Guzmán‑Terán et al. Ann Clin Microbiol Antimicrob (2020) 19:19 Annals of Clinical Microbiology https://doi.org/10.1186/s12941‑020‑00360‑4 and Antimicrobials REVIEW Open Access Venezuelan equine encephalitis virus: the problem is not over for tropical America Camilo Guzmán‑Terán1, Alfonso Calderón‑Rangel2, Alfonso Rodriguez‑Morales3,4 and Salim Mattar2* Abstract The equine encephalitis viruses, Venezuelan (VEEV), East (EEEV) and West (WEEV), belong to the genus alphavirus, family Togaviridae and still represent a threat for human and animal public health in the Americas. In both, these infections are characterized by high viremia, rash, fever, encephalitis and death. VEEV encephalitis is similar, clinically, to other arboviral diseases, such as dengue, Zika or chikungunya. Most of the alphaviruses are transmitted between vertebrates and mosquitoes. They are able to replicate in a wide number of hosts, including mammals, birds, reptiles, amphibian and arthropods. The VEEV has enzootic and epizootic transmission cycles. At the enzootic one, enzootic strains (subtype I, serotypes D–F and serotypes II–VI) are continuously circulating between mosquitoes and wild rodents in tropical forests and mangroves of the Americas. The main reseroivrs are wild rodent species of the sub‑ family Sigmodontinae. However, bats can be also accidental reservoirs of VEEV. In this article, we reviewed the main features, epidemiology, clinical aspects and the current perspectives of the VEEV. Keywords: Arbovirus, Equine, Chiroptera, Alphavirus, Zoonoses, Americas Background VEEV are amplifed in Equidae, where they spread rap- Venezuelan equine encephalomyelitis is caused by the idly and can be highly pathogenic in horses, donkeys, Venezuelan equine encephalitis virus (VEEV). Mos- and mules. Te disease in horses is characterized by quito vectors transmit the virus, mainly afects Equidae, fever, loss of appetite, and disorders of the central nerv- humans, and wild animals. Te enzootic cycle of VEEV ous system, such as muscle deterioration, blindness, and is complex and infects many diferent species of mam- seizures. In humans, early symptoms of VEEV infection mals and mosquitoes. Some of the enzootic viral spe- include fu-like symptoms, such as fever, chills, malaise, cies within the Alphavirus genus are known as VEEV, severe headache, myalgia in the legs and lower back, Mosso das Pedras virus, Everglades virus, Mucambo tachycardia, and in some cases, nausea, vomiting, and virus, Tonate virus, Pixuna virus, Cabassou virus, and Río diarrhea. If there are neurological signs, they can include Negro virus [1]. seizures, drowsiness, confusion, and photophobia. Chil- Te spread of VEEV varies in speed and intensity dren are more likely to sufer permanent neurological according to the viral subtype and the densities of mos- damage. After 4 to 6 days of acute illness, the patient may quito populations, and the transmission is produced feel weak for several weeks. Lethal cases manifest with by the vector that feeds on an infected animal and sub- difuse congestion and edema in the brain, gastrointes- sequently infects a new host. Te epizootic subtypes of tinal tract, and pulmonary hemorrhage and sometimes triggers meningoencephalitis. *Correspondence: [email protected] Biological characteristics of VEEV 2 Instituto de Investigaciones Biológicas del Trópico (IIBT), Facultad de Te International Virus Taxonomy Committee classifed Medicina Veterinaria y Zootecnia, Universidad de Córdoba, Montería, Córdoba, Colombia the virus into the Togaviridae family, genus Alphavirus, Full list of author information is available at the end of the article and according to the Baltimore classifcation: Group IV © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 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Te VEEV has single-stranded RNA extending northward into Saskatchewan, Canada [7], the approximately 70 nm in diameter, with icosahedral sym- epizootic reached the east side of the Canadian Rock- metry. Te 5′ end of the genome encodes four non-struc- ies [8, 9]. Te incidence of WEEV has decreased over tural proteins, nsP1, nsP2, nsP3 and nsP4, and the 3′ end the past four decades [10], the last human case in North is responsible for three structural proteins, the capsid and America occurred in 1994, and the virus has not been the envelope proteins E1 and E2. Non-structural proteins detected in mosquito pools since 2008. Te WEEV was participate in the replication of the viral genome involved isolated in Argentina in 2009. Subsequently, an outbreak in functions of the cytoplasm of the host. in Uruguay resulted in a fatal human case [11] (Fig. 1). With respect, the North American variant of the EEEV VEEV and other similar equine encephalitis in America is found in Eastern Canada, and in all states east of the In addition to VEEV, Eastern equine encephalitis Mississippi, it has also been isolated in Arkansas, Min- (EEEV), Western (WEEV) are frequent viral infections nesota, South Dakota, and Texas. Te South American in the Americas (Fig. 1), which also belong to the genus variant is found in areas of Central and South America Alphavirus (Togaviridae). In humans, WEEV, EEEV and along the coast of the Gulf of Mexico. Te numer- viruses, like VEEV, cause symptoms ranging from mild ous strains of the EEEV can be grouped into two variants. febrile illness to severe encephalitis that can lead to death Te variant found in North America is more pathogenic [2]. As a result of vaccination, in some countries such as than the variant of Central and South America. Most the United States, there are no longer periodically severe of the Caribbean strains belong to the North American epidemics of EEEV and WEEV encephalitis (Fig. 1). How- EEEV group, but the South American variant can also be ever, sporadic cases and small outbreaks are observed. found (Fig. 1). Te VEEV continues to present epidemic outbreaks in Due to genetic divergence and signifcant diferences South America in equine and human populations [3, 4]. in ecology and pathogenesis, the isolations of South WEEV is a natural chimera resulting from the recombi- America from EEEV were recently classifed as a dis- nation of the EEEV virus and the Sindbis virus (SINV) [5]. tinct species that was called Madariaga virus (MADV) It circulates in North and South America among espe- [12, 13]. However, unlike the EEEV of North America, cially passerine birds and Culex tarsalis mosquitoes its the MADV, formerly known as equine encephalitis of main vector, mammals can participate in a second cycle the South American East, was not associated with out- [4, 6]. Between 1930 and 1950, WEEV produced wide- breaks in humans before 2010 when the frst outbreak of spread outbreaks that covered western North America, the MADV was reported in the Darien region of Panama. Fig. 1 Geographical distribution of the equine encephalitis in the Americas. a VEEV. b EEEV. c WEEV Guzmán‑Terán et al. Ann Clin Microbiol Antimicrob (2020) 19:19 Page 3 of 8 Before the Darién outbreak, in South America, there diagnosis requires specialized laboratory tests that are were only three reported cases of EEEV in humans in difcult to implement in regions with limited resources. Brazil and Trinidad. Unlike the epidemiological profle Terefore, an endemic disease in developing countries in South America, in North America, eight human cases remains mostly unknown. Surveillance suggests that of neuroinvasive EEEV disease have been reported on it may represent up to 10% of the burden of dengue in average between 2004 and 2013 [12, 13]. From the epi- neo-tropical cities, or tens of thousands of cases per year demiological perspective, it is interesting to observe that throughout Latin America [19] (Fig. 2). when comparing the epidemics and epizootics of MADV and VEEV, the latter are explosive and involve equine Relationship of the antigenic subgroups amplifcation, which has resulted in 100,000 cases or and the epidemiology of VEEV more in humans and thousands of equine deaths in Latin Te essential antigenic subgroups of VEEV are subtype America. (I), which also includes fve subtypes of diferent origins: lA (Venezuela and Trinidad), IB (Peru and Argentina), IC Epidemiology of Venezuelan equine encephalitis (Venezuela and Colombia), ID (Colombia and Panama), Te clinical manifestation of the disease was described lE (Panama and Mexico); Subtype (II) Florida; Subtype as a “mad plague” in South America in the 1920s [14]. (III) Mucambo.