Knowledge
Japanese encephalitis and vaccines
JE is an important disease in East, Southeast, and South Asia, which lead to serious complication and high mortality rate. it caused by viral infection transmitted by Culex mosquitoes. Complete cure is shown in only one third of the patients. However an inapparent infection presents in 1 of 25 to 1,000 infections manifests neurological symptoms. There is not any effective medication however prevention of JE is possible by avoiding visits to epidemic season, avoiding mosquito bites, and receiving vaccine.
 
Epidemiology
Epidemics and sporadic cases of JE occur in many Asian countries, including Cambodia, China, Indonesia, India, Japan, Malaysia, Myanmar, Nepal, Pakistan, Philippines, Republic of Korea, Sri Lanka, Thailand, Vietnam, and the south eastern Russian federation. Gradual spread to other non-Asian regions-for example, Torres strait of Australian mainland has been reported.

Patterns of JE transmission vary within individual countries and from year to year. In endemic areas, the annual incidence of disease ranges from 10-100 per 100 000 population. An endemic situation, with occurrence of sporadic cases throughout the year, is present in tropical zones. In temperate regions of Asia and the northern tropical region, JEV is transmitted seasonally. A probable explanation could be the prolonged mosquito larval development time and longer extrinsic period of JEV at cooler temperatures in temperate regions, which can reduce the viral transmission. In some instances, outbreaks have been associated with rainfall, floods, or irrigation of rice fields.
 
Pathogen
  JEV belongs to the family Flaviviridae, the genus Flavivirus. The genome of JEV is a single and plus-stranded RNA nearly 11 kb in length. JEV genome encodes an open reading frame which codes for three structural proteins, the capsid (C), preM which is the precursor to the membrane (M) protein, and the envelope (E) protein, and seven nonstructural proteins, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. JE virion has a spherical shape with 40 to 50 nm in diameter.
   
Vector
  The mosquito vector of JE differs in different regions. The major mosquito vector of JE in South East Asia is Culex tritaeniorhynchus. Culex vishnui complex is also incriminated as a vector in India. JEV has been isolated from 10 different species of culex, four species of anopheles, and three species of mansonia mosquitoes. Humans are considered as the dead end host, as the brief periods of viremia and low titers of virus do not facilitate transmission.
   
Clinical feature
  There are 3 stages of disease including prodromal stage after couple of weeks of incubation period. The main symptoms of the first stage are fever, meningeal irritation, and encephalitis. Most patients show sudden high grade of fever and headache. Other non specific symptoms such as vomiting, diarrhea, pains at different parts of the body, etc. Then the second stage (encephalic stage) the clinical is worsen, meningeal irritation becomes apparent, and the cerebral symptoms rapidly develop, including alteration of consciousness ranging from mild to coma. Kernig’ s sign and babinski’s sign also become presented. After several days the illness reaches a peak and many dead. After a couple of weeks (recovery stage), fever gradually subsides and patients begin to recover from the symptoms.

Generally prognosis is not good. The proportion of fatal cases and those recovering with sequelae such as impaired intelligence and dyskinesia due to the damaged central nervous system is high. Complete recovery was one third of the cases. Recently, the proportion of fatal cases tended to decline because of a progressed treatment, however, that of completely cured cases is still at the same level as before, one third. The mortality rate in the aged patients is high and sometimes over 40%.
   
Clinical diagnostic laboratory
  Leucocytosis (WBC > 10,000 cumm.) and neutrophilia (PMN> 50%) was found about 80%, 90% of the cases respectively. The cerebrospinal fluid (CSF) appears clear but rises in its pressure and increases in the number of cells and amount of proteins. The level of sugar in the CSF is mostly normal. The differential count of CSF cell is lymphocytic predominate. Cranial MRI appears to sensitive in the detection of brain abnormalities. Typical MRI features consist of either mixed-intensity, predominantly in the thalami, but also in the basal ganglia, brain stem, cerebellum and cortical areas. Brain autopsy grossly appears edematous with changes mainly involving grey matter.
   
Etiologic diagnosis
 
  • Viral isolation by mosquito inoculation and various cell cultures
     
  • Antigen detection by RT-PCR subsequent with nested PCR
     
  • Antibody detection by IgM and Ig G antibody capture ELISA (Mac-ELISA), hemagglutination inhibition, the complement fixation test, and the neutralization
       
    Treatment
      No specific antiviral therapy is available for JE. Treatment is mainly supportive and symptomatic.
     
    Vaccination
      Recently the vaccine is recommended for all children aged greater than 1 year who living in endemic area. In Thailand this vaccine recommendation has been included in EPI program

    This vaccine also should be recommended for the travelers who exposed to high risk area such as journal in rural area, or stay in endemic area longer than 1 month which estimated risk was equal as the native people.

    Three types of JE vaccines are available included

     
    1.
    inactivated vaccine employing mouse brain,
     
    2.
    inactivated vaccine employing primary hamster kidney cell culture, and
     
    3.
    live vaccine employing primary hamster kidney cell culture. The other new developing vaccine included Vero cell Inactivated JE vaccine and Chimerivax-JE
       
     

    Kriengsak Limkittikul
    Department of Tropical Pediatrics

     
    Last updated: June 8, 2009
     
     
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