Description
Japanese encephalitis is the term used to describe infection by Japanese encephalitis virus (JEV), a single-stranded RNA virus that belongs to the genus Flavivirus and is closely related to West Nile and Saint Louis encephalitis viruses.JEV is transmitted to humans through the bite of an infected mosquito, particularly Culex species. The virus normally cycles between vertebrate hosts such as pigs and wading birds (herons and egrets) and biting mosquitoes. Humans and horses are considered accidental dead-end hosts, because they usually do not develop a level or duration of viraemia sufficient to infect mosquitoes and continue the life cycle of the virus.
JEV evades the immune system during early infection, probably by replicating in macrophages and monocytes. Normally flaviviruses are detected by
intracellular receptors which trigger the production of interferon, a key element in the immune response to viral infections. JEV is able to suppress or delay interferon production sufficiently to allow the virus to replicate within the cell and infect neighbouring cells. Eventually the immune system generates a T cell response that destroys infected cells and the virus is eliminated.
In some cases the immune system is unable to prevent spread of the virus to the central nervous system. The virus crosses the blood brain barrier by passage from infected endothelial cells in blood vessel walls or by infected macrophages or monocytes. The virus destroys neurons and astrocytes in a variety of areas of the brain including the thalamus, basal ganglia, brain stem, cerebellum, hippocampus, and cerebral cortex. Persistent infection and congenital transmission may occur.
It is not known if the destruction of neurons and astrocytes is caused directly by the action of the virus or indirectly by a virus activated inflammatory response.
In addition to destroying the neurons of the brain, JEV is thought to block the regeneration of new neurons from neural stem cells, preventing the normal repair mechanisms and causing permanent brain damage.
Areas where Japanese encephalitis is endemic
JEV is thought to have originated in the Indonesia Malaysia region and has spread, probably by migratory birds, to infect most of southern and eastern Asia and parts of Russia and Northern Australia. There are an estimated 50,000 cases of encephalitis each year with approximately 10000 deaths, making JEV one of the most important causes of viral encephalitis in the world. Countries affected by JEV include Bangladesh, Bhutan, Cambodia, China, India, Indonesia, Japan, Laos, Malaysia, Myanmar, Nepal, Papua New Guinea, the Philippines, Russia, Sri Lanka, Thailand, East Timor, Vietnam, North Korea, and South Korea.
Virus transmission occurs mainly in rural agricultural areas, usually in association with rice cultivation and flooding irrigation.
In temperate areas of Asia, transmission is seasonal, and human disease usually peaks in summer and fall. In the subtropics and tropics, seasonal transmission varies with monsoon rains and irrigation practices and may occur year-round.
In endemic countries, Japanese encephalitis (JE) is primarily a disease of children. When the virus spreads to new areas it may also affect adults. Travel-associated JE can occur among people of any age. The risk for JE for most travelers to Asia is extremely low but varies based on destination, duration, season, and activities.
Signs & Symptoms
Most JEV infections are asymptomatic. Approximately 1 in 300 patients will develop clinical symptoms including fever, headache, chills, nausea, vomiting muscle pain and diarrhoea, which may last for several days. Signs of CNS involvement include seizures, reduced consciousness and focal neurological signs. As the disease progresses a poliomyelitis-like flaccid paralysis or Parkinson like syndrome may develop with a dull, flat, mask like face, wide, unblinking eyes, tremors, generalized muscle rigidity or hypertonia (abnormal muscle contraction or tension), and other movement disorders.In fatal cases there is severe vascular congestion, oedema and necrosis in the brain. Mortality rates vary from 10 -30%.
Approximately 33-50% of survivors with CNS disease have persisting neurological problems, including seizure disorders, motor or cranial nerve deficits or movement disorders. At 5 years, nearly 75% of such patients score lower on standardized tests than control subjects.
Treatment
Treatment is mainly supportive with anticonvulsants for seizures and mannitol for intracranial pressure.Some experimental antiviral therapies including suramin, diethyldithiocarbamate and arctigenin have been used with limited success.
Vaccines
Until recently Japanese Encephalitis-VAX (JE-VAX) has been widely used to protect against JEV. It is formalin inactivated virus preparation derived from mouse brains infected with the Nakayama strain of JEV. This has been largely superseded by an inactivated Vero cell culture–derived vaccine, Ixiaro, manufactured by Intercell and distributed by Novartis Vaccines
The primary immunization schedule for Ixiaro is 2 doses administered intramuscularly on days 0 and 28. The dose is 0.5 mL for people aged ≥17 years, and the 2-dose series should be completed at least week before travel.
Vaccination is recommended for individuals who spend more than one month in endemic areas.
Patient Management
Individuals at risk of exposure should be vaccinated. Mosquito bites should be prevented by use of appropriate clothing, mosquito nets and insect repellent.
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