis Encephalitis is a disease caused by the Culex mosquito borne St. Louis Encephalitis virus. St. Louis encephalitis virus is related to Japanese encephalitis virus and is a member of the Flaviviridae subgroup. This disease mainly affects the United States...
virus. The positive sense single stranded RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
genome is packaged in the capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
which is 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
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
of the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
(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
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
.
Viral antigen can also be shown in tissues by indirect fluorescent antibody staining
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
.
Based on the envelope gene (E) there are five genotypes (I - V). The Muar strain, isolated from patient in Malaya
Federation of Malaya
The Federation of Malaya is the name given to a federation of 11 states that existed from 31 January 1948 until 16 September 1963. The Federation became independent on 31 August 1957...
in 1952, is the prototype strain of genotype V. Genotype IV appears to be the ancestral strain and the virus appears to have evolved in the Indonesian-Malayasian region. The first clinical reports date from 1870 but the virus appears to have evolved in the mid 1500s.
Over 60 complete genomes of this virus have been sequenced as of 2010.
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 three vaccines used (two of which are unlicensed) which are JE-Vax, Green Cross and IXIARO (licensed). JE-Vax however has subsequentally been removed from market. JE-Vax and Green Cross require three doses 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.
IXIARO the new vaccine has been produced by Intercell Biomedical Ltd and requires only 2 doses, and is currently licensed in the U.S., Europe (inc UK), Canada and Australia.
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. However in the case of IXIARO where the vaccine is not produced in mouse brains but in vitro using cell culture there is little adverse effects compared to the Placebo, the main side effects are Headache and myalgia
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
.
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 three years for people who remain at risk http://www.dh.gov.uk/dr_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_112475.pdf. Furthermore there is also no data available regarding the interchangeability of other JE vaccines and IXIARO and recommended those previously immunised with other JE vaccines receive Green Cross or JE-Vax or a primary course of IXIARO.
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; with assistance given for feedingFeeding tube
A feeding tube is a medical device used to provide nutrition to patients who cannot obtain nutrition by swallowing. The state of being fed by a feeding tube is called gavage, enteral feeding or tube feeding...
, breathing
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...
or seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
control as required. Raised intracranial pressure may be managed with mannitol
Mannitol
Mannitol is a white, crystalline organic compound with the formula . This polyol is used as an osmotic diuretic agent and a weak renal vasodilator...
. 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
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
receptor CLEC5A
CLEC5A
C-type lectin domain family 5 member A or CLEC5A, also known as C-type lectin superfamily member 5 and myeloid DAP12-associating lectin 1 is a C-type lectin that in humans is encoded by the CLEC5A gene. It appears to be a member of a significant myeloid lineage activating pathway....
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.
Epidemiology
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, 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
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
, Korea
Korea
Korea ) is an East Asian geographic region that is currently divided into two separate sovereign states — North Korea and South Korea. Located on the Korean Peninsula, Korea is bordered by the People's Republic of China to the northwest, Russia to the northeast, and is separated from Japan to the...
, Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, Taiwan
Taiwan
Taiwan , also known, especially in the past, as Formosa , is the largest island of the same-named island group of East Asia in the western Pacific Ocean and located off the southeastern coast of mainland China. The island forms over 99% of the current territory of the Republic of China following...
and Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...
. Other countries that still have periodic epidemics include Vietnam
Vietnam
Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...
, Cambodia
Cambodia
Cambodia , officially known as the Kingdom of Cambodia, is a country located in the southern portion of the Indochina Peninsula in Southeast Asia...
, Myanmar
Myanmar
Burma , officially the Republic of the Union of Myanmar , is a country in Southeast Asia. Burma is bordered by China on the northeast, Laos on the east, Thailand on the southeast, Bangladesh on the west, India on the northwest, the Bay of Bengal to the southwest, and the Andaman Sea on the south....
, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
, Nepal
Nepal
Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...
, and Malaysia. Japanese encephalitis has been reported on the Torres Strait Islands
Torres Strait Islands
The Torres Strait Islands are a group of at least 274 small islands which lie in Torres Strait, the waterway separating far northern continental Australia's Cape York Peninsula and the island of New Guinea but Torres Strait Island known and Recognize as Nyumaria.The islands are mostly part of...
and two fatal cases were reported in mainland northern Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
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. However, the current presence on mainland Australia is minimal. 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 Culex tritaeniorhynchus
Culex tritaeniorhynchus
Culex tritaeniorhynchus is a species of mosquitoes which transmits Japanese encephalitis. This mosquito is a native of northern Asia, and parts of Africa . The females target large animals for blood extraction, including cattle and swine.- External links :*...
, which feeds on cattle in preference to humans, it has been proposed that moving swine away from human habitation can divert the mosquito away from humans and swine. The natural host of the Japanese encephalitis virus is bird, not human, and many believe the virus will therefore never be completely eliminated. In November 2011, Japanese encephalitis virus was reported in Culex bitaeniorhynchus in the Republic of Korea.
Recently whole genome microarray research of neuron in JE virus infection has shown that neurons play an important role in
their own defense against Japanese encephalitis viral infection. Although this challenges the long-held belief that neurons are immunologically quiescent,an improved understanding of the proinflammatory effects responsible for immune-mediated control of viral infection and neuronal injury during JEV infection is an essential step for developing strategies for limiting the severity of CNS disease.
A number of drugs have been investigated to either reduce viral replication or provide neuroprotection in cell lines or studies upon mice. None are currently advocated in treating human patients.
- The use of rosmarinic acidRosmarinic acidRosmarinic acid, C18H16O8, is a natural phenol antioxidant carboxylic acid found in many Lamiaceae herbs used commonly as culinary herbs such as lemon balm, rosemary, oregano, sage, thyme and peppermint. Chemically, rosmarinic acid is an ester of caffeic acid with 3,4-dihydroxyphenyl lactic acid...
, and arctigeninArctigeninArctigenin is a lignan found in certain plants of the Asteraceae, including the Greater burdock and Saussurea heteromalla. It has shown antiviral and anticancer effects. It is the aglycone of arctiin.- External links :...
, have been shown to be effective in a mouse model of Japanese encephalitis
- CurcuminCurcuminCurcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family . The other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are natural phenols and are responsible for the yellow color of turmeric...
has been shown to impart neuroprotection against JEV infection in an in vitro study. Curcumin possibly acts by decreasing cellular reactive oxygen species level, restoration of cellular membrane integrity, decreasing pro-apoptotic signaling molecules, and modulating cellular levels of stress-related proteins. It has also been shown that the production of infective viral particles from previously infected neuroblastoma cells are reduced, which is achieved by the inhibition of ubiquitin-proteasome system.
- MinocyclineMinocyclineMinocycline is a broad-spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type...
in mice resulted in marked decreases in the levels of several markers, viral titer, and the level of proinflammatory mediators and also prevents blood brain barrier damage.
External links
- Centers for Disease Control and Prevention Questions and Answers About Japanese Encephalitis
- Australian government Department of Health and Aging, Japanese Encephalitis, 2004
- UK Department of Health. (2006) Immunisation against Infectious Disease Chapter 20: Japanese Encephalitis
- WHO. http://www.who.int/water_sanitation_health/diseases/encephalitis/en/
- PATH's Japanese encephalitis project http://www.path.org/je
- Japanese encephalitis resource library http://www.path.org/vaccineresources/japanese-encephalitis.php