Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses

Abstract

In this review, we mainly focus on zoonotic encephalitides caused by arthropod-borne viruses (arboviruses) of the families Flaviviridae (genus Flavivirus) and Togaviridae (genus Alphavirus) that are important in both humans and domestic animals. Specifically, we will focus on alphaviruses (Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus) and flaviviruses (Japanese encephalitis virus and West Nile virus). Most of these viruses were originally found in tropical regions such as Africa and South America or in some regions in Asia. However, they have dispersed widely and currently cause diseases around the world. Global warming, increasing urbanization and population size in tropical regions, faster transportation and rapid spread of arthropod vectors contribute in continuous spreading of arboviruses into new geographic areas causing reemerging or resurging diseases. Most of the reemerging arboviruses also have emerged as zoonotic disease agents and created major public health issues and disease epidemics.

Keywords: Alphaviruses; Arboviruses; Arthropod-borne viruses; Encephalitis; Equine Encephalomyelitis; Flaviviruses; Zoonoses.

Fig. 1

Classification of arboviruses. Arboviruses are included in six different taxonomic virus families. ^a)Arboviruses that cause human encephalitides belong to four genera in four virus families.

Fig. 2

Vertebrate host and vector transmission cycles. (A) Enzootic cycle (sylvatic or jungle cycle). The natural transmission of virus between wild animals (vertebrate hosts) and primary or enzootic insect vectors and that leads to the amplification of the virus in the vector. The vertebrate host is the reservoir host that can harbor a virus indefinitely with no ill effects. Therefore, reservoir host is the primary host of a virus and may be re-infected several times during their life. (B) Epizootic cycle (rural cycle). The virus is transmitted between non-wild or domestic animals and the primary or accessory insect vectors. This can lead to an epidemic outbreak of viral disease in a domestic animal population where the virus is amplified (amplifying host), often with the implication that it may extend to humans by insect vectors (e.g., Japanese encephalitis virus, Venezuelan equine encephalitis virus [VEEV]). (C) Urban cycle. Humans are the source of infection for mosquitoes due to high level of viremia. The virus cycles between humans and insect vectors (urban vector e.g., A. aegypti) repeatedly, as reinfection occurs with every new insect bite (e.g.,dengue virus, yellow fever virus, St. Louis encephalitis virus, VEEV, chikungunya virus, Rift Valley fever virus). (D) Humans are dead-end hosts in the infection chain and do not develop sufficient viremia and do not serve for amplification of the virus to be transmitted again to insect vector (e.g., Eastern equine encephalitis virus, Western equine encephalitis virus, West Nile virus, and Sindbis virus). ^a)Amplifying host is in which the level of virus can become high enough that an insect vector such as a mosquito that feeds on it will probably become infectious. ^b)Dead-end host or incidental host is an intermediate host that does generally not allow transmission of the virus to the definitive host. They do not develop sufficient viremia to be picked up by the insect vectors. ^c)Bridge vector is an arthropod that acquires virus from an infected wild animal and subsequently transmits the agent to human or secondary host.

Fig. 3

Vertical transmission cycle (transovarial and transstadial). A vertical transmission exists in some arthropod vectors and is epidemiologically important. This type of transmission is found in viruses that belong to tick-borne encephalitis complex. However, it is also found in some of the mosquito-transmitted viruses (e.g., La Crosse encephalitis, Murray Valley encephalitis, St. Louis encephalitis, Japanese encephalitis,West Nile, and Western equine encephalitis).

Fig. 4

Enzootic and epizootic/epidemic transmission cycles of Eastern equine encephalitis virus (EEEV). The enzootic EEEV transmission cycle is maintained between passerine birds as reservoir/amplification hosts and Culiseta melanura, as the main enzootic vector in swamp habitats. Rodents/marsupials may serve as principal enzootic vectors and reservoirs in South America. Passerine birds develop extremely high levels of viremia, enough to infect both enzootic vectors as well as a variety of bridge vectors. Humans and equids are dead-end hosts since they do not develop sufficient viremia to transmit the virus.

Fig. 5

Enzootic and epizootic/epidemic transmission cycles of Western equine encephalitis virus (WEEV). WEEV is maintained in an enzootic cycle between passerine birds as reservoirs and its specific mosquito vector, C. tarsalis. Domestic and wild birds are considered important reservoir and epizootic amplifying hosts. It has also been suggested that lagomorphs and rodents can serve as amplification hosts when they are infected with WEEV by Aedes mosquitos.

Fig. 6

Enzootic and epizootic/epidemic transmission cycles of Venezuelan equine encephalitis virus (VEEV). The enzootic transmission cycle of VEEV is maintained among rodents and other vertebrates (e.g., cotton rats, spiny rats, bats, and opossums) as reservoirs and mosquitoes in the subgenus Culex (Melanoconion) as primary vectors. In contrast, epizootic VEEV strains are transmitted by several mosquito vectors (e.g., Aedes and Psorophora spp.) to susceptible amplification hosts, horses. During epizootic or epidemic cycles, horses are efficient amplification hosts with high titered viremia for mosquito transmission.

Fig. 7

Enzootic and epizootic/epidemic transmission cycles of Japanese encephalitis virus (JEV) and West Nile virus (WNV). Left: JEV is transmitted by primarily Culex tritaeniorhynchus. Pigs and aquatic birds are the efficient amplification and reservoir hosts of JEV that develop high-titered viremia. Humans and horses are dead-end hosts since the level of viremia is insufficient for mosquito transmission. Right: WNV maintains an enzootic transmission cycle between Culex mosquitoes and birds (reservoir host). Horses, humans, and other mammals infected in a spillover transmission are "dead-end" hosts.