JAPANES ENCEPHALITIS

1. Management of
Japanese
Encephalitis
Dr. Samiul Ahsan Hussain
IAP, Barak valley

2. • Japanese encephalitis (JE) is a
leading cause of viral encephalitis in
Asia.
• It has been controlled effectively
through national vaccination
programs in several countries like
Japan, Korea, China and Thailand
IAP, Barak valley

3. Geographic Distribution
IAP, Barak valley

4. JE ENDEMIC AREAS IN INDIA
4
JE affected
areas
• Andhra
Pradesh
• Assam
• Bihar
• Haryana
• Kerala
• Karnataka
• Maharashtra
• Manipur
• Nagaland
• Tamil Nadu
• Uttar Pradesh
• West Bengal

6. IAP, Barak valley

7. THE VIRUS
• Japanese Encephalitis (JE) is an
infection of the brain by a Flavi virus.
IAP, Barak valley

8. LIFE CYCLE OF JAPANESE ENCEPHALIIAPT, BIarSak valley

9. CULEX MOSQUITO BBIITTIINNGG HHUUMMAANN IAP, Barak valley

10. CULEX MOSQUITO LLAAYYIINNGG EEGGGGIASSP, Barak valley

11. JE PATHOGENESIS
Amplification of virus in blood of animal reservoir
Culex mosquito
Skin of Man
Phagocytosis by macrophage in dermis & subcut-tissue
VIREMIA Replication of virus
Passage through BBB
Infection of neuron
IAP, Barak valley
Neuronal degeneration & death

12. JE
PATHOGENESIS (Contd.)
Neuronal degeneration & death
Microglial & astrocytic proliferation
Inflammatory & immune response
Congestion of blood vessels, edema,
perivascular cuffing of mononuclear cells
IAP, Barak valley

13. PATHOLOGY
Macroscopically
The brain appears oedematous
and focal haemorrhages are
seen in brain tissue and
meninges. There is congestion
of blood vessels.
The areas mostly affected are
–
The thalamus,
Substantia nigra,
Anterior horn of the spinal
cord,
Cerebral cortex and
Cerebellum
IAP, Barak valley

14. Acute encephalitis syndrome
(AES) is a term used by WHO for
syndromic surveillance in the
context of Japanese encephalitis
(JE)
IAP, Barak valley

15. JAPANESE ENCEPHALITIS
(ACUTE ENCEPHALITIS SYNDROME )
• Clinical Case Definition:
Clinically a case of AES is defined as a person of
any age at any time of year with acute onset of
fever and a change in mental status (including
symptoms such as confusion, disorientation,
coma, or inability to talk).
• And/Or
• New onset of seizures (excluding simple febrile
seizures).
IAP, Barak valley

16. Partial Differential Diagnosis
Japanese
encephalitis
Cerebrospinal
meningitis
Viral meningo-encephalitis
AES Meningitis
Meningococcal or
epidemic
meningitis
Viral
TB, Hib or St pn
meningitis
Viral encephalitis
Encephalitis
TB
meningoencephalitis
Cerebral malaria
Other suspect
meningitis or
encephalitis
Pyogenic or meningitis
purulent
meningitis
IAP, Barak valley

17. AES Case classification
Adequate blood/ CSF
specimen
No adequate blood/
CSF specimen
AES
IgM -ve
IgM +ve
Geographic / temporal
link to a lab confirmed
JE during an outbreak
AES- unknown
Lab confirmed JE
No geographic / temporal
link to a lab confirmed JE
AES Unknown
Other diagnostic
tests
AES- other agent
Probable JE
IAP, Barak valley

18. Evaluation and
Management
Step I: Rapid assessment
and stabilization
IAP, Barak valley

19. AIRWAY
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20. BREATHING
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21. CIRCULATION
• Circulatory failure: fluid bolus (20 mL/kg-
Normal saline)
• Hypoglycemia is present:intravenous
glucose
• Seizure :intravenous benzodiazepine followed
by phenytoin loading 20 mg/kg
• Acid base and electrolyte
abnormalities should be corrected
• Normothermia should be
maintained.
IAP, Barak valley

22. Step 2: Detailed History
and Examination
IAP, Barak valley

23. • Fever, headache, vomiting, seizures, abnormal posturing
• Altered behavior, cognition, personality changes, altered
consciousness
• Prodromal symptoms- flu-like illness, diarrhea
• Rash, vesicles, past history of chicken pox
• Residence of child: Rural/urban, endemic for cerebral
malaria, any epidemic of AES in neighborhood
• History of animal contact, insect bite, dog bite
• Drug or toxin exposure- enquire for presence of any drugs
at home
• Recent history of travel
• History of trauma IAP, Barak valley

24. • Personal or family history of seizure disorder
• Recent immunizations
• History of recurrent episodes of encephalopathy: These are
characteristic of some inborn errors of metabolism (urea cycle
defects, organic acidemias and fatty acid oxidation defects), but
may also be present in migraine, epilepsy, substance abuse, and
Munchausen syndrome by proxy
• Other concurrent systemic illness e.g. jaundice (hepatic failure),
pneumonia (hypoxic encephalopathy), diarrhea
(dyselectrolytemia), dysentery (shigella encephalopathy)
• Past medical illness: Diabetes, congenital heart disease, chronic
kidney or liver disease
• Family history of previous infant/child deaths
• Pre-morbid developmental/ neurological status of the child
• Risk factors for immunodeficiency- HIV risk factors, cancer
treatment, steroid/immunosuppressant treatment
IAP, Barak valley

25. Sudden fever Lethargy
Headache Change in
Vomiting and
diarrhea
Tremors or
convulsions
consciousness
Irritability or
restlessness
Common symptoms of encephalitis

26. Physical examination of a
patient with suspected
encephalitis
• Assess ABC’s (airway, breathing, and
circulation).
• Rule out Cushings triad:
− Hypertension + bradycardia + irregular
respirations
− This is a medical emergency! (indicates
increased intracranial pressure and impending
cerebral herniation)
• Perform thorough neurological exam.

27. Overview of physical exam
(1)
• Vital signs:
− Temperature, heart rate, respiratory rate, blood
pressure, weight
• General appearance:
− Drowsy, severe wasting, edema?
• Skin:
− Turgor, capillary refill, palmar pallor
− Rash: petechiae, vesicles, bruising?
− Diffuse adenopathy?

28. Overview of physical exam
(2)
• Head, eyes, ears, nose and throat:
− pupils equal and reactive, corneal clouding, neck
stiffness?
• Heart:
− gallop rhythm, slow heart rate?
• Chest:
− rales, crackles, signs of pneumonia, respiratory
distress?
• Abdomen:
− enlargement of liver or spleen?

29. The neurologic exam
1. Mental status
− Level of alertness:
 AVPU scale for rapid assessment: Alert / Responds
to voice / Reacts to pain / Unconscious
 Glasgow Coma Scale or other coma scale
− Orientation, memory, speech, etc.
− Irritability, aphasia?

30. The neurologic exam (2)
2. Cranial nerves
— Pupil reactivity, eye movements, fundoscopic
exam for papilledema, facial muscles
3. Motor exam
− Assess strength, tone of upper and lower
extremities
 Compare sides
− Abnormal movements or posturing?
4. Sensory system
− Assess pain, vibration, temperature sensation
 Compare sides
Testing facial nerve (VII)

31. The neurologic exam (3)
5. Deep tendon reflexes
6. Coordination and Gait
− Finger-to-nose test, Romberg test
− Tandem (heel to toe) walking
Romberg Test
Tandem
walking

32. Step 3: Investigations
IAP, Barak valley

33. SAMPLE COLLECTION
SAMPLES: CSF, Serum
First specimens (blood and CSF) should
be collected on admission to hospital or
when patient first seen.
 Brain biopsy obtained post morterm
by Vim Silverman needle – pass
through cribriform plate.

34. SAMPLE COLLECTION
(CONT’D.)
• A follow up specimen (blood) should be
collected at least 10 days after onset
(before discharge or death).
• The collection of CSF should only be
performed by experienced personnel
under aseptic conditions in the
hospital

35. RATIONALE FOR TIMING OF SPECIMEN
COLLECTION
 IgM antibody levels rise steadily after onset of
encephalitis.
 The percentage of patients with IgM detectable in
serum increases with days after onset.
 The finding of JE IgM in CSF confirms the
diagnosis of JE.
 IgM to JE virus rises earlier in CSF than in serum
and rises to higher levels in CSF than in serum (2
to 4 times)
 Whenever possible when CSF is collected for
management purposes, an additional tube should
be collected for ELISA testing .

36. JE VIRUS INFECTION
IgG antibody may
be result of past
infection and not
related to this
episode of AES
IgM antibody: result of
recent infection related to
this episode of AES. CSF
more specific than serum

37. LABORATORY DIAGNOSIS
General investigations:
• Blood: Total count vary between 10000-25000 cells /
cumm
with 60 to 90% polymorphs.
Malaria parasite should be excluded in
peripheral blood smear
• CSF: Clear or Turbid.
20 to 1000 cells/ cumm predominantly
mononuclear cells.
Protein raised.
Sugar normal or raised.

38. LABORATORY DIAGNOSIS CONTD.
CONVENTIONAL ASSAYS:
• Antibody detection - CFT, HI, Neutralization test
• Virus isolation - Suckling mouse inoculation i/c
RAPID ASSAYS:
• Antibody Detection : IgM capture ELISA
• Antigen Detection : IFA
• Virus Isolation : C6/36 cell line,
Toxorhynchites
Splendens larvae

39. How does the JE IgM
capture enzyme
linked immunosorbent
assay (ELISA) work

40. Plate coated with capture
antibody
(anti human-IgM)
Anti-human IgM
Plate surface

41. Unused binding sites blocked
with protein
Blocking proteins
Plate surface

42. Mixing of antigen and
conjugate
Antigen "Monoclonal
Tracer" conjugate

43. Add serum sample
IgM

44. Wash away unbound IgG and
add JE Antigen with HRP
enzyme conjugate
JE IgM
JJEE aannttiiggeenn
AAnnttii JJEE IIggGG
ccoonnjjuuggaatteedd ttoo HHRRPP
JJEE ssppeecciiffiicc IIggMM NNoonn JJEE IIggMM

45. Wash away unbound IgG and add
JE Antigen with HRP enzyme
conjugate
JE IgM
JJEE aannttiiggeenn
AAnnttii JJEE IIggGG
ccoonnjjuuggaatteedd ttoo HHRRPP
JJEE ssppeecciiffiicc IIggMM NNoonn JJEE IIggMM

46. Wash away unbound HRP
enzyme and add substrate

47. Add acid to stop reaction
Positive

48. Basic investigations:
• complete blood count
• blood glucose
• serum electrolytes
• liver and kidney function tests
• blood culture
• arterial blood gas, and lactate
• malarial parasite
• chest X-ray
IAP, Barak valley

49. Lumbar puncture:
• Cytology
• Biochemistry
• Gram stain
• Ziehl-Nielsen stain for acid fast bacilli
• Bacterial culture
• Latex agglutination, PCR for HSV 1
and 2
• IgM antibodies for JE and for
Dengue virus (if suspected)
IAP, Barak valley

50. Neuroimaging: CT
• Presence of bleed
• Cerebral edema
• Temporal lobe hypodensities in
herpes simplex encephalitis
• Thalamic abnormalities in JE
• Basal exudates and hydrocephalus in
tubercular meningitis
• Brain herniation
• Brain abscesses and subdural
empyema.
IAP, Barak valley

51. IAP, Barak valley

52. Step 4: Empirical
Treatment
IAP, Barak valley

53. Antibiotic
• Ceftriaxone
• Acyclovir
• Anti-malarial (artemisin-based
combination therapy)
IAP, Barak valley

54. Step 5: Supportive
Care
IAP, Barak valley

55. • Maintenance intravenous fluids
• Management of raised intracranial
pressure
Intubation if the GCS is less than 8
Hyperventilation(paco2 of 30-35
mm)
Mannitol
Hypertonic (3%) saline
• Maintain euglycemia IAP, Barak valley

56. • Treatment and prevention of seizures
• Corticosteroids ???
• Oral ribavirin was not found to be
useful in children with Japanese B
encephalitis in a randomized
controlled trial [56].
• There is experimental evidence of
benefit of minocycline in JE [57].
Movement disorders such as dystonia
may need treatment with
trihexyphenidyl. IAP, Barak valley

57. Step 6:
Prevention/treatment of
complications and
rehabilitation
IAP, Barak valley

58. • (i) Surveillance for cases of AES;
• (ii) Vector control;
• (iii) Reduction in man-vector contact;
and
• (iv) Vaccination
IAP, Barak valley

59. • In any AES outbreak, pediatricians
will see affected patients. They
should be aware of what information
and samples they should collect, and
whom to inform. All pediatricians
need to be aware of the case
definition of AES. The cases should
be notified to the District
Surveillance Unit.
IAP, Barak valley

60. Mosquitoes and JE
• The spread of JE depends
on the life cycle of the
mosquito.
• Adult mosquitoes lay their
eggs on water.
• The eggs hatch to become
larvae and then pupae,
before turning into adults.
• Adult females mosquitoes
only live 2 to 4 weeks.
• So you can reduce JE by
attacking any of these
four stages of the
mosquito.

61. How can you kill mosquito larvae?
• Some fish, such as
mosquitofish, carps, and Tilapia,
eat mosquito larvae.
• Dragonflies, and perhaps also
birds, bats, and lizards also kill
larvae.
• Larvae can also be killed by
surface films or by some
chemicals such as methoprene
that are toxic to mosquitoes.
• Check with your local health
department to see what steps
they are taking.

62. The main strategy for JE control:
Attack the adult mosquitoes, or
prevent them from biting people.
Some risks:
1. Toxicity of DDT
2. Resistance of
mosquitoes

63. What are ways to prevent
mosquito bites?
• Use mosquito repellants.
• Wear long pants and long sleeves.
• Wear light-colored clothes.
• Use window screens
• Use bed nets.

64. JE vaccination
• Recommended only for individuals living in
the rural areas of endemic districts
Three types :
• live attenuated, cell culture-derived SA-
14-14-2
• inactivated JE vaccines, namely ‘vero cell
culture-derived SA 14-14-2 JE vaccine’
(JEEV® by BE India) and
• ‘vero cell culture derived,821564XY, JE
vaccine’ (JENVAC® by Bharat BiotecIAhP, B)arak valley

65. Live attenuated, cell culture-derived
SA-14-14-2:
• Minimum age: 8 months;
• Two dose schedule, first dose at 9
months along with measle svaccine
and second at 16 to 18 months along
with DTP booster
• Not available in private market for
office use
IAP, Barak valley

66. Inactivated Vero cell culture-derived
Kolar strain, 821564XY, JE
vaccine (JENVAC® by Bharat Biotech)
• Minimum age: 1 year
• Primary immunization schedule: 2
doses of 0.5 mL each
• administered intramuscularly at 4
weeks interval
• Need of boosters still undetermined.
IAP, Barak valley

67. Inactivated cell culture-derived
SA-14-14-2 (JEEV® by BE India) :
• Minimum age: 1 year (US-FDA: 2
months)
• Primary immunization schedule: 2
doses of 0.25 mL eachadministered
intramuscularly on days 0 and 28 for
childrenaged ≥ 1 to ≤ 3 years
• 2 doses of 0.5 ml for children > 3
years and adults aged ≥18years IAP, Barak valley

68. Prognosis
• JE has high mortality (20-50%)
• Neurologic sequelae in 25%-75% of
survivors
• Reduced IQ was reported among
32% of JE survivors
IAP, Barak valley

69. Decrease morbidity by early
recognition of danger
• Pupils, tone and posture, respiration
and doll’s eye movement
examination helps us in assessing
severity .
IAP, Barak valley

70. Misery of Mystery of
Muzaffarpur
Most children reported being
apparently well in the evening with a
sudden onset of altered
consciousness in the early hours of
next day, with or without seizures
and hypoglycemia with absence of
clues for an infection such as
prodromal symptoms, fever, brain
edema or inflammatory response in
the cerebrospinal fluid
IAP, Barak valley

71. • Heat stroke
• Lychee seeds
• Japanese encephalitis
IAP, Barak valley

72. • Importance of case reporting and
sharing experience with peers.
• Information on clustering of cases.
• All pediatricians are requested to
report unusual outbreak cases and
keep an accurate clinical and
laboratory records for data analysis
when needed by the investigatoIAPr, Bsarak. valley