Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella

Abstract

Venezuelan equine encephalitis (VEE) is an emerging infectious disease in Latin America. Outbreaks have been recorded for decades in countries with enzootic circulation, and the recent implementation of surveillance systems has allowed the detection of additional human cases in countries and areas with previously unknown VEE activity. Clinically, VEE is indistinguishable from dengue and other arboviral diseases and confirmatory diagnosis requires the use of specialized laboratory tests that are difficult to afford in resource-limited regions. Thus, the disease burden of endemic VEE in developing countries remains largely unknown, but recent surveillance suggests that it may represent up to 10% of the dengue burden in neotropical cities, or tens-of-thousands of cases per year throughout Latin America. The potential emergence of epizootic viruses from enzootic progenitors further highlights the need to strengthen surveillance activities, identify mosquito vectors and reservoirs and develop effective strategies to control the disease. In this article, we provide an overview of the current status of endemic VEE that results from spillover of the enzootic cycles, and we discuss public health measures for disease control as well as future avenues for VEE research.

Figure 1. Map showing the known distribution of Venezuelan equine encephalitis complex alphaviruses in the Americas

VEEV: Venezuelan equine encephalitis virus. Reproduced with permission from [116] © Elsevier.

Figure 2. Phylogenetic tree showing relationships of epizootic and enzootic/endemic Venezuelan equine encephalitis virus strains

Clades including isolates from outbreaks discussed in the text are color-coded to correspond to the shading of the maps shown in Figures 4–7. The tree was generated using 817-nucleotide sequences from the PE2 envelope glycoprotein gene using maximum likelihood methods. Scale shows 20% nucleotide sequence divergence. VEE: Venezuelan equine encephalitis; VEEV: Venezuelan equine encephalitis virus.

Figure 3. The enzootic and epizootic transmission cycles of Venezuelan equine encephalitis virus

The vertical red arrow indicates host range changes involving adaptive E2 envelope glycoprotein amino acid substitutions that adapt epizootic strains for equine amplification or transmission by epizootic vectors.

Figure 4. Map of Peru, Ecuador and Bolivia showing regions of endemic Venezuelan equine encephalitis

Shading of individual states/departments corresponds to the lineages found in Figure 2, and black circles indicate exact locations of virus isolation. VEE; Venezuelan equine encephalitis; VEEV: Venezuelan equine encephalitis virus.

Figure 5. Map of Colombia showing regions of endemic Venezuelan equine encephalitis

Shading of individual departments corresponds to the lineages found in Figure 2, and black dots indicate exact locations of virus isolation. VEE: Venezuelan equine encephalitis; VEEV: Venezuelan equine encephalitis virus.

Figure 6. Map of Mexico showing regions of endemic and epizootic Venezuelan equine encephalitis

Shading of individual states corresponds to the lineages found in Figure 2, and black dots indicate exact locations of virus isolation. VEE: Venezuelan equine encephalitis; VEEV: Venezuelan equine encephalitis virus.

Figure 7. Map of Panama showing regions of endemic Venezuelan equine encephalitis

Shading of individual states corresponds to the lineages found in Figure 2, and black dots indicate exact locations of virus isolation. VEE: Venezuelan equine encephalitis; VEEV: Venezuelan equine encephalitis virus.