Factsheet for health professionals about Japanese encephalitis

Pathogen and clinical features

The pathogen

Japanese encephalitis virus is an enveloped RNA virus of the genus Flavivirus, family Flaviviridae, and is in the same antigenic complex as West Nile virus. The virus was first isolated in 1935 from the brain of a fatal encephalitis case in Japan. Although five distinct viral genotypes have been identified, the diseases caused by these different viruses seem to present the same way in humans.

Clinical features

Most human infections are asymptomatic or pauci-symptomatic, with fever and headache. On average, 1 in 250 infected people develops a severe neuroinvasive illness that is characterised by rapid onset of high fever, headache, neck stiffness, disorientation, coma, seizures and spastic paralysis, which can lead to death.

The case fatality rate in patients with severe disease is up to 30% and up to 50% of patients who survive severe illness have significant neurologic or psychiatric sequelae.

Transmission  

The incubation period is usually 5 to 15 days. The viremia in humans is low and of short duration, limited to the early phase of the disease.

Japanese encephalitis virus is maintained in an enzootic cycle between Culicidae mosquitoes and Ardeidae water birds (e.g. egrets, heron) and pigs. Humans and horses are dead-end hosts, meaning that they can be infected but do not contribute to the transmission cycle. In Asia, Culex tritaeniorhynchus and Culex vishnui appear to be the most important maintenance vectors for the virus. However, other mosquito species (e.g. Culex pipiens pipiens, Culex pipiens molestus, Culex quinquefasciatus) show a moderate efficiency for transmission and transovarial transmission has been demonstrated in some Aedes species, including Aedes albopictus.

Diagnostics and treatment

Diagnostics

The diagnosis of Japanese encephalitis virus infection relies on the detection of specific IgM antibodies that are present in the cerebrospinal fluid and serum of patients four to seven days after the onset of clinical symptoms. Diagnostic tests should always include other closely related flaviviruses (e.g. West Nile virus, Usutu virus, dengue virus, tick-borne encephalitis virus) for comparison and interpretation, and history of vaccination against Japanese encephalitis virus and other flaviviruses should be checked. Confirmation of the diagnosis needs to be done by neutralisation assays.

Viral direct detection by RT-PCR could be performed on blood or cerebrospinal fluid from patients in the early phase of the disease and on cerebral biopsies from deceased patients. Very few commercial diagnostic assays for serology are available.

Case management and treatment

There is no specific treatment for Japanese encephalitis virus infection. In more severe cases, patients usually need to be hospitalised for supportive treatment and management of complications.

Epidemiology

Geographical distribution

Human cases of Japanese encephalitis virus have occurred in southern, south-eastern and eastern Asia, as well as in Oceania.

In some areas the virus may be transmitted year-round, but in tropical climates epidemics tend to correspond with monsoons or rainy seasons and in temperate climates transmission generally occurs during the summer.

The overall global incidence of Japanese encephalitis is unknown, but estimates suggest that there are approximately 14 000 to 20 000 fatal cases of acute illness per year.

Risk groups

Japanese encephalitis primarily affects children. In endemic countries, adults are likely to have developed natural immunity from prior infection during their childhood; however, infection may occur at any age.

Those at higher risk of exposure to Japanese encephalitis virus include:

• Residents of rural areas in endemic locations
• Expatriates or travellers with long-term exposure to rural endemic areas
• Travellers to areas where irrigation flooding is used who spend the night outdoors without a mosquito net (e.g. camping and trekking).

Areas of uncertainty

There is a possible risk of introduction of Japanese encephalitis virus in European Union/European Economic Area countries via international travel and commerce with Asia and Oceania, which could facilitate the introduction of mosquitoes infected with the virus. If the virus is introduced, it could become established in Europe due to the significant number of susceptible mosquito vectors and vertebrate hosts.
 

The identification of a Japanese encephalitis viral RNA fragment in one Culex mosquito pool in northern Italy in 2010 might demonstrate a wider range of distribution of the virus and a potential public health threat in Europe. However, this result should be taken with caution, as no further laboratory confirmation could be performed and, to date, there have been no confirmatory findings in Europe.

Personal protective measures

There are several safe and effective vaccines available to prevent Japanese encephalitis. In Europe, the European Medicines Agency has granted a marketing authorisation to the Ixiaro vaccine, which is an inactivated vaccine that can be given to adults and children aged two months and older.

Japanese encephalitis can also be prevented by avoiding mosquito bites in endemic rural areas, particularly those close to irrigated rice fields and pig farms. Many mosquitoes are most active at dusk and dawn. Personal protective measures to reduce the risk of mosquito bites include using mosquito nets (preferably insecticide-treated nets), sleeping or resting in screened or air-conditioned rooms, wearing clothes that cover most of the body, and using mosquito repellent in accordance with the instructions indicated on the product label.

Public health measures

Changes in agricultural practices seem to have substantially decreased the risk of transmission to humans. Measures to control adult mosquito vectors can be applied in an outbreak situation, but the impact of such actions is not well known.

References

1.           Solomon T. Flavivirus encephalitis. N Engl J Med. 2004 Jul 22;351(4):370-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15269317

2.           Petersen LR, Marfin AA. Shifting epidemiology of Flaviviridae. J Travel Med. 2005 Apr;12 Suppl 1:S3-11. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16225801

3.           European Medicines Agency (EMA). Ixiaro, Japanese encephalitis vaccine (inactivated, adsorbed). Amsterdam: EMA; 2009. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/ixiaro#:~:text=Ixiaro%20is%20a%20vaccine%20that,Asia%2C%20particularly%20in%20rural%20areas.

4.           Fulmali PV, Sapkal GN, Athawale S, Gore MM, Mishra AC, Bondre VP. Introduction of Japanese encephalitis virus genotype I, India. Emerg Infect Dis. 2011 Feb;17(2):319-21. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21291622

5.           Litzba N, Klade CS, Lederer S, Niedrig M. Evaluation of serological diagnostic test systems assessing the immune response to Japanese encephalitis vaccination. PLoS Negl Trop Dis. 2010 Nov 16;4(11):e883. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21103412

6.           Ravanini P, Huhtamo E, Ilaria V, Crobu MG, Nicosia AM, Servino L, et al. Japanese encephalitis virus RNA detected in Culex pipiens mosquitoes in Italy. Euro Surveill. 2012 Jul 12;17(28):20221.

7.           Zeller H. Is Japanese encephalitis emerging in Europe? Euro Surveill. 2012 Aug 9;17(32):20242. Available at: https://www.eurosurveillance.org/content/10.2807/ese.17.32.20242-e