VEEV was first isolated in 1938 from the brain of a horse that had died of encephalitis.[5]Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, et al. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella. Future Virol. 2011;6(6):721-40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134406
http://www.ncbi.nlm.nih.gov/pubmed/21765860?tool=bestpractice.com
The virus was first reported as a cause of human disease in Colombia in 1950.[5]Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, et al. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella. Future Virol. 2011;6(6):721-40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134406
http://www.ncbi.nlm.nih.gov/pubmed/21765860?tool=bestpractice.com
Six subtypes of VEEV have been identified (classified I-VI). In subtype I, five antigenic varieties exist (IAB, IC, ID, IE, and IF). Varieties IAB and IC are epizootic and have been responsible for most large outbreaks in humans.[4]Vilcarromero S, Aguilar PV, Halsey ES, et al. Venezuelan equine encephalitis and 2 human deaths, Peru. Emerg Infect Dis. 2010 Mar;16(3):553-6.
https://wwwnc.cdc.gov/eid/article/16/3/09-0970_article
http://www.ncbi.nlm.nih.gov/pubmed/20202445?tool=bestpractice.com
Varieties ID, IE, and IF are enzootic viruses in Central and South America. Subtypes II to VI are also enzootic viruses. Subtype II (Everglades virus) circulates in Florida. Subtypes III to VI (also known as Mucambo/Tonate, Pixuna, Cabassou, and Rio Negro, respectively) circulate in Central and South America.[6]Weaver SC, Ferro C, Barrera R, et al. Venezuelan equine encephalitis. Annu Rev Entomol. 2004 Jan;49:141-74.
http://www.ncbi.nlm.nih.gov/pubmed/14651460?tool=bestpractice.com
The enzootic subtypes are transmitted between rodents and Culex mosquito species of the subgenus Melanoconion. At the same time, the epizootic strains are amplified in horses and transmitted by a variety of mosquito species, one of the most important of which is the Aedes (Ochlerotatus) taeniorhynchus mosquito.[6]Weaver SC, Ferro C, Barrera R, et al. Venezuelan equine encephalitis. Annu Rev Entomol. 2004 Jan;49:141-74.
http://www.ncbi.nlm.nih.gov/pubmed/14651460?tool=bestpractice.com
There have also been reports of transmission of VEEV via aerosol, leading to laboratory-acquired infections. There is no evidence, however, for human-to-human transmission.[7]Daza E, Lopez I, Alcala A, et al; Centers for Disease Control and Prevention (CDC). Update: Venezuelan equine encephalitis - Colombia, 1995. MMWR Morb Mortal Wkly Rep. 1995 Oct 20;44(41):775-7.
https://www.cdc.gov/mmwr/preview/mmwrhtml/00039331.htm
http://www.ncbi.nlm.nih.gov/pubmed/7565561?tool=bestpractice.com
VEEV is widely distributed throughout Central and Southern America, with human and horse outbreaks reported in at least 13 countries, including Venezuela, Colombia, Peru, Ecuador, Costa Rica, Nicaragua, Honduras, El Salvador, Guatemala, Panama, Trinidad, and Mexico.[5]Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, et al. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella. Future Virol. 2011;6(6):721-40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134406
http://www.ncbi.nlm.nih.gov/pubmed/21765860?tool=bestpractice.com
[8]Groot, H. The health and economic impact of Venezuelan equine encephalitis. Paper presented at: Venezuelan encephalitis—proceedings of the workshop-symposium on Venezuelan encephalitis virus. 1972. Washington D.C., United States of America.
https://www.cabidigitallibrary.org/doi/full/10.5555/19732219327
There have also been outbreaks reported in the US. In 1969, a widespread and long-lasting outbreak began in El Salvador and Guatemala and spread through most of Central America and Mexico, reaching southern Texas in the US in 1971.[5]Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, et al. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella. Future Virol. 2011;6(6):721-40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134406
http://www.ncbi.nlm.nih.gov/pubmed/21765860?tool=bestpractice.com
During this outbreak, hundreds of thousands of cases of infection in humans were reported. The outbreak was contained when a large vaccination programme was initiated.
Venezuelan equine encephalitis resulting from VEEV infection occurs throughout much of Latin America and the Caribbean and is likely responsible for 10% of the cases attributed to dengue and could account for as many as 50,000 cases of acute febrile illness per year throughout Latin America.[5]Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, et al. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella. Future Virol. 2011;6(6):721-40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134406
http://www.ncbi.nlm.nih.gov/pubmed/21765860?tool=bestpractice.com
One of the largest epizootic outbreaks recorded resulted in 75,000 to 100,000 cases of human infection in Colombia and Venezuela in 1995, with around 3000 neurological complications and 300 deaths reported.[9]Rivas F, Diaz LA, Cardenas VM, et al. Epidemic Venezuelan equine encephalitis in La Guajira, Colombia, 1995. J Infect Dis. 1997 Apr;175(4):828-32.
https://jid.oxfordjournals.org/content/175/4/828.long
http://www.ncbi.nlm.nih.gov/pubmed/9086137?tool=bestpractice.com
In one large study involving febrile patients in South America, males were more often infected with enzootic VEEV than females, but all age groups were equally represented.[10]Forshey BM, Guevara C, Laguna-Torres VA, et al. Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007. PLoS Negl Trop Dis. 2010 Aug 10;4(8):e787.
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000787
http://www.ncbi.nlm.nih.gov/pubmed/20706628?tool=bestpractice.com
In an outbreak of epizootic VEEV in Texas (US) the infection rate was highest among males aged 20 to 39 years, but neurological symptoms and encephalitis were most common in children.[11]Bowen GS, Fashinell TR, Dean PB, et al. Clinical aspects of human Venezulean equine encephalitis in Texas. Bull Pan Am Health Organ. 1976;10(1):46-57.
https://hist.library.paho.org/English/BUL/ev10n1p46.pdf
http://www.ncbi.nlm.nih.gov/pubmed/949558?tool=bestpractice.com
Although VEEV infection is more common in rural areas, transmission can also occur within urban areas. Through a clinic-based febrile surveillance programme, an outbreak of VEEV infections was detected in Iquitos, Peru, in 2006.[12]Morrison AC, Forshey BM, Notyce D, et al. Venezuelan equine encephalitis virus in Iquitos, Peru: urban transmission of a sylvatic strain. PLoS Negl Trop Dis. 2008;2(12):e349.
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000349
http://www.ncbi.nlm.nih.gov/pubmed/19079600?tool=bestpractice.com
An epidemic of VEEV occurred in Colombia between February and March 2008. Approximately 13% (250/2000) of the area’s inhabitants had a febrile illness compatible with VEEV, with two fatalities.[13]Guzmán-Terán C, Calderón-Rangel A, Rodriguez-Morales A, et al. Venezuelan equine encephalitis virus: the problem is not over for tropical America. Ann Clin Microbiol Antimicrob. 2020 May 19;19(1):19.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7236962
http://www.ncbi.nlm.nih.gov/pubmed/32429942?tool=bestpractice.com
Outbreaks of VEEV occur alongside other alphaviruses. In 2010, an outbreak of Madariaga virus and VEEV occurred in the eastern province of Darién, Panama. Among hospitalised patients, there were 7 confirmed cases of Madariaga virus, 3 confirmed cases of VEE, and 1 confirmed case of co-infection with these viruses.[14]Carrera JP, Forrester N, Wang E, et al. Eastern equine encephalitis in Latin America. N Engl J Med. 2013 Aug 22;369(8):732-44.
https://www.nejm.org/doi/full/10.1056/NEJMoa1212628#t=article
http://www.ncbi.nlm.nih.gov/pubmed/23964935?tool=bestpractice.com
VEEV is clinically indistinguishable from other arboviruses and can only be confirmed with consultant laboratory testing, which has limited availability in resource-limited countries, therefore endemic disease incidence rates in these countries are uncertain.[13]Guzmán-Terán C, Calderón-Rangel A, Rodriguez-Morales A, et al. Venezuelan equine encephalitis virus: the problem is not over for tropical America. Ann Clin Microbiol Antimicrob. 2020 May 19;19(1):19.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7236962
http://www.ncbi.nlm.nih.gov/pubmed/32429942?tool=bestpractice.com
Expansion and development of disease surveillance networks is required in these countries to improve case and outbreak detection.
Overall mortality during outbreaks of VEEV does not typically exceed 1% of cases.[1]Centers for Disease Control and Prevention. Biosafety in microbiological and biomedical laboratories (BMBL) 6th edition. May 2024 [internet publication].
https://www.cdc.gov/labs/bmbl
Mortality occurs mainly in children and is generally attributable to consequences of neurological involvement.[2]Quiroz E, Aguilar PV, Cisneros J, et al. Venezuelan equine encephalitis in Panama: fatal endemic disease and genetic diversity of etiologic viral strains. PLoS Negl Trop Dis. 2009 Jun 30;3(6):e472.
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000472
http://www.ncbi.nlm.nih.gov/pubmed/19564908?tool=bestpractice.com