Japanese Encephalitis: Epidemiology, Prevention and Control

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Japanese EncephalitisEpidemiology, Prevention
and Control

• Dr Monjori Mitra

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JE Global Burden

• A disease of public health importance
• - Epidemic potential
• - High case fatality
• - Complications leading to life long
  sequelae
• Previously disease of East Asia - Japan, Korea
  and China
• Recent years spread to SEA - Thailand, Indonesia,
  India, Vietnam, Myanmar and Sri Lanka.
• Estimated 43,000 cases with 11,000 deaths and
  9,000 disabilities occur / year globally

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JE in India Historical Background
1952 - First evidence of JE viral activity by
VRC (NIV) 1955 - First human case of JE
1956 - First viral isolation from mosquitoes
1958 - First viral isolation from JE case 1973
- First outbreak in Bankura Burdwan in West
Bengal 1976 - Repeat outbreak in Burdwan
1978 - Several states reported outbreaks of JE
2003 - JE prevention and control under integrated
NVBDCP
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JE endemic areas in India

• Uttar Pradesh
• Andhra Pradesh
• Assam
• Bihar
• Goa
• Karnataka
• Maharashtra
• Tamilnadu
• West Bengal
• Kerala
• Jharkhand
• Orissa
• Manipur
• Punjab
• Haryana

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Agent-Host-Vector-Environment

• Agent
• 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
• 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
• 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

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How Japanese Encephalitis is transmitted?

• 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.

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Clinical Manifestations

• High ratio of symptomatic to asymptomatic
  infections
• (1250 to 11000)
• 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

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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)

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• 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

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Disease Burden

• Leading cause of viral encephalitis in Asia
• 35,000-50,000 cases annually
• (SourceCDC,2004)

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Death and disability from JE

• 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.

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Management

• 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

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Preventive strategies

• Surveillance for cases of encephalitis
• Vector control
• vaccination

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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.

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Vaccination

• 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.

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Vacine Type Strain substrate Producer Remarks on licensure marketing
Inactivated, Purified Nakayama Strain Mouse brain Biken - Japan International
Inactivated, Purified Nakayama Strain Mouse brain Green Cross - Korea Local Regional
Inactivated, Purified Nakayama Strain Mouse brain Vabiotech - Vietnam Local
Inactivated, Purified Nakayama Strain Mouse brain GPO - Thailand Local Regional
Inactivated, Purified Beijing 1 strain Mouse-brain Kaketsuken, Biken Kitasota - Japan Production stopped, bulk storage.
Inactivated, Purified P3 strain PHK or Vero cells Several - China Domestic only.
Live, attenuated SA 14-14-2 strain on PHK 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.
Under development 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 Submitted for licensing for paediatric use locally in Japan. International marketing plans not known.
  SA 14-14 - 2 pr M E in 17D YF backbone Sanofi Pasteur, Bharat Biotech, Panecea - India Under various stages of development and licensing

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• 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.
• It also appears feasible that a single dose of
  vaccine will provide life-long protection.

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Prevention and Control of JE

• Behaviour Change Communication for community
  participation and inter-sectoral convergence
• Capacity building through training on case
  management and control of JE
• Vaccination of children in JE endemic areas
• (1 and 15 years)
• Operational research
• Monitoring and Evaluation

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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.

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Gaps and Challenges of the Prevention and Control
of JE

• 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.

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National Vector Borne Disease Control Programme

• Vision
• A well-informed and self-sustained, healthy
  India free from vector borne diseases with
  equitable access to quality health care
• Mission
• Integrated and accelerated action towards
  reducing mortality on account of Malaria,
  Japanese Encephalitis, Dengue by half and
  elimination of Kala-azar by 2010 and elimination
  of Lymphatic Filariasis by 2015

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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
• 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

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Strategies of NVBDCP

• 3. Supporting Interventions
• 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

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Strategy

• A one time mass campaign targeting all children
  in the age group of 1-15 years in the districts.
• 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.
• A special campaign has been planned for 2010 in
  selected districts in the country to cover left
  outs and new cohorts.
• Age distribution pattern of the lab confirmed JE
  cases will be reviewed to further inform strategy.

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JE vaccination coverage 2006-2009
Year No. of Districts covered till date Total Population Target Population - 1-15 years Total JE vaccination canpaign coverage JE vaccination campaign Reported coverage
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