JEV zoonotic disease that infects humans accidentally.
this presentation will briefly discussed virus propertie, it geographic distributions and diagnosis an treatment
4. • INTRODUCTION:
Japanese virus Is an Arbovirus
Enveloped, single stranded RNA-virus.
Name is derived from two words;
• Japanese -- where it was first isolated.
• Encephalites -- its involvement in neurological malignancy.
Virus have three core proteins,
• Envelope protein
• Core protein
• Membrane protein.
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5. • HISTORY:
First case of Japanese encephalitis viral disease was documented in 1871 in Japan and was called
“Summer Endemic”.
“Great epidemic” in Japan in 1924 affecting 6,125 people and cause death of 3,797 people.
In 1934 it was first isolated from person suffering from fatal encephalitis.
In 1938 it was isolated from Culex tritaeniorhynchus mosquito.
From 1940-1978 it was epidemic in China, Korea, and India.
Its first vaccine was prepared by Korea in 1983 and was administered to common people.
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6. • GEOGRAPHIC
DISTRIBUTION:
The global incidence of Japanese encephalitis
virus is still unknown, because of the intensity and
quality of virus and variation in laboratory
diagnosis.
Virus is endemic in many countries of South East
Asia, including Japan, China, Taiwan, Korea,
Thailand, Nepal and some parts of India.
According to World Health Organization
approximately 68,000 people annually infected by
Japanese encephalitis virus.
In Pakistan still no case have been reported yet,
but some areas are marked suspicious.
August 10, 2020 6Areas shown as Yellow are Japanese encephalitis virus endemic areas.
7. • STRUCTURE OF VIRUS:
Japanese virus is enveloped, positive sense single stranded RNA
virus belongs to family Flaviviridea.
Diameter: 40-50 nm
Lipid envelope enclosed nucleocapsid.
Inside the capsid single stranded genome is present along with
virion associated Polymerase i-e RNA-dependent polymerase.
Genome encodes a polyprotein of ~3400 amino acids.
This encoded polyprotein is than cleaved by viral and host
proteases.
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8. • GENOMIC REPLICATION:
Japanese virus genomic replication involves following steps;
Entire replication occurs in cytoplasm but two of its proteins C and NS5 are found in
nucleus as well.
Attachment of virion with cell membrane
Viral entry into cell is supported by process of endocytosis.
Following the membrane fusion the genomic RNA is released into cytoplasm where it is
translated to produce two precursor polyprotein;
• Three structural proteins, C, prM, E.
• Seven non-structural proteins, NS1, to NS5 August 10, 2020 8
9. Continue….
After translation all of seven non-structural protein along with other factors involve in
genomic RNA-replication that occurs in virus-induced ER-derived membranous organelle.
Viral RNA-replication is catalyzed by NS3 and NS5.
The immature virions are believed to pass through constitutive secretory pathway to the
extracellular spaces .
During exocytosis, viral maturation occurs in trans-Golgi network by cleavage of preM to M
protein accompanied by other structural rearrangement.
M-containing completely mature virions are infectious and spread infection
Mature virion than assemble in cytoplasm and release by cell by budding.
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11. • TRANSMISSION:
Japanese virus transmission cycle exist between mosquitos, pig and water birds.
The disease predominating regions are mainly rural and pre-urban settings where people live
I close entities with vertebral host.
Disease occurs coincidence with rainy season and predominate mosquito is involve in
transmission of virus that breed in rice fields and water surfaces.
Mosquito carry Japanese virus and transmit them to pigs and water birds as well, where they
act as amplifying host for virus.
Man and other cattle's like horses and cow are infected either from birds, pigs, duckling or
through mosquito bites.
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12. Continue………
Human are accidental and death end host.
Man-to-man transmission cannot occur because human do not produce enough viral load
that it could transfer from one person to other through mosquito bite.
Transmission usually seasonal, like in temperate zones of China and northern areas of
Southeast Asia it is transmitted during summer and early autumn
In north India and Nepal transmission occurs from June to November.
While in Pakistan it transmission season is from June to November in areas beside Indus
river
August 10, 2020 12But in Pakistan no case of JEV transmission is still reported.
14. • PATHOGENESIS:
Japanese virus incubation period is about 5-15 days after virus starts its pathogenesis.
Most of the infected patients are asymptomatic only 1 in 300 patient result severe febrile disease.
Pathogenesis of Japanese virus is from its entry to site of infection is still not well defined.
Virus enters into body through mosquito bits and infect Langerhans dendritic cell in skin and from
there carried to nearest Lymph nodes initiating early immune response.
Virus than enters into secondary lymphoid organs before entering into blood circulation through
efferent lymphatic system.
While ensuing transient viraemia peripheral organs such as kidney, liver, spleen are known to be
infected.
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15. August 10, 2020 15
JEV entry into body
Mononuclear phagocyte
Blood circulation viraemia.
Blood circulation adequate immune response subclinical or mild systemic disease
Weak immune response invades CNS and induce mortality.
16. Continue……
Once the virus invades the CNS by crossing blood brain barrier by passive transport across
the endothelium by active replication of endothelial cells or by a Trojan Horse mechanism
in which virus is carried into brain by inflammatory cells.
Japanese encephalitis virus when enter into CNS causes destruction of brain cell by
unknown mechanism, though in many cases virus is not directly involve its body own
immune mechanism that may causes destruction.
Degeneration and necrosis of neurocytes.
Formation of malacoma focus.
Hyperplasy of colloid cell.
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18. • CLINICAL MANIFECTTION:
Most infections are subclinical or asymptomatic.
Incubation period of virus is from 5 to 15 days.
1 out of 300 patient develop severe neurological disorder.
50% patients start developing neurological malignancies before reporting it.
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19. • STAGES OF CLINICAL MANIFESTATIONS:
A Prodromal Stage;
• From 1to 6 days.
• Fever with headache and malaise.
• Nausea., vomiting, abdominal pain.
• Drowsy, neck rigidity
An Acute Encephalitis Stage
• starts from 3rd day.
• High fever.
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20. • Changes in mental activity, dullness, paralysis, coma
• Edema localized or generalized.
• Respiratory due to high intracranial pressure and edema in brain.
The Convalescence Stage;
• Last for at least two weeks.
• Defeverscence of fever.
The Squeal Stage;
• Mental and speech impairment.
• Increased deep tendon reflexes.
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21. • LABORATORY DIAGNOSIS:
Peripheral blood diagnosis;
• Neutrophils >80%
• Lymphocyte count.
Serological Diagnosis:
• Antibody titer will be high.
Diagnosis made by;
ELISA, Immunofluorescence assay.
• JE-specific IgM in serum.
• IgG antibody may leads to false diagnosis.
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22. Cerebrospinal Fluid Analysis;
• Clear, tension elevated.
• Protein is slightly elevated.
• Leukocytosis.
Radiological Examination:
• MRI of brain.
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23. Continue……
Viral Isolation;
• Isolated from CSF of laboratory mice.
• Virus is identify by heamagglutination inhibition test.
• Virus is inoculated in Cell lines of chick embryo, hamster kidney cells.
Molecular Detection:
• RT-PCR is done to check Japanese virus in blood.
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24. • TREATMENT AND PREVENTION:
No specific antiviral treatment is available for Japanese encephalitis virus.
Only supportive treatment is given to patient.
Safe and effective vaccine is available against virus, which is available is four forms;
• Inactivated mouse brain cell-derived vaccine.
• Inactivated Vero cell-derived vaccine.
• Live attenuated vaccine.
• Live recombinant vaccine.
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