JAPANESE JAPANESE BB

ENCEPHALITISENCEPHALITIS

Dr.T.V.Rao MDDr.T.V.Rao MD

Japanese B virus InfectionJapanese B virus Infection

Infection is caused by a flavivirus, a single Infection is caused by a flavivirus, a single stranded RNA virus. It is transmitted by stranded RNA virus. It is transmitted by the bite of the the bite of the Culex tritaeniorhynchusCulex tritaeniorhynchus mosquito. The virus multiplies at the site mosquito. The virus multiplies at the site of the bite and in regional lymph nodes of the bite and in regional lymph nodes before viraemia develops. Viraemia can before viraemia develops. Viraemia can lead to inflammatory changes in the heart, lead to inflammatory changes in the heart, lungs, liver, and reticuloendothelial lungs, liver, and reticuloendothelial system. system.

A FlavivirusA Flavivirus

Japanese encephalitisJapanese encephalitis ( ( previously previously known as known as Japanese B encephalitisJapanese B encephalitis is a is a disease caused by the disease caused by the mosquitomosquito-borne -borne Japanese encephalitis virus. The Japanese Japanese encephalitis virus. The Japanese encephalitis virus is a encephalitis virus is a virusvirus from the from the family family FlaviviridaeFlaviviridae. Domestic . Domestic pigspigs and and wild birds are reservoirs of the virus; wild birds are reservoirs of the virus; transmission to humans may transmission to humans may

A leading cause of viral A leading cause of viral encepalitisencepalitis

Japanese encephalitis is the leading cause Japanese encephalitis is the leading cause of viral encephalitis in of viral encephalitis in AsiaAsia, with 30,000–, with 30,000–50,000 cases reported annually. Case-50,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and fatality rates range from 0.3% to 60% and depends on the population and on age. depends on the population and on age.

A Vector born- Arboviral A Vector born- Arboviral InfectionInfection

Culex tritaeniorhynchusCulex tritaeniorhynchus a rural Mosquito that a rural Mosquito that

breeds in rice fields, is breeds in rice fields, is the principle vector.the principle vector.

In India in 1955 the virus In India in 1955 the virus were isolated from Culex were isolated from Culex vishnui mosquitoes in vishnui mosquitoes in Vellore region in Tamil Vellore region in Tamil NaduNadu

INCIDENCEINCIDENCE

Leading cause of viral encephalitis in Asia Leading cause of viral encephalitis in Asia with 30-50,000 cases reported annually with 30-50,000 cases reported annually

Fewer than 1 case/year in U.S. civilians Fewer than 1 case/year in U.S. civilians and military personnel travelling to and and military personnel travelling to and living in Asia living in Asia

Rare outbreaks in U.S. territories in Rare outbreaks in U.S. territories in Western PacificWestern Pacific

Distribution of Japanese Distribution of Japanese Encephalitis in Asia, 1970-1998Encephalitis in Asia, 1970-1998

Japanese B EncepalitisJapanese B EncepalitisVirusVirus

The causative agent The causative agent Japanese encephalitis Japanese encephalitis virus is an enveloped virus is an enveloped virus of the genus virus of the genus Flavivirius; Positive sense Flavivirius; Positive sense single stranded RNA single stranded RNA genome is packaged in genome is packaged in the capsid, formed by the the capsid, formed by the capsid protein. The outer capsid protein. The outer envelope is formed by envelope is formed by envelope (E) protein and envelope (E) protein and is the protective antigen. is the protective antigen.

Genus - FlavivirusGenus - Flavivirus Japanese B encepalitis Japanese B encepalitis

virus isvirus is Spherical, 40 – 60 nm in Spherical, 40 – 60 nm in

diameterdiameter Contain a positive sense Contain a positive sense

Single stranded RNA, 11 Single stranded RNA, 11 kb in size kb in size

RNA genome is infectiousRNA genome is infectious Several viruses in this Several viruses in this

group are related.group are related.

Structure of VirusStructure of Virus The outer envelope is formed by envelope (E) The outer envelope is formed by envelope (E)

protein and is the protective antigen. It aids in protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The entry of the virus to the inside of the cell. The genome also encodes several non-structural genome also encodes several non-structural proteins also proteins also (NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5). NS1 is (NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5). NS1 is produced as secretary form also. NS3 is a produced as secretary form also. NS3 is a putative helicase, and NS5 is the viral putative helicase, and NS5 is the viral polymerase. polymerase.

Cycle of Events in Japanese B Cycle of Events in Japanese B encepalitisencepalitis

Pass through two prominent Pass through two prominent HostsHosts

Herons act as Herons act as reservoir hosts and reservoir hosts and pigs as amplifier pigs as amplifier hosts.hosts.

Human infection is a Human infection is a tangential ‘dead end’ tangential ‘dead end’ and infections are and infections are spread when the spread when the infected mosquitoes infected mosquitoes reach high density.reach high density.

Clinical ManifestationsClinical Manifestations The incubation period is 6 to 16 days. The incubation period is 6 to 16 days. There is a prodrome of fever, headache, nausea, There is a prodrome of fever, headache, nausea,

diarrhoea, vomiting, and myalgia, which may diarrhoea, vomiting, and myalgia, which may last for several days. last for several days.

This may be followed by a spectrum of This may be followed by a spectrum of neurological disease ranging from mild neurological disease ranging from mild confusion, to agitation, to overt coma. confusion, to agitation, to overt coma.

Two thirds of patients have seizures. It is more Two thirds of patients have seizures. It is more common in children, while headache and common in children, while headache and meningismmeningism are more common in adults. are more common in adults.

Can lead to Neurological Can lead to Neurological damagedamage

Tremor or other involuntary movements Tremor or other involuntary movements are common. are common.

Mutism has been described as a Mutism has been described as a presenting symptom. So has a syndrome presenting symptom. So has a syndrome of acute flaccid paralysis. of acute flaccid paralysis.

Fever resolves by the second week, and Fever resolves by the second week, and choreoathetosischoreoathetosis or or extra pyramidal extra pyramidal symptoms develop as the other symptoms develop as the other neurological symptoms disappear. neurological symptoms disappear.

Diagnosis of Japanese B Diagnosis of Japanese B EncephalitisEncephalitis

The isolation of virus The isolation of virus from Blood, CSF, or from Blood, CSF, or tissues.tissues.

Detection of Arboviral Detection of Arboviral specific RNA in specific RNA in blood,CSF, or Tissueblood,CSF, or Tissue

However very few However very few reference laboratories can reference laboratories can perform the isolation in perform the isolation in view of the biosafety view of the biosafety considerationsconsiderations

Serology by ELISASerology by ELISA IgM capture enzyme-linked immunoassay IgM capture enzyme-linked immunoassay

(ELISA) of serum or CSF is the standard (ELISA) of serum or CSF is the standard diagnostic test. Sensitivity is nearly 100% when diagnostic test. Sensitivity is nearly 100% when both serum and CSF are tested. False-negatives both serum and CSF are tested. False-negatives may result if the samples are tested too early, as may result if the samples are tested too early, as in the first week of illness. in the first week of illness.

New IgM dot enzyme immunoassays for CSF and New IgM dot enzyme immunoassays for CSF and serum are portable and simple tests that can be serum are portable and simple tests that can be used in the field. Compared with ELISA as the used in the field. Compared with ELISA as the gold standardgold standard, the sensitivity and specificity are , the sensitivity and specificity are around 98 and 99% respectively. around 98 and 99% respectively.

False Positive TestsFalse Positive Tests

There is some cross-reactivity with other There is some cross-reactivity with other flavivirus and from Japanese encephalitis flavivirus and from Japanese encephalitis and yellow fever vaccinations. and yellow fever vaccinations.

Arboviral Specific RNA Arboviral Specific RNA detectiondetection

Viral RNA is extracted Viral RNA is extracted from serum or from from serum or from suspected tissues of the suspected tissues of the patients or mosquito patients or mosquito homogenates.homogenates.

The product is amplified The product is amplified by RTPCR and the by RTPCR and the products analyzed by products analyzed by restriction digestion and restriction digestion and determined by nucleotide determined by nucleotide sequence of PCR product.sequence of PCR product.

The identified sequence is The identified sequence is compared with nucleotide compared with nucleotide sequence found in Gene sequence found in Gene bank or other data basesbank or other data bases

Preventive measuresPreventive measures Preventive measures include mosquito control Preventive measures include mosquito control

and locating piggeries away from human and locating piggeries away from human dwellingsdwellings

A formalin inactivated mouse brain vaccine A formalin inactivated mouse brain vaccine using the Nakayama strain has been employed using the Nakayama strain has been employed in human immunization in Japan – Two doses at in human immunization in Japan – Two doses at two week’s interval followed by a booster 6 – 12 two week’s interval followed by a booster 6 – 12 months later constitute a full course.months later constitute a full course.

However the immunity was short livedHowever the immunity was short lived

Later vaccinesLater vaccines

A live attenuated vaccine has been A live attenuated vaccine has been developed in China from JE strain SA 14-developed in China from JE strain SA 14-14-2, passed through weanling mice14-2, passed through weanling mice

The vaccine is produced in primary baby The vaccine is produced in primary baby hamster kidney cells.hamster kidney cells.

Administered in two doses, one year Administered in two doses, one year apart, the vaccine has been reportedly apart, the vaccine has been reportedly effective in preventing clinical diseaseeffective in preventing clinical disease

Basics on VaccinationsBasics on Vaccinations Vaccine: formaldehyde-inactivated, purified from Vaccine: formaldehyde-inactivated, purified from

mouse brainmouse brain minimum age: 1 year - safety/efficacy in infants minimum age: 1 year - safety/efficacy in infants

uncertainuncertain primary course: day 1, day 7-14 and day 28 (3 primary course: day 1, day 7-14 and day 28 (3

doses)doses) dose: adults & children over 3 years 1ml dose: adults & children over 3 years 1ml

s.c./i.m.; children under 3 years 0.5ml s.c./i.m.s.c./i.m.; children under 3 years 0.5ml s.c./i.m. booster interval: 2 yearsbooster interval: 2 years

Indications for VaccinationIndications for Vaccination

for long-stay travellers, especially children, for long-stay travellers, especially children, to endemic areas of India, Nepal, Bhutan, to endemic areas of India, Nepal, Bhutan, China and SE Asia (May-Sept in SE Asia, China and SE Asia (May-Sept in SE Asia, July-Dec in Nepal or India)July-Dec in Nepal or India)

Slaughter of PIGSSlaughter of PIGS

During major epidemics, slaughter of pigs During major epidemics, slaughter of pigs has been employed as a measure of has been employed as a measure of containment.containment.

RESEARCH PRIORITIESRESEARCH PRIORITIES

Facilitate implementation of attenuated vaccine Facilitate implementation of attenuated vaccine in unvaccinated populations in endemic areas in unvaccinated populations in endemic areas

Develop improved vaccines Develop improved vaccines Identify risk factors for progression to Identify risk factors for progression to

symptomatic encephalitis and viral persistence symptomatic encephalitis and viral persistence Describe clinical features of JE in AIDS and Describe clinical features of JE in AIDS and

determine its potential as an opportunistic determine its potential as an opportunistic infection infection

Created for Medical and Created for Medical and Paramedical students in Paramedical students in

Developing WorldDeveloping World

Dr.T.V.Rao MDDr.T.V.Rao MDEmailEmail

doctortvrao@gmail.comdoctortvrao@gmail.com