Arboviral encephalitides

(medicine) Diseases which are caused by arthropod-borne viruses (arboviruses), such as the encephalitis infections.

A number of diseases, such as St. Louis, Japanese B, and equine encephalitis, which are caused by arthropod-borne viruses (abbreviated “arboviruses”). In their most severe human forms, the diseases invade the central nervous system and produce brain damage, with mental confusion, convulsions, and coma; death or serious aftereffects are frequent in severe cases. Inapparent infections are common.

The arbovirus “group” comprises more than 250 different viruses, many of them differing fundamentally from each other except in their ecological property of being transmitted through the bite of an arthropod. A large number of arboviruses of antigenic groups A and B are placed in the family Togaviridae, in two genera, alphavirus (serological group A) and flavivirus (serological group B). Still other arboviruses, related structurally and antigenically to one another but unrelated to Togaviridae, are included in the family Bunyaviridae, consisting chiefly of the numerous members of the Bunyamwera supergroup—a large assemblage of arboviruses in several antigenic groups which are cross-linked by subtle interrelationships between individual members. The nucleic acid genomes of all arboviruses studied thus far have been found to be RNA.

Members of serological group A include western equine encephalitis, eastern equine encephalitis, and Venezuelan equine encephalitis viruses; and Mayaro, Semliki Forest, Chikungunya, and Sindbis viruses, which have nonencephalitic syndromes. Group A viruses are chiefly mosquito-borne. Serological group B viruses include Japanese B, St. Louis, and Murray Valley encephalitis viruses (mosquito-borne), and the viruses of the Russian tick-borne complex, some of which produce encephalitis (Russian spring-summer), whereas others cause hemorrhagic fevers (Omsk, Kyasanur Forest) or other syndromes, such as louping ill. Also in group B are the nonneurotropic viruses of West Nile fever, yellow fever, dengue, and other diseases. See also Louping ill; Yellow fever.

There is no proved specific treatment. In animals, hyperimmune serum given early may prevent death. Killed virus vaccines have been used in animals and in persons occupationally subjected to high risk. A live, attenuated vaccine against Japanese B encephalitis virus, developed in Japan, has been used experimentally with some success, not only in pigs to reduce amplification of the virus in this important vertebrate reservoir but also in limited trials in humans. In general, however, control of these diseases continues to be chiefly dependent upon elimination of the arthropod vector. See also Virus.

The viruses that cause arboviral encephalitides are all arthropod-borne. They are maintained in nature through biological transmission between susceptible vertebrate hosts (primarily birds and rodents) by blood-feeding arthropods, primarily mosquitoes, and ticks (see Table 1). Arboviruses replicate and produce viremia (virus in the blood of the host) in the vertebrate host and infect the arthropod when it takes a blood meal. They replicate in the tissue of the arthropod and are passed on to a new vertebrate host when a subsequent blood meal is taken, generally ten to fourteen days later.

All arboviruses that cause meningoencephalitis in humans are zoonoses, having animals other than humans as their natural host. They are maintained in complex life cycles involving a primary vertebrate host and a primary arthropod vector that usually does not feed on humans. These natural cycles usually remain undetected until humans encroach on the area where the virus escapes the primary cycle via a secondary arthropod vector or vertebrate host as a result of some ecological change. Humans and domestic animals generally become involved only after the virus is introduced into the periodomestic environment (areas where humans normally live) by a bridge vector or vertebrate host. Humans and domestic animals, when infected with these arboviruses, usually do not produce significant viremia and, therefore, do not contribute to the transmission cycle.

The arboviruses that cause meningoencephalitis in humans are found in nearly all parts of the world. Each virus has a geographic distribution that is usually limited by the ecological parameters governing its transmission cycle. Important limiting factors include temperature, rainfall patterns, and the distribution and population densities of the arthropod vectors and the vertebrate reservoir hosts. The greatest number of arboviruses are found in the tropics, where the flora and fauna are diverse.

The majority of these arbovirus infections in humans cause an inapparent infection or a nonspecific febrile illness. Onset of illness is usually sudden, with fever, headache, muscle pain, malaise, rash, and occasionally prostration. A small proportion of these patients with febrile illness may develop mild to severe neurologic disease characterized by one or more of the following signs: confusion, delirium, drowsiness, abnormal reflexes, spasticity, muscle weakness, paralysis, cranial-nerve palsies, and convulsions. The cerebrospinal fluid (CSF) is usually under pressure, has elevated protein, and pleocytosis is common. Specific antibodies can be detected in the CSF in properly timed samples. Case fatality rates range from less than 1 percent to 30 percent, depending on the virus.

Globally, the most important arbovirus encephalitis is Japanese encephalitis (JE), an Asian virus ranging from Japan and eastern Siberia in the east to India and Pakistan in the west and Indonesia and northern Australia in the south. Annually, there are 30,000 to 50,000 cases reported, depending on epidemic activity, which occurs primarily in

temperate or subtropical latitudes. The principal mosquito vector of human infection is Culex tritaeniorhynchus, which breeds in rice fields. Pigs and certain bird species act as amplification hosts; humans and horses are considered "dead-end" hosts. The highest incidence of disease occurs in children, as persons in older age groups have generally been exposed to infection and are immune. Elderly persons who are not immune are at highest risk for severe neurologic illness. The case fatality rate (CFR) is about 25 percent, but neuropsychiatric sequelae may occur in 30 to 70 percent of survivors.

In the western hemisphere, there are numerous viruses that can cause neurologic illness in humans. Discussion of all of these viruses is beyond the scope of this encyclopedia, but two viruses that are closely related to the Japanese encephalitis virus are important. The St. Louis encephalitis virus occurs from Canada to Argentina, periodically causing epidemics. Surveillance data are not available for most countries, but in the United States there have been 4,480 cases reported since surveillance began in 1964, with an annual average of 124 cases and a median of 26 cases. Like JE, most outbreaks occur in temperate and subtropical latitudes. Culex species mosquitoes are the principal vectors, and certain bird species serve as amplification hosts; humans are "dead-end" hosts. The highest incidence of severe disease occurs in persons over sixty years of age. The CFR is about 8 percent overall, but may be 15 to 20 percent in persons over sixty.

Historically, the West Nile (WN) virus has been infrequently associated with severe human illness. The virus has a wide geographic range throughout most of Africa, west and central Asia, and the Middle East. It was occasionally introduced into Europe, where it caused small outbreaks. In recent years, a number of epidemics of WN virus have been reported in the Middle East, Europe, and North America. These outbreaks have been associated with an increased incidence of neurologic disease and death in humans, horses, and birds. It is uncertain at this time why this apparent change has occurred. WN virus has a wide vector and host range; Culex mosquito species and birds are the principal hosts of this virus.

In the U.S., WN virus was introduced for the first time in 1999 and caused large epizootics in 1999 and 2000 among the American crow and other bird species, and in horses in a twelve-state area of the Northeast. Human cases were documented in New York, New Jersey, and Connecticut—in 1999 and 2000. There were 83 laboratory positive cases, 79 of which had neurologic disease. Age ranged from five to ninety-five years, but 85 percent of these patients were over fifty. There were nine deaths (CFR = 11%), all in persons over sixty-five.

In recent years there has been a dramatic global resurgence of epidemic arboviral diseases, including those that cause encephalitis. This has been caused by a number of demographic, and societal changes that have created ideal conditions for the increased movement and transmission of vector-borne diseases. Increased population growth; increased movement of people, animals, and commodities via modern transportation; uncontrolled urbanization; and changes in agricultural practices all contribute to increased geographic spread, human exposure; and infection by these zoonotic viruses.

(SEE ALSO: Communicable Disease Control; Vector-Borne Diseases)

Bibliography

Gubler, D. J. (1998). "Resurgent Vector-Borne Diseases as a Global Health Practice." Emerging Infectious Diseases 4:442–450.

Gubler, D. J., and Roehrig, J. T. (1998). "Arboviruses (Togaviridae and Flaviviridae)." In Topley and Wilson's Microbiology and Microbial Infections, Vol 1: Virology, eds. B. W. J. Mahy and L. Collier. New York: Oxford University Press.

Monath, T. P., ed. (1988). The Arboviruses: Epidemiology and Ecology. Boca Raton, FL: CRC Press.

— DUANE J. GUBLER