JAPANESE ENCEPHALITIS

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JAPANESE ENCEPHALITIS
Lin Chaoshuang The Third Affiliated Hospital
Sun-Yet sen University
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Overview

• Etiology
• Epidemiology and history
• Pathogenesis and Pathology
• Clinical Manifestation
• Diagnosis
• Treatment
• Prevention and Control

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Etiology The Organism

• Arbovirus
• Flavivirus
• Enveloped
• Single positive-stranded RNA virus 11kb
• Morphology sphere 4050nm
• The name is Latin for flavus
• Flavus means yellow
• Refers to yellow fever virus

Flaviviridae
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• It has three proteins
• Envelope protein
• Core protein
• Membrane protein

Etiology The Organism
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Replication
Flaviviruses replication process includes the
entry by receptor-mediated endocytosis,
uncoating, protein synthesis, viral genome
synthesis, assembly, and virus release by budding
from plasma membrane or internal membrane.
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History

• 1870's Japan
• Summer encephalitis epidemics
• 1924 Great epidemic in Japan
• 6,125 human cases 3,797 deaths
• (62 case-fatality rate)
• 1935 First isolated in Japan
• From a fatal human encephalitis case
• 1938 Isolated from Culex tritaeniorhynchus

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History

• 1940-1978
• Disease spread with epidemics in China. Korea
  5,548 human cases in 1949
• India recognized in 1954, over 6,000 cases in
  1978
• 1983 Immunization in South Korea
• Started as early as age 3
• Endemic areas started earlier
• 1983-1987 Vaccine available in U.S. on
  investigational basis

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Epidemiology

• Geographic Distribution
• Endemic in temperate and tropical regions of Asia
• Reduced prevalence in Japan
• 30,000-50,000 cases annually
• Less than 1 case/year in U.S.

www.cdc.gov/ncidod/dvbid/jencephalitis
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JE Outbreaks in India

• Outbreaks of JE occur in India for 27 years
• Larger outbreak 1988 1228 deaths
• Total deaths in 27 years 4000 deaths
• Outbreak 2004 50 deaths

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Outbreak 2005 in India

• Index case Nepal, mid-June
• First case India July 20th
• First outbreak alert August 12th
• Confirmation JE August 21th
• Total death 1302
• Total cases gt 5000

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JE in CHINA

• Pandemic from 1960s to early 1970s.
• Incident rate decreased since late 1970s
• Case reports were 500010000 cases /y these few
  years.
• Outbreak in some areas.
• Prevalence in Shanxi Province Yuncheng From
  13 July to 14 Augest, 2006.
• 65 cases,19 deaths.

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Transmission Sources of Infection

• Arthropod-borne viruses (Arboviruses, ????)
• Enzootic or zoonoses disease
• Amplifying hosts
• Pigs (the main reservoir)
• Wading birds (egrets, herons), Bats
• Incidental hosts
• Horses, humans (dead-end hosts)
• Others

herons
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Transmission Routes of Transmission

• Vectors Mosquitoes
• Culex species tritaeniorhynchus
• The mosquitoes that transmit the virus breed in
  rice fields, and standing water.
• In winter, virus persist in arthropod (????) eggs
  or migrate with birds.
• Death of infected no-human vertebrates occurs
  before human outbreak.

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Transmission Susceptible Population

• Age 2-10 years
• Living in rural areas
• People who live near
• stagnant water
• (mosquito breeding)

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Epidemiologic Feature

• The major outbreaks coincided with the heavy
  rainfall or floods.
• Seasonal more common in summer, July to October
• Infection provides life long immunity.

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DYNAMICS OF JE TRANSMISSION
Vector Mosquito
Environment
Victim-Accidental
Recovery with residual complications
Full Recovery
Death
Host - Amplifying
Host - Carrier
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Pathogenesis

• The nature of flavivirus disease is determined
  primarily by
• The specific tropisms of the individual virus
  type
• The concentration of infecting virus
• Individual host response to the infection

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Pathogenesis

• JE Virus
• mononuclear phagocyte
• blood circulation
• viremia
• Adequate immunological
  Weak immunological
• response
  
  response
• subclinical or mild invades
  the CNS
• systemic disease induce
  mortality

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Pathogenesis

• Initial viral replication may occur in local
  regional lymph nodes
• Initially brain damage is due to viral infection
  and multiplication in neurons per se
• Later immunopathological mechanisms may play a
  role.

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Pathology

• Degeneration and necrosis of neurocyte
• Formation of malacoma focus (???)
• Blood vessel change and inflammatory reaction
• Hyperplasy of colloid (??) cell

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Manifestation

• Most asymptomatic or mild signs
• Ratio of subclinical to clinical ratio
  (2503001)
• 50 develop permanent neurological damage
• Incubation Period - 5 to 15 days

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Clinical Manifestations

• Clinical manifestations depend upon
• Severity of infection
• Susceptibility of the host
• Location of the agent

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Four stages

• A Prodromal Stage
• An Acute encephalitic Stage
• The Convalescence Stage
• A Sequela Stage

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Prodromal Stage

• The Prodromal stage usually lasts for 1 to 6
  days. It can be as short as less than 24 hours or
  as long as 14 days
• Acute
• Fever with severe rigors, headache and malaise
• Nausea, Vomiting, Abdominal pain
• Drowsy
• Neck rigidity
• Convulsions, Seizures

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The Acute Encephalitic Stage

• Begins by the third to fifth day.
• The symptoms include
• High fever for about 710 days
• Changes in consciousness dullness, tremor,
  stupor, ataxia, focal or diffuse paralysis, coma
• Convulsions localized or generalized, Tremors in
  fingers, tongue, eyelids and eyes
• Respiratory failure maybe due to high
  intracranial pressure, edema of the brain, hernia
  of the brain.
• Meningeal irritation sign Stiff neck, positive
  Kernigs sign and pathological reflexes.

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The Convalescence Stage

• Defervescence of fever
• Defervescence of neurologic improvement
• Usually lasts for at least two weeks.

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A Sequela Stage

• Neuropsychiatric sequelae
• 30-50 of survivors
• Characterised by
• Persistance of signs of CNS injury
• Mental impairment     
• Increased deep Tendon reflexes     
• Paresis either of the upper or lower motor neuron
  
• 
  (???????)     
• Speech impairment     
• Epilepsy, Abnormal movements, Behaviour
  abnormalities

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Clinical spectrum of JE infection
Die
Severe
Moderate
Mild
Asymptomatic

• For every symptomatic JE case, there are likely
  to be about 300 1000 people infected with JE
  virus but without any clinical manifestation
• People of any age can be infected. Adult
  infection most often occurs in areas where the
  disease is newly introduced.

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Laboratory Investigation

• Peripheral blood analysis
• leucocytosis (1020)X109/L with
  neutrophilicgt80
• Cerebrospinal fluid (CSF) analysis
• Routine clear, tension elevated,
• leucocytosis (50500)X106/L
• Neutrophils may
  predominate in early CSF samples but a
  lymphocytic pleocytosis is typical
• Biochemistry
• protein is moderately elevated
  
• glucose and chloride normal
  level

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Laboratory Investigation

• Serological tests
• Specific IgM antibody
• A significant rise in IgG antibody titer
  should be seen with paired samples from the
  acute and convalescent stages.
• The virus isolation
• Isolated from CSF by inoculating into 2-4
  day old mice and the virus is identified by
  haemagglutination inhibition.
• JE virus may also be identified by infection
  of cell cultures (chicken embryo or hamster
  kidney cells, or the mosquito cell line C3/36).

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Diagnosis

• Materials of epidemiology
• Clinical
• Laboratory Tests
• Tentative diagnosis
• Antibody titer HI, IF, CF, ELISA
• JE-specific IgM in serum or CSF
• Definitive diagnosis
• Virus isolation Blood, CSF sample, brain

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Differential Diagnosis

• Toxic shigellosis and other Toxic Encephalopathy
• Cerebral Malaria
• Meningitis (other viral meningitis or
  encephalitis, partially treated bacterial
  meningitis, meningococcal meningitis, tuberculous
  or fungal meningitis)
• Febrile Convulsions
• Reys Syndrome
• Rabies

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Prognosis

• Approximately 5-35 of cases are fatal, some with
  a fulminate course lasting a few days and others
  run a more protracted course in coma.
• About 30-50 of those who survive may have
  serious neurologic sequelae.

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Treatment

• No specific therapy
• Supportive care intensive life support is
  indicated
• Surveillance for cases of encephalitis

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Treatment

• Treatment of high fever
• Physical method ice, alcohol, cool saline.
• Artificial hibernation
• Seizure and convulsions management
• Sedation, Corticosteroids may be used
• For respiratory failure
• Oxygen supply, artificial respiration
• For raised intracranial pressure
• Mannitol iv.drip 1mg/Kg every 68 hrs.

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Prevention

• Vector (Mosquito) control
• Eliminate mosquito breeding areas Chemical
  larvicides, Biolarvicides, Environmental
  management
• Adult and larval control Anti-larval treatment
• Vaccination
• Personal protective measures
• Avoid prime mosquito hours from dusk to dawn
• Indoor spray and fogging Use of Insecticide

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Vaccination

• Live attenuated vaccine
• Successful for reducing incidence
• SA 14-14-2 (Chinese live attenuated vaccine at
  affordable cost, safe, effective).
• This vaccine was developed in China and has been
  used since 1988.
• It has been licensed and used in South Korea.

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Vaccination

• Inactivated mouse brain vaccine(JE-VAX)
• Comprising 3 doses 0.5ml each time and
• the interval is 12 weeks in infancy,
• boosting 1.0ml in children.
• Used for endemic or epidemic areas.
• Recommended for travelers visiting
• endemic areas for gt 30 days.

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THANKS