Japanese Encephalitis - An Arboviral Disease

Dr Jairaj Pukhrambam *

Japanese Encephalitis (JE) popularly called "Brain fever" is an acute viral encephalopathic illness which has got public health importance because of its epidemic potential and high fatality rate. In patients who survive, complications lead to lifelong sequelae.

Japanese Encephalitis presents a significant risk to humans and animals particularly in South East Asia where around 50,000 cases and 10,000 deaths occur per year, particularly affecting children below 10 years (WHO report). The statistics reveal that 50 per cent of the patients who develop Japanese Encephalitis suffer from permanent neurological defects and 30 per cent of them die due to the disease. The disease was first recorded in Japan in 1924 (Gatus and Rose, 1983).

Presently it is seen in epidemic proportion in most countries like Korea, Malaysia, Singapore, Bangladesh, Thailand, Vietnam, China, Nepal, Myanmar and India. In recent years, JE has spread to newer geographic locations like Australia and Pakistan. In India, the first major outbreak of Japanese Encephalitis of occurred in 1973 in Bankura and Burdwan districts of West Bengal. During the last decade, there has been a major upsurge of JE in Assam, Andhra Pradesh, Karnataka, Goa, Manipur, Maharashtra, Madhya Pradesh, Tamil Nadu, Uttar Pradesh, Pondicherry and West Bengal.

Aetiology : Japanese Encephalitis (JE) is caused by an arbo (arthropod borne) virus of type B (Flavi virus) sub-group, of Togaviradae. It is a RNA virus 40mm in diameter having marked neurotropism (Rhodes, 1968). It is a zoonotic disease having its natural cycle in wild or domestic animals and haematophagus arthropods. The disease is transmitted to man by the bite of infected Culicine mosquitoes. Man being the only incidental "dead end host".

Man to Man transmission has not so far been recorded. Eating pork cannot transmit the disease. The JE virus multiplies in the pig's body. When the female Culex mosquito sucks the blood of pig, she picks up the JE virus. After an incubation period of 14 days, the Culex mosquito is able to transmit the JE virus to a new host usually pig. It has high morbidity and mortaliity rates. Usually affected age group is 5-10 years though children from 3-14 years can be affected.

Morbidity rate estimated at 0.3 to 1.5 per 100000 populations, whereas Fatality rates ranged from 10% to 60% and 50% of those who recover left are with neurological deficit. Incidence is higher in males but sub-clinical infection has occurred equally in both sexes. Nearly 10% of cases are among those over 60 years, perhaps reflecting waning protective immunity.

Susceptible Hosts :

Animal Hosts : Among the animal hosts, pigs have been incriminated as the major vertebrate hosts for JE virus. In some places, up to 100 percent of pigs may be infected with JE virus. Infected pigs do not manifest any overt symptoms of illness but circulate the virus so that mosquitoes get infected and can transmit the virus to man.

Serological surveys showed that 1.2 to 44% pigs tested in different parts of the country had antibody to Japanese Encephalitis. The pigs are thus considered as "amplifiers" of the virus. Cattle and buffaloes may also be infected with the JE virus; although they may not be natural hosts of JE virus, they act as "mosquito attractants". Horses are the only domestic animals so far known which show signs of encephalitis due to JE virus infection.

Birds : Swamp dwelling birds are natural reservoir of virus. Some species of birds such as pond herons, egrets and perhaps poultry and ducks appear to be involved in the natural history of JE virus. The virus does not cause any disease among its natural hosts and the transmission continues through mosquitoes. It is carried by female mosquitoes from infected pigs or water birds, pond herons and ducks to susceptible children.

Mosquito Vectors : The main vector, culex mosquito (Culex tritaeniorhynchus, C.vishnui, C.gelidus and others—totally 8 species) lives in rural rice growing and pig farming regions. [Ecological studies implicate that mosquito (Culex tritaeniorhynchus) act as primary vector in many South East Asian countries as well as other parts of India.

The mosquito breeds in flooded rice fields, marshes, and standing water around planted fields. This is the reason; JE is mostly a rural disease. Culex mosquitoes can fly up to 5 kms. Venereal transmission of JE virus occurs in Culex bitaeniorhynchus mosquitoes. This may have epidemiological significance. The virus is transmitted occasionally by Anopheles (3 species) and rarely Mansonia (1 species).

JE is a seasonal disease. Epidemics coincide with the monsoon and post monsoon period (August to December), and Agricultural practices, due to high density of the mosquito vector (because of stagnant water), and presence of reservoir hosts (pigs). Northern India, including Northeastern India, receives summer monsoons and as such the transmission season begins from May, with the incidence reaching peak in August—October depending on the advancement of monsoon. With onset of winter JE outbreaks subside.

However, in endemic areas, sporadic cases may occur throughout the year due to congenial climate conditions throughout the year (eg Southern India). Susceptible children are infected by infected mosquito bites. After mosquito bite disease appears in 5-16 days. The virus then invades the Central Nervous System and causes disease. Although infection in human is incidental, the virus can cause serious neurological disease with high morbidity and mortality.

JE does not spread from child to child or from cattle to humans because of the low and transient viremia. This is the reason increase in cattle to pig ratio may reduce the risk of JE (mosquito bites are shared by cattle and pigs). The incidence of JE disease is never an indication of the risk at which the population is living in JE endemic areas, because of inapparent infections, which tend to outnumber the apparent infections, and also due to the lifelong immunity, which develops despite inapparent infection. The ratio of overt diseases to inapparent infection varies from 1:250 to 1:1000. Thus cases of JE represent only the tip of the iceberg compared to the large number of inapparent infections. Usually the number of cases reported from each village is 1 or 2.

Clinical manifestation :

Animals : With the lapse of incubation period of 2-4 days, animals show loss of appetite and fever ranging from 38°to 40.7°C. At the height of fever animals show signs of depression, photophobia, tremor, ataxia and hyperaesthesia. Animals are extremely exhausted and unable to stand. Respiration is laboured. Death occurs after 3-5 days of illness. Few animals may survive.

Man : JE has an incubation period of 5-15 days and the vast majority of infections are asymptomatic only, 1 in 250 infections develop into encephalitis. Severe rigors mark the onset of this disease in humans. Fever, headache and malaise are other non-specific symptoms of this disease which may last for a period of between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised body temperature between 38 to 41 degrees Celsius.

Mental retardation developed from this disease usually leads to coma. Mortality of this disease varies but is generally much higher in children. Trans-placental spread has been noted. Life-long neurological defects such as deafness, emotional lability and hemiparesis may occur in those who have had Central Nervous System involvement. In known cases some effects also include nausea, headache, fever, vomiting.

The course of the disease may be outlined as follows:-

1. Prodromal stage: A stage with fever and malaise without involvement of central nervous system.
2. Encephalitic stage: A stage characterised by coma, convulsion, neurological deficits and continuing fever.
3. Late stage: A stage marked by gradual recovery and sequelae.

The fatality rate varies between 20-40 percent, but may reach over 58 percent. The average period between the onset of illness and death is about 9 days.

Diagnosis: Aetiological diagnosis of JE is based on serological testing using ELISA (enzyme-linked immunosorbent assay) that detects specific IgM in CSF or in blood of almost patients within 4-7 days of onset of disease. Other diagnostic methods include dot-blot or immunoprecipitation IgM assay suitable for field use and to monitor changes of JE specific antibody titres in sequential serum samples.

Treatment: There is no specific treatment for Japanese Encephalitis (JE) and management consists of supportive measures – antipyretics, anticonvulsants, maintenance of nutrition and treatment of secondary bacterial infection.

Prevention: The virus multiplies in pigs and water birds like pond herons and ducks. The JE Virus can spread to subsequent generations of mosquitoes by transovarial transmission. Infected pigs do not suffer from encephalitis. Presence of cattle reduces the risk of JE Japanese Encephalitis does not spread from man to man. So there is no danger of spread from patients of Japanese Encephalitis to attendants.

It is always from pig/pond herons/ducks to man. The virus is transmitted by 12 species of mosquitoes (8 species of Culex, 3 species of Anopheles and 1 species of Mansonia), some of which bite mainly in the evening and some during the nights. Precautions should always be taken to avoid being bitten by any mosquito both in the daytime and night.

The following precautions should be adopted as preventive measures, such as

1. Using full-sleeved clothes.
2. Use mosquito nets (small mesh, preferably pyrethroid impregnated) at night tucked under mattress.
3. Door and window curtains impregnated with pyrethroid, and
4. Mosquito repellents.
5. Burn mosquito/insect coils during evening.
6. Use insecticidal spray indoors in the evening.
7. While going out, use insect repellent on all exposed skin. Instructions on the package insert must be followed carefully.
8. Scented products attract mosquitoes. So use non-perfumed cosmetic and toiletries.
9. Avoid sleeping in or near pigsties.
10. All the stagnant water areas around human habitation should be filled up and the surroundings of each house and the habitation kept clean and dry.
11. Air coolers, if used regularly, will not breed mosquitoes. But in winter, when they are not in use, will breed mosquitoes if there is any water inside. So remove water, dry up and cover the air cooler after summer.
12. Open drains should be kept clean and stagnation should not be allowed.
13. Rank vegetation in around habitations should be cleared.
14. Smoke generated by burning neem leaves repels mosquitoes from the vicinity of houses.
15. Isolation of pigs is essential. The minimum distance for pigsties is 5 kms from human habitations.
16. Water management practice of paddy cultivation. At least one dry day every week will conserve water, reduce larval population increase rice grain yield, and reduce the emission of methane into Global warming effect. Using neem products as fertilizers will reduce the mosquito population.
17. Report any suspected case of Japanese Encephalitis to Health Authorities so that immediate vector control measures like spraying of insecticides and fogging can be undertaken. Sprays of appropriate insecticides in breeding place of the vectors i.e. inside house, cattle sheds, pig sites and vegetation surrounding the affected villages are to be made. The vector mosquito/es of JE are widely scattered and not easily amenable to control. An effective way to deal with them is to resort to aerial or ground fogging with ultra-low volume(ULV) insecticides(e.g. malathion, fenitrothion). Uninfected villages falling within 2 to 3 km radius of the infected village should also receive spraying as preventive measures.

Control : Infection with JE confers lifelong immunity. All current vaccines are based on genotype III virus. A formalin—inactivated mouse derived vaccine was first produced in Japan in 1930s and was validated for use in Taiwan in the 1960s and in Thailand in the 1980s. The widespread use of vaccine and urbanisation has led to control of the disease in Japan, Korea, and Taiwan and in Singapore. The high cost of the vaccine, which is grown in live mice, means that poorer countries have not been able to afford to give it as part of a routine immune immunisation programme.

Vaccination in Animals : Vaccine against this disease is not executed in India. In Japan, restriction on pigs rearing and its location and vaccination of pigs has proven effective. This may not be practicable in India where pigs are reared as food source by small farm and mass pig rearing as Industry is not feasible at present.

Vaccination in Man : JE vaccination is the single most important control measure. As there is no Man-to-Man transmission and man is a dead end for the virus, vaccination (unlike polio) protects only the vaccinated individual and not the community. In epidemic situation, vaccination programme should take into consideration, the one-month gap (after the second dose) before actual protection starts, the necessity of two doses and a third one for longer protection. This is the reason JE vaccine is not useful for control of epidemics and so must be during inter-epidemic periods.

Three types of vaccine are currently in large production and use, namely:
Mouse brain—derived and inactivated vaccine based on the Nakayama strain or Beijing-1 strain is currently the only vaccine available on the international market. A killed JE vaccine is produced at the Central Research Institute (CRI), Kasauli from the brain of Suckling mice inoculated with the Nakayama JE strain. Controlled studies have shown that the commercially available mouse-derived vaccine is efficacious without serious side effects for childhood vaccination for prevention from JE disease in JE endemic areas. At present JE vaccine is available only on a very limited scale and at a high cost for Govt Institutions.

Two doses of 1 ml each (0.5ml for children under the age of 3 years) should be administered subcutaneously at an interval of 7-14 days. A booster injection of 1ml should be given after 4 weeks to 1 year in order to develop full protection. Revaccinations may be given after 3 years.

The vaccine is best used in the inter-epidemic period. It should be offered to the most vulnerable and high-risk groups. Unless 80-90% of children less than 15 years are vaccinated, there will not be any obvious effect on morbidity and mortality. Since the risk of JE is not universal and is limited to focal areas, JE immunisation is not included in the National Immunisation Programme in India, because the disease is restricted to agricultural regions of India. But inclusion of an effective and affordable vaccine for JE in endemic areas in India will reduce mortality and life-long sequelae and prevent further spread.

Role of Belladonna : Qualified Homeopathy Physicians assure that Belladonna, a homeopathic drug, can prevent Japanese Encephalitis. Homeopathic medicine Belladonna is effective in preventing Japanese Encephalitis (JE); a recent study conducted by the Kolkata-based School of Tropical Medicine has shown. Belladonna is derived from a plant A belladonna which is also source of the drug atropine. Conducted in collaboration with the Centre Council for Research in Homeopathy (CCRH) under Department of AYUSH, researchers claim to have found a probable role for Belladonna in preventing JE virus infection.

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* Dr Jairaj Pukhrambam wrote this article for The Sangai Express
This article was webcasted on August 06, 2010.

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