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The New England journal of medicine2013; 369(8); 732-744; doi: 10.1056/NEJMoa1212628

Eastern equine encephalitis in Latin America.

Abstract: The eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE) viruses are pathogens that infect humans and horses in the Americas. Outbreaks of neurologic disease in humans and horses were reported in Panama from May through early August 2010. Methods: We performed antibody assays and tests to detect viral RNA and isolate the viruses in serum samples from hospitalized patients. Additional cases were identified with enhanced surveillance. Results: A total of 19 patients were hospitalized for encephalitis. Among them, 7 had confirmed EEE, 3 had VEE, and 1 was infected with both viruses; 3 patients died, 1 of whom had confirmed VEE. The clinical findings for patients with EEE included brain lesions, seizures that evolved to status epilepticus, and neurologic sequelae. An additional 99 suspected or probable cases of alphavirus infection were detected during active surveillance. In total, 13 cases were confirmed as EEE, along with 11 cases of VEE and 1 case of dual infection. A total of 50 cases in horses were confirmed as EEE and 8 as VEE; mixed etiologic factors were associated with 11 cases in horses. Phylogenetic analyses of isolates from 2 cases of equine infection with the EEE virus and 1 case of human infection with the VEE virus indicated that the viruses were of enzootic lineages previously identified in Panama rather than new introductions. Conclusions: Cases of EEE in humans in Latin America may be the result of ecologic changes that increased human contact with enzootic transmission cycles, genetic changes in EEE viral strains that resulted in increased human virulence, or an altered host range. (Funded by the National Institutes of Health and the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama.).
Publication Date: 2013-08-24 PubMed ID: 23964935PubMed Central: PMC3839813DOI: 10.1056/NEJMoa1212628Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines cases of Eastern Equine Encephalitis (EEE) and Venezuelan Equine Encephalitis (VEE) in Latin America, specifically in Panama during a 2010 outbreak, offering an understanding of how humans and horses are affected by these viruses, and conclusions about their origin and transmission.

Study Methodology

  • The study utilized different diagnostic tools to verify EEE and VEE outbreaks amongst hospitalized patients in Panama between May and August 2010.
  • Serum samples from these patients were subjected to antibody assays and tests to detect viral RNA, with the aim to isolate the viruses.
  • The researchers extended their methods to identify additional cases through enhanced surveillance.

Study Findings

  • Out of 19 hospitalized patients for encephalitis, 7 were confirmed to have EEE, 3 had VEE, and 1 was infected with both viruses.
  • Three patients died and one among them was confirmed to have VEE. The patients with EEE exhibited symptoms such as brain lesions, seizures leading to status epilepticus, and neurologic sequelae.
  • Using active surveillance, they detected 99 suspected or probable cases of alphavirus infection.
  • A total of 13 cases were confirmed as EEE, and 11 cases of VEE with 1 case of dual infection.
  • 50 horse cases were confirmed to have EEE and 8 had VEE. Mixed etiologic factors were associated with 11 horse cases.
  • Through phylogenetic analyses of isolated viruses, it was found that the viruses were enzootic lineages already identified in Panama and not newly introduced.

Conclusion

  • The researchers concluded that human EEE cases in Latin America could be due to ecological changes that increased human contact with enzootic transmission cycles.
  • Genetic changes in EEE viral strains that resulted in increased human virulence, or a change in the host range, could also be reasons.

Financing for the research was provided by the National Institutes of Health and the Secretaría Nacional de Ciencia, Tecnología e Innovación, Panama. This suggests that the findings have been positively reviewed and validated by scientists globally.

Cite This Article

APA
Carrera JP, Forrester N, Wang E, Vittor AY, Haddow AD, López-Vergès S, Abadía I, Castaño E, Sosa N, Báez C, Estripeaut D, Díaz Y, Beltrán D, Cisneros J, Cedeño HG, Travassos da Rosa AP, Hernandez H, Martínez-Torres AO, Tesh RB, Weaver SC. (2013). Eastern equine encephalitis in Latin America. N Engl J Med, 369(8), 732-744. https://doi.org/10.1056/NEJMoa1212628

Publication

ISSN: 1533-4406
NlmUniqueID: 0255562
Country: United States
Language: English
Volume: 369
Issue: 8
Pages: 732-744

Researcher Affiliations

Carrera, Jean-Paul
  • Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama City, Panama.
Forrester, Naomi
    Wang, Eryu
      Vittor, Amy Y
        Haddow, Andrew D
          López-Vergès, Sandra
            Abadía, Ivan
              Castaño, Elizabeth
                Sosa, Nestor
                  Báez, Carmen
                    Estripeaut, Dora
                      Díaz, Yamilka
                        Beltrán, Davis
                          Cisneros, Julio
                            Cedeño, Hector G
                              Travassos da Rosa, Amelia P
                                Hernandez, Humberto
                                  Martínez-Torres, Alex O
                                    Tesh, Robert B
                                      Weaver, Scott C

                                        MeSH Terms

                                        • Adolescent
                                        • Animals
                                        • Antibodies, Viral / blood
                                        • Child
                                        • Child, Preschool
                                        • Disease Outbreaks
                                        • Encephalitis Virus, Eastern Equine / genetics
                                        • Encephalitis Virus, Eastern Equine / immunology
                                        • Encephalitis Virus, Eastern Equine / isolation & purification
                                        • Encephalitis Virus, Venezuelan Equine / genetics
                                        • Encephalitis Virus, Venezuelan Equine / immunology
                                        • Encephalitis Virus, Venezuelan Equine / isolation & purification
                                        • Encephalomyelitis, Eastern Equine / epidemiology
                                        • Encephalomyelitis, Eastern Equine / veterinary
                                        • Encephalomyelitis, Venezuelan Equine / epidemiology
                                        • Encephalomyelitis, Venezuelan Equine / veterinary
                                        • Fatal Outcome
                                        • Female
                                        • Horse Diseases / epidemiology
                                        • Horses
                                        • Humans
                                        • Infant
                                        • Male
                                        • Panama / epidemiology
                                        • Phylogeny
                                        • RNA, Viral / blood

                                        Grant Funding

                                        • U54 AI057156 / NIAID NIH HHS
                                        • HHSN272201000040I / NIAID NIH HHS
                                        • HHSN27200004/DO4 / PHS HHS
                                        • HHSN27220100004OI / PHS HHS
                                        • U54-AI057156 / NIAID NIH HHS
                                        • HHSN272201000040C / NIAID NIH HHS

                                        References

                                        This article includes 30 references
                                        1. Smith DW, Mackenzie JS, Weaver SC. Alphaviruses. .
                                        2. Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, Ferro C, Haddow AD, Weaver SC. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella. Future Virol 2011;6:721–40.
                                          pmc: PMC3134406pubmed: 21765860
                                        3. Dietz WH Jr, Galindo P, Johnson KM. Eastern equine encephalomyelitis in Panama: the epidemiology of the 1973 epizootic. Am J Trop Med Hyg 1980;29:133–40.
                                          pubmed: 7352621
                                        4. Sabattini MS, Daffner JF, Monath TP. Localized eastern equine encephalitis in Santiago del Estero Province, Argentina, without human infection. Medicina (B Aires) 1991;51:3–8.
                                          pubmed: 1921689
                                        5. Alice FJ. Infeccao humana pelo virus “leste” da encefalite equina. Bol Inst Biol da Bahia (Brazil) 1956;3:3–9.
                                        6. Corniou B, Ardoin P, Bartholomew C, Ince W, Massiah V. First isolation of a South American strain of eastern equine virus from a case of encephalitis in Trinidad. Trop Geogr Med 1972;24:162–7.
                                          pubmed: 5037688
                                        7. Aguilar PV, Robich RM, Turell MJ. Endemic eastern equine encephalitis in the Amazon region of Peru. Am J Trop Med Hyg 2007;76:293–8.
                                          pubmed: 17297038
                                        8. Aguilar PV, Paessler S, Carrara AS. Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus. J Virol 2005;79:11300–10.
                                          pmc: PMC1193634pubmed: 16103182
                                        9. Aguilar PV, Adams AP, Wang E. Structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence. J Virol 2008;82:4920–30.
                                          pmc: PMC2346730pubmed: 18353963
                                        10. Gardner CL, Yin J, Burke CW, Klimstra WB, Ryman KD. Type I interferon induction is correlated with attenuation of a South American eastern equine encephalitis virus strain in mice. Virology 2009;390:338–47.
                                          pmc: PMC3404509pubmed: 19539968
                                        11. Gardner CL, Burke CW, Tesfay MZ, Glass PJ, Klimstra WB, Ryman KD. Eastern and Venezuelan equine encephalitis viruses differ in their ability to infect dendritic cells and macrophages: impact of altered cell tropism on pathogenesis. J Virol 2008;82:10634–46.
                                          pmc: PMC2573165pubmed: 18768986
                                        12. Johnson KM, Shelokov A, Peralta PH, Dammin GJ, Young NA. Recovery of Venezuelan equine encephalomyelitis virus in Panama: a fatal case in man. Am J Trop Med Hyg 1968;17:432–40.
                                          pubmed: 5690051
                                        13. Franck PT, Johnson KM. An outbreak of Venezuelan encephalitis in man in the Panama Canal Zone. Am J Trop Med Hyg 1970;19:860–5.
                                          pubmed: 5453912
                                        14. Quiroz E, Aguilar PV, Cisneros J, Tesh RB, Weaver SC. Venezuelan equine encephalitis in Panama: fatal endemic disease and genetic diversity of etiologic viral strains. PLoS Negl Trop Dis 2009;3(6):e472.
                                          pmc: PMC2697379pubmed: 19564908
                                        15. Walton TE, Alvarez O Jr, Buckwalter RM, Johnson KM. Experimental infection of horses with enzootic and epizootic strains of Venezuelan equine encephalomyelitis virus. J Infect Dis 1973;128:271–82.
                                          pubmed: 4728689
                                        16. Obaldia N, Dutary B, Clavel F. Encefalomielitis equina del este, epizootic de 1986 en Panama. Notas Veterinarias. Assoc Panameña de Medicos Veterinarios 1991;1:4–7.
                                        17. Srihongse S, Galindo P. The isolation of eastern equine encephalitis virus from Culex (Melanoconion) taeniopus Dyar and Knab in Panama. Mosq News 1967;27:74–6.
                                        18. Beaty BJ, Calisher CH, Shope RE. Arbo-viruses. Diagnostic procedures for viral, rickettsial and chlamydial infections. 1995. In: Lennete ET, Lennete DA, editors. 7th American Public Health Association; Washington, DC. pp. 189–212.
                                        19. Johnson BW, Kosoy O, Wang E. Use of sindbis/eastern equine encephalitis chimeric viruses in plaque reduction neutralization tests for arboviral disease diagnostics. Clin Vaccine Immunol 2011;18:1486–91.
                                          pmc: PMC3165225pubmed: 21752946
                                        20. Sánchez-Seco MP, Rosario D, Quiroz E, Guzmán G, Tenorio A. A generic nested-RT-PCR followed by sequencing for detection and identification of members of the alphavirus genus. J Virol Methods 2001;95:153–61.
                                          pubmed: 11377722
                                        21. Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 2004;5:113.
                                          pmc: PMC517706pubmed: 15318951
                                        22. Swofford DL. PAUP*: Phylogenetic Analysis Using Parsimony (and Other Methods) Version 4. 1998. Sinauer Associates; Sunderland, MA.
                                        23. Anishchenko M, Bowen RA, Paessler S, Austgen L, Greene IP, Weaver SC. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation. Proc Natl Acad Sci U S A 2006;103:4994–9.
                                          pmc: PMC1458783pubmed: 16549790
                                        24. Brault AC, Powers AM, Ortiz D, Estrada-Franco JG, Navarro-Lopez R, Weaver SC. Venezuelan equine encephalitis emergence: enhanced vector infection from a single amino acid substitution in the envelope glycoprotein. Proc Natl Acad Sci U S A 2004;101:11344–9.
                                          pmc: PMC509205pubmed: 15277679
                                        25. Deresiewicz RL, Thaler SJ, Hsu L, Zamani AA. Clinical and neuroradiographic manifestations of eastern equine encephalitis. N Engl J Med 1997;336:1867–74.
                                          pubmed: 9197215
                                        26. Lury KM, Castillo M. Eastern equine encephalitis: CT and MRI findings in one case. Emerg Radiol 2004;11:46–8.
                                          pubmed: 15309665
                                        27. Piliero PJ, Brody J, Zamani A, Deresiewicz RL. Eastern equine encephalitis presenting as focal neuroradiographic abnormalities: case report and review. Clin Infect Dis 1994;18:985–8.
                                          pubmed: 8086564
                                        28. Arrigo NC, Adams AP, Watts DM, Newman PC, Weaver SC. Cotton rats and house sparrows as hosts for North and South American strains of eastern equine encephalitis virus. Emerg Infect Dis 2010;16:1373–80.
                                          pmc: PMC3294987pubmed: 20735920
                                        29. Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog 2007;3(12):e201.
                                          pmc: PMC2134949pubmed: 18069894
                                        30. Tsetsarkin KA, Weaver SC. Sequential adaptive mutations enhance efficient vector switching by chikungunya virus and its epidemic emergence. PLoS Pathog 2011;7(12):e1002412.
                                          pmc: PMC3234230pubmed: 22174678

                                        Citations

                                        This article has been cited 70 times.
                                        1. Corrales R, Díaz Y, Pineda V, Pitti Y, Saenz L, Carrera JP, Aguilar C, Martínez A, Chen-Germán M, Hanley KA, Vasilakis N, Tesh RB, Saldaña A, López-Vergès S. Seroprevalence of Arboviruses and Genetic Characterization of Orbiviruses in Sloths from Western Panama. Viruses 2025 Nov 17;17(11).
                                          doi: 10.3390/v17111507pubmed: 41305528google scholar: lookup
                                        2. Liu Y, Chen C, Liao B, Geng X, Huang W, Nie J. Development of in vitro and in vivo neutralization assays for New World alphaviruses based on the VSV pseudovirus system. Emerg Microbes Infect 2025 Dec;14(1):2555721.
                                          doi: 10.1080/22221751.2025.2555721pubmed: 40890032google scholar: lookup
                                        3. Piche-Ovares M, Mendoza MPG, Moreira-Soto A, Fischer C, Brünink S, Figueroa-Romero MD, Merino-Sarmiento NS, Marcelo-Ñique AI, Málaga-Trillo E, Gatty-Nogueira M, Cabezas Sanchez CA, Drexler JF. Venezuelan Equine Encephalitis, Peruvian Amazon, 2020. Emerg Infect Dis 2025 May;31(5):995-999.
                                          doi: 10.3201/eid3105.241694pubmed: 40305379google scholar: lookup
                                        4. Valles-Morera A, Murillo T, Lizano-Bolaños J, Gutierrez-Roche S, Alvarado M, Alfaro-Alvarado J, Calvo-Salas GA, Prado-Hidalgo G, Ortega J, Corrales-Aguilar E. Exposure to non-endemic arboviruses (alphaviruses) in Costa Rica assessed from human samples collected in areas with contrasting levels of dengue endemicity. Front Public Health 2025;13:1537019.
                                          doi: 10.3389/fpubh.2025.1537019pubmed: 40046122google scholar: lookup
                                        5. Parashar B, Malviya R, Sridhar SB, Wadhwa T, Talath S, Shareef J. Eastern equine encephalitis virus: Pathogenesis, immune response, and clinical manifestations. Infect Med (Beijing) 2025 Mar;4(1):100167.
                                          doi: 10.1016/j.imj.2025.100167pubmed: 40026316google scholar: lookup
                                        6. VanderGiessen M, de Jager C, Leighton J, Xie H, Theus M, Johnson E, Kehn-Hall K. Neurological manifestations of encephalitic alphaviruses, traumatic brain injuries, and organophosphorus nerve agent exposure. Front Neurosci 2024;18:1514940.
                                          doi: 10.3389/fnins.2024.1514940pubmed: 39734493google scholar: lookup
                                        7. Rivera LF, Lezcano-Coba C, Galué J, Rodriguez X, Juarez Y, de Souza WM, Capitan-Barrios Z, Valderrama A, Abrego L, Cedeño H, Jackman C, Waggoner JJ, Aguilar PV, Guzman H, Weaver SC, Tesh RB, López-Vèrges S, Donnelly CA, Estofolete CF, Nogueira ML, Faria NR, Vasilakis N, Vittor AY, Smith DR, Carrera JP. Characteristics of Madariaga and Venezuelan Equine Encephalitis Virus Infections, Panama. Emerg Infect Dis 2024;30(14):94-104.
                                          doi: 10.3201/eid3014.240182pubmed: 39530903google scholar: lookup
                                        8. Nurmukanova V, Matsvay A, Gordukova M, Shipulin G. Square the Circle: Diversity of Viral Pathogens Causing Neuro-Infectious Diseases. Viruses 2024 May 15;16(5).
                                          doi: 10.3390/v16050787pubmed: 38793668google scholar: lookup
                                        9. Fongsaran C, Jirakanwisal K, Peng BH, Fracassi A, Taglialatela G, Dineley KT, Paessler S, Cisneros IE. Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model. Brain Behav Immun Health 2024 Jul;38:100780.
                                          doi: 10.1016/j.bbih.2024.100780pubmed: 38706571google scholar: lookup
                                        10. Nguyen TL, Kim H. Designing a Multiepitope Vaccine against Eastern Equine Encephalitis Virus: Immunoinformatics and Computational Approaches. ACS Omega 2024 Jan 9;9(1):1092-1105.
                                          doi: 10.1021/acsomega.3c07322pubmed: 38222668google scholar: lookup
                                        11. Carrera J-P, Araúz D, Rojas A, Cardozo F, Stittleburg V, Morales Claro I, Galue J, Lezcano-Coba C, Romero Rebello Moreira F, -Rivera LF, Chen-Germán M, Moreno B, Capitan-Barrios Z, López-Vergès S, Pascale JM, Sabino EC, Valderrama A, Hanley KA, Donnelly CA, Vasilakis N, Faria NR, Waggoner JJ. Real-time RT-PCR for Venezuelan equine encephalitis complex, Madariaga, and Eastern equine encephalitis viruses: application in human and mosquito public health surveillance in Panama. J Clin Microbiol 2023 Dec 19;61(12):e0015223.
                                          doi: 10.1128/jcm.00152-23pubmed: 37982611google scholar: lookup
                                        12. Mukhopadhyay K, Sengupta M, Misra SC, Majee K. Trends in emerging vector-borne viral infections and their outcome in children over two decades. Pediatr Res 2024 Jan;95(2):464-479.
                                          doi: 10.1038/s41390-023-02866-xpubmed: 37880334google scholar: lookup
                                        13. Vasilakis N, Hanley KA. The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO). Zoonoses 2023;3(1).
                                          doi: 10.15212/zoonoses-2022-0047pubmed: 37860630google scholar: lookup
                                        14. Carrera JP, Galué J, de Souza WM, Torres-Cosme R, Lezcano-Coba C, Cumbrera A, Vasilakis N, Tesh RB, Guzman H, Weaver SC, Vittor AY, Samudio R, Miguel Pascale J, Valderrama A, Cáceres Carrera L, Donnelly CA, Faria NR. Madariaga and Venezuelan equine encephalitis virus seroprevalence in rodent enzootic hosts in Eastern and Western Panama. bioRxiv 2023 Aug 29;.
                                          doi: 10.1101/2023.08.28.555226pubmed: 37693579google scholar: lookup
                                        15. Bonilla-Aldana DK, Bonilla Carvajal CD, Moreno-Ramos E, Barboza JJ, Rodriguez-Morales AJ. Mapping Eastern (EEE) and Venezuelan Equine Encephalitides (VEE) among Equines Using Geographical Information Systems, Colombia, 2008-2019. Viruses 2023 Mar 8;15(3).
                                          doi: 10.3390/v15030707pubmed: 36992416google scholar: lookup
                                        16. Reyna RA, Weaver SC. Sequelae and Animal Modeling of Encephalitic Alphavirus Infections. Viruses 2023 Jan 28;15(2).
                                          doi: 10.3390/v15020382pubmed: 36851596google scholar: lookup
                                        17. Romero-Vega LM, Piche-Ovares M, Soto-Garita C, Barantes Murillo DF, Chaverri LG, Alfaro-Alarcón A, Corrales-Aguilar E, Troyo A. Seasonal changes in the diversity, host preferences and infectivity of mosquitoes in two arbovirus-endemic regions of Costa Rica. Parasit Vectors 2023 Jan 26;16(1):34.
                                          doi: 10.1186/s13071-022-05579-ypubmed: 36703148google scholar: lookup
                                        18. Kim AS, Diamond MS. A molecular understanding of alphavirus entry and antibody protection. Nat Rev Microbiol 2023 Jun;21(6):396-407.
                                          doi: 10.1038/s41579-022-00825-7pubmed: 36474012google scholar: lookup
                                        19. Fourie I, Snyman J, Williams J, Ismail A, Jansen van Vuren P, Venter M. Epidemiological and Genomic Characterisation of Middelburg and Sindbis Alphaviruses Identified in Horses with Febrile and Neurological Infections, South Africa (2014-2018). Viruses 2022 Sep 11;14(9).
                                          doi: 10.3390/v14092013pubmed: 36146819google scholar: lookup
                                        20. Löscher W, Howe CL. Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection. Front Mol Neurosci 2022;15:870868.
                                          doi: 10.3389/fnmol.2022.870868pubmed: 35615063google scholar: lookup
                                        21. Coates EE, Edupuganti S, Chen GL, Happe M, Strom L, Widge A, Florez MB, Cox JH, Gordon I, Plummer S, Ola A, Yamshchikov G, Andrews C, Curate-Ingram S, Morgan P, Nagar S, Collins MH, Bray A, Nguyen T, Stein J, Case CL, Kaltovich F, Wycuff D, Liang CJ, Carlton K, Vazquez S, Mascola JR, Ledgerwood JE. Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial. Lancet Infect Dis 2022 Aug;22(8):1210-1220.
                                          doi: 10.1016/S1473-3099(22)00052-4pubmed: 35568049google scholar: lookup
                                        22. Tian L, Pang Z, Li M, Lou F, An X, Zhu S, Song L, Tong Y, Fan H, Fan J. Molnupiravir and Its Antiviral Activity Against COVID-19. Front Immunol 2022;13:855496.
                                          doi: 10.3389/fimmu.2022.855496pubmed: 35444647google scholar: lookup
                                        23. Moreira Marrero L, Botto Nuñez G, Frabasile S, Delfraro A. Alphavirus Identification in Neotropical Bats. Viruses 2022 Jan 28;14(2).
                                          doi: 10.3390/v14020269pubmed: 35215862google scholar: lookup
                                        24. Ortiz DI, Piche-Ovares M, Romero-Vega LM, Wagman J, Troyo A. The Impact of Deforestation, Urbanization, and Changing Land Use Patterns on the Ecology of Mosquito and Tick-Borne Diseases in Central America. Insects 2021 Dec 23;13(1).
                                          doi: 10.3390/insects13010020pubmed: 35055864google scholar: lookup
                                        25. Fourie I, Williams J, Ismail A, Jansen van Vuren P, Stoltz A, Venter M. Detection and genome characterization of Middelburg virus strains isolated from CSF and whole blood samples of humans with neurological manifestations in South Africa. PLoS Negl Trop Dis 2022 Jan;16(1):e0010020.
                                          doi: 10.1371/journal.pntd.0010020pubmed: 34979534google scholar: lookup
                                        26. Gil LHVG, Magalhaes T, Santos BSAS, Oliveira LV, Oliveira-Filho EF, Cunha JLR, Fraiha ALS, Rocha BMM, Longo BC, Ecco R, Faria GC, Furtini R, Drumond SRM, Maranhão RPA, Lobato ZIP, Guedes MIMC, Teixeira RBC, Costa EA. Active Circulation of Madariaga Virus, a Member of the Eastern Equine Encephalitis Virus Complex, in Northeast Brazil. Pathogens 2021 Aug 3;10(8).
                                          doi: 10.3390/pathogens10080983pubmed: 34451447google scholar: lookup
                                        27. Hasan SS, Dey D, Singh S, Martin M. The Structural Biology of Eastern Equine Encephalitis Virus, an Emerging Viral Threat. Pathogens 2021 Jul 31;10(8).
                                          doi: 10.3390/pathogens10080973pubmed: 34451437google scholar: lookup
                                        28. Gutiérrez-Vera E, Patiño L, Castillo-Segovia M, Mora-Valencia V, Montesdeoca-Agurto J, Regato-Arrata M. Seroprevalence of arboviruses in Ecuador: Implications for improved surveillance. Biomedica 2021 Jun 29;41(2):247-259.
                                          doi: 10.7705/biomedica.5623pubmed: 34214266google scholar: lookup
                                        29. Li Y, O'Donnell AC, Ochman H. Discriminating arboviral species. J Gen Virol 2021 Apr;102(4).
                                          doi: 10.1099/jgv.0.001572pubmed: 33830905google scholar: lookup
                                        30. Read CM, Plante K, Rafael G, Rossi SL, Braun W, Weaver SC, Schein CH. Designing multivalent immunogens for alphavirus vaccine optimization. Virology 2021 Sep;561:117-124.
                                          doi: 10.1016/j.virol.2020.11.010pubmed: 33823988google scholar: lookup
                                        31. Carrera JP, Cucunubá ZM, Neira K, Lambert B, Pittí Y, Liscano J, Garzón JL, Beltran D, Collado-Mariscal L, Saenz L, Sosa N, Rodriguez-Guzman LD, González P, Lescano AG, Pereyra-Elías R, Valderrama A, Weaver SC, Vittor AY, Armién B, Pascale JM, Donnelly CA. Endemic and Epidemic Human Alphavirus Infections in Eastern Panama: An Analysis of Population-Based Cross-Sectional Surveys. Am J Trop Med Hyg 2020 Dec;103(6):2429-2437.
                                          doi: 10.4269/ajtmh.20-0408pubmed: 33124532google scholar: lookup
                                        32. Carrera JP, Pittí Y, Molares-Martínez JC, Casal E, Pereyra-Elias R, Saenz L, Guerrero I, Galué J, Rodriguez-Alvarez F, Jackman C, Pascale JM, Armien B, Weaver SC, Donnelly CA, Vittor AY. Clinical and Serological Findings of Madariaga and Venezuelan Equine Encephalitis Viral Infections: A Follow-up Study 5 Years After an Outbreak in Panama. Open Forum Infect Dis 2020 Sep;7(9):ofaa359.
                                          doi: 10.1093/ofid/ofaa359pubmed: 33005697google scholar: lookup
                                        33. Clé M, Eldin P, Briant L, Lannuzel A, Simonin Y, Van de Perre P, Cabié A, Salinas S. Neurocognitive impacts of arbovirus infections. J Neuroinflammation 2020 Aug 10;17(1):233.
                                          doi: 10.1186/s12974-020-01904-3pubmed: 32778106google scholar: lookup
                                        34. Azar SR, Campos RK, Bergren NA, Camargos VN, Rossi SL. Epidemic Alphaviruses: Ecology, Emergence and Outbreaks. Microorganisms 2020 Aug 1;8(8).
                                          doi: 10.3390/microorganisms8081167pubmed: 32752150google scholar: lookup
                                        35. Baxter VK, Heise MT. Immunopathogenesis of alphaviruses. Adv Virus Res 2020;107:315-382.
                                          doi: 10.1016/bs.aivir.2020.06.002pubmed: 32711733google scholar: lookup
                                        36. More S, Bøtner A, Butterworth A, Calistri P, Depner K, Edwards S, Garin-Bastuji B, Good M, Gortázar Schmidt C, Michel V, Miranda MA, Nielsen SS, Raj M, Sihvonen L, Spoolder H, Stegeman JA, Thulke HH, Velarde A, Willeberg P, Winckler C, Baldinelli F, Broglia A, Dhollander S, Beltrán-Beck B, Kohnle L, Morgado J, Bicout D. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): Venezuelan equine encephalitis. EFSA J 2017 Aug;15(8):e04950.
                                          doi: 10.2903/j.efsa.2017.4950pubmed: 32625617google scholar: lookup
                                        37. More S, Bøtner A, Butterworth A, Calistri P, Depner K, Edwards S, Garin-Bastuji B, Good M, Gortázar Schmidt C, Michel V, Miranda MA, Nielsen SS, Raj M, Sihvonen L, Spoolder H, Stegeman JA, Thulke HH, Velarde A, Willeberg P, Winckler C, Baldinelli F, Broglia A, Dhollander S, Beltrán-Beck B, Kohnle L, Morgado J, Bicout D. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): equine encephalomyelitis (Eastern and Western). EFSA J 2017 Jul;15(7):e04946.
                                          doi: 10.2903/j.efsa.2017.4946pubmed: 32625598google scholar: lookup
                                        38. Stromberg ZR, Fischer W, Bradfute SB, Kubicek-Sutherland JZ, Hraber P. Vaccine Advances against Venezuelan, Eastern, and Western Equine Encephalitis Viruses. Vaccines (Basel) 2020 Jun 3;8(2).
                                          doi: 10.3390/vaccines8020273pubmed: 32503232google scholar: lookup
                                        39. Sandrock C, Aziz SR. Travel/Tropical Medicine and Pandemic Considerations for the Global Surgeon. Oral Maxillofac Surg Clin North Am 2020 Aug;32(3):407-425.
                                          doi: 10.1016/j.coms.2020.05.001pubmed: 32473858google scholar: lookup
                                        40. Gomes FA, Jansen AM, Machado RZ, Jesus Pena HF, Fumagalli MJ, Silva A, Alves BF, Roque ALR, Moraes Figueiredo LT. Serological evidence of arboviruses and coccidia infecting horses in the Amazonian region of Brazil. PLoS One 2019;14(12):e0225895.
                                          doi: 10.1371/journal.pone.0225895pubmed: 31830142google scholar: lookup
                                        41. Pérez JG, Carrera JP, Serrano E, Pittí Y, Maguiña JL, Mentaberre G, Lescano AG, Valderrama A, Mayor P. Serologic Evidence of Zoonotic Alphaviruses in Humans from an Indigenous Community in the Peruvian Amazon. Am J Trop Med Hyg 2019 Dec;101(6):1212-1218.
                                          doi: 10.4269/ajtmh.18-0850pubmed: 31571566google scholar: lookup
                                        42. Barba M, Fairbanks EL, Daly JM. Equine viral encephalitis: prevalence, impact, and management strategies. Vet Med (Auckl) 2019;10:99-110.
                                          doi: 10.2147/VMRR.S168227pubmed: 31497528google scholar: lookup
                                        43. Stechina OS, Oria GI, Torres C, Diaz LA, Contigiani M, Stein M. First Detection of Madariaga virus in Mosquitoes Collected in a Wild Environment of Northeastern Argentina. Am J Trop Med Hyg 2019 Oct;101(4):916-918.
                                          doi: 10.4269/ajtmh.19-0475pubmed: 31482786google scholar: lookup
                                        44. Jonsson CB, Cao X, Lee J, Gabbard JD, Chu YK, Fitzpatrick EA, Julander J, Chung DH, Stabenow J, Golden JE. Efficacy of a ML336 derivative against Venezuelan and eastern equine encephalitis viruses. Antiviral Res 2019 Jul;167:25-34.
                                        45. Cho JJ, Wong JK, Henkel J, DeJesus RO, Nazario-Lopez B. Acute Seroconversion of Eastern Equine Encephalitis Coinfection With California Serogroup Encephalitis Virus. Front Neurol 2019;10:242.
                                          doi: 10.3389/fneur.2019.00242pubmed: 30941092google scholar: lookup
                                        46. Lednicky JA, White SK, Mavian CN, El Badry MA, Telisma T, Salemi M, OKech BA, Beau De Rochars VM, Morris JG Jr. Emergence of Madariaga virus as a cause of acute febrile illness in children, Haiti, 2015-2016. PLoS Negl Trop Dis 2019 Jan;13(1):e0006972.
                                          doi: 10.1371/journal.pntd.0006972pubmed: 30629592google scholar: lookup
                                        47. Hasan SS, Sun C, Kim AS, Watanabe Y, Chen CL, Klose T, Buda G, Crispin M, Diamond MS, Klimstra WB, Rossmann MG. Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization. Cell Rep 2018 Dec 11;25(11):3136-3147.e5.
                                          doi: 10.1016/j.celrep.2018.11.067pubmed: 30540945google scholar: lookup
                                        48. Pouch SM, Katugaha SB, Shieh WJ, Annambhotla P, Walker WL, Basavaraju SV, Jones J, Huynh T, Reagan-Steiner S, Bhatnagar J, Grimm K, Stramer SL, Gabel J, Lyon GM, Mehta AK, Kandiah P, Neujahr DC, Javidfar J, Subramanian RM, Parekh SM, Shah P, Cooper L, Psotka MA, Radcliffe R, Williams C, Zaki SR, Staples JE, Fischer M, Panella AJ, Lanciotti RS, Laven JJ, Kosoy O, Rabe IB, Gould CV. Transmission of Eastern Equine Encephalitis Virus From an Organ Donor to 3 Transplant Recipients. Clin Infect Dis 2019 Jul 18;69(3):450-458.
                                          doi: 10.1093/cid/ciy923pubmed: 30371754google scholar: lookup
                                        49. Carrera JP, Bagamian KH, Travassos da Rosa AP, Wang E, Beltran D, Gundaker ND, Armien B, Arroyo G, Sosa N, Pascale JM, Valderrama A, Tesh RB, Vittor AY, Weaver SC. Human and Equine Infection with Alphaviruses and Flaviviruses in Panamá during 2010: A Cross-Sectional Study of Household Contacts during an Encephalitis Outbreak. Am J Trop Med Hyg 2018 Jun;98(6):1798-1804.
                                          doi: 10.4269/ajtmh.17-0679pubmed: 29737271google scholar: lookup
                                        50. Blohm GM, Lednicky JA, White SK, Mavian CN, Márquez MC, González-García KP, Salemi M, Morris JG Jr, Paniz-Mondolfi AE. Madariaga Virus: Identification of a Lineage III Strain in a Venezuelan Child With Acute Undifferentiated Febrile Illness, in the Setting of a Possible Equine Epizootic. Clin Infect Dis 2018 Aug 1;67(4):619-621.
                                          doi: 10.1093/cid/ciy224pubmed: 29718127google scholar: lookup
                                        51. Burgueño A, Frabasile S, Díaz LA, Cabrera A, Pisano MB, Rivarola ME, Contigiani M, Delfraro A. Genomic Characterization and Seroprevalence Studies on Alphaviruses in Uruguay. Am J Trop Med Hyg 2018 Jun;98(6):1811-1818.
                                          doi: 10.4269/ajtmh.17-0980pubmed: 29633690google scholar: lookup
                                        52. Tan Y, Lam TT, Heberlein-Larson LA, Smole SC, Auguste AJ, Hennigan S, Halpin RA, Fedorova N, Puri V, Stockwell TB, Shilts MH, Andreadis T, Armstrong PM, Tesh RB, Weaver SC, Unnasch TR, Ciota AT, Kramer LD, Das SR. Large-Scale Complete-Genome Sequencing and Phylodynamic Analysis of Eastern Equine Encephalitis Virus Reveals Source-Sink Transmission Dynamics in the United States. J Virol 2018 Jun 15;92(12).
                                          doi: 10.1128/JVI.00074-18pubmed: 29618651google scholar: lookup
                                        53. Smith JL, Pugh CL, Cisney ED, Keasey SL, Guevara C, Ampuero JS, Comach G, Gomez D, Ochoa-Diaz M, Hontz RD, Ulrich RG. Human Antibody Responses to Emerging Mayaro Virus and Cocirculating Alphavirus Infections Examined by Using Structural Proteins from Nine New and Old World Lineages. mSphere 2018 Mar-Apr;3(2).
                                          doi: 10.1128/mSphere.00003-18pubmed: 29577083google scholar: lookup
                                        54. Torres R, Samudio R, Carrera JP, Young J, Márquez R, Hurtado L, Weaver S, Chaves LF, Tesh R, Cáceres L. Enzootic mosquito vector species at equine encephalitis transmission foci in the República de Panamá. PLoS One 2017;12(9):e0185491.
                                          doi: 10.1371/journal.pone.0185491pubmed: 28937995google scholar: lookup
                                        55. Ronca SE, Smith J, Koma T, Miller MM, Yun N, Dineley KT, Paessler S. Mouse Model of Neurological Complications Resulting from Encephalitic Alphavirus Infection. Front Microbiol 2017;8:188.
                                          doi: 10.3389/fmicb.2017.00188pubmed: 28223982google scholar: lookup
                                        56. Ronca SE, Dineley KT, Paessler S. Neurological Sequelae Resulting from Encephalitic Alphavirus Infection. Front Microbiol 2016;7:959.
                                          doi: 10.3389/fmicb.2016.00959pubmed: 27379085google scholar: lookup
                                        57. Vittor AY, Armien B, Gonzalez P, Carrera JP, Dominguez C, Valderrama A, Glass GE, Beltran D, Cisneros J, Wang E, Castillo A, Moreno B, Weaver SC. Epidemiology of Emergent Madariaga Encephalitis in a Region with Endemic Venezuelan Equine Encephalitis: Initial Host Studies and Human Cross-Sectional Study in Darien, Panama. PLoS Negl Trop Dis 2016 Apr;10(4):e0004554.
                                          doi: 10.1371/journal.pntd.0004554pubmed: 27101567google scholar: lookup
                                        58. Eastwood G, Loaiza JR, Pongsiri MJ, Sanjur OI, Pecor JE, Auguste AJ, Kramer LD. Enzootic Arbovirus Surveillance in Forest Habitat and Phylogenetic Characterization of Novel Isolates of Gamboa Virus in Panama. Am J Trop Med Hyg 2016 Apr;94(4):786-93.
                                          doi: 10.4269/ajtmh.15-0445pubmed: 26834200google scholar: lookup
                                        59. Beatman EL, Massey A, Shives KD, Burrack KS, Chamanian M, Morrison TE, Beckham JD. Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain. J Virol 2015 Dec 30;90(6):2767-82.
                                          doi: 10.1128/JVI.02949-15pubmed: 26719256google scholar: lookup
                                        60. Silva MLCR, Auguste AJ, Terzian ACB, Vedovello D, Riet-Correa F, Macário VMK, Mourão MPG, Ullmann LS, Araújo JP Jr, Weaver SC, Nogueira ML. Isolation and Characterization of Madariaga Virus from a Horse in Paraíba State, Brazil. Transbound Emerg Dis 2017 Jun;64(3):990-993.
                                          doi: 10.1111/tbed.12441pubmed: 26608567google scholar: lookup
                                        61. Honnold SP, Mossel EC, Bakken RR, Lind CM, Cohen JW, Eccleston LT, Spurgers KB, Erwin-Cohen R, Glass PJ, Maheshwari RK. Eastern equine encephalitis virus in mice II: pathogenesis is dependent on route of exposure. Virol J 2015 Sep 30;12:154.
                                          doi: 10.1186/s12985-015-0385-2pubmed: 26423229google scholar: lookup
                                        62. Honnold SP, Mossel EC, Bakken RR, Fisher D, Lind CM, Cohen JW, Eccleston LT, Spurgers KB, Erwin-Cohen R, Bradfute SB, Maheshwari RK, Glass PJ. Eastern equine encephalitis virus in mice I: clinical course and outcome are dependent on route of exposure. Virol J 2015 Sep 29;12:152.
                                          doi: 10.1186/s12985-015-0386-1pubmed: 26420265google scholar: lookup
                                        63. Carrera JP, Guzman H, Beltrán D, Díaz Y, López-Vergès S, Torres-Cosme R, Popov V, Widen SG, Wood TG, Weaver SC, Cáceres-Carrera L, Vasilakis N, Tesh RB. Mercadeo Virus: A Novel Mosquito-Specific Flavivirus from Panama. Am J Trop Med Hyg 2015 Nov;93(5):1014-9.
                                          doi: 10.4269/ajtmh.15-0117pubmed: 26304915google scholar: lookup
                                        64. Luciani K, Abadía I, Martínez-Torres AO, Cisneros J, Guerra I, García M, Estripeaut D, Carrera JP. Madariaga virus infection associated with a case of acute disseminated encephalomyelitis. Am J Trop Med Hyg 2015 Jun;92(6):1130-2.
                                          doi: 10.4269/ajtmh.14-0845pubmed: 25870420google scholar: lookup
                                        65. Barraza SJ, Delekta PC, Sindac JA, Dobry CJ, Xiang J, Keep RF, Miller DJ, Larsen SD. Discovery of anthranilamides as a novel class of inhibitors of neurotropic alphavirus replication. Bioorg Med Chem 2015 Apr 1;23(7):1569-87.
                                          doi: 10.1016/j.bmc.2015.01.054pubmed: 25740634google scholar: lookup
                                        66. Voss K, Amaya M, Mueller C, Roberts B, Kehn-Hall K, Bailey C, Petricoin E 3rd, Narayanan A. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells. Virology 2014 Nov;468-470:490-503.
                                          doi: 10.1016/j.virol.2014.09.005pubmed: 25261871google scholar: lookup
                                        67. Honnold SP, Bakken RR, Fisher D, Lind CM, Cohen JW, Eccleston LT, Spurgers KB, Maheshwari RK, Glass PJ. Second generation inactivated eastern equine encephalitis virus vaccine candidates protect mice against a lethal aerosol challenge. PLoS One 2014;9(8):e104708.
                                          doi: 10.1371/journal.pone.0104708pubmed: 25116127google scholar: lookup
                                        68. Trobaugh DW, Ryman KD, Klimstra WB. Can understanding the virulence mechanisms of RNA viruses lead us to a vaccine against eastern equine encephalitis virus and other alphaviruses?. Expert Rev Vaccines 2014 Dec;13(12):1423-5.
                                          doi: 10.1586/14760584.2014.944168pubmed: 25073901google scholar: lookup
                                        69. Wolfe DN, Heppner DG, Gardner SN, Jaing C, Dupuy LC, Schmaljohn CS, Carlton K. Current strategic thinking for the development of a trivalent alphavirus vaccine for human use. Am J Trop Med Hyg 2014 Sep;91(3):442-50.
                                          doi: 10.4269/ajtmh.14-0055pubmed: 24842880google scholar: lookup
                                        70. Navia-Gine WG, Loaiza JR, Miller MJ. Mosquito-host interactions during and after an outbreak of equine viral encephalitis in Eastern Panama. PLoS One 2013;8(12):e81788.
                                          doi: 10.1371/journal.pone.0081788pubmed: 24339965google scholar: lookup