JAPANESE

B
ENCEPHALITIS

Dr.T.V.Rao MD
 Japanese B virus Infection
Infection is caused by a flavivirus, a
single stranded RNA virus. It is
transmitted by the bite of the Culex
tritaeniorhynchus mosquito. The
virus multiplies at the site of the bite
and in regional lymph nodes before
viraemia develops. Viraemia can lead
to inflammatory changes in the
heart, lungs, liver, and
reticuloendothelial system.
 A Flavivirus
 Japanese encephalitis ( previously
known as Japanese B 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 are
reservoirs of the virus; transmission
to humans may
 A leading cause of viral
encepalitis
 Japanese encephalitis 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.
 A Vector born- Arboviral
Infection
 Culex
tritaeniorhynchus
a rural Mosquito that
breeds in rice fields, is
the principle vector.
In India in 1955 the
virus were isolated
from Culex vishnui
mosquitoes in Vellore
region in Tamil Nadu
 INCIDENCE

 Leading cause of viral encephalitis in

Asia with 30-50,000 cases reported
annually
 Fewer than 1 case/year in U.S.
civilians and military personnel
travelling to and living in Asia
 Rare outbreaks in U.S. territories in
Western Pacific
 Distribution of Japanese
Encephalitis in Asia, 1970-1998
 Japanese B Encepalitis
Virus
 The causative agent
Japanese encephalitis
virus is an enveloped
virus of the genus
Flavivirius; Positive
sense single stranded
RNA genome is
packaged in the
capsid, formed by the
capsid protein. The
outer envelope is
formed by envelope
(E) protein and is the
protective antigen.
 Genus - Flavivirus
 Japanese B encepalitis
virus is
Spherical, 40 – 60 nm
in diameter
Contain a positive
sense Single stranded
RNA, 11 kb in size
RNA genome is
infectious
Several viruses in this
group are related.
 Structure of Virus
 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
non-structural proteins also
(NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5).
NS1 is produced as secretary form also.
NS3 is a putative helicase, and NS5 is the
viral polymerase.
Cycle of Events in Japanese B
encepalitis
 Pass through two prominent
Hosts
 Herons act as
reservoir hosts and
pigs as amplifier
hosts.
 Human infection is
a tangential ‘dead
end’ and infections
are spread when
the infected
mosquitoes reach
high density.
 Clinical Manifestations
 The incubation period is 6 to 16 days.
 There is a prodrome of fever, headache,
nausea, diarrhoea, vomiting, and myalgia,
which may last for several days.
 This may be followed by a spectrum of
neurological disease ranging from mild
confusion, to agitation, to overt coma.
 Two thirds of patients have seizures. It is
more common in children, while headache
and meningism are more common in
adults.
Can lead to Neurological damage
 Tremor or other involuntary movements
are common.
 Mutism has been described as a
presenting symptom. So has a syndrome
of acute flaccid paralysis.
 Fever resolves by the second week, and
choreoathetosis or extra pyramidal
symptoms develop as the other
neurological symptoms disappear.
 Diagnosis of Japanese B
Encephalitis
 The isolation of virus
from Blood, CSF, or
tissues.
 Detection of Arboviral
specific RNA in
blood,CSF, or Tissue
 However very few
reference laboratories
can perform the
isolation in view of the
biosafety
considerations
 Serology by ELISA
 IgM capture enzyme-linked immunoassay
(ELISA) of serum or CSF is the standard
diagnostic test. Sensitivity is nearly 100%
when both serum and CSF are tested.
False-negatives may result if the samples
are tested too early, as in the first week of
illness.
 New IgM dot enzyme immunoassays for
CSF and serum are portable and simple
tests that can be used in the field.
Compared with ELISA as the gold
standard, the sensitivity and specificity are
around 98 and 99% respectively.
 False Positive Tests
 There is some cross-reactivity with
other flavivirus and from Japanese
encephalitis and yellow fever
vaccinations.
Arboviral Specific RNA detection
 Viral RNA is extracted
from serum or from
suspected tissues of
the patients or
mosquito
homogenates.
 The product is
amplified by RTPCR
and the products
analyzed by restriction
digestion and
determined by
nucleotide sequence of
PCR product.
 The identified
 Preventive measures
 Preventive measures include mosquito
control and locating piggeries away from
human dwellings
 A formalin inactivated mouse brain
vaccine using the Nakayama strain has
been employed in human immunization in
Japan – Two doses at two week’s interval
followed by a booster 6 – 12 months later
constitute a full course.
 However the immunity was short lived
 Later vaccines
 A live attenuated vaccine has been
developed in China from JE strain SA
14-14-2, passed through weanling
mice
 The vaccine is produced in primary
baby hamster kidney cells.
 Administered in two doses, one year
apart, the vaccine has been
reportedly effective in preventing
clinical disease
 Basics on Vaccinations
 Vaccine: formaldehyde-inactivated,
purified from mouse brain
 minimum age: 1 year - safety/efficacy in
infants uncertain
 primary course: day 1, day 7-14 and day
28 (3 doses)
 dose: adults & children over 3 years 1ml
s.c./i.m.; children under 3 years 0.5ml
s.c./i.m.
 booster interval: 2 years
 Indications for Vaccination

 for long-stay travellers, especially

children, to endemic areas of India,
Nepal, Bhutan, China and SE Asia
(May-Sept in SE Asia, July-Dec in
Nepal or India)
 Slaughter of PIGS

 During major epidemics, slaughter of

pigs has been employed as a
measure of containment.
 RESEARCH PRIORITIES

 Facilitate implementation of attenuated

vaccine in unvaccinated populations in
endemic areas
 Develop improved vaccines
 Identify risk factors for progression to
symptomatic encephalitis and viral
persistence
 Describe clinical features of JE in AIDS and
determine its potential as an opportunistic
infection
Created for Medical and
Paramedical students in
Developing World
Dr.T.V.Rao MD
Email
doctortvrao@gmail.com