Facts about Japanese encephalitis
The Japanese encephalitis virus is present in Asia, from Japan to India and Pakistan, and outbreaks are erratic and spatially and temporally limited phenomena, occurring quite unpredictably, even if all conditions appear to be present in a definite place. It is a leading cause of viral encephalitis in Asia, with 30-50,000 cases reported annually. It seems that there is a decrease of incidence in Asia which has been attributed to widespread vaccination (in children) and changes in agricultural practices and human behaviours.
Pathogen, clinical features
Japanese encephalitis virus is an enveloped RNA virus of the genus Flavivirus, family Flaviviridae, and 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. Five distinct viral genotypes have been identified but it seems that there are not apparent differences in humans between diseases resulting from infection by these different viruses.
Most human infections are asymptomatic. On average, one person in 200 infected develops a severe neuroinvasive illness which is characterized by rapid onset of high fever, headache, neck stiffness, disorientation, coma, seizures (second to elderly, in children), spastic paralysis. Milder forms of disease, such as aseptic meningitis or undifferentiated febrile illness can also occur.
The case fatality rate in patients with severe disease is 20- 30% and about 30% of the patients surviving the illness have significant neurological sequelae (motor paresis, spasticity, movement disorders, chronic seizures, and developmental delay).
The incubation period is usually 5 to 15 days. The viremia in humans is low and of short duration. Humans do not contribute in the chain of transmission and are considered dead-end hosts.
Japanese encephalitis virus is maintained in an enzootic cycle between Culicidae mosquitoes present in irrigated rice fields and Ardeidae water birds (e.g. egrets, heron). Environmental conditions may favour high viral amplification with passage to pigs. When these zoophilic mosquito populations reach high numbers the biting rate increases in humans. Horses are susceptible to viral infection (some strains) and can develop encephalitis. In Asia, Culex tritaeniorhynchus and Culex vishnui appear to be the most important maintenance vectors for Japanese encephalitis virus. However other mosquito species e.g. Culex pipiens pipiens, Culex pipiens molestus or Culex quinquefasciatus, show a moderate efficiency for transmission, and transavarial transmission has been demonstrated in some Aedes species including Aedes albopictus.
Diagnostics and treatment
The diagnosis of Japanese encephalitis infection relies on the detection of specific IgM antibodies which are present in cerebrospinal fluid and serum specimens from patients after 4-7 days post onset clinical symptoms. The test should always include other closely related flaviviruses (e.g. West Nile, Usutu, dengue, tick borne encephalitis) for comparison and interpretation including the vaccination history status (e.g. tick-borne encephalitis, yellow fever). Confirmation of the diagnosis needs to be done by neutralisation assays.
Viral direct detection by RT-PCR could be performed on blood or CSF in early stage of the disease and on cerebral biopsies from deceased patients. The viremia is very short and limited to the early phase of the disease. There are only very few commercial diagnostic assays for serology 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.
The geographic distribution of Japanese encephalitis (JE) virus extends from the East the Western Pacific islands (Japan, The Philippines) to India and Pakistan on the Westand from northern China (up to Tibet region) to Papua New Guinea and northern Australia where the virus expanded in the 90’s. The distribution of JE is linked to irrigated rice fields combined to pig breeding. In some locations, the virus may be transmitted year round, in other tropical areas, the timing of seasonal epidemics corresponds to the appearance of annual monsoons or rainy seasons and generally in areas with a temperate climate, the transmission prevails during the summer season.
The overall global incidence of Japanese encephalitis is unknown, but estimates suggest approximately 14,000 to 20,000 fatal cases of acute illness and 14,000 to 27,000 JE survivors with long-term neuropsychological sequelae.
Risk groups of Japanese encephalitis include:
- Residents of rural areas in endemic locations, particularly children
- Expatriates or travellers with long time exposure in rural endemic areas
- Travellers in areas where irrigation flooding is used and lasting night in the open without a mosquito net, e.g. camping and trekking.
The disease risk is extremely low in travellers and evaluated to 1 case/1 million. However, one should consider vaccinating travellers to JE-endemic countries that spend more than 1-2 months in risk areas during mosquito season. The risk of Japanese encephalitis in children travellers but beyond the morbidity of the acute illness extends to potentially chronic or persistent neuropsychological deficits.
Areas of uncertainties
There is a possible risk of introduction of Japanese encephalitis virus (JEV) in EU countries via international travel and commerce with Asia, potentially allowing the introduction of mosquitoes infected with JEV. If JEV is introduced, the virus might become established due to the significant number of susceptible mosquito vectors and vertebrate hosts. The identification of risk factors for progression to symptomatic encephalitis and viral persistence need further investigation.
The recent identification of a Japanese encephalitis viral RNA fragment in one Culex mosquito pool in Northern Italy might demonstrate a wider range of distribution of the virus and a potential public health threat in Europe. Additional studies are required to confirm this preliminary result.
Personal protective measures
Different kinds of vaccines (inactivated, attenuated and chimeric) are available and used in several Asiatic countries. In Europe an inactivated vaccine is currently available.
Several inactivated and live attenuated Japanese encephalitis vaccines are manufactured and used in Asia, mostly in children. One inactivated vaccine produced on Vero-cells is available in Europe for use in > 18 years adults. Paediatric clinical trials are being conducted to enable licensure this vaccine for use in children.
The implementation of attenuated vaccine in unvaccinated populations will continue to decrease the incidence of the disease in endemic areas.
Another way to prevent Japanese encephalitis infection is to avoid mosquito bites in endemic rural areas more specifically close to irrigated rice fields and pig farms. Many mosquitoes are most active at dusk and dawn. People can use insect repellents when they are outdoors and wear long sleeves and trousers at these times, or consider staying indoors during these hours.
As there is no specific treatment, the best way to prevent Japanese encephalitis infection is to avoid mosquito bites. Inactivated vaccine is available under restrictive regulations for adults with potential risk of exposure (e.g. travel for more than 1-2 months in rural areas).
Public health measures
It seems that the change of agricultural practices has substantially decreased the risk of transmission to humans. Measures aiming to control adult mosquito vectors can be applied in an outbreak situation but its impact is not well known. - See more at: http://ecdc.europa.eu/en/healthtopics/Japanese-encephalitis/public-heal…
Rosen L, Tesh RB, Lien JC, Cross JH Transovarial transmission of Japanese encephalitis virus by mosquitoes. Science. 1978 Feb 24;199(4331):909-11.
Solomon T. Flavivirus encephalitis. N Engl J Med. 2004 Jul 22;351(4):370–8. Petersen LR, Marfin AA. Shifting Epidemiology of Flaviviridae. J Travel Medicine 2005; 12:S3–S11 Burchard GD et al, Expert Opinion on Vaccination of Travelers Against Japanese Encephalitis. J Travel Med 2009; 16: 204–216 DOI: 10.1111/j.1708-8305.2009.00330.x Hills SL, Griggs AC, Fischer M. Japanese encephalitis in travelers from non-endemic countries, 1973–2008. Am J Trop Med Hyg. 2010 May;82(5):930–6. Fischer M, Lindsey N, Staples JE, Hills S. Japanese encephalitis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Mar 12;59(RR-1):1–27. 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
Litzba N, S. Christoph S. Klade, S. Lederer, M. Niedrig (2010) Evaluation of serological diagnostic assays in detecting the immune answer after Japanese Encephalitis vaccination., PLoS Negl Trop Dis. 2010 Nov 16;4(11):e883 Ravanini P, Huhtamo E, Ilaria V, Crobu MG, Nicosia AM, Servino L, Rivasi F, Allegrini S, Miglio U, Magri A, Minisini R, Vapalahti O, Boldorini R.Japanese encephalitis virus RNA detected in Culex pipiens mosquitoes in Italy. Euro Surveill. 2012;17(28):pii=20221.