Acute Encephalitis Syndrome (AES) is defined as the acute onset of fever and altered mental status or seizures in a person of any age. AES is usually caused by viral infections, mainly from herpes simplex virus, West Nile virus, Japanese encephalitis virus (JEV), or dengue virus. JEV is the leading cause of viral encephalitis in Asia, where it spreads between mosquitoes and amplifying hosts like pigs and birds. Most human infections are asymptomatic, but less than 1% result in encephalitis with high mortality and neurologic sequelae in survivors. Nepal reports over 1,800 JEV cases between 2007-2015, mostly in children under 15 during the monsoon season.

1. Acute Encephalitis Syndrome (AES)
Dr Kamala Sanjel
Internal medicine, ,NAMS

2. Introduction
• Acute encephalitis syndrome (AES) is defined as the
acute-onset of fever and a change in mental status
(including signs and symptoms such as confusion,
disorientation, delirium or coma) and/or new-onset
of seizures(excluding simple febrile seizures) in a
person of any age at any time of the year.(WHO)
• Other early clinical findings could include an increase
in irritability, somnolence or abnormal behaviour
greater than that seen with usual febrile illness.

3. Introduction
• The clinical definition of AES was introduced to
facilitate surveillance for Japanese encephalitis (JE) and
other mosquito-borne viral encephalitis.
• Most AES is due to viral-encephalitis, mainly Herpes
simplex virus, West Nile virus, Flavivirus like JE and
dengue virus.
• HSV 1 is the most common cause of sporadic
encephalitis worldwide.
• Japanese encephalitis is one of the most important
forms of epidemic and sporadic encephalitis in the
tropical regions of Asia, including Japan, China, Taiwan,
Korea, Philippines, all of Southeastern Asia, and India.

4. (Common organisms causing encephalitis) -Spencer et al)

5. Virus causing Encephalitis syndrome

6. Virus causing Encephalitis syndrome

7. Virus causing Encephalitis syndrome

8. Japanese encephalitis
Introduction
• Japanese encephalitis virus (JEV), a mosquito-
borne flavivirus, is the most important cause of
viral encephalitis in Asia based on its frequency
and severity.
• JEV is now the leading cause of childhood viral
neurological infection and disability in Asia.
• JEV is closely related to other flaviviruses like
West Nile, St. Louis encephalitis, and Murray
Valley encephalitis viruses.

9. Introduction
• Most human JEV infections are asymptomatic
or cause a nonspecific febrile illness.
• Fewer than 1 percent of JEV infections results
in symptomatic neuroinvasive disease
• When neurologic disease does occur, it is
usually very severe with a high case-fatality
rate, among survivors, neurological sequelae
are common.

10. Epidemiology
• About 68,000 cases of Japanese encephalitis
(JE) are estimated to occur each year.
• JE is endemic throughout most of Asia and
parts of the Western Pacific region.
• JE affects over 50,000 people annually, leading
to 8-30% mortality and 50-60% disability, with
children most affected. (Solomon et al)

11. Epidemiology
• Within the JE-endemic region, there are two
typical patterns of transmission
• In areas with temperate climates (including
China, Japan, South Korea, Nepal, northern
Vietnam, and northern India), most cases
occur over a period of several months when
the weather is warmest, usually after the
monsoons begin or associated with heavy
rainfall .

12. Epidemiology
• The peak months of transmission and the length
of the season vary from place to place. There are
sometimes large, explosive outbreaks.
• In areas with tropical climates (including
Cambodia, Indonesia, southern Vietnam, and
southern Thailand), there is year-round
transmission.
• An increase in cases may be observed during the
rainy season .

13. Epidemiology
• In endemic areas, JE typically affects children <15
years of age.
• By early adulthood, the majority of the population
has protective immunity following natural exposure
to JEV as a result of ongoing environmental
transmission .
• However, when the virus enters new geographic
areas where there is no immunity, JE affects both
adults and children.
• In regions where childhood immunization programs
have been introduced, the age distribution of disease
shifts to older ages.

14. Epidemiology
• Among immunologically naïve travelers visiting JEV-
endemic regions, the disease can affect individuals at
any age.
• For travelers to Asia, the risk of JE is very low but
varies based on season, destination, duration, and
activities.
• The estimated incidence of JE among travelers to
Asia from non-endemic countries is <1 case per 1
million travelers.
• Major outbreaks of JE occur every 2-15 years.

15. Japanese Encephalitis in Nepal
• From 2007 to 2015, 1,823 JE cases were reported
with a cumulative mean incidence of
0.735/100,000 population and a case fatality rate
of 6.6%.
• The JE cases were most commonly reported in
the age group of 1–14 years.
• The death rate in the up-to-24 years of age group
was 74%.
Pant et al.

16. Japanese Encephalitis in Nepal
• There is a strong seasonal pattern of JE occurrence in
Nepal which peaked in August and declined by
October each year, which corresponds to the
monsoon season.
• The JE cases were reported in 63 of 75 districts
(84%), expanding in the mountain and hill regions.
• There was a strong clustering of JE incidence in the
south-western and south-eastern Terai region, which
is endemic for JE.
Pant et al.

17. Transmission
• JEV is transmitted in an enzootic cycle involving
mosquitoes and vertebrate amplifying hosts,
primarily pigs and wading birds.
• Humans are incidental and dead-end hosts in the
JEV transmission cycle as they do not develop
sufficiently high viremia to infect feeding
mosquitoes.
• Therefore, mosquitoes do not transmit the virus
directly from one person to another person.

18. Transmission
• Mosquitoes of the Culex vishnui subgroup,
particularly Culex tritaeniorhynchus, are the major
vectors of JEV, although JEV has been isolated from
over 30 mosquito species .
• C. tritaeniorhynchus commonly breeds in rice fields,
marshes, and other shallow pools of water.
• It is an evening and night-time biting mosquito and
mainly feeds outdoors, preferentially on large animals
and birds and only infrequently on humans.
• Pigs and wading birds, such as herons and egrets, are
the most important hosts for maintenance and
amplification of JEV.

19. Transmission
• Pigs are a key host as they develop high levels of
viremia, and in Asia, large numbers of pigs are
frequently kept near human dwellings.
• The risk for JEV infection is highest in rural,
agricultural areas of Asia, as all the elements of
the enzootic transmission cycle are in close
proximity to humans.
• Japanese encephalitis cases are occasionally
reported from urban or peri-urban areas .
• Transmission via infected blood products has
been reported.

20. Clinical features
• The most commonly recognized clinical presentation
of JEV infection is acute encephalitis.
• Milder forms of disease such as aseptic meningitis or
nonspecific febrile illness with headache also occur.
• After an incubation period of 5 to 15 days, initial
symptoms are usually nonspecific and may include
fever, diarrhea, and rigors followed by headache,
vomiting, and generalized weakness.
• Many patients lapse into coma and some require
ventilatory assistance.

21. Clinical features
• Over the next few days, mental status changes, focal
neurologic deficits (including paresis, hemiplegia,
tetraplegia, or cranial nerve palsies), and/or movement
disorders develop.
• In some patients, the initial presentation may consist of
abnormal behavior or acute psychosis, leading to
potential misdiagnosis.
• Seizures (usually generalized tonic-clonic) are very
common, especially among children.
• In some children, subtle motor seizures occur and may
present with twitching of a digit, eye deviation, or
irregular breathing.

22. Clinical features
• Acute flaccid paralysis due to anterior horn cell
damage, without any alteration in consciousness.
• Patients with JEV infection can also present with
Guillain Barré syndrome.
• Clinical signs associated with a poor prognosis include
multiple prolonged seizures and raised intracranial
pressure.
• Changes in the respiratory pattern, flexor and extensor
posturing, and abnormalities of the pupillary and
oculocephalic reflexes are also poor prognostic signs
and may reflect brainstem encephalitis with or without
transtentorial herniation .

23. Laboratory findings
• The white blood cell count is moderately
elevated in most patients.
• Thrombocytopenia, mild anemia, and elevated
hepatic enzymes may also occur but are
relatively nonspecific laboratory features.
• Hyponatremia may be observed due to the
syndrome of inappropriate antidiuretic
hormone secretion.

24. Cerebrospinal fluid findings
• The cerebrospinal fluid (CSF) opening pressure
is elevated in about 50 percent of patients.
• CSF findings are typically a mild to moderate
pleocytosis of 10 to several hundred white
blood cells/mm3 with lymphocytic
predominance, slightly elevated protein, and
normal CSF to plasma glucose ratio.
• Early in disease, there may be no pleocytosis
or neutrophils may predominate.

25. Imaging
• Magnetic resonance imaging is more sensitive
than computed tomography scanning for
detecting JEV-associated abnormalities such as
changes in the thalamus, basal ganglia, midbrain,
pons, and medulla.
• Thalamic lesions are the most commonly
described abnormality.
• Although these can be highly specific for JE in the
appropriate clinical context, they are not a very
sensitive marker of JE.

26. Magnetic resonance image of a child with Japanese encephalitis,
demonstrating characteristic bilateral thalamic hyperintensities

27. EEG
• Electroencephalogram abnormalities may
include theta and delta coma, burst
suppression, epileptiform activity, and
occasionally alpha coma.

28. Diagnostic testing
• JE is diagnosed serologically by detection of JEV-
specific immunoglobin IgM antibodies in CSF or
serum by an enzyme-linked immunosorbent assay
(ELISA).
• The presence of JEV-specific IgM antibodies in CSF
confirms recent central nervous system infection.
• IgM antibody in serum is suggestive of JE but could
indicate asymptomatic infection or recent JEV
vaccination.

29. Diagnostic testing
• Important considerations for interpretation of serology
results include vaccination history, date of onset of
symptoms, and information regarding other
flaviviruses known to circulate in the geographical area
that may cross-react in serologic assays (such as
dengue or West Nile viruses).
• Serodiagnosis of Flavi-viral infections is not
straightforward and cross-reactivity is common.
• Samples positive by ELISA should be referred to a
reference laboratory for confirmatory plaque reduction
neutralization testing.

30. Diagnostic testing
• Virus isolation or detection of viral RNA with a nucleic
acid amplification test (NAAT) can provide a definitive
diagnosis, but positive results from CSF or blood are
rare.
• Because humans have low levels of transient viremia
and high levels of neutralizing antibodies by the time
distinctive clinical symptoms are recognized, virus
isolation and NAATs are insensitive for the detection of
JEV or JE viral RNA in blood or CSF.
• JEV isolates have been obtained postmortem from
brain tissue.

31. Differential diagnoses for infective
encephalitis

32. Treatment
• No definite antiviral treatment available for
JE.
• Treatment of JE consists of supportive care
with emphasis on control of intracranial
pressure, maintenance of adequate cerebral
perfusion pressure, seizure control, and
prevention of secondary complications.

33. Outcome
• Mortality among hospitalized patients is about
20 to 30 percent.
• Some deaths come after a short fulminant
course while others occur after a prolonged
period of coma.
• Among JE survivors, long-term sequelae occur
in at least 30 to 50 percent.

34. Outcome
• The most common sequelae are upper and lower
motor neuron weakness and cerebellar and
extrapyramidal signs.
• Severe cognitive or language impairment,
psychiatric problems, and recurrent seizures also
occur.
• Among patients who appear to have recovered
well, subtle sequelae such as learning or
behavioral problems may be observed in about
50 percent

35. JE and pregnancy
• There is limited information on JEV infection in
pregnancy.
• In India, four miscarriages were reported
among nine infected pregnant women; all of
the women were in the first or second
trimester of pregnancy.
• JEV was isolated from one of the four aborted
fetuses, suggesting that intrauterine
transmission of JEV can occur.

36. Prevention
• Personal protective measures — Measures
include using insect repellent, permethrin-
impregnated clothing, staying in screened or
air-conditioned rooms, or sleeping under a
bed net.
• Proper management of pigs.
• Vaccination

37. JE Vaccine
• Live attenuated Chengdu SA-14-14-2 strain
vaccine
• Live recombinant (chimeric) vaccine
• Inactivated vero cell vaccine
• Inactivated mouse brain-derived vaccine

38. JE vaccine in Nepal
• The live attenuated Japanese encephalitis (JE)
vaccine SA14-14-2 strain vaccine has been used in
Nepal for catch-up campaigns and is now included in
the routine immunisation schedule.
• Given to infants at age of 12 months
• It is indicated for active immunization against
Japanese Encephalitis in individuals from the age of
>= 1 to <= 49 years of age.

39. JE vaccine in Nepal
Dosage
• Pediatric (Children between>=1 to <3 years of age)
The primary vaccination schedule consists of two
separate doses of 0.25 ml each.
• Children, Adolescents, and Adults (>=3 to <=49 years)
The primary vaccination schedule consists of two
separate doses of 0.5 ml each.
First Dose: Day 0
Second Dose: 28 days after the first dose.
• Single shot offers protection for up to 5 years however,
a booster at one year is recommended for long term
protection

40. JE vaccine

41. References
• Harrision’s principle of internal medicine,20th
edition
• UPTODATE

42. Thank you