Japanese B

JAPANESE B ENCEPHALITIS Dr.T.V.Rao MD

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

A Flavivirus 

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

A leading cause of viral encepalitis 

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

A Vector born- Arboviral Infection 

Culex tritaeniorhynchus a rural Mosquito that breeds in rice fields, is the principle vector. In India in 1955 the virus were isolated from Culex vishnui mosquitoes in Vellore region in Tamil Nadu

INCIDENCE 

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Leading cause of viral encephalitis in Asia with 30-50,000 cases reported annually Fewer than 1 case/year in U.S. civilians and military personnel travelling to and living in Asia Rare outbreaks in U.S. territories in Western Pacific

Distribution of Japanese Encephalitis in Asia, 1970-1998

Japanese B Encepalitis Virus 

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

Genus - Flavivirus 

Japanese B encepalitis virus is Spherical, 40 – 60 nm in diameter Contain a positive sense Single stranded RNA, 11 kb in size RNA genome is infectious Several viruses in this group are related.

Structure of Virus 

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

Cycle of Events in Japanese B encepalitis

Pass through two prominent Hosts 

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Herons act as reservoir hosts and pigs as amplifier hosts. Human infection is a tangential ‘dead end’ and infections are spread when the infected mosquitoes reach high density.

Clinical Manifestations  

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The incubation period is 6 to 16 days. There is a prodrome of fever, headache, nausea, diarrhoea, vomiting, and myalgia, which may last for several days. This may be followed by a spectrum of neurological disease ranging from mild confusion, to agitation, to overt coma. Two thirds of patients have seizures. It is more common in children, while headache and meningism are more common in adults.

Can lead to Neurological damage 

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Tremor or other involuntary movements are common. Mutism has been described as a presenting symptom. So has a syndrome of acute flaccid paralysis. Fever resolves by the second week, and choreoathetosis or extra pyramidal symptoms develop as the other neurological symptoms disappear.

Diagnosis of Japanese B Encephalitis 

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The isolation of virus from Blood, CSF, or tissues. Detection of Arboviral specific RNA in blood,CSF, or Tissue However very few reference laboratories can perform the isolation in view of the biosafety considerations

Serology by ELISA 

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IgM capture enzyme-linked immunoassay (ELISA) of serum or CSF is the standard diagnostic test. Sensitivity is nearly 100% when both serum and CSF are tested. False-negatives may result if the samples are tested too early, as in the first week of illness. New IgM dot enzyme immunoassays for CSF and serum are portable and simple tests that can be used in the field. Compared with ELISA as the gold standard, the sensitivity and specificity are around 98 and 99% respectively.

False Positive Tests 

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

Arboviral Specific RNA detection 

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Viral RNA is extracted from serum or from suspected tissues of the patients or mosquito homogenates. The product is amplified by RTPCR and the products analyzed by restriction digestion and determined by nucleotide sequence of PCR product. The identified

Preventive measures 

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Preventive measures include mosquito control and locating piggeries away from human dwellings A formalin inactivated mouse brain vaccine using the Nakayama strain has been employed in human immunization in Japan – Two doses at two week’s interval followed by a booster 6 – 12 months later constitute a full course. However the immunity was short lived

Later vaccines 

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A live attenuated vaccine has been developed in China from JE strain SA 14-14-2, passed through weanling mice The vaccine is produced in primary baby hamster kidney cells. Administered in two doses, one year apart, the vaccine has been reportedly effective in preventing clinical disease

Basics on Vaccinations 

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Vaccine: formaldehyde-inactivated, purified from mouse brain minimum age: 1 year - safety/efficacy in infants uncertain primary course: day 1, day 7-14 and day 28 (3 doses) dose: adults & children over 3 years 1ml s.c./i.m.; children under 3 years 0.5ml s.c./i.m. booster interval: 2 years

Indications for Vaccination 

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

Slaughter of PIGS 

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

RESEARCH PRIORITIES

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Facilitate implementation of attenuated vaccine in unvaccinated populations in endemic areas Develop improved vaccines Identify risk factors for progression to symptomatic encephalitis and viral persistence Describe clinical features of JE in AIDS and determine its potential as an opportunistic infection

Created for Medical and Paramedical students in Developing World Dr.T.V.Rao MD Email [email protected]