A 20-year-old Spanish man traveling in Thailand for a martial arts competition was admitted to a local hospital in Koh Samui, Thailand with fever, headache, and decreased consciousness. His condition worsened over 48 hours, developing seizures, paralysis, and decreased responsiveness. Testing revealed positive IgM antibodies for Japanese encephalitis virus (JEV) in his serum. JEV is a mosquito-borne virus that causes viral encephalitis, with high incidence in parts of Asia. Personal protection from mosquito bites and vaccination are recommended for travelers to endemic areas.

1. A 20 year-old Spanish man, without relevant past medical
history, travelled to Thailand on 25 January 2013 to
participate in a martial art competition.
The expected duration of the trip was a month and a half.
He had not attended a travel clinic before departure and
was not prescribed or did not take malaria
chemoprophylaxis.
Upon arriving in Thailand, he visited Bangkok during two
days where he stayed in a hotel.
On 28 January he travelled by bus to Surat Thani, and on
the same day he took the ferry to Koh Samui island.
He stayed at bungalows in the beach (Chaweng and Lamai
beaches) during all the stay. In Koh Samui, he trained every
day but he also visited rural areas, went in the forest and
visited waterfalls where was bitten by mosquitoes.
Case study

2. On 21 February, he was admitted to a local hospital
in Koh Samui with a 48 hours history of fever (38‹C), myalgia,
malaise and headache.
Twenty-four hours after admittance, his condition worsened and
photophobia, vomiting and decreased level of consciousness
occurred.
Physical examination revealed neck stiffness and Glasgow coma
score (GCS) 11.
Forty-eight hours later the patient presented seizures, V and VII
left peripheral nerves palsy with right hemiparesis, and GCS
decreased to nine.
Intubation and invasive mechanical ventilation were required.
Empiric treatment was initiated with ceftriaxone, doxycycline,
acyclovir, dexamethasone and phenytoin.
After five days the patient was tetraparetic and did not respond
to simple commands. A tracheotomy was made and weaning
from mechanical ventilation was started.

3. Initial full blood count, urine test and chest X-ray were
normal. A cerebral computed tomography (CT) showed
meningeal enhancement. Cerebrospinal fluid (CSF)
analyses revealed a clear fluid with 960 leucocytes/mm3
(norm: 4,000–10,000/mm3) with 86% of mononuclear
cells, and normal glucose and proteins.
Multiple bacterial cultures including mycobacteria,
polymerase chain reaction (PCR) for herpes virus,
varicella-zoster virus, enterovirus, and rabies virus, blood
and CSF Cryptococcus antigen, malaria blood smear and
serological tests for human immunodeficiency virus (HIV),
dengue virus, Leptospira species, Rickettsia species and
Burkholderia pseudomallei were negative.
Lab IX ?

4. Real time-polymerase chain reaction (RT-PCR) for
Japanese encephalitis virus (JEV) in CSF was negative.
The result of IgM against JEV in serum was positive using
an IgM capture enzyme-linked immunosorbent assay
(ELISA) (IgM in CSF was not performed).

5. Japanese Encephalitis
&
KFD
Dr Naresh T Chauhan

7. Introduction
• Encephalitis is an acute inflammatory process affecting the brain
• Viral infection is the most common and important cause, with
over 100 viruses implicated worldwide
• Symptoms
– Fever
– Headache
– Altered level of consciousness
– Focal neurologic deficits
– Seizures
– Behavioral changes
• Incidence of 3.5-7.4 per 100,000 persons per year

8. Causes of Viral Encephalitis
• Herpes viruses – HSV-1, HSV-2, varicella zoster virus,
cytomegalovirus, Epstein-Barr virus, human herpes virus 6
• Adenoviruses
• Influenza A
• Enteroviruses, poliovirus
• Measles, mumps, and rubella viruses
• Rabies
• Arboviruses – examples: Japanese encephalitis; St. Louis
encephalitis virus; West Nile encephalitis virus; Eastern,
Western and Venzuelan equine encephalitis virus; tick borne
encephalitis virus
• Bunyaviruses – examples: La Crosse strain of California virus
• Reoviruses – example: Colorado tick fever virus
• Arenaviruses – example: lymphocytic choriomeningitis virus

9. What Is An Arbovirus?
• Arboviruses = arthropod-borne viruses
• Arboviruses are maintained in nature through
biological transmission between susceptible
vertebrate hosts by blood-feeding arthropods
• Vertebrate infection occurs when the infected
arthropod takes a blood meal

10. http://www.cdc.gov/ncidod/dvbid/arbor/schemat.pdf

11. Japanese Encephalitis
• Most important cause of arboviral
encephalitis worldwide, with over 50,000
cases reported annually
• Transmitted by culex mosquito, which
breeds in rice fields
– Mosquitoes become infected by feeding
on domestic pigs and wild birds infected
with Japanese encephalitis virus.
Infected mosquitoes transmit virus to
humans and animals during the feeding
process.

12. Epidemiology
• Primarily a disease of rural Asia
– Vector mosquitoes proliferate in close
association with birds and pigs
– Birds and pigs are the major amplifying
hosts
• Culex tritaeniorhynchus the principal vector
but many other mosquitoes are competent
and can transmit
– C. pipiens
– C. quinquefasciatus
– Species of Aedes, Anopheles

13. Transmission cycle of the Japanese encephalitis virus

14. Epidemiology
BiharContribution of Japanese encephalitis cases by Uttar Pradesh in
national figures by year, 1997–2009

15. Evolution of average number of Japanese encephalitis cases from
1988 to 2009 showing shift of seasonal peak in Uttar Pradesh

16. Distribution of Japanese encephalitis cases by age and sex, Gorakhpur
division, Uttar Pradesh 7A: Distribution of JE cases by age/sex, Gorakhpur,
2009

17. Incidence and Prevalence
• Ratio of apparent to inapparent infection ranges
from 1:300 to 1:1000
• Ratio affected by age, virulence of the strain of
virus, cross protective immunity from other
Flaviviruses (dengue)
• Risk to travelers 1 case per 50,000 months of
exposure

18. History of Japanese Encephalitis
• 1871s – recognized in Japan
• 1924 – Japan epidemic. 6125 cases,
3797 deaths
• 1935 – virus isolated in brain of
Japanese patient who died of
encephalitis
• 1938 – virus isolated from Culex
mosquitoes in Japan
• 1948 – Japan outbreak
• 1949 – Korea outbreak
• 1966 – China outbreak

19. Flaviviruses
Japanese Encephalitis Virus
St. Louis encephalitis virus
West Nile Virus

20. Overview of Flaviviruses
• RNA viruses related to Yellow Fever virus
• At least 80 different ones, over 40 can infect
humans
• Most are arthropod borne,
• One with the greatest impact on human health
– Yellow fever virus
– Dengue fever virus
– Japanese encephalitis virus
– West Nile virus
– St Louis encephalitis virus

21. Pathogenesis
• Pathology
• Usually gray matter is involved. Lesions are seen
in thalami, substantia nigra, cerebral cortex,
cerebellum, Ammon’s horn, and anterior horn of
spinal cord

22. Clinical Manifestations
• Incubation 6-16 days.
Spectrum from mild febrile
headache to severe
encephalitis
• Headache, fever, nausea,
vomiting, drowsiness.
Abdominal pain and diarrhea
common in children

23. Clinical manifestation
• Symptoms and signs of infection:
• Symptoms and signs of focal brain damage due to
infection
• Symptoms and signs of raised intracranial tension:
• Symptoms and signs of meningeal irritation
• Non-neurologic signs

24. Developing Signs
• Altered LOC – mild lethargy to deep coma.
• AMS – confused, delirious, disoriented.
• Mental aberrations:
– hallucinations
– agitation
– personality change
– behavioral disorders
– occasionally frank psychosis
• Focal or general seizures in >50% severe
cases.
• Severe focused neurologic deficits.

25. Clinical Manifestations
• Death in 5-40%
• Children under 10 more likely to
die or have residual
neurological defects
• Poor prognosis associated with
– Respiratory dysfunction
– Babinsky’s sign
– Frequent or prolonged
seizures
– Prolonged fever
– Albuminuria
– High viral replication in the
brain

26. Neurologic Signs
• Most Common
– Aphasia
– Ataxia
– Hemiparesis with hyperactive tendon reflexes
– Involuntary movements
– Cranial nerve deficits (ocular palsies, facial
weakness)

27. Neuropsychiatric Sequelae
• Occur in 45-70% of survivors,
particularly severe in children
• Parkinsonism
• Seizures
• Paralysis
• Mental retardation
• Psychiatric disorders

28. Differential Diagnosis
• Distinguish Etiology
– Bacterial infection and other infectious conditions
– Parameningeal infections or partially treated bacterial
meningitis
– Nonviral infectious meningitides where cultures may be
negative (e.g., fungal, tuberculous, parasitic, or syphilitic
disease)
– Meningitis secondary to noninfectious inflammatory
diseases
• MRI
– Can exclude subdural bleeds, tumor, and sinus thrombosis
• Biopsy

29. Standard Case definition
Suspect (History)
• A person of any age at any time of year with
acute onset of fever and change in mental status
AND/OR new onset of seizures (Exclude SFS)
Probable (History and clinical Exan)
• A suspect case that occurs in close geographical
and temporal relationship to a laboratory
confirmed case of JE, in the context of an
outbreak
Confirmed (laboratory Test)
• Presence of JE virus specific Ig-M antibodies

30. Laboratory Diagnosis
• Diagnosis is usually based on CSF
– Normal glucose
– Absence of bacteria on culture.
– Viruses occasionally isolated directly from CSF
– IgM-capture ELISA
• Polymerase Chain Reaction techniques
– Detect specific viral DNA in CSF

31. Treatment
• ‘ABCs’ of resuscitation
• Seizure management:
• For raised intracranial tension:
• Prevent and treat pain
• Nutrition and fluids
• Antibiotics to be used as and when necessary.

32. Dexamethasone
• Synthetic adrenocortical steroid
• Potent anti-inflammatory effects
• Dexamethasone injection is generally
administered initially via IV then IM
• Side effects: convulsions; increased ICP after
treatment; vertigo; headache; psychic
disturbances

33. Prevention
• Personal protective measures and
mosquito elimination are the most
important
• travellers going to endemic areas
may consider vaccination

34. • Keep all drains free from
blockage
• Cover tightly all water
containers, wells and water
storage tanks
• Top up all defective ground
surfaces to prevent the
accumulation of stagnant water
Prevent mosquito breeding

35. • Put all used cans and bottles into
covered dustbins
• Change water for plants at least
once a week, leaving no water in
the saucers underneath flower
pots
Prevent mosquito breeding

36. Prevention of Mosquito Bites
• Avoid going to rural area during dusk
and dawn when the mosquitoes are
most active
• Wear light-colored, long-sleeved
clothing and trousers
• Apply DEET-containing mosquito-
repellents over exposed parts of the
body and clothes every 4 to 6 hours
• For DEET products used by children,
its concentration should be less than
10%

37. Prevention of Mosquito Bites
•hang mosquito screens
around your bed, use
insecticides or coil incenses to
repel mosquitoes
•Place of accommodation
should have air-conditioners
or mosquito nets; or
•Install mosquito nets to doors
and windows so that
mosquitoes can’t get in

38. Vaccination
– Appears to be 91% effective
– There is no JE-specific therapy other than
supportive care
– Live-attenuated vaccine developed and
tested in China
• Appears to be safe and effective
– Vero cell-derived inactivated vaccines
have been developed in China

39. Vaccines for JE virus
– Inactivated vaccine grown in primary
hamster kidney cells
– Live attenuated vaccine (SA14-14-2)
grown in hamster kidney cells
– Licensed as JE-VAXR
– Three subcutaneous injections over a
month with a booster at 3 years
– 91% efficacy in a large field trial in
Thailand

41. References
• A review of Japanese encephalitis in Uttar Pradesh,India, Roop Kumaria,
Pyare L Joshib WHO South-East Asia Journal of Public Health
2012;1(4):374-395
• Japanese Encephalitis, Potharaju Nagabhushana Rao,Indian Pediatrics
2001; 38: 1252-1264
• Doti P, Castro P, Martinez MJ, Zboromyrska Y, Aldasoro E, Inciarte A,
Requena A, Milisenda J, Fernandez S, Nicolas JM, Munoz J. A case
of Japanese encephalitis in a 20 year-old Spanish sportsman,
February 2013. Euro Surveill. 2013;18(35)
• JE ICMR document
• Map of geographical distribution WHO
• Japanese encephalitis: a review of the Indian perspective Sarika Tiwari,
Rishi Kumar Singh, Ruchi Tiwari, Tapan N. Dhole. braz j infect dis.
2012;16(6):564–573

42. Kyasanur Forest Disease

43. History …..
• Heavy mortality in two species of monkey
( Langur & Red faced bonnet ) in 1955 in forests of
Shimoga led to the discovery of KFD
• Mortality in monkeys was followed by acute
febrile prostrating illness among villagers and few
human deaths

44. History …….
Autopsy on monkeys
Place of reporting of First
monkey death in march 1957

45. Kyasanur forest disease
• Found in India
• Limited originally to
Shimoga district in
Karnataka (800 sq km
• Newer foci in 3 more
districts namely
U.kannada,D. Kannada
and Chikmangaluru
( 6000 sq km )
• Serosurveys reveal KFD
in Kutch & Saurashthra

46. Problem statement
 The outbreak during 1983-1984 is the largest with
2167 cases and 69 deaths.
 In 1997 the cases came down to75 and deaths to 4.
 The number of human deaths varied between 4-15%
of the cases
 Even today few hundreds of cases and some deaths
are reported

47. Agent factors ..
• Kyasanur forest disease (KFD) is a febrile disease
associated with hemorrhages caused by an arbovirus
flavivirus.
• KFD virus is a member of group B togaviruses
• Belongs to Russian spring summer encephalitis
(RSSE) group of viruses

48. HOST FACTORS
• Age :majority between 20 and 40 years.
• Sex: males
• Occupation: Cultivators who visit forest with cattle
or cutting wood.
• Epidemic correlates with peak human activity in
forests i.e between January and June

49. Natural hosts & reservoirs
• Circulates in small mammals rats, squirrels,
shrews and bats are the main reservoirs .
• Neutralizing antibodies have also been found in
cattle, buffaloes, goats and porcupines
• Maintenance hosts – maintain the infection in
nature

50. Natural hosts & reservoirs
• Monkeys are the amplifying hosts for the virus.
• Amplifying hosts --- multiplication of the virus
takes place at very high levels such that the
intensity of infection is very high.

51. Natural cycle
• In enzootic states the infection is maintained in
small mammals and also in ticks
• When monkeys come in contact with infected
ticks , they get infected , amplify and disseminate
the infection in “hot spots ”of infection
• Humans in these hot spots are infected by bite of
infected anthrophilic ticks like H. spinigera

52. VECTORS
Female tick laying eggs
Virus has been isolated
from 16 species of ticks
but Hard tick species of
the genus
Haemophysalis
particularly H.spinigera
and H.turtura are the
main vectors
Ticks act as both as
vectors and reservoirs of
infection in KFD

53. Vector bionomics and seasonal
transmission of KFD
• Adult Ticks become active after few monsoon
rains in June
• Adult population reaches peak during July &
August and gradually declines in September
• Larval activity builds in post monsoon Oct-Dec
• Nymphal activity high from January to May

54. Vector bionomics and seasonal transmission
of KFD
• Epidemics coincide with
nymphal activity
• Nymph most important
stage for human
transmission of infection
as viraemia is significant
in nymphs
• Adults ticks feed on
cattle and viraemia is not
significant

55. Environmental factors
 Tropical evergreen,
deciduous forests
 Clearing of forests for
cultivation and other
developmental activities
leads to change in tick
flaura and fauna and is
an important
determinant for
outbreaks

56. MODE OF TRANSMISSION
• By the bite of infective ticks.(nymphal stage )
• Human is dead end in the natural cycle
• There is no evidence of man to man
transmission
• Transtadial transmission is common in ticks but
transovarial transmission is absent except in
Ixodides species

57. CLINICAL FEATURES
• Acute phase with sudden onset of fever,
headache ,severe myalgia with prostration lasting
for 2 weeks.
• GI disturbances and hemorrhagic manifestations
in severe cases
• Second phase characterized by mild
meningoencephalitis after an afebrile period of 7-
21 days.
• Case fatality varies between 4-16%

58. Treatment
Conservative
• Antipyretics
• Analgesics
• Supportive therapy

59. Diagnosis
• Diagnosis by suspicion by clinical signs and
symptoms
• H/O occupation/travel in forests
• Detecting the presence of virus in blood.
• Serological evidence by haemagglutination and
immunofloresence

60. CONTROL
• Timely control decreases morbidity and mortality
in humans
CONTROL OF TICKS
• By aircraft mounted equipment to dispense
lindane , cabaryl fenthion at 2.24 kg / hectare at
forest floor
• Spraying carried out within 50m around hot spots
• Restriction of cattle movement brings reduction in
vector population

61. CONTROL
Personal protection
• Adequate clothing
• Insect repellants such as DMP, DEET provide 90-
100% protection against tick bites
• Examine themselves for ticks and promptly
remove them
• Health education

62. CONTROL
Vaccination
• Inactivated chick embryo tissue culture
vaccine developed by NIV, Pune
• Neutralizing antibodies in 70% of vaccinated
persons
• Vaccinating at risk population i.e villagers
living near forests , forest workers ,
occupational personnel concerned with
forests

63. Bio safety concerns
• One of the highest risk category
pathogens
• Bio safety level 4
• One of the potential bioterrorist weapon

64. THANKS