EPIDEMIOLOGY OF JAPANESE ENCEPHALITIS AND CONTROL MEASURES

Dr.I.Selvaraj, I.R.M.SB.SC., M.B.B.S., ( M. D COMMUNITY MEDICINE )., D.P.H.,

D.I.H., P.G.C.H & FW (NIHFW, NEW DELHI)

Sr.D.M.O (ON STUDY LEAVE)

INDIAN RAILWAY MEDICAL SERVICE

Seen in picture is a man rushing his child to a hospital in Ghorakpur, Uttar Pradesh.)

Doctors look at a child who is being treated for Japanese Encephalitis at a hospital in Lucknow, India, Thursday, Sept. 8, 2005. The death toll from an outbreak of Japanese Encephalitis in northern India has reached nearly 600, as another 53 people died overnight.

•Japanese Encephalitis is a viral zoonotic 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. •Man to man transmission is not possible. •The detection of cases are difficult due to the disease apparent and in apparent nature.•Once the human is infected with the disease it leads to death in most of the cases. •If survive the patient will be with severed physical and neurological complications.

Japanese Encephalitis is a mosquito-borne viral infection that occurs chiefly in three areas: (1) China and Korea, (2) the Indian sub-continent consisting of India, parts of Bangladesh, southern Nepal, and Sri Lanka, and (3) the southeast Asian countries of Burma, Thailand, Cambodia, Laos, Vietnam, Malaysia, Indonesia and the Philippines. Japanese Encephalitis also may occur with a lower frequency in Japan, Taiwan, Singapore, Hong Kong, and eastern Russia.

•The virus was isolated for the first time in the world from a post-mortem human brain in Japan in 1933

•JE was clinically diagnosed for the first time in India in 1955 at Vellore, erstwhile North Arcot district of Tamil Nadu.

•Approximately 3 billion people and 60% of the world's population live in endemic region

•50,000 cases with 10,000 deaths were notified annually from a wide geographic range.

•In India there was a rise of JE incidence in 1980s and has dropped significantly and maintained till 1995

•. The major outbreaks coincided with the heavy rainfall and or floods.

•In India, JE is considered mainly as a pediatric problem.

JE OUTBREAK INDIA

• Nagpur (1954-1955)• North Arcot , Madras (1955)• Agra,U.P- 1958• W.Bengal – 1973• TN, KA,WB,AP,Bihar,Assam,&U.P-1977-1979• Goa, Kerala, Haryana (samuel et.al.2000) .• 1145 cases of Japanese encephalitis have been

reported from 14 districts of Uttar Pradesh Province, India from 29 July to 30 August 2005. About one-fourth of these (n=296) have died. 90 cases from the adjoining districts of Bihar have also been admitted to the hospitals in Uttar Pradesh.

Children romp in a rice field near Rakshwapar village in the northern Indian state of Uttar Pradesh, a bowl-shaped breeding ground for mosquitos that spread Japanese encephalitis. This year has been exceptionally rainy, leaving mosquito-friendly pools of water everywhere. At least 850 people, mostly children, have already died

from the incurable disease.

AREA OF HIGH OCCURRENCE IN INDIA

• The three southern states of Tamil Nadu (TN), Andra Pradesh, Karnataka were reporting higher incidence.

• JE is emerging as a public health problem in Kerala

• In a few villages of Cuddalore district of Tamil Nadu, a known JE-endemic area (Chidambaram, Virudhachalam, Thittakudi)

TAMILNADU

• In the early 80s cases were reported from Tamilnadu in the following revenue districts Tiruvannamalai, Dharmapuri, Namakkal, Trichirapalli, Dindigul, Theni, Madurai,Virdhunagar, Tirinelveli,  and Tuticorin.

• However for the past 5 years sporadic cases are reported from Villupuram, Cuddalore,and Perambalur districts only.

Incidence of Japanese Encephalitis - Tamil Nadu

 YEAR CASES DEATH

 1995 115 57

 1996  111  53

 1997  89  42

 1998  25  14

  1999  14  05

 2000  116  17

 2001  119  18

  2002  126  28

  2003  163  36

  2004  82  09

• The viruses responsible for these diseases are classified as arbovirus and these diseases are collectively called as arbovirus encephalitis.

• JEV is related to St. Louis encephalitis virus, Murray Valley virus and West Nile virus.

• The virus is antigenically related to several other flaviviruses including dengue virus.

• JE virus is a member of the family Flaviviridae. • I t is a single stranded RNA virus.• It has three proteins• A) envelope protein• B) core protein• C) & membrane protein

Culex mosquito biting human.

FEMALECULEX QUINQUEFASCIATUS

                     

     

Image: Culex mosquito laying eggs.(Photograph by Richard G. Weber)

VECTORS• JEV can be transmitted by mosquitoes in the genera Culex • major vectors for JEV transmission in India belong to Culex vishnui subgroup

which comprises of Cx. pseudovishnui colles.• Though JEV has been isolated from 16 species of mosquitoes, the majority of the

isolations are from Cx. vishnui complex, which breed extensively in rice eco system.• The disease occurrence coincide with the rainy season • The predominant mosquito species involved in JEV transmission breed in rice

fields and water surfaces.• The birds (egrets, pond herons, paddy birds) which a have role in JEV

transmission have close link with rice fields and water. • . Among the vertebrate hosts, though the cattle populations do not circulate the

virus (dead end), they support the mosquito species by providing blood meal to them.

• . Establishment of pig forms for economical reasons are related to human activities in the country side.

• Building reservoirs and canals for agricultural purposes may harbor potentials for JEV transmission.

• Cx. tritaeniorhynchus -TN, KA, KL • Cx. vishnui - TN, KA, WB • Cx. Pseudovishnui - KA, GOA • Cx. bitaeniorhynchus - KA, WB • Cx. epidesmus - WB • Cx. fuscocephala - TN, KA • Cx. gelidus - TN, KA • Cx. quinquefasciatus - KA • Cx. whitmorei - TN,KA, AP, WB • An. barbirostris - WB • An. paeditaeniatus - KA • An. Subpictus - TN, KA, KL • Ma. annulifera - KL, ASSAM • Ma. indiana - KL • Ma. uniformis - KA, KL

• Man is an incidental and dead-end host.

• Man-to-man transmission does not occur in nature.

• Cattle also act as dead-end host in the transmission cycle.

• From Ardeid birds, JE infection is transmitted by mosquitoes to pigs/ducklings.

• The pigs/ducklings serve as amplifying hosts since thevirus multiplies in them.

. Man or cattle get infected either from birds or pigs/ducklings through mosquito bite.

. Ardeid bird–mosquito–Ardeid bird and pig/duckling–mosquito–pig/duckling cycle exist in nature.

• Transmission is usually seasonal

• In temperate zones of China, Japan, Korea and northern areas of Southeast Asia, Japanese encephalitis is transmitted during summer and early autumn -- May to September.

• In north India and Nepal transmission occurs from June to November

• In south India and Sri Lanka epidemics are found from September to January.

• The vast majority of JE infections are in apparent • only 1 in 250 infections results symptomatic illness • Most infected persons develop mild symptoms or no symptoms at all. • Symptoms soon after exposure appear 6-8 days after the bite of an

infected mosquito. • The incubation period is about 5-15 days. • Extrinsic incubation period in vector mosquitoes is 9-12 days.• Approximately 25-30% of cases are fatal, some with a fulminate

course lasting a few days and others run a more protracted course in coma.

• . About 30% of those who survive may have sequelae. • Young children (under 10 years) are more likely to die, and if they

survive, they are likely to have residual neurological disability and principal sequelae

JE disease manifestations can be divided into three stages.

•A Prodromal Stage

•An Acute encephalitic Stage

•and a late stage

Prodromal Stage : is characterised by •Fever •Rigors •Headache •Nausea •and Vomiting

The Prodromal stage usually lasts for 1 to 6 days. It can be as short as less than 24 hours or as long as 14 days

An Acute Encephalitic Stage:

Begins by the third to fifth day. The symptoms include:

•Convulsions •Altered sensorium, unconsciousness, coma •Mask like face •Stiff Neck •Muscular Rigidity •Tremors in fingers, tongue, eyelids and eyes. •Abnormal movements of limbs •Speech impairment

A Late Stage:

Characterised by •the persistance of signs of CNS injury such as,      •Mental impairment.      •Increased deep Tendon reflexes      •Paresis either of the upper or lower motor neuron type.      •speech impairment      •Epilepsy, Abnormal movements, Behaviour abnormalities.

Differential Diagnosis

• Cerebral Malaria

• Meningitis

• Febrile Convulsions

• Rey’s Syndrome

• Rabies

• Toxic Encephalopathy

LABORATORY INVESTIGATION• Peripheral blood picture shows moderate peripheral leucocytosis with

neurophilia and mild anemia. • CSF: (cerbro spinal fluid) analysis: Neutrophils may predominate in

early CSF samples but a lymphocytic pleocytosis is typical.• CSF protein is moderately elevated in about 50% of cases.• Serological tests: These are to detect antibodies to viral antigens,

which include the plaque reduction virus neutralization test, hemagglutination inhibition, and complement fixation. . A significant rise in titer should be seen with paired samples from the acute and convalescent stages.

• The virus is isolated from CSF by inoculating into 2-4 day old mice and the virus is identified by haemagglutination inhibition. Japanese encephalitis virus may also be identified by infection of cell cultures (chicken embryo or hamster kidney cells, or the mosquito cell line C3/36) and by IFA.

DIAGNOSTIC FACILITIES: TAMILNADU

• Sera  are collected from the J.E. cases and sent to Virology department, Madurai Medical college (or) King Institute, Guindy, Chennai (or) Institute of Vector Control and Zoonoses, Hosur for Laboratory  diagnosis of J.E. case.

• Vector mosquitoes collected from the field are sent to CRME, Madurai and Institute of Vector control and Zoonoses, Hosur for PCR analysis for detection of virus.

JE CASE CLASSIFICATION, NICD, NEW DELHI

• SUSPECT: A CASE THAT IS COMPATIBLE WITH THE CLINICAL DESCRIPTION

• PROBABLE: A SUSPECT CASE WITH PRESUMPTIVE LABORATORY RESULTS

• CONFIRMED: A SUSPECTED CASE THAT IS LABORATORY CONFIRMED

JE CONTROL STRATEGY

• Early Case Detection and Treatment • Vector Control A)REDUCTION OF BREEDING SOURCE FOR

LARVAE B) REDUCTION IN MAN-MOSQUITO CONTACTC) CONTROL OF ADULT MOSQUITOES

. Prevention A) JE VACCINATION

Reduction of Breeding Source for Larvae

• They are water management system with intermittent irrigation system

• incorporation of neem products in rice fields • The water management is nothing but a strategy of

alternate drying and wetting water management system in the rice fields.

• This can be implemented only with the co-ordination of the farmers.

• Introduction of composite fish culture for mosquito control in rice fields have been evaluated and proved to be successful.

PIG CONTROL

• segregation

• slaughtering,

• and vaccinationMOSQUITO CONTROL

• spraying,

• draining mosquito habitats,

• or using bednets

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.

NEW DELHI, DECEMBER 31: The worst of encephalitis is over but India has finally identified a potential provider for bulk vaccines — China. The health ministry has sent a letter of intent to China and plans to procure five to eight 8 million doses in 2006. The order, sources in the Health Ministry said, would be placed in a few days. China is the only country in the world which produces ‘tissue culture vaccines’ for the disease. Both WHO and PATH, a US-based non-profit organisation, have assured the Centre it is “safe and effective”, the official said. Once the vaccines are procured, the Ministry plans to immunise all children in the 19 high-risk districts in Uttar Pradesh, where the disease has been reported since 1952. ‘‘Procuring vaccine was necessary to prevent deaths of children in the country,’’ said P.K.Hota, Secretary in the Health Ministry. Ref:In 2006, India’s JE vaccines to come from China   Posted online: Sunday, January 01, 2006 at 0127 hours IST

OTHER NEW VACCINE

• A live, attenuated “chimeric” vaccine which uses a yellow fever vaccine virus strain as its backbone (ChimeriVax-JE, manufactured by Acambis).

• Clinical trials also are underway for a JE vaccine candidate manufactured by Intercell. Following a successful Phase II study in the United States, Intercell initiated Phase III trials in September 2005 to test the vaccine’s safety and immunogenicity in nearly 5,000 adult subjects throughout the United States, Europe, and other countries. This vaccine is inactivated but does not require mouse brains for production.

RESEARCH PROJECT: TAMILNADUIn collaboration with the public health department, the CRME, Madurai is undertaking the impregnated curtains trials at Sirimangalam and Nallur Primary Health Centres in Cuddalaore district for control of J.E. vectors.

REFERENCE• http://www.path.org/projects/JE_in_depth.php

• http://www.pon.nic.in/vcrc/jemanag.html

• K.PARK

• LECTURE NOTES ON MALARIA CONTROL AND OTHER VECTOR BORNE DISEASES, HOSUR

• MANSON’S TROPICAL DISEASES

• JAPANESE ENCEPHALITIS GLOBALLY AND IN INDIA-INDIAN JOURNAL OF PUBLIC HEALTH VOL.XXXXVIII No.2APRIL-JUNE 2004

• Japanese encephalitis in India: An overviewKabilan Lalitha, Rajendran R, Arunachalam N, Ramesh S, Srinivasan S, Philip Samuel P, Dash APCentre for Research in Medical Entomology, Madurai, India

Year : 2004  |  Volume : 71  |  Issue : 7  |  Page : 609-615