Present and future arboviral threats

Abstract

Arthropod-borne viruses (arboviruses) are important causes of human disease nearly worldwide. All arboviruses circulate among wild animals, and many cause disease after spillover transmission to humans and agriculturally important domestic animals that are incidental or dead-end hosts. Viruses such as dengue (DENV) and chikungunya (CHIKV) that have lost the requirement for enzootic amplification now produce extensive epidemics in tropical urban centers. Many arboviruses recently have increased in importance as human and veterinary pathogens using a variety of mechanisms. Beginning in 1999, West Nile virus (WNV) underwent a dramatic geographic expansion into the Americas. High amplification associated with avian virulence coupled with adaptation for replication at higher temperatures in mosquito vectors, has caused the largest epidemic of arboviral encephalitis ever reported in the Americas. Japanese encephalitis virus (JEV), the most frequent arboviral cause of encephalitis worldwide, has spread throughout most of Asia and as far south as Australia from its putative origin in Indonesia and Malaysia. JEV has caused major epidemics as it invaded new areas, often enabled by rice culture and amplification in domesticated swine. Rift Valley fever virus (RVFV), another arbovirus that infects humans after amplification in domesticated animals, undergoes epizootic transmission during wet years following droughts. Warming of the Indian Ocean, linked to the El Niño-Southern Oscillation in the Pacific, leads to heavy rainfall in east Africa inundating surface pools and vertically infected mosquito eggs laid during previous seasons. Like WNV, JEV and RVFV could become epizootic and epidemic in the Americas if introduced unintentionally via commerce or intentionally for nefarious purposes. Climate warming also could facilitate the expansion of the distributions of many arboviruses, as documented for bluetongue viruses (BTV), major pathogens of ruminants. BTV, especially BTV-8, invaded Europe after climate warming and enabled the major midge vector to expand is distribution northward into southern Europe, extending the transmission season and vectorial capacity of local midge species. Perhaps the greatest health risk of arboviral emergence comes from extensive tropical urbanization and the colonization of this expanding habitat by the highly anthropophilic (attracted to humans) mosquito, Aedes aegypti. These factors led to the emergence of permanent endemic cycles of urban DENV and CHIKV, as well as seasonal interhuman transmission of yellow fever virus. The recent invasion into the Americas, Europe and Africa by Aedes albopictus, an important CHIKV and secondary DENV vector, could enhance urban transmission of these viruses in tropical as well as temperate regions. The minimal requirements for sustained endemic arbovirus transmission, adequate human viremia and vector competence of Ae. aegypti and/or Ae. albopictus, may be met by two other viruses with the potential to become major human pathogens: Venezuelan equine encephalitis virus, already an important cause of neurological disease in humans and equids throughout the Americas, and Mayaro virus, a close relative of CHIKV that produces a comparably debilitating arthralgic disease in South America. Further research is needed to understand the potential of these and other arboviruses to emerge in the future, invade new geographic areas, and become important public and veterinary health problems.

Fig. 1

Probable temporal sequence and dispersal routes of WNV from its proposed center of origin in sub-Saharan Africa (Powers et al., 2000)(Lanciotti et al. 2002).

Fig. 2

Probable sequence and dispersal routes of JEV from its putative center of origin in the Malay Archipelago (Burke and Leake 1988, Solomon et al. 2003). Pattern of lineage dispersal was difficult to trace.

Fig. 3

Temporal patterns of dispersal by RVFV in Africa (Bird et al. 2003). Dates indicate the earliest detection and possible establishment of virus in each area.

Fig. 4

Geographic distribution of epidemic/epizootic VEEV strains responsible for major outbreaks, and enzootic VEE complex strains isolated principally in swamp or forest habitats.

Fig. 5

Phylogenetic tree of DENV strains derived from complete open reading frames available in the GenBank library. The phylogeny was inferred using Bayesian analysis (one million reiterations) and all horizontal branches are scaled according to the number of substitutions per site. Bayesian probability values are shown for key nodes. Virus strains and branches are colored green for sylvatic (nonhuman primate and arboreal mosquito isolates) and red for endemic (human and peridomestic Aedes isolates) and strains coded by abbreviated country of collection/strain name/year of collection. Dashed green line indicates hypothetical sylvatic DENV-3 lineage suggested by nonhuman primate seroconversions in Malaysia (Rudnick, 1978).

Fig. 6

Map showing the locations of the 2 major enzootic genotypes of CHIKV in Africa, and historical introductions into the Indian Ocean islands, Asia and Europe, as well as recent importations via viremic travelers, based on (Lanciotti et al., 2007; Powers et al., 2000; Rezza et al., 2007; Sang et al., 2008).