Japanese Encephalitis:
Epidemiology, Prevention and Control
Dr Monjori Mitra
JE : Global Burden
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A disease of public health importance:
- Epidemic potential
- High case fatality
- Complications leading to life long sequelae
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Previously disease of East Asia - Japan, Korea
and China
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Recent years spread to SEA - Thailand, Indonesia,
India, Vietnam, Myanmar and Sri Lanka.
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Estimated 43,000 cases with 11,000 deaths and
9,000 disabilities occur / year globally
JE endemic areas in India
Uttar Pradesh
Andhra Pradesh
Assam
Bihar
Goa
Karnataka
Maharashtra
Tamilnadu
West Bengal
Kerala
Jharkhand
Orissa
Manipur
Punjab
Haryana
Agent-Host-Vector-Environment
Agent:
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JE is a viral disease - an Arbovirus (Flavivirus)
Closely linked antigenically to other flaviviruses
Single serotype, but geographic strains differ by RNA
sequencing
Neurotorpic and primarily affects central nervous system
Host:
JE virus is primarily zoonotic in its natural cycle.
 Natural hosts: Animals and Birds
- Pigs: amplifier host - allow manifold virus multiplication
without suffering from disease & maintain prolonged viraemia.
- Cattle and buffaloes: ‘mosquito attractants’
 Man is an accidental ‘dead-end’ host.
-usual age group below 15 years with no sex predilection
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Vectors:
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Culex tritaeniorhynchus, C. vishnui and C. pseudovishnui.
Breeding habit: Irrigated rice fields, shallow ditches and pools etc.
Resting habit: Exophilic but may rest indoor in extreme summer
Feeding habit: Zoophilic and outdoor as well as indoor feeders
The average life span of mosquito is about 21 days
Flight Range: long distance (1 - 3 kms or even more)
Environment:
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Mainly prevalent in rural areas
Outbreak is a seasonal phenomenon
Mosquito vector prefers large and clean water collections for
breeding - paddy cultivation areas offer typical favourable situation
Rural setting offers the amplifier hosts in abundance
Occurrence in monsoon and post-monsoon season: in north India
from May-October, in southern part from August to November
How Japanese Encephalitis is transmitted?
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Transmission Cycle:
Pig – Mosquito – Pig
Bird – Mosquito – Bird
Due to prolonged viraemia, mosquitoes get
opportunity to pick up infection from pigs easily.
After an extrinsic incubation period of 9 –12 days Infected
female mosquito transmits the virus to other hosts
Man is a dead end in transmission cycle due to low
and short-lived viraemia. Mosquitoes do not get
infection from JE patient.
Clinical Manifestations
 High ratio of symptomatic to asymptomatic infections
(1:250 to 1:1000)
 Incubation period : 6-16 days
 Course of the disease can be divided into three stages:
Prodromal stage
- Acute onset - fever, chills, headache and malaise
Acute encephalitic stage
- High fever (38 to 40.7o C), neck rigidity, photophobia, nausea, vomiting,
seizures and altered sensorium.
- Variable neurological signs appear (cranial nerve palsies, tremors, ataxia,
abnormal reflexes, paralysis, delirium and ultimately coma)
Late stage and sequelae
- Active inflammation subsides, neurological signs stable
- Sequelae: Parkinsonism, paralysis and mental retardation
 Case Fatality Rate: Exceeds 25%
Case Definitions for JE Diagnosis and
Reporting
Suspect case Acute Encephalitis Syndrome
Febrile illness of variable severity associated with
neurological symptoms ranging from headache to
meningitis or encephalitis.
Symptoms can include headache, fever, meningeal
signs, stupor, disorientation, coma, tremors, paralysis
(generalized), hypertonia , loss of coordination.
- (Patient with fever, altered sensorium lasting more
than 6 hours, no skin rash and other known causes of
encephalitis excluded)
Probable Case
A suspected case with presumptive laboratory results:
Detection of an acute phase anti-viral antibody response
through one of the following - Elevated and stable JE antibody titres in serum through
ELISA or HI or virus neutralization assays OR
- IgM antibody to the virus in serum
Confirmed Case
A suspect case with confirmed laboratory result :
- Detection of JE virus, antigen or genome in tissue, blood or
other body fluid by immuno-chemistry, immuno-fluorescence
or PCR, or
- JE virus specific IgM in CSF or
- Four fold or greater rise in paired sera (acute & convalescent
phases) through IgM/IgG ELISA, HI or virus neutralization
test
Disease Burden
 Leading
cause of
viral encephalitis
in Asia
 35,000-50,000
cases annually
(Source:CDC,2004)
Death and disability from JE
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Up to 30% of all
patients with JE die.
For those that survive
the illness, more than
30% cases are left with
disability.
Disability is both
physical and cognitive.
Management
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Mainly symptomatic & supportive
Therapeutic norms for the supportive
therapy are not established
Fluid and electrolyte balance
Reduction of intra-cranial pressure
Control of convulsions, if present
Maintenance of airway is crucial
Preventive strategies
• Surveillance for cases of encephalitis
• Vector control
• vaccination
Prevention and Control of JE
 Early diagnosis and proper management of JE cases
 Strengthening of referral mechanism
 Integrated Vector Management:
- Insecticide residual spray not recommended
- Reduction of breeding sources: Water management system with
intermittent irrigation system; incorporation of neem products in
rice fields
- Anti-larval operations wherever feasible: larvivorous fish,
biolarvicides
- Fogging with Malathion for immediate killing of mosquitoes during
outbreak
- Reduction in man-vector contact: personal protection with ITNs,
repellents, clothing etc. and exploring possibility of segregation of
pigs, mosquito proofing of piggeries.
Vaccination
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Not an outbreak response vaccine
Universal vaccine for JE endemic areas
All children from 1 – 15 years should be
vaccinated
Phillipines study shows acceptable efficacy
when coadministered with measles vaccine at 9
months.
Travellers vaccine in JE endemic areas when
expected to stay for 4 weeks and should
complete the doses prior to 1 week before travel.
Producer
Remarks on licensure &
marketing
Biken - Japan
International
Green Cross - Korea
Local & Regional
Vabiotech - Vietnam
Local
GPO - Thailand
Local & Regional
Kaketsuken, Biken Kitasota Japan
Production stopped, bulk
storage.
Several - China
Domestic only.
Chengdu - China
Marketed for both domestic use
and for use in Nepal, S. Korea,
Sri Lanka and India.
Prequalification status: Product
Summary File under
preparation.
SA 14-14-2 strain on PHK
Wuhan, Lanzhou - China
Marketed for domentic use in
China only.
SA 14-14-2 strain
Verocells
Intercell, Biological Evans India
Under various stages of
development and licensing
Beijing 1 strain
Vero cells
Biken - Japan
Kaketsuken - Japan
SA 14-14 - 2 pr
M & E in 17D YF
backbone
Sanofi Pasteur,
Bharat Biotech,
Panecea - India
Vacine Type
Strain & substrate
Inactivated,
Purified
Nakayama Strain
Mouse brain
Beijing 1 strain
Mouse-brain
P3 strain
PHK or Vero cells
Live,
attenuated
Under development
SA 14-14-2 strain
on PHK
Submitted for licensing for
paediatric use locally in Japan.
International marketing plans
not known.
Under various stages of
development and licensing
JE VACCINE
•INACTIVATED MOUSE BRAIN VACCINE
•It is expensive vaccine, complicated dosing schedule, side effect of
this vaccine.
•Inactivated Mouse brain vaccine
•3-5 US dollars/dose
•9 – 15 US dollars/per child
•The ‘mouse brain vaccine’ manufactured by killing populations of
mice was being manufactured by Central Research Institute, Kasauli.
•LIVE ATTENUATED VACCINE
•SA 14 - 14-2 (Chinese live attenuated vaccine at affordable cost, safe,
effective).
•This vaccine was developed in China and has been used there since
1988.
•it has been licensed and used in South Korea and Nepal and licensed
in Sri Lanka.
Gaps and Challenges of the Prevention and
Control of JE
 Outdoor habit of the vector – variation in vector
bionomics
 Scattered distribution of cases spread over relatively
large areas
 Role of different reservoir hosts
 Specific vectors for different geographical and
ecological areas
 Immune status of various population groups is not
known making it difficult to delineate vulnerable
population groups.
Gaps and Challenges of the Prevention
and Control of JE
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Difficulties in segregation of pigs
Inadequate surveillance
Efficient rapid diagnostics for field use not available
Inadequate epidemic forecasting & preparedness
Lack of supervision & monitoring.
Limited inter-sectoral convergence and community
participation
 JE immunization programme-supply of vaccines and
cold chain arrangements, cost factor, coverage.
Strategies of National Vector Borne
Disease Control Programme
1. Parasite Elimination and Disease Management
• Early case detection and complete treatment
• Strengthening of referral services
• Epidemic preparedness and rapid response
2. Integrated Vector Management
for Transmission Risk Reduction
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Indoor residual spraying in selected high risk areas
Use of insecticide treated bed nets
Use of larvivorous fish
Anti larval measures in urban areas
Minor environmental engineering
Strategies of NVBDCP
3. Supporting Interventions
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Behaviour Change Communication
Public Private Partnership
Human Resource Development through Capacity Building
Operational Research
Monitoring and Evaluation through periodic reviews/field visits
and web based Management Information System
Strategy
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A one time mass campaign targeting all children in the age group
of 1-15 years in the districts.
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Followed by integration of the JE vaccine into the Routine
Immunization Program to cover the new cohort (children attaining
more than 1 year of age) in the districts covered previously under
the JE vaccination campaign. These children would be
administered the JE vaccine between 1-2 years of age along with
the DPT booster dose, under the Routine Immunization
Programme.
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A special campaign has been planned for 2010 in selected districts
in the country to cover left outs and new cohorts.
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Age distribution pattern of the lab confirmed JE cases will be
reviewed to further inform strategy.
JE vaccination coverage 2006-2009
JE
Total JE
Target
vaccination
Total
vaccination
Population campaign
Population
canpaign
1-15 years
Reported
coverage
coverage %
Year
No. of
Districts
covered till
date
2006
11
29420139
9708646
9308688
88.30%
2007
27
65934009
21758223
18431087
85%
2008
22
57772199
20040262
16881941
84.20%
2009*
30
45032191
27161011
17441254
64.21%
90
198158538
78668142
62062970
78.89%