Overview: Japanese encephalitis
Introduction
Japanese encephalitis virus (JEV) belongs to the family flaviviridae and is transmitted between animals and human host by culex mosquitoes. Japanese encephalitis is prevalent throughout Eastern and Southern Asia and the Pacific Rim. The related neurotropic flaviviruses are found throughout the globe: Equine encephalitis virus and St. Louis encephalitis virus in North America, West Nile virus in Africa and the Middle East, Murray Valley encephalitis virus in Australia, Roccio virus in South America and Tick borne encephalitis virus in Russia. These viral encephalitides share many virological, epidemiological and clinical features (Solomon, 2004). Molecular studies have suggested that all the flaviviruses originated from a common ancestor about 10,000–20,000 years ago and are rapidly evolving to fill the ecological niches. Japanese encephalitis (JE) is the most important cause of viral encephalitis in Eastern and Southeast Asia. Up to 50,000 cases and 15,000 deaths annually are due to JE especially in the rural areas (Tsai, 1997, Solomon, 1997). The majority of JE victims are children and nearly half of the surviving patients have cognitive or motor sequelae. This review focuses on basic, clinical and preventive aspects of JE.
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Historical aspects
Japanese encephalitis was recognized in horses and humans as early as 1871. In 1924 a severe epidemic was reported from Japan; a filterable agent was extracted from human brain and passed to rabbits, although the agent could not be characterized. Every 10 years, major epidemics were reported in Japan affecting over 6000 patients (Miyake, 1964). In 1934, Hyashi reproduced the disease in monkey by intra-cerebral inoculation. In 1935, JE virus was isolated from human brain in Tokyo, Japan, and its
Japanese encephalitis virus
Japanese encephalitis virus is a single stranded positive sense RNA virus wrapped in a nucleocapsid and is surrounded by a 50 nm glycoprotein containing envelope. The RNA comprises a 5′ untranslated region (UTR, a longer 3′ UTR and between them a single open reading frame (ORF) (Chambers et al., 1990). This encodes 3 structural proteins, capsid protein (C), precursor to the membrane protein (PrM), and envelope protein (E), and 7 nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). The
Age
JE is a disease of children in the endemic areas; however, it affects both adults and children in newly affected areas. In some areas of Northern India, Nepal and Sri Lanka, all age groups are affected by JE suggesting recent introduction of JEV into these countries. The travelers to endemic areas may have devastating illness due to lack of protective antibodies. The highest age specific attack rates are between 3 and 6 years of age. This has been attributed to high outside exposure especially
Pathogenesis and pathology
After the bite of an infected mosquito, the virus amplifies peripherally producing transient viremia before entering into the central nervous system. The sites of peripheral amplification are dermal tissue and then lymph nodes. The mechanism of entry of JEV across the blood brain barrier is not known. In experimental studies using Hamster model, St. Louis encephalitis has been shown to enter the central nervous system through the olfactory route (Monath et al., 1983). Intranasal spraying is
Immunology
Both humoral and cellular immune responses occur after JEV infection. Following the primary infection (first JEV infection), a rapid and potent IgM response occurs in serum and CSF within days. By the seventh day, all the patients have raised IgM titers (Burke et al., 1985). Usually the virus cannot be isolated from such patients; however, the failure to mount IgM response is associated with viral isolation and fatal outcome (Leake et al., 1986). Antibodies to JEV probably protect the host by
Investigations
In JE, there may be peripheral leucocytosis and hyponatremia. The typical CSF findings include moderate pleocytosis (10–100 mm−3), mild protein rise (50–200 mg/dl) and normal glucose. Usually there is lymphocytic pleocytosis but in the early stage polymorphs may predominate. Very rarely CSF may be acellular.
Prognosis and sequelae
Twenty to forty percent of patients with JE die during the acute stage (Misra and Kalita, 2002). About 50% of the survivors have severe neurological sequelae in the form of cognitive impairment, behavioral abnormality, focal weakness, seizures and a variety of movement disorders. About 20% of the patients may have seizures. Motor deficits have been reported in 30%. The poor prognostic predictors include extremes of age, high fever, deep coma, hypotonia, features of seizures, raised intracranial
Summary
JE continues to be an important health problem especially in the developing countries of South and Southeast Asia. In the absence of specific antiviral therapy, JE has to be managed by symptomatic and supportive measures and preventive strategies. Measures like vector control, environmental manipulation and change in agricultural practices are difficult to achieve. Control of JE in economically advanced countries suggests the important role of socioeconomic parameters such as education and
References (120)
- et al.
Nucleotide changes responsible for loss of neuroinvasiveness in Japanese encephalitis virus neutralization-resistant mutants
Virology
(1991) - et al.
Heat shock protein 70 on Neuro2a cells is a putative receptor for Japanese encephalitis virus
Virology
(2009) - et al.
Diagnosis and immediate prognosis of Japanese B encephalitis
Am. J. Med.
(1952) - et al.
Origins, evolution, and vector/host coadaptations within the genus Flavivirus
Adv. Virus Res.
(2003) The global emergence/resurgence of arboviral diseases as public health problems
Arch. Med. Res.
(2002)Studies of Japanese encephalitis in China
Adv. Virus. Res.
(1982)- et al.
Brainstem auditory evoked potentials in Japanese encephalitis
J. Neurol. Sci.
(1999) - et al.
Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis
J. Neurol. Sci.
(2000) - et al.
EEG in Japanese encephalitis: A clinicoradiological correlation
Electoencephalogr. Clin. Neurophysiol.
(1998) - et al.
Surveillance for Japanese encephalitis in villages near Madurai, Tamil Nadu, India
Trans. R. Soc. Trop. Med. Hyg.
(1991)