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Japanese encephalitis

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Japanese encephalitis
SpecialtyInfectious diseases Edit this on Wikidata

Japanese encephalitis
Virus classification
Group:
Group IV ((+)ssRNA)
Family:
Flaviviridae
Genus:
Flavivirus
Species:
Japanese encephalitis virus

Japanese encephalitis ([日本脳炎, Nihon-nōen] Error: {{Lang-xx}}: text has italic markup (help))—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. Amongst the most important vectors of this disease are the mosquitoes Culex tritaeniorhynchus and Culex vishnui. This disease is most prevalent in Southeast Asia and the Far East.

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, 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.[1]

In animals, key signs include infertility and abortion in pigs, neurological disease in horses and systemic signs including fever, lethargy and anorexia.[2]

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.[3] 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 flavivirus 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)[4][5] 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.[6]

Viral antigen can also be shown in tissues by indirect fluorescent antibody staining.[2]

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.

Prevention

Main article: Japanese encephalitis vaccine

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,[7] 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.[8]

Neutralising antibody persists in the circulation for at least two to three years, and perhaps longer.[9][10] 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 [1]. 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.[11]

Treatment

There is no specific treatment for Japanese encephalitis and treatment is supportive; with assistance given for feeding, breathing or seizure control as required. Raised intracranial pressure may be managed with mannitol.[12] 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.[13]

Epidemiology

Disability-adjusted life year for Japanese encephalitis per 100,000 inhabitants in 2002.
  no data
  less than 1
  1-5
  5-10
  10-15
  15-20
  20-25
  25-30
  30-35
  35-40
  40-45
  45-50
  more than 50
Geographic distribution of Japanese encephalitis (in yellow).

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.[14] In November 2011, Japanese encephalitis virus was reported in Culex bitaeniorhynchus in the Republic of Korea.[15]

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.[16]

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.

  • Curcumin 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.[19]
  • Minocycline in mice resulted in marked decreases in the levels of several markers, viral titer, and the level of proinflammatory mediators[20] and also prevents blood brain barrier damage.[21]

References

  1. ^ Ghoshal, A; Das, S; Ghosh, S; Mishra, MK; Sharma, V; Koli, P; Sen, E; Basu, A. (2007). "Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis". Glia. 55 (5): 483–96. doi:10.1002/glia.20474. PMID 17203475.
  2. ^ a b Japanese Encephalitis Virus reviewed and published by WikiVet, accessed 11 October 2011.
  3. ^ Mohammed MA, Galbraith SE, Radford AD, Dove W, Takasaki T, Kurane I, Solomon T (2011). "Molecular phylogenetic and evolutionary analyses of Muar strain of Japanese encephalitis virus reveal it is the missing fifth genotype". Infect Genet Evol. 11 (5): 855–62. doi:10.1016/j.meegid.2011.01.020. PMID 21352956. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ He B (2006). "Viruses, endoplasmic reticulum stress, and interferon responses". Cell Death Differ. 13 (3): 393–403. doi:10.1038/sj.cdd.4401833. PMID 16397582. {{cite journal}}: Unknown parameter |month= ignored (help)
  5. ^ Su HL, Liao CL, Lin YL (2002). "Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response". J. Virol. 76 (9): 4162–71. doi:10.1128/JVI.76.9.4162-4171.2002. PMC 155064. PMID 11932381. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Shrivastva A, Tripathi NK, Parida M, Dash PK, Jana AM, Lakshmana Rao PV (2008). "Comparison of a dipstick enzyme-linked immunosorbent assay with commercial assays for detection of Japanese encephalitis virus-specific IgM antibodies". J Postgrad Med. 54 (3): 181–5. doi:10.4103/0022-3859.40959. PMID 18626163.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  7. ^ Jelinek T (2008). "Japanese encephalitis vaccine in travelers". Expert Rev Vaccines. 7 (5): 689–93. doi:10.1586/14760584.7.5.689. PMID 18564023. {{cite journal}}: Unknown parameter |month= ignored (help)
  8. ^ EMEA Approval of Vaccine http://www.emea.europa.eu/pdfs/human/opinion/Ixiaro_66231608en.pdf
  9. ^ Gambel JM, DeFraites R, Hoke C; et al. (1995). "Japanese encephalitis vaccine: persistence of antibody up to 3 years after a three-dose primary series (letter)". J Infect Dis. 171 (4): 1074. doi:10.1093/infdis/171.4.1074. PMID 7706798. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  10. ^ Kurane I, Takashi T (2000). "Immunogenicity and protective efficacy of the current inactivated Japanese encephalitis vaccine against different Japanese encephalitis virus strains". Vaccine. 18 (Suppl): 33–5. doi:10.1016/S0264-410X(00)00041-4. PMID 10821971.
  11. ^ Solomon T (2006). "Control of Japanese Encephalitis—within our grasp?". New England Journal of Medicine. 355 (9): 869–871. doi:10.1056/NEJMp058263. PMID 16943399.
  12. ^ Japanese encephalitis~treatment at eMedicine
  13. ^ Nimesh Gupta, Vinay Lomash and P.V. Lakshmana Rao (2010). "Expression profile of Japanese encephalitis virus induced neuroinflammation and its implication in disease severity". Journal of Clinical Virology. 49 (1): 04–10. doi:10.1016/j.jcv.2010.06.009. PMID 20637688. {{cite journal}}: Unknown parameter |month= ignored (help)
  14. ^ Ghosh D, Basu A (September 2009). "Japanese encephalitis-a pathological and clinical perspective". PLoS Negl Trop Dis. 3 (9): e437. doi:10.1371/journal.pntd.0000437. PMC 2745699. PMID 19787040.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  15. ^ Kim, Heung Chul, Terry A. Klein, Ratree Takhampunya, Brian P. Evans, Sirima Mingmongkolchai, Ampornpan Kengluecha, John Grieco, Penny Masuoka, Myung-Soon Kim, Sung-Tae Chong, Jong-Koo Lee, and Won-Ja Lee. 2011. Japanese Encephalitis Virus in Culicine Mosquitoes (Diptera: Culicidae) Collected at Daeseongdong, a Village in the Demilitarized Zone of the Republic of Korea. Journal of Medical Entomology 48(6): 1250-1256.
  16. ^ Nimesh Gupta, S.R. Santhosh, J. Pradeep Babu, M.M. Parida, P.V. Lakshmana Rao (2010). "Chemokine profiling of Japanese encephalitis virus-infected mouse neuroblastoma cells by microarray and real-time RT-PCR: Implication in neuropathogenesis". Virus Research. 147 (1): 107. doi:10.1016/j.virusres.2009.10.018. PMID 19896511. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Swarup V, Ghosh J, Ghosh S, Saxena A, Basu A (2007). "Antiviral and anti-inflammatory effects of rosmarinic acid in an experimental murine model of Japanese encephalitis". Antimicrob. Agents Chemother. 51 (9): 3367–70. doi:10.1128/AAC.00041-07. PMC 2043228. PMID 17576830. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ Swarup V, Ghosh J, Mishra MK, Basu A (2008). "Novel strategy for treatment of Japanese encephalitis using arctigenin, a plant lignan". J. Antimicrob. Chemother. 61 (3): 679–88. doi:10.1093/jac/dkm503. PMID 18230688. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  19. ^ Dutta K, Ghosh D, Basu A (2009). "Curcumin Protects Neuronal Cells from Japanese Encephalitis Virus-Mediated Cell Death and also Inhibits Infective Viral Particle Formation by Dysregulation of Ubiquitin-Proteasome System". J Neuroimmune Pharmacol. 4 (3): 328. doi:10.1007/s11481-009-9158-2. PMID 19434500. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ Mishra MK, Basu A (2008). "Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis". J. Neurochem. 105 (5): 1582–95. doi:10.1111/j.1471-4159.2008.05238.x. PMID 18208541. {{cite journal}}: Unknown parameter |month= ignored (help)
  21. ^ Mishra MK, Dutta K, Saheb SK, Basu A (December 2009). "Understanding the molecular mechanism of blood–brain barrier damage in an experimental model of Japanese encephalitis: correlation with minocycline administration as a therapeutic agent". Neurochem Int. 55 (8): 717–23. doi:10.1016/j.neuint.2009.07.006. PMID 19628016.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Further reading

  • Clark, Michael; Kumar, Parveen J. (2002). Clinical Medicine (5th ed.). London: W B Saunders. ISBN 0-7020-2579-8.{{cite book}}: CS1 maint: multiple names: authors list (link)

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Japanese_encephalitis&oldid=494378204"