What is Japanese encephalitis?

Japanese encephalitis is a central nervous system disease and caused by group B arbovirus (Flavivirus, and other Flavivirus diseases are dengue fever, West Nile fever, Kayasanur Forest Disease). Japanese encephalitis is basically a zoonotic disease, which means it generally infects animals and humans are affected (infected) incidentally.

After entering human body by bite of infectious mosquitoes, the initial replication of virus occurs in the regional and local lymph nodes. The invasion of CNS (Central Nervous System) occurs via blood stream.

Japanese encephalitis commonly (approximately 85% of all cases of Japanese encephalitis) occur among children of less than 15 years of age and approximately 10% of the cases of Japanese encephalitis occurs in individuals above 60 years of age.

How Japanese encephalitis is transmitted?

Japanese encephalitis (JE) is a mosquito borne encephalitis and it is transmitted by infected culicine mosquito bites. Culicine tritaeniorhynchus, C. vishnui, and C. gelidus are the vectors for Japanese encephalitis virus. These species of mosquitoes generally breeds irrigated rice fields, shallow ditches and water pools and in many parts of the South East Asia and South Asia, irrigated rice fields are the commonest breeding places for mosquitoes. Not surprisingly, rice is the major staple diet in the areas where Japanese encephalitis is endemic. Female mosquitoes can transmit Japanese encephalitis virus 9-12 days after having a blood meal from an animal harboring the virus. Japanese encephalitis virus infects many extrahuman hosts like animals (e.g. pigs) and birds. Man is the incidental host (man is “dead-end” for the virus) and man to man transmission of Japanese encephalitis does not occur.

Pigs are the natural host for Japanese encephalitis virus. Among animals pigs are the main vertebrate host foe Japanese encephalitis virus. There are reports of 100% infection if pigs by Japanese encephalitis virus in certain areas. The infected pigs do not get the disease, but transmit the virus to the feeding mosquitoes (culicine mosquito), and these mosquitoes can infect man. Pigs thus act as “amplifiers” of the Japanese encephalitis virus. Cows and buffaloes may also get infected by Japanese encephalitis virus, but they are not natural host for the virus and incidentally get infected, but no symptoms are seen due to Japanese encephalitis virus in cattle. Among domestic animals only horses show the signs of encephalitis if infected with Japanese encephalitis virus.

Pond herons, cattle egrets etc. are the birds which act as natural host for Japanese encephalitis virus and probably poultry and ducks may also acts as reservoirs for Japanese encephalitis virus in nature.

What is the epidemiology of Japanese encephalitis?

Till early 1980s Japanese encephalitis was endemic mainly in East Asia, especially in Japan, China and Korea. But Japanese encephalitis has now spread to other parts of the world like South East Asia, South Asia like India, Sri Lanka, and Myanmar etc. where Japanese encephalitis is causing the disease. At present yearly approximately 50,000 cases of Japanese encephalitis occurs worldwide with approximately 10,000 deaths (approximately 20% of reported cases) annually, and approximately 15,000 get some physical disability due to Japanese encephalitis.

Even at present approximately 75% of cases of Japanese encephalitis occurs in Western Pacific nations like China and adjoining countries and the rest occurs in South East Asia and South Asia (India, Sri Lanka). In other parts of the world Japanese encephalitis very rare and if seen it is generally seen among travelers who traveled to (returned from) endemic areas of Japanese encephalitis.

What are the signs & symptoms of Japanese encephalitis in man?

The incubation period of Japanese Encephalitis is most likely 5-15 days, although clearly not known. All the individuals bitten by mosquitoes (culicine mosquito) do not develop the disease (Japanese encephalitis) and there are more sub clinical infections than overt clinical infections. The ratio of overt clinical to sub clinical infection varies from 1:300 to 1:1000. The clinical infections represent only the tip of the iceberg of Japanese encephalitis as there are many more sub clinical infections than overt clinical infection.

The clinical course of Japanese Encephalitis is divided into three stages, namely (a) prodromal stage, (b) acute encephalitic stage and (c) late stage and sequelae.

Prodromal stage:

The onset of illness in Japanese Encephalitis is generally acute with fever (generally fever is high with temperature of 38 to more than 40 degree Centigrade), headache and malaise. These symptoms of prodromal stage may last from 1-6 days.

Acute encephalitic stage:

Acute encephalitic stage is characterized by high fever, neck rigidity, focal central nervous system (CNS) signs, altered sensation, convulsions and sometimes coma in very serious cases.

Late stage and sequelae:

This stage starts when temperature becomes normal and active inflammation is at the end (ESR becomes normal). Neurological signs are no more progressing (sometimes improves), but there may be recovery may take longer with some neurological deficit.

The fatalities occur at this stage and ranges from 20-40%, but sometimes may be as high as approximately 60%. Generally death from Japanese Encephalitis occurs on an average 9 days after onset of illness. The suspected deaths from Japanese Encephalitis should be confirmed with laboratory investigation.

How Japanese Encephalitis is diagnosed?

The laboratory diagnosis of Japanese Encephalitis is generally done by serology. IgM-captured ELISA (Enzyme Linked Immunosorbant Assay) can detect specific IgM of Japanese Encephalitis in CSF (cerebrospinal fluid) or blood within a week of onset of illness in practically all patients of Japanese Encephalitis and is preferred for diagnosis. Conventional antibody assay on paired sera to demonstrate significant rise in JE-specific antibody is also used. For use in the field area dot-blot IgM assay is suitable. The Japanese Encephalitis virus can be found in brain during autopsy, but rarely in blood or CSF. In rare occasions Japanese Encephalitis virus RNA can be demonstrated in CSF.

How Japanese Encephalitis is treated?

Treatment of Japanese Encephalitis is essentially symptomatic. Temperature should be controlled with cold sponging, ice packs and simple antipyretics like paracetamol. Hydration should be maintained with adequate fluid intake. The patient should be given proper rest and sedatives if required to control convulsions.

Japanese Encephalitis in pregnant women:

Generally pregnant women do not get infection with Japanese Encephalitis virus, as the infection is mainly among children of below 15 years (85% of total cases) and individuals of more than 60 years of age (10% of total cases).

How to prevent Japanese Encephalitis?

Japanese Encephalitis can be prevented effectively with vaccine. Vaccination is recommended for populations at risk of Japanese Encephalitis and travelers from Western countries to rural Asia. There are three types of vaccines available for Japanese Encephalitis and used in large scale are (i) a formalin-inactivated vaccine purified from mouse brain is produced either from Nakayama or Beijing strains of Japanese Encephalitis virus in many Asian countries and licensed for human use in many countries including the United States (ii) a cell culture-derived inactivated Japanese Encephalitis vaccine from Beijing P-3 strain and (iii) a cell culture-derived live attenuated vaccine based on SA 14-14-2 strain of Japanese Encephalitis virus.

The formalin-inactivated vaccine purified from mouse brain is produced either from Nakayama or Beijing strains of Japanese Encephalitis virus is most extensively and successfully used to prevent Japanese Encephalitis in many countries. The drawbacks of the vaccine are limited duration of protection, need of multiple doses (given 3 doses on day 0, 7 and 30) and high cost. The cell culture-derived live attenuated vaccine based on SA 14-14-2 strain of Japanese Encephalitis virus is widely manufactured and used in China and replacing the inactivated vaccines.

Japanese Encephalitis vaccination schedules and recommendations:

The vaccination schedule foe all three major Japanese Encephalitis vaccines vary according to the type of vaccine and also depending on the local epidemiological circumstances and recommended schedules of other childhood vaccines.

In children between 1-3 years the formalin-inactivated vaccine purified from mouse brain can give adequate protection from Japanese Encephalitis throughout the childhood if 2 primary doses are given at 4 weeks apart and booster vaccination given after 1 year of primary vaccine and subsequently every 3 years till 15 years of age. The vaccine (the formalin-inactivated vaccine purified from mouse brain) is given subcutaneously in the dose of 0.5 ml per dose for children below 3 years of age and 1 ml for children above 3 years of age. The protective immunity develops one month after the second primary dose. The vaccine is ideally suitable in between epidemics.

The live attenuated cell-cultured vaccine is equally effective with single primary dose and a single booster dose after 1 year of primary dose. This vaccine is gaining popularity due to good compliance (equally effective protection with only 2 doses, 1 primary and 1 booster dose).

Japanese Encephalitis vaccination for infants:

Japanese Encephalitis vaccine is not recommended for infants below 6 months of age. Because, Japanese Encephalitis rarely if ever affects infants and also infants acquire passive immunity from mother which can interfere with the vaccine.

Japanese Encephalitis vaccination for international travelers:

International travelers (age more than 1 year) visiting an endemic area of Japanese Encephalitis should get vaccinated. The present recommendation is administration of 3 primary doses at days 0, 7 and 28 days. Alternately 2 doses can be given with 4 weeks apart. If there is requirement of continuous protection a booster should be given after 1 year of last primary dose and subsequently every 3 years.

How to control Japanese Encephalitis?

Control of Japanese Encephalitis can be done by vaccination (already discussed), controlling vector (culicine mosquito) and vaccination of main vertebrate host i.e. pigs (and also horses and cattle if possible).

Vaccination of pigs is very important (for public health and economic reasons, as Japanese Encephalitis virus infection in pigs can cause abortion). Vaccination in pigs prevents viremia and reduces their role of “amplifier” of Japanese Encephalitis virus. An inactivated and a live attenuated vaccine for Japanese Encephalitis virus in pigs are available. But it is difficult to maintain vaccination coverage in pigs due to rapid multiplication of pigs.

Control of vector of Japanese Encephalitis:

Control of mosquitoes need integrated approach and it is a gigantic task to control mosquitoes, especially in the developing countries where Japanese Encephalitis is endemic. In many developing countries like India ultra-low-volume aerial or ground fogging with insecticides like malathion, fenitrothion etc. is done in all the villages reporting cases of Japanese Encephalitis. Indoor residual spraying is also done. The spraying is also done in vegetation around houses, breeding places, and animal shelters. The spraying is also recommended in the adjoining villages with radius of 2-3 kilometers. Mosquito nets can also reduce the transmission of Japanese Encephalitis.