Emerging arboviral encephalitisBMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7275.1484 (Published 16 December 2000) Cite this as: BMJ 2000;321:1484
Newsworthy in the W est but much more common in the East
- Tom Solomon, lecturer in neurology and medical microbiology (, )
- Mary Jane Cardosa, professor
- Department of Neurological Science, University of Liverpool, Walton Centre for Neurology and Neurosurgery, Fazakerley, Liverpool L9 7LJ
- Institute of Health and Community Medicine, Universiti Malaysia, Sarawak
The recent outbreaks of West Nile encephalitis in New York and Israel are drawing the western world's attention to the potential threat of arthropod-borne virus (arbovirus) encephalitis.1 But in many parts of Asia, infection with West Nile virus's sister, Japanese encephalitis virus, is a daily reality.
Epidemics of encephalitis were described in Japan from the 1870s onwards, and Japanese encephalitis virus was first isolated from a fatal case in the 1930s.2 West Nile virus was isolated from the blood of a febrile woman in Uganda a few years later in 1937.3 Both viruses are small enveloped RNA viruses, members of the genus Flavivirus (family Flaviviridae), named after the prototype yellow fever virus (flavus is the Latin for yellow). The flaviviruses are relatively new viruses, derived from a common ancestor 10-20 000 years ago, that are rapidly evolving to fill new ecological niches.4 Both West Nile and Japanese encephalitis virus are transmitted in an enzootic cycle between small birds by Culex mosquitoes, though for Japanese encephalitis pigs are important amplifying hosts. Humans become infected by Culex mosquitoes coincidentally, but are not part of the natural cycle.
Although known to be widely distributed across much of Africa, southern Europe, and the Middle East, West Nile virus was, until recently, considered to be relatively benign.3 It causes a non-specific febrile illness, or a characteristic fever-arthralgia-rash syndrome, which occurred in large epidemics in Israel in the 1950s and South Africa in the 1970s. Direct invasion of the central nervous system to cause encephalitis was thought to be a rarity. In contrast, Japanese encephalitis virus has always been recognised as a killer. Over the past 50 years it has spread relentlessly across Southeast Asia, India, southern China, and the Pacific — reaching Australia in 1998.5
Culex mosquitoes are unavoidable in rural Asia, and almost everyone is exposed to the virus. Only about 1 in 300 infections results in disease, and there is a wide range of presentations from a simple febrile illness to a severe meningoencephalitis, as well as a newly recognised polio-like acute flaccid paralysis.6 There are estimated to be 50 000 cases of Japanese encephalitis annually, with 15 000 deaths. The actual numbers may become clearer with the application of new simple rapid diagnostic tests.7 In addition to the high mortality, about half the survivors have severe neuropsychiatric sequelae, with their associated socioeconomic burden.
The epidemiology of West Nile virus has also changed in recent years. Increasing numbers of cases of encephalitis are being seen in all areas where the virus occurs, and during a large outbreak in Romania in 1996, 393 patients with neurological disease had laboratory evidence of West Nile virus infection.8 Then, in 1999, West Nile virus reached America for the first time. A quick-witted physician had noticed a cluster of cases of encephalitis in the Bronx, New York. Initial serological tests pointed to St Louis encephalitis virus (the American sister of the neurotropic flaviviruses, which caused encephalitis epidemics in America in the 1930s, but is not normally found this far north). However, sick birds at the Bronx zoo and crows dropping from the sky suggested something else,9 since the local virus would not normally cause disease in its natural hosts. West Nile virus was isolated subsequently from both avian and human cases.10 By the time mosquito spraying and the arrival of winter had reduced the population of Culex mosquitoes 62 people had developed encephalitis and seven had died.
These recent findings in Asia and the West raise important issues about the spread, control, and pathogenesis of arboviral encephalitis. Many theories have been proposed on how West Nile virus reached New York, including illegally imported exotic birds, airplane-borne mosquitoes, European refugees, and even biological terrorism, but infected birds migrating from Israel now seems the most likely.11 However it arrived, surveillance has shown that the virus is now well established in the region. Japanese encephalitis virus is also thought to be spread by birds, but mosquitoes blown between Pacific islands may contribute too.5
Although we can do little to limit the spread of enzootic flaviviruses, we can minimise the number of human cases. Surveillance of mosquitoes, sentinel birds, and dead birds for West Nile virus in America warned of this summer's impending outbreak. Consequently the number of human cases was minimised by advising people to avoid mosquito bites and by implementing measures to reduce the mosquito population, such as removing breeding sites and spraying. Unfortunately such measures are impracticable in Asia, where the rice fields in which Culex mosquitoes breed are a mainstay of the economy. There are no vaccines against West Nile virus yet. An expensive formalin-inactivated and newer live attenuated vaccine against Japanese encephalitis are available, but not for the majority of the 2.8 billion people living in affected regions. 12 13 For them, the factors determining who, of all those infected with Japanese encephalitis virus, develops neurological disease may be critically important. The relative contributions of the human immune response and viral strain differences are currently being investigated.