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Topic:Vector-borne disease

Vector-borne diseases in horses are illnesses transmitted by vectors such as mosquitoes, ticks, and flies. These diseases can affect equine health by introducing pathogens like viruses, bacteria, or parasites into the horse's system. Common vector-borne diseases in horses include West Nile Virus, Equine Infectious Anemia, and Lyme disease. The transmission dynamics, clinical manifestations, and management strategies for these diseases vary depending on the pathogen and vector involved. Understanding these aspects is important for developing preventive measures and treatment protocols. This page compiles peer-reviewed research studies and scholarly articles that explore the epidemiology, pathogenesis, and management of vector-borne diseases in equines.
West Nile Virus: An Update Focusing on Southern Europe.
Microorganisms    December 18, 2024   Volume 12, Issue 12 2623 doi: 10.3390/microorganisms12122623
Carrasco L, Utrilla MJ, Fuentes-Romero B, Fernandez-Novo A, Martin-Maldonado B.West Nile Virus (WNV) is a zoonotic, vector-borne pathogen affecting humans and animals, particularly in Europe. The virus is primarily transmitted through mosquitoes that infect birds, which serve as the main reservoirs. Humans and horses are incidental hosts. This review focuses on the epidemiology of WNV in southern Europe, particularly its increasing prevalence. Methods included an extensive literature review and analysis of recent outbreaks. WNV is largely asymptomatic in humans, but a small percentage can develop West Nile neuroinvasive disease (WNND), leading to severe neurological symp...
[Equine granulocytic anaplasmosis (EGA): Case description and overview of the epidemiological situation with focus on Germany].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    December 4, 2024   Volume 52, Issue 6 352-360 doi: 10.1055/a-2418-6540
Axt CW, Springer A, Besse A, Naucke TJ, Müller E, Strube C, Schäfer I.Equine granulocytic anaplasmosis (EGA) is a tick-borne disease caused by Anaplasma (A.) phagocytophilum. In Central, Northern, Western, and Eastern Europe, ticks of the Ixodes (I.) ricinus/I. persulcatus complex, in Germany mainly I. ricinus, are considered as vectors. Ixodes ricinus ticks show peaks of activity during the spring and summer months, particularly April to July. Changing climatic conditions, however, have meanwhile led to a year-round risk of tick exposure and thus infections with A. phagocytophilum. The presented case report underlines the seasonal peak phase of the infection ri...
Genetic diversity and phylogenetic relationships of Theileria equi inferred from heat shock protein 70 kDa gene sequences in Brazilian horses.
Veterinary research communications    November 19, 2024   Volume 49, Issue 1 16 doi: 10.1007/s11259-024-10599-3
Paulino PG, Amaral FB, de Oliveira RT, de Andrade SG, Rabello CA, Meirelles N, de Souza Santana M, Galdino KCP, Jacob JCF, Peckle M, Massard CL....Equine piroplasmosis, a tick-borne disease caused by hemoparasites of the Babesia and Theileria genera, has significant clinical and economic impacts worldwide. This study aims to characterize the heat shock protein 70 kDa (hsp70) gene sequences of Theileria equi from naturally infected horses across the five geographic regions in Brazil, and to analyze the phylogenetic relationships between T. equi and other parasites within the order Piroplasmida. Primers specific to T. equi were designed through in silico analysis of hsp70 gene sequences available in GenBank. Forty samples of equine whole ...
Environmental and Historical Determinants of African Horse Sickness: Insights from Predictive Modeling.
Transboundary and emerging diseases    August 13, 2024   Volume 2024 5586647 doi: 10.1155/2024/5586647
Kim K, Xu T, Kannan Villalan A, Chi T, Yu X, Jin M, Wu R, Ni G, Sui S, Wang Z, Wang X.African horse sickness (AHS) is a viral disease transmitted by arthropods that impacts Equidae, specifically horses and related species. Recognized as a notifiable disease by the World Organisation for Animal Health (WOAH), AHS is associated with a high mortality rate of 80%-90% in susceptible hosts and exhibits rapid transmission dynamics. Historical records document numerous instances of mass horse deaths attributed to AHS, with recent occurrences in Thailand and Malaysia in 2020 causing heightened concerns within the local horse industry. The lack of a comprehensive global perspective on th...
Modelling the Influence of Climate and Vector Control Interventions on Arbovirus Transmission.
Viruses    July 30, 2024   Volume 16, Issue 8 doi: 10.3390/v16081221
Fairbanks EL, Daly JM, Tildesley MJ.Most mathematical models that assess the vectorial capacity of disease-transmitting insects typically focus on the influence of climatic factors to predict variations across different times and locations, or examine the impact of vector control interventions to forecast their potential effectiveness. We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle, and incorporates host availability and preference. Applying this...
Leishmania spp. in equids and their potential vectors in endemic areas of canine leishmaniasis.
PLoS neglected tropical diseases    July 18, 2024   Volume 18, Issue 7 e0012290 doi: 10.1371/journal.pntd.0012290
Carbonara M, Mendoza-Roldan JA, Bezerra-Santos MA, de Abreu Teles PP, Lia RP, Locantore F, Iatta R, Volf P, Otranto D.Equids may be infected by zoonotic Leishmania spp., including Leishmania infantum, in regions where canine leishmaniasis (CanL) is endemic, and Leishmania martiniquensis, which has been reported in horses from Central Europe. This study was designed to evaluate the occurrence of both Leishmania spp. among equids living in CanL endemic areas of Italy, as well as to identify dipteran vectors from the same habitats. From March to October 2023, blood, serum and tissue samples from skin lesions were collected from equids (n = 98; n = 56 donkeys and n = 42 horses) living in Italy, as well as sand fl...
Tabanidae (Diptera) collected on horses in a Cerrado biome in the state of Tocantins, Brazil. Costa MVD, Rodrigues GD, Lima HIL, Krolow TK, Krüger RF.Tabanidae (Diptera), popularly known as horse flies, is an important vector group. This is the first study to ascertain the abundance and diversity of horse flies in horses at the cerrado biome of the state of Tocantins, Brazil. Collecting took place in typical Cerrado, and sampling occurred in the dry and rainy seasons. The horseflies were collected from horses using an entomological net. A total of 249 individuals were collected and spread over 25 species. The prevalent species were Stypommisa aripuana (25.8%) and Catachlorops rufescens (6.4%), in the dry period, and Fidena lissorhina (22.5%...
Spatiotemporal analysis of equine infectious anemia and prediction of risk areas in Europe.
Preventive veterinary medicine    July 8, 2024   Volume 230 106281 doi: 10.1016/j.prevetmed.2024.106281
An Q, Li Y, Sun Z, Gao X, Wang H.Equine Infectious Anemia (EIA) is a vector-borne persistent viral infection in equine animals. The EIA is characterized by recurrent fever, thrombocytopenia, depression, anemia, rapid weight loss, and lower body edema. Control of EIA is achieved through the elimination or isolation of infected animals, resulting in significant economic losses. In recent years, many countries in Europe have experienced outbreaks of EIA, which could potentially develop into a new wave of epidemic and pose a significant threat to the healthy development of the equine industry. This study utilized spatiotemporal a...
The Potential of Plant-Produced Virus-like Particle Vaccines for African Horse Sickness and Other Equine Orbiviruses.
Pathogens (Basel, Switzerland)    May 28, 2024   Volume 13, Issue 6 458 doi: 10.3390/pathogens13060458
Pitchers KG, Boakye OD, Campeotto I, Daly JM.African horse sickness is a devastating viral disease of equids. It is transmitted by biting midges of the genus with mortalities reaching over 90% in naïve horses. It is endemic to sub-Saharan Africa and is seasonally endemic in many parts of southern Africa. However, outbreaks in Europe and Asia have occurred that caused significant economic issues. There are attenuated vaccines available for control of the virus but concerns regarding the safety and efficacy means that alternatives are sought. One promising alternative is the use of virus-like particles in vaccine preparations, which have...
Seroprevalence of West Nile Virus among Equids in Bulgaria in 2022 and Assessment of Some Risk Factors.
Veterinary sciences    May 9, 2024   Volume 11, Issue 5 209 doi: 10.3390/vetsci11050209
Rusenova N, Rusenov A, Chervenkov M, Sirakov I.The aim of this study was to analyze the seroprevalence of West Nile virus (WNV) among equids in Bulgaria, confirm the results of a competitive ELISA versus the virus neutralization test (VNT) and investigate some predisposing factors for WNV seropositivity. A total of 378 serum samples from 15 provinces in northern and southern Bulgaria were tested. The samples originated from 314 horses and 64 donkeys, 135 males and 243 females, aged from 1 to 30 years. IgG and IgM antibodies against WNV protein E were detected by ELISA. ELISA-positive samples were additionally tested via VNT for WNV and Usu...
Vaccination and Control Methods of West Nile Virus Infection in Equids and Humans.
Vaccines    May 1, 2024   Volume 12, Issue 5 485 doi: 10.3390/vaccines12050485
Cendejas PM, Goodman AG.West Nile virus (WNV) is capable of causing severe neurologic disease in both humans and equines, making it a disease of importance in both human medicine and veterinary medicine. No targeted treatments exist for WNV infection in either humans or equines. Infection is treated symptomatically through management of symptoms like fever and seizures. As treatment for WNV is purely supportive, the response to WNV has focused primarily on methods of disease prevention. To this end, research efforts have yielded several effective vaccines for equine use as well as numerous conventional mosquito contr...
Equine Infectious Anaemia: The Active Surveillance of an Entire Equid Population Reduces the Occurrence of the Infection.
Transboundary and emerging diseases    April 30, 2024   Volume 2024 3439871 doi: 10.1155/2024/3439871
Carvelli A, Nardini R, Carnio A, Ricci I, Rosone F, Sala M, Simeoni S, Maccarone D, Scicluna MT.Equine infectious anaemia (EIA) is a life-long viral infection affecting equids, transmitted mechanically by biting flies and iatrogenic means. Despite its global distribution, active surveillance is limited, with passive clinical surveillance or control of specific equine sectors prevailing. In Italy, a national surveillance plan in horse, donkey, and mule populations has been established and includes mandatory passive and active surveillance through annual serological tests. During 2007-2010, the agar gel immunodiffusion (AGID) test served as both screening and confirmatory tests. Since 2011...
Revisiting the genotypes of Theileria equi based on the V4 hypervariable region of the 18S rRNA gene.
Frontiers in veterinary science    March 15, 2024   Volume 11 1303090 doi: 10.3389/fvets.2024.1303090
Nehra AK, Kumari A, Moudgil AD, Vohra S.Equine theileriosis, an economically important disease that affects horses and other equids worldwide, is caused by a tick-borne intracellular apicomplexan protozoa . Genotyping of based on the 18S rRNA gene revealed the presence of two, three, four or five genotypes. In previous published reports, these genotypes have been labelled either alphabetically or numerically, and there is no uniformity in naming of these genotypes. The present study was aimed to revisit the phylogeny, genetic diversity and geographical distribution of based on the nucleotide sequences of the V4 hypervariable regio...
Vesicular Stomatitis Virus.
The Veterinary clinics of North America. Food animal practice    February 23, 2024   Volume 40, Issue 2 251-259 doi: 10.1016/j.cvfa.2024.01.005
Pelzel-McCluskey AM.Vesicular stomatitis (VS) is a vector-borne livestock disease caused by either VS New Jersey virus or VS Indiana virus. The disease circulates endemically in northern South America, Central America, and Mexico and only occasionally causes outbreaks in the United States. During the past 20 years, VS outbreaks in the southwestern and Rocky Mountain regions occurred periodically with incursion years followed by virus overwintering and subsequent expansion outbreak years. Regulatory response by animal health officials prevents spread from lesioned animals and manages trade impacts. Recent US outb...
An investigation of the prevalence of equine filariosis in North and Northeast of Iran.
Journal of parasitic diseases : official organ of the Indian Society for Parasitology    January 19, 2024   Volume 48, Issue 1 163-167 doi: 10.1007/s12639-023-01643-1
Faghihzadeh Gorji F, Sadr S, Eshrati H, Borji H.Worldwide, equines are affected by equine filariosis, an endemic vector-borne disease caused by heterogenous parasitic nematodes. The main objective of this study was to determine the prevalence of filarial infection among horses in the North and Northeast of Iran. Between October 2021 and July 2022, 145 equine blood samples were investigated, of which 49 cases were from the northeast and 96 were from the north of Iran. Blood samples were taken for microfilariae using Knott's method. Out of 145 blood samples, only 2 cases (1.37%) from northern Iran were positive for microfilaria of , and no po...
Study on species distribution and seasonal dynamics of equine tick infestation in Ardabil province, northwest of Iran.
Veterinary parasitology, regional studies and reports    January 14, 2024   Volume 48 100987 doi: 10.1016/j.vprsr.2024.100987
Gholmohammadi S, Malekifard F, Yakhchali M.Ticks are important ectoparasites in equids, causing economic losses in animal husbandry in Iran and worldwide. This study was aimed to determine frequency and species diversity of hard ticks in equids in Ardabil province, during the four seasons in 2021. A total of 240 equids (187 horses, 53 donkeys) were randomly selected and examined. Ixodid ticks were collected from body surface of examined animals and identified. Of all examined equids, 32.5% horses, and 4.58% donkeys were infested with a total number of 412 ixodid ticks. Tick indices (tick number per animal) were 4.62. There was signific...
Evidence of West Nile Virus Circulation in Horses and Dogs in Libya.
Pathogens (Basel, Switzerland)    December 31, 2023   Volume 13, Issue 1 41 doi: 10.3390/pathogens13010041
West Nile virus (WNV) is a globally significant mosquito-borne Flavivirus that causes West Nile disease (WND). In Libya, evidence of WNV circulation has been reported in humans but never in animals. The aim of this study was to determine the seroprevalence of WNV infection in horses and dogs in Libya. In total, 574 and 63 serum samples were collected from apparently healthy, unvaccinated horses and dogs, respectively, between 2016 and 2019. A commercially available competitive enzyme-linked immunosorbent assay (c-ELISA) kit was initially used to test the collected samples for the presence of W...
Reoccurrence of West Nile virus lineage 1 after 2-year decline: first equine outbreak in Campania region.
Frontiers in veterinary science    November 30, 2023   Volume 10 1314738 doi: 10.3389/fvets.2023.1314738
de Martinis C, Cardillo L, Pesce F, Viscardi M, Cozzolino L, Paradiso R, Cavallo S, De Ascentis M, Goffredo M, Monaco F, Savini G, D'Orilia F....West Nile virus (WNV) is the most widespread arbovirus worldwide, responsible for severe neurological symptoms in humans as well as in horses and birds. The main reservoir and amplifier of the virus are birds, and migratory birds seem to have a key role in the introduction and spread of WNV during their migratory routes. WNV lineage 1 (L1) has been missing in Italy for almost 10 years, only to reappear in 2020 in two dead raptor birds in southern Italy. The present study reports the first equine outbreak in the Campania region. A 7-year-old horse died because of worsening neurological signs ...
First report of Amblyomma sculptum (Amblyomma cajennense complex) in a Brazilian state classified as a silent area for human rickettsiosis.
Veterinary world    November 1, 2023   Volume 16, Issue 11 2200-2204 doi: 10.14202/vetworld.2023.2200-2204
da Gama BC, Martins TF, Labruna MB, Vieira RFDC, de Almeida JC.Studies on ticks of public health concern in equine husbandry are scarce in the Northeastern region of Brazil. This study aimed to investigate the presence of ticks on horses in the State of Alagoas, which is classified as a silent area for human rickettsiosis. Unassigned: Ticks infesting horses were collected using anatomical tweezers or a commercial hook and kept in ethanol-labeled tubes for taxonomic identification. Unassigned: A total of 2,238 ticks were found. Ticks were identified as 2,215 (98.89%, 95% CI: 98.41-99.28) , 19 (0.98%, 95% CI: 0.05-1.38) , and 4 (0.18%; 95% CI: 0.007-0.46) ....
Culicoides-borne Orbivirus epidemiology in a changing climate.
Journal of medical entomology    October 20, 2023   Volume 60, Issue 6 1221-1229 doi: 10.1093/jme/tjad098
Hudson AR, McGregor BL, Shults P, England M, Silbernagel C, Mayo C, Carpenter M, Sherman TJ, Cohnstaedt LW.Orbiviruses are of significant importance to the health of wildlife and domestic animals worldwide; the major orbiviruses transmitted by multiple biting midge (Culicoides) species include bluetongue virus, epizootic hemorrhagic disease virus, and African horse sickness virus. The viruses, insect vectors, and hosts are anticipated to be impacted by global climate change, altering established Orbivirus epidemiology. Changes in global climate have the potential to alter the vector competence and extrinsic incubation period of certain biting midge species, affect local and long-distance dispersal ...
Host-mosquito interactions in rural and urban equestrian facilities from temperate Argentina.
Medical and veterinary entomology    August 10, 2023   Volume 37, Issue 4 816-825 doi: 10.1111/mve.12686
Cardo MV, Vezzani D.Targeted vector surveillance informed by data on mosquito biting patterns can help limit arboviral zoonotic diseases. To characterise host-biting networks in rural and urban equestrian facilities from temperate Argentina, adult resting mosquitoes were collected (December 2018-April 2019) with a battery-powered aspirator. Engorged females were sorted to species, and their blood source was identified using molecular techniques. Bipartite network analysis was performed for rural and urban matrices. A total of 177 bloodmeals from 11 mosquito species of Aedes and Culex were identified, with seven m...
Distribution of West Nile virus cases in horses reveals different spatiotemporal patterns in eastern and western Canada.
Journal of the American Veterinary Medical Association    August 9, 2023   1-9 doi: 10.2460/javma.23.05.0259
Levasseur A, Arsenault J, Paré J.West Nile virus (WNV) became notifiable in horses in 2003 in Canada and has been reported every year since. The objective of this study was to describe the spatiotemporal distribution of WNV in horses between 2003 and 2020 in Canada. Methods: The 848 symptomatic and laboratory-confirmed WNV cases in horses reported to the Canadian Food Inspection Agency between 2003 and 2020. Methods: Canada was divided into eastern and western regions for analysis. For each case, location and date of notification were captured. Triennial maps were made to describe the spatiotemporal distribution and expansion...
JMM Profile: West Nile virus.
Journal of medical microbiology    July 17, 2023   Volume 72, Issue 7 doi: 10.1099/jmm.0.001730
Sewgobind S, McCracken F, Schilling M.West Nile virus (WNV) is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family and is maintained in an enzootic cycle between avian hosts and mosquito vectors. Humans, horses and other mammals are susceptible to infection but are dead-end hosts due to a low viraemia. The disease can manifest itself in a variety of clinical signs and symptoms in people and horses from mild fever to severe encephalitis and morbidity. There are no vaccines licensed for human protection, but parts of Europe, North America, Africa and Australia have vaccines commercially available for hors...
Diversity of the Bacterial and Viral Communities in the Tropical Horse Tick, Dermacentor nitens, in Colombia.
Pathogens (Basel, Switzerland)    July 16, 2023   Volume 12, Issue 7 doi: 10.3390/pathogens12070942
Holguin-Rocha AF, Calle-Tobon A, Vásquez GM, Astete H, Fisher ML, Tobon-Castano A, Velez-Tobon G, Maldonado-Ruiz LP, Silver K, Park Y....Ticks are obligatory hematophagous ectoparasites that transmit pathogens among various vertebrates, including humans. The microbial and viral communities of ticks, including pathogenic microorganisms, are known to be highly diverse. However, the factors driving this diversity are not well understood. The tropical horse tick, Dermacentor nitens, is distributed throughout the Americas and it is recognized as a natural vector of Babesia caballi and Theileria equi, the causal agents of equine piroplasmosis. In this study, we characterized the bacterial and viral communities associated with partial...
Is leishmaniasis the new emerging zoonosis in the world?
Veterinary research communications    July 12, 2023   doi: 10.1007/s11259-023-10171-5
Montaner-Angoiti E, Llobat L.Leishmania is a genus of parasitic protozoa that causes a disease called leishmaniasis. Leishmaniasis is transmitted to humans through the bites of infected female sandflies. There are several different species of Leishmania that can cause various forms of the disease, and the symptoms can range from mild to severe, depending on species of Leishmania involved and the immune response of the host. Leishmania parasites have a variety of reservoirs, including humans, domestic animals, horses, rodents, wild animals, birds, and reptiles. Leishmaniasis is endemic of 90 countries, mainly in South Amer...
Venezuelan Equine Encephalitis
   July 3, 2023  
Crosby B, Crespo ME.Venezuelan Equine Encephalitis Virus (VEEV) is the causative viral pathogen of Venezuelan Equine Encephalitis (VEE). Outbreaks frequently involve both equines – including horses, donkeys, mules, zebras – and humans. Outbreaks may range over a large geographic area and may last for several months to years. Sporadic epidemic outbreaks occur most commonly in Central and South America. VEEV exists as both a natural pathogen and a laboratory-developed biologic weapon. Outbreaks have been reported in several South and Central American countries, including Venezuela, Colombia, Peru, Ecuador, C...
Seroprevalence of Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum Infections in German Horses.
Animals : an open access journal from MDPI    June 14, 2023   Volume 13, Issue 12 doi: 10.3390/ani13121984
Gehlen H, Inerle K, Bartel A, Stöckle SD, Ulrich S, Briese B, Straubinger RK.There are limited data on Lyme borreliosis (LB), a tick-borne disease caused by the Borrelia burgdorferi sensu lato complex, in horses. Seropositivity is not necessarily associated with clinical disease. Data on seropositivity against Borrelia burgdorferi and Anaplasma phagocytophilum in German horses are sparse. Therefore, serum samples from horses (n = 123) suspected of having Lyme borreliosis and clinically healthy horses (n = 113) from the same stables were tested for specific antibodies against Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum. The samples were screened for an...
Dynamics of eastern equine encephalitis virus during the 2019 outbreak in the Northeast United States.
Current biology : CB    June 8, 2023   Volume 33, Issue 12 2515-2527.e6 doi: 10.1016/j.cub.2023.05.047
Hill V, Koch RT, Bialosuknia SM, Ngo K, Zink SD, Koetzner CA, Maffei JG, Dupuis AP, Backenson PB, Oliver J, Bransfield AB, Misencik MJ, Petruff TA....Eastern equine encephalitis virus (EEEV) causes a rare but severe disease in horses and humans and is maintained in an enzootic transmission cycle between songbirds and Culiseta melanura mosquitoes. In 2019, the largest EEEV outbreak in the United States for more than 50 years occurred, centered in the Northeast. To explore the dynamics of the outbreak, we sequenced 80 isolates of EEEV and combined them with existing genomic data. We found that, similar to previous years, cases were driven by multiple independent but short-lived virus introductions into the Northeast from Florida. Once in the ...
Diversity of the bacterial and viral communities in the tropical horse tick, Dermacentor nitens in Colombia.
bioRxiv : the preprint server for biology    May 5, 2023   2023.05.04.539352 doi: 10.1101/2023.05.04.539352
Holguin-Rocha AF, Calle-Tobon A, Vásquez GM, Astete H, Fisher ML, Tobon-Castano A, Velez-Tobon G, Maldonado-Ruiz LP, Silver K, Park Y....Ticks are obligatory hematophagous ectoparasites that transmit pathogens among various vertebrates, including humans. The composition of the microbial and viral communities in addition to the pathogenic microorganisms is highly diverse in ticks, but the factors driving the diversity are not well understood. The tropical horse tick, , is distributed throughout the Americas and it is recognized as a natural vector of and , the causal agents of equine piroplasmosis. We characterized the bacterial and viral communities associated with partially-fed females collected by a passive survey on hors...
Efficacy of a brain-penetrant antiviral in lethal Venezuelan and eastern equine encephalitis mouse models.
Science translational medicine    April 12, 2023   Volume 15, Issue 691 eabl9344 doi: 10.1126/scitranslmed.abl9344
Cao X, Yang D, Parvathareddy J, Chu YK, Kim EJ, Fitz-Henley JN, Li X, Lukka PB, Parmar KR, Temrikar ZH, Dhole P, Adcock RS, Gabbard J, Bansal S....Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV, respectively) are mosquito-borne, neuroinvasive human pathogens for which no FDA-approved therapeutic exists. Besides the biothreat posed by these viruses when aerosolized, arthropod transmission presents serious health risks to humans, as demonstrated by the 2019 outbreak of EEE disease in the United States that resulted in 38 confirmed cases, 19 deaths, and neurological effects in survivors. Here, we describe the discovery of a 2-pyrrolidinoquinazolinone scaffold, efficiently synthesized in two to five steps, whose structural...