1. JAPANESE ENCEPHALITIS
Manish Chaudhary
BPKIHS, Dharan

2. Out line of Presentation
Introduction
History
Magnitude of Disease
Epidemiology
Clinical features
Laboratory Diagnosis
Prevention and Treatment
National Intervention

3. Introduction
Japanese Encephalitis is a viral disease of Public health importance, because of its epidemic potential and high case mortality rate. 
It is a mosquito borne zoonotic disease.  
The virus infects mainly animals through migrating birds.  Pig is the amplifier host.  Man is affected incidentally.  
J.E. is primarily a disease of rural,semi urban, agricultural areas where vector mosquitoes proliferate in close association with pigs and other animal reservoirs. 

4. History 1870’s: Japan 1924: Great epidemic in Japan
“Summer encephalitis” epidemics
1924: Great epidemic in Japan
6,125 human cases; 3,797 deaths
1935: First isolated
From a fatal human encephalitis case
1938: Isolated from Culex tritaeniorhynchus
The first historic mention of Japanese encephalitis occurred during the “summer encephalitis” outbreaks in the late 1870’s. The next documented epidemic in Japan occurred in 1924 with 6,125 human cases resulting in 3,797 human deaths (62% case-fatality rate). The virus was first isolated in Japan in 1935 from a fatal human case of encephalitis. In 1938, the virus was first isolated from its primary vector species, Culex tritaeniorhynchus.

5. History 1940-1978 1983: Immunization in South Korea
Disease spread with epidemics in China, Korea and India
1983: Immunization in South Korea
: Vaccine available in U.S. on investigational basis
In 1940, JE was first identified in China and in 1949 it was identified in Korea during a major epidemic that resulted in 5,548 human cases. In 1954 the virus was recognized in India and a major epidemic occurred in 1978 with over 6,000 human cases occurring. In 1983, in South Korea, JE immunizations started in children as young as age 3 except in endemic areas where the vaccine was recommended in children even younger. From 1983 to 1987 the JE vaccine was available in the U.S. on an investigational basis.

6. JE in Nepal
Clinical cases were reported before 1975 and an epidemic of JE was recognized for the first time in Rupandehi district of the Western Development Region in 1978
Subsequently, epidemics occurred in Morang district of eastern Nepal gradually spreading into other districts in successive years.
Though this disease is endemic in 24 districts, sporadic cases from other districts have been reported in recent years.
The three viral strains namely B-2524, B-9548 and Nep- 1/90 have been isolated in Nepal.

7. Global scenario Major public health disease in Asia
As per WHO estimates 50 thousand serious cases and 10 thousand deaths each year
Disease is prevalent in Indian Sub-continent: Nepal, India Sri Lanka and some areas in Bangladesh

8. Global scenario contd…,
Other SE Asian countries reporting cases include:
Myanmar, Thailand, Cambodia, China
Indonesia, Laos, Vietnam, Malaysia, Philippines Taiwan,
Hong Kong and
Korea

9. DISTRIBUTION OF JAPANESE ENCEPHALITIS
Japanese encephalitis is endemic in India, China, Japan, and all of South East Asia.
Japanese encephalitis is the leading cause of viral encephalitis in Asia, with 30,000–50,000 cases reported annually.
JE virus infection occurs throughout the temperate and tropical regions of Asia. Although initially prevalent in Japan in the late 1800’s, control methods (vaccination and pesticides) have reduced the incidence of the disease in this country. Currently, the disease occurs in China, India, Nepal, the Philippines, Sri Lanka and Northern Thailand. Occasionally sporadic cases of disease occur in Indonesia and northern Australia. The disease has not occurred in the rest of the world. Photo shows distribution of Japanese encephalitis from , from CDC website at

10. National Scenario
24 districts of terai and inner terai regions are affected by JE .
12.5 million people are estimated to be at the risk of the disease.
Since, 1978 seasonal outbreak of JE has been reported annually.
At present, in terms of morbidity and mortality this disease is one of the major public health problems in Nepal.

11. Annually between 1000-3000 total cases and 200-400 deaths occur.
A total of 9,495 cases and 1,163 deaths have been reported from 2001 to 2006.
More than 50 percent of morbidity and 60 percent mortality occur in the age group below 15 years.
Thus 5.4 millions people aged below 15 years are at high risk.
The case fertility rates range from 8 to 46.3 % between and But, in the recent years, CFR is declined and has been contained below 20%.

12. Japanese Encephalitis Endemic District, DOHS 2005/06

13. Figure : Distribution of cases and deaths during the years 2001-2006
 Cases of acute encephalitis syndrome (including cases of JE) are reported throughout the year every year. Upsurge of cases takes place after the rainy season (Monsoon). So far, total of 9,495 cases and 1,163 deaths have been reported from 2001 to More than 50 percent of morbidity and 60 percent mortality occur in the age group below 15 years. Thus 5.4 millions people aged below 15 years are at high risk. Among 24 districts also, 10 districts are mostly affected.
Acute Encephalitis Syndrome (AES) is defined as a person 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) who resides in the endemic geographical region, at any time of year
Figure : Distribution of cases and deaths during the years

14. Source: Annual Report DOHS
JE in Nepal is transmitted seasonally from June to October. Cases start to build up in the month of April-may, and peak is observed during the months of August and early September and start declining by the end of September to level off during the month of October. 90 percent of the total cases are concentrated in the period from mid July to September.
Acute Encephalitis Syndrome (AES) is defined as a person 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) who resides in the endemic geographical region, at any time of year
Figure : Reported case of Acute Encephalitis Syndrome (JE) by Epidemiological weeks,
Source: Annual Report DOHS

15. Agent Epidemiology Flaviviridae Enveloped Single stranded RNA virus
Flavivirus
Enveloped
Single stranded RNA virus
Morphology not well defined
The name is Latin for flavus
Flavus means “yellow”
Refers to yellow fever virus
JE is in the family Flaviviridae and the genus Flavivirus (related to St. Louis encephalitis virus, Murray valley virus and West Nile virus). It is an enveloped single stranded RNA virus. Currently, the morphology of the virus is not well defined. Two subtypes of the virus exist, Nakayama and JaGar 01. The name of the family (flavus) is Latin meaning yellow, which refers to yellow fever which is also a member of this family. Photo: Flaviviridae.

16. Hosts Vector-borne disease Enzootic cycle Mosquitoes: Culex species
Culex tritaeniorhynchus
Reservoir: Ardeid (wading) birds
Amplifying hosts
Pigs, bats
Possibly reptiles and amphibians
Incidental hosts
Horses, humans, others
JE is a zoonotic disease that affects humans and several species of animals. It is transmitted by mosquitoes. The most important vectors are Culex species (top picture), with Culex tritaeniorhynchus being the primary vector. The enzootic cycle involves mosquitoes and an amplifying host (also known as reservoir hosts). Known amplifying hosts include domestic pigs and wading bird species i.e., egrets, herons (bottom picture). Studies have demonstrated that bats are susceptible to infection with JE and that their levels of viremia are also sufficient to infect mosquitoes, thereby serving as a reservoir as well. There have also been limited studies done on snakes and frogs. Their importance at this point is unclear but more research may provide interest. Several additional species can become infected with JE but are incidental hosts since they do not achieve high enough viremias to cycle the virus in nature. Incidental host species include horses, donkeys, cattle, water buffalo, sheep, dogs, chickens and ducks. Humans are also incidental hosts.

17. DYNAMICS OF JE TRANSMISSION
Vector Mosquito
Environment
Victim-Accidental
JE is a zoonotic disease that affects humans and several species of animals. It is transmitted by mosquitoes. The most important vectors are Culex species (top picture), with Culex tritaeniorhynchus being the primary vector. The enzootic cycle involves mosquitoes and an amplifying host (also known as reservoir hosts). Known amplifying hosts include domestic pigs and wading bird species i.e., egrets, herons (bottom picture). Studies have demonstrated that bats are susceptible to infection with JE and that their levels of viremia are also sufficient to infect mosquitoes, thereby serving as a reservoir as well. There have also been limited studies done on snakes and frogs. Their importance at this point is unclear but more research may provide interest. Several additional species can become infected with JE but are incidental hosts since they do not achieve high enough viremias to cycle the virus in nature. Incidental host species include horses, donkeys, cattle, water buffalo, sheep, dogs, chickens and ducks. Humans are also incidental hosts.
Recovery with residual complications
Full Recovery
Death
Host - Amplifying
Host - Carrier

18. Transmission of JE viruses
Transmitted by rice field breeding mosquitoes, mainly Culex tritaeniorhychus
mosquitoes infected by feeding on infected pigs and wild birds (amplifying hosts)
Human as dead end hosts
No person-person or animal-person
transmission

19. Enzootic cycle for Japanese encephalitis. From Tsai, TF
Enzootic cycle for Japanese encephalitis. From Tsai, TF. Japanese Encephalitis Vaccines. Accessed at

20. Clinical spectrum of JE infection
Die
Severe
Moderate
Mild
Asymptomatic
For every symptomatic JE case, there are likely to be about 300 – 1000 people infected with JE virus but without any clinical manifestation
Children between 1 to 15 years of age are mainly affected in endemic areas.
But people of any age can be infected. Adult infection most often occurs in areas where the disease is newly introduced.

21. Prognosis Depends on cause and severity of illness and patient’s age.
Mild cases recover in 2 to 4 weeks with supportive care.
Severe encephalitis can lead to numerous complications.
Hearing and/or speech loss, blindness, permanent brain and nerve damage, behavioral changes, cognitive disabilities, lack of muscle control, seizures, memory loss.

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

23. Symptoms of JE infection
Most cases asymptomatic
Incubation 5 to 15 days.
Mild -fever with headache
Severe infection
quick onset
headache & high fever
neck stiffness,
stupor, disorientation,
coma, tremors,
occasional convulsions (especially in infants) and spastic (but rarely flaccid) paralysis.

24. Differential Diagnosis
Cerebral Malaria
Meningitis
Febrile Convulsions
Rabies
Toxic Encephalopathy

25. LABORATORY INVESTIGATION
Peripheral blood picture shows moderate peripheral leucocytosis with neurophilia and mild anemia.
CSF: Neutrophils may predominate in early CSF samples but a lymphocytic leucocytosis is typical.
CSF protein is moderately elevated in about 50% of cases.

26. Lab ……….. Virus Isolation Viral antigen detection
In Serum, Plasma, Blood , CSF & Tissue
Viral antigen detection
In tissue by Immunoflorescence and Immunohistochemistry
Detection of Viral genome
RT-PCR , Nucleic Acid amplification Test
Detection of antibody( JE specific IgM in CSF or serum)
IgM capture ELISA
4 fold rise in IgG antibody in serum ( Acute and convalescent phase, 14 days intervals)

27. JE DIAGNOSIS IN NEPAL Referral lab centers
BP Koirala Institute of Health Sciences (BPKIHS), Dharan;
Vector Borne Disease Research and Training Center (VBDRTC), Hetauda;
National Public Health Laboratory (NPHL), Kathmandu;
NPHL, jointly with EDCD, will also be responsible for transferring JE specimens from the district to zonal hospitals to the referral laboratories, then from referral laboratories to NPHL for internal quality assurance and finally to AFRIMS in Bangkok for external quality assurance.

28. PREVENTION & CONTROL OF JE
Vector Control Program/Insecticide Spraying .
DDT in very first intervention during 1994/95,
Malathion during 1995/96, Lambdacyhalothrin and K-ornithrine etc.
Currently, Lambdacyhalothrin is extensively being used in the Visceral leishmaniasis, malaria and JE endemic districts of Nepal

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

30. Prevention Personal protective measures
Travellers going to endemic areas may consider vaccination

31. Pig Control
Segregation
Slaughtering
Vaccination

32. JE VACCINE INACTIVATED MOUSE BRAIN VACCINE
It is expensive vaccine, complicated dosing schedule, side effect of this vaccine.
LIVE ATTENUATED VACCINE
SA (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.

33. Awareness Program for JE
It has been found that there is general lack of knowledge about JE in Nepal.
Mass awareness and public health education campaigns are one of the important aspects for changing the perception about the disease, its origin and implementation of effective program for its prevention and control.
It has been found that Epidemiology and Disease Control Division has well established the coordination with NHEICC to develop IEC materials in local languages.

34. If there is raised intracranial pressure, mannitol is given.
Disease Management
There is no specific treatment for the disease and management is purely supportive.
Support often includes feeding, airway management, and anticonvulsants.
If there is raised intracranial pressure, mannitol is given.

35. National intervention
The Ministry of Health and Population of Nepal (MOHP) has identified JE as a priority program.
MOHP has carried out different control activities, diagnostic capacity has been strengthened and national protocol has been developed for JE diagnosis
Treatment of acute encephalitis cases is provided by all governmental hospitals and some of the medical collage hospitals free of cost

36. Intervention………
A systematic surveillance system has been introduced in the year 2005 with the assistance of the program for Immunization Preventable Diseases (IPD), WHO.
EDCD has carried out a mass vaccination of children (1-15 years) in 3 Terai districts (Bardiya, Banke and Kailali) in 1999 with SA live attenuated BHK vaccine. Similarly, vaccination with three doses of inactivated JE vaccines was carried out in six districts (Kanchanpur, Kaillai, Bardiya, Banke, Dang and Rupandehi) in

37. References:
WHO Manual for the Laboratory Diagnosis of Japanese Encephalitis Virus Infection For Evaluation Purposes ,March 2007.
Center for Food Security and Public Health Iowa State University – 2004.
Jaffery Patriage et al.Endemic Japanese Enephalit in Kathmandu Valley,Nepal American Jaurnal of Public Health.htm.
Bista MB, Shrestha JM. Epidemiological situation of Japanese Encephalitis in Nepal, Journal of Nepal Medical Association, 2005 April-June 44(158)
Japanese Encephalitis :2010 Yellow Book CDC Travelers Health.htm.
DOHS, Annual Report 2005/06
Park Text Book of Preventive and Social Medicine 19th Edition.

38. THANK YOU