**2. Epidemiology of encephalitic arboviruses**

Arboviruses are usually transmitted through bites of blood-feeding arthropods (primarily mosquitoes and ticks) in two major cycles (Figure 1). The man-arthropod-man cycle is char‐ acteristic of dengue virus, while EEE, WEE, WN, JE, and CE viruses are transmitted by an alternative cycle involving non-human mammals and birds [10]. For the infections by arbo‐ viruses that cause encephalitis, humans or horses become an incidental or dead-end host, while animals such as birds and pigs serve as reservoirs or amplifying hosts [20].

*Togaviridae.* Viruses causing EEE, WEE, and VEE are all members of the Alphavirus genus in the family Togaviridae [21]. In fact, they are the only viruses in this group that commonly cause encephalitis and are restricted to the Americas. There are other Alphaviruses also with limited distributions, such as CHIKV (Asia and Africa), O'nyong-nyong virus (Africa), Sind‐ bis virus (Africa, Europe, and Asia), Mayaro virus (South America), and Ross River virus (Australia), however these are expected to eventually become distributed worldwide [22]. Epidemiologically, all Togaviridae are similar in that these viruses have wild avian hosts, are transmitted from birds to mammals by mosquitoes, and may cause encephalitis in hors‐ es and humans [22].

*Flaviviridae.* At least 7 arboviruses including TBE, Kyasanur Forest disease (KFD), JE, Mur‐ ray Valley encephalitis (MVE), SLE, Rocio, and WN viruses are reported to be associated with causing encephalitic symptoms [23]. Some of these are described below.

The TBE virus is a member of the family Flaviviridae, which is geographically distributed worldwide, usually in rural areas at temperate latitudes, including all over Europe and the Scandinavia, the former Soviet Union, and East Asia [24]. Incidences of human cases mark‐ edly increased in the early 1990s, mostly in Europe [25]. It was reported that the TBE inci‐ dence was 8690 cases during 1965~1992, while 8674 cases were documented in a smaller window of time between 1993 and 2006 in the Czech Republic, indicating a steep rise in this region [25]. Rodents are the primary reservoir hosts of this virus, which is transmitted by the bites of hard ticks (*Ixodes*) in nature [24].

The Bunyaviridae is one of the largest groupings of animal viruses, containing more than 300 viruses [12]. Except for the genus *Hantavirus*, all of them are transmitted by arthropods [12]. Viral particles are spherical with a size >100 nm in diameter, and are composed of four structural proteins encoded on its tripartite single-stranded negative-sense RNA genome

Various arboviruses belonging to those three major families can specifically cause encephali‐ tis. Of these, Eastern equine encephalitis (EEE) virus, Western equine encephalitis (WEE) vi‐ rus, and Venezuelan encephalitis (VEE) virus belong to the Togaviridae [14], Japanese encephalitis (JE) virus, St. Louis encephalitis (SLE) virus, WN virus, and tick-borne encepha‐ litis (TBE) virus are from the Flaviviridae [15, 16], while California encephalitis (CE) virus and La Crosse (LAC) virus are members of the Bunyaviridae [7]. Recently, increasing evi‐ dence has shown that certain arboviruses such as dengue (DENV) and chikungunya viruses (CHIKV) may occasionally cause encephalitis in addition to their conventional symp‐

Arboviruses are usually transmitted through bites of blood-feeding arthropods (primarily mosquitoes and ticks) in two major cycles (Figure 1). The man-arthropod-man cycle is char‐ acteristic of dengue virus, while EEE, WEE, WN, JE, and CE viruses are transmitted by an alternative cycle involving non-human mammals and birds [10]. For the infections by arbo‐ viruses that cause encephalitis, humans or horses become an incidental or dead-end host,

*Togaviridae.* Viruses causing EEE, WEE, and VEE are all members of the Alphavirus genus in the family Togaviridae [21]. In fact, they are the only viruses in this group that commonly cause encephalitis and are restricted to the Americas. There are other Alphaviruses also with limited distributions, such as CHIKV (Asia and Africa), O'nyong-nyong virus (Africa), Sind‐ bis virus (Africa, Europe, and Asia), Mayaro virus (South America), and Ross River virus (Australia), however these are expected to eventually become distributed worldwide [22]. Epidemiologically, all Togaviridae are similar in that these viruses have wild avian hosts, are transmitted from birds to mammals by mosquitoes, and may cause encephalitis in hors‐

*Flaviviridae.* At least 7 arboviruses including TBE, Kyasanur Forest disease (KFD), JE, Mur‐ ray Valley encephalitis (MVE), SLE, Rocio, and WN viruses are reported to be associated

The TBE virus is a member of the family Flaviviridae, which is geographically distributed worldwide, usually in rural areas at temperate latitudes, including all over Europe and the Scandinavia, the former Soviet Union, and East Asia [24]. Incidences of human cases mark‐ edly increased in the early 1990s, mostly in Europe [25]. It was reported that the TBE inci‐ dence was 8690 cases during 1965~1992, while 8674 cases were documented in a smaller

with causing encephalitic symptoms [23]. Some of these are described below.

toms,which usually involves headaches, muscle and joint pain, and rashes [17-19].

while animals such as birds and pigs serve as reservoirs or amplifying hosts [20].

consisting of the L, M, and S segments [13].

74 Encephalitis

**2. Epidemiology of encephalitic arboviruses**

es and humans [22].

**Figure 1.** Transmission cycles of arboviruses in nature. Two major cycles cover the transmission of most arboviruses, one is mam-to-man and the other usually involves non-human mammals and birds.

The JE virus is mainly amplified in pigs and birds and are transmitted by *Culex* mosquitoes (primarily *Cx. tritaeneorhunchus*) between vertebrates [26]; it causes a significant number of human encephalitis cases in most areas of Asia, especially eastern, southern, and southeast‐ ern Asia, as well as the South Pacific regions [27]. It recently expanded to the Torres Strait of northern Australia in 1999, and has now become endemic in Australia [28, 29]. JE virus is estimated to cause about 30,000~50,000 cases each year worldwide [15, 30]; of which, 10,000~15,000 may be fatal [31].

WN virus was first isolated from a febrile patient in the West Nile region of Uganda in 1937 [32]. It has caused epidemics in Africa, Europe, the Middle East, Asia, and, more recently, in North America [33]. Since the emergence of WN virus in the United States in 1999, it has spread all over North America and caused more than 20,000 humans to be ill and 770 deaths (http://www.cdc.gov/ncidod/dvbid/westnile/surv and control.htm). Neuroinvasive disease due to WN virus infection can occur, 2946 and 2866 cases were reported in 2002 and 2003, respectively [34].

The SLE virus is a close relative to WN virus, and actually is a member of the Japanese ence‐ phalitis serocomplex [35]. Predominantly, SLE virus is naturally maintained in a transmis‐ sion cycle between ornithophilic mosquitoes and birds, but occasionally these arthropods feed on mammalian blood, causing encephalitis in humans [36]. Nearly 5000 human infec‐ tions were reported between 1964 and 2005, making it the major cause of epidemic encepha‐ litis in association with flaviviral infections before the introduction of WN virus into the United States (http://www.cdc.gov/ncidod/dvbid/arbor/pdf/SLEDOC07132006.pdf).

*Buynaviridae.* In this family, viruses involving symptoms of encephalitis include Rift Valley fever (RVF), LAC, CE, and Jamestown Canyon [37]; all are mosquito-borne. RVF virus most‐ ly occurs in Africa and the Middle East, while the other three, which are classified in the California serogroup, are restrictedly distributed in North America [37]. Of these, the LAC virus causes the most human disease, with dozens to hundreds of hospitalized cases report‐ ed each year in the United States [38]; unlike EEE, California serogroup including LAC is not dependent on avian hosts for natural transmission. Rodents usually serve as its major vertebrate host [37].
