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Chapter 55 : Alphaviruses

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Abstract:

The alphaviruses are principally mosquito-borne, positive-strand RNA viruses in the family that exhibit a broad range of pathogenicity in humans and animals (1, 2). Members of the genus are distributed worldwide in diverse ecological niches, where they are usually maintained in cycles between mosquitoes and birds or mammals. While human infections generally are incidental to the transmission cycles, in some instances human-mosquito-human cycles can maintain transmission and lead to large outbreaks and epidemics. Among the 24 alphaviruses listed in Table 1, 16 have been associated with human illness. Clinically, these manifest most commonly as polyarthralgia, often accompanied by fever and/or rash, or as central nervous system (CNS) infections. In addition to the alphaviruses circulating between mosquitoes and vertebrate hosts, a single example of an alphavirus, restricted to mosquitoes, has recently been described, Eilat virus (EILV) (3), and there are two known aquatic species, southern elephant seal virus (SESV) and salmon pancreatic disease virus (SPDV), that are likely to have lice as vectors (4, 5). This chapter reviews general aspects of the virology, pathogenesis, laboratory diagnosis, and prevention of the alphavirus infections, followed by more detailed discussion of those that cause human disease.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 1
FIGURE 1

Phylogenetic tree of the alphavirus species and selected variants based on the structural protein (E2, 6K, E1) amino acid sequences constructed using Bayesian methods and midpoint rooting. Terminal nodes are labeled by virus species, subtype, or variant, in parentheses. The dashed line indicates the point at which ancestors of Sindbis and Madariaga viruses recombined to form the recombinant WEEV group. All posterior probabilities were 1 except nodes with a symbol had posterior probabilities less than 0.9 and nodes with a had no posterior support. Adapted from reference with permission.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 2
FIGURE 2

Ross River virus (RRV): (Left) Cryoelectron microscopic image reconstruction of RRV showing the flower-like envelope protein spikes, virion membrane, and nucleocapsid core. (Right) Relationships of spike and capsid proteins and virion RNA. Courtesy of R. J. Kuhn.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 3
FIGURE 3

Schematic diagram of alphavirus genome [positive (+) sense RNA with poly(A) (A) tail and 5′ terminal cap (CAP); viral complementary RNA (vcRNA) of negative (-) sense; and subgenomic mRNA of positive sense]. Viral nonstructural proteins are translated from the 5′ two-thirds region of the genome, yielding polyprotein intermediates and nonstructural proteins nsP1 to nsP4. RNA is replicated into negative-sense RNA templates and transcribed into 26S subgenomic RNA. Cotranslational processing of the subgenomic mRNA yields the three principal structural proteins: capsid and envelope glycoproteins (E1 and E2). ORF, open reading frame; nt, nucleotide.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 4
FIGURE 4

Replication of alphaviruses. After binding to the cell membrane (step 1), virions are taken up in endocytic vesicles (steps 2 and 3). The virion and vesicular membranes fuse, releasing the nucleocapsid (step 4). The viral nucleocapsid binds to a ribosome (step 5) and is uncoated, freeing viral RNA (step 6) from the individual capsid (gray dots). Positive-sense viral RNA (heavy line) is replicated (step 7), producing complementary negative-sense RNA (gray line) (step 8), which, in turn, is transcribed to full-length genomic positive-sense RNA (step 9) or subgenomic RNA (step 10). Nonstructural proteins (nsp) are translated from genomic RNA. Subgenomic RNA is translated to produce capsid proteins (black dots) and envelope proteins, which are modified before insertion into the cell membrane (gray bars) (step 11). Genomic RNA is packaged with capsid proteins into nucleocapsid cores (step 12); capsid and E2 proteins associate (step 13) prior to viral budding (step 14).

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 5
FIGURE 5

Reported cases of EEE among humans in the United States, 2004 to 2013. The reported incidence is highest in Florida, where equine cases are reported perennially from the northeastern coast and throughout the peninsula. Relatively constant inland foci of transmission have been identified in upstate New York, southwestern Michigan, northeastern Indiana, and southcentral Georgia. In Massachusetts, human cases have been reported almost entirely from the eastern counties and, in New Jersey, from the southern counties. Reprinted from the CDC at http://www.cdc.gov/easternequineencephalitis/tech/epi/html.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 7
FIGURE 7

Reported cases of EEE by month, United States, 2003–2015. Data from reference .

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 6
FIGURE 6

Schematic diagram of the EEE transmission cycle; solid lines show known portions, and broken lines show speculative portions. The principal enzootic mosquito vector, transmits the virus among birds and occasionally initiates an outbreak among pheasants or other captive birds. Various other species bridge the enzootic cycle to infect humans and horses, which are dead-end hosts; the principal species include found in salt marsh coastal habitat; associated with open meadows and flooded ground pools; associated with woodland pools; and found in open freshwater swamps with emerging vegetation. The viral overwintering mechanism is unknown but potentially includes vertically infected mosquitoes, persistently infected birds, and other vertebrates.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 8
FIGURE 8

Geographic distribution of VEE epizootics and sylvatic viral subtypes.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 9
FIGURE 9

Life cycles of Venezuelan equine encephalitis virus. (A) Sylvatic VEEVs circulate continuously in silent tropical and subtropical foci among () mosquitoes and small mammals or aquatic birds. Humans (e.g., soldiers on jungle bivouacs) are infected when they chance upon transmission foci. Bridging vectors (e.g., ) that feed on viremic vertebrates in a sylvatic focus can carry the virus to nearby areas of human activity. (B) In contrast to the continuous cycling of sylvatic VEEV subtypes, epizootic VEEV had never been isolated until recently, except during periodic outbreaks. Once introduced, epizootic viruses are rapidly amplified among equines (horses and burros). Equines develop high viremia levels, so various mosquito species can function as biological vectors (only some important species are shown), and other biting insects, such as blackflies, can spread the virus mechanically. Humans develop illness with high viremia levels but probably have an insignificant role, if any, in viral amplification. Transmission declines as susceptible equines are exhausted by natural infection or immunization. It is speculated that epizootic IC viruses arise by mutation from sylvatic ID viruses; the subpopulation circulates in a sylvatic cycle and under appropriate conditions is amplified, leading to epizootic and epidemic spread.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 10
FIGURE 10

Origin, spread, and distribution of chikungunya virus and its vectors showing the African origins of enzootic chikungunya virus strains and the patterns of emergence and spread of the Asian lineage and Indian Ocean lineage (IOL) of the virus and the distributions of and . ECSA denotes eastern, central, and southern African. Reprinted from reference with permission.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 11
FIGURE 11

Small papular lesions seen in Sindbis (Ockelbo) fever. Courtesy of B. Niklasson.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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Image of FIGURE 12
FIGURE 12

Notifications and notification rates of RRV infections, Australia, 2005–2006, by Statistical Division of residence. Reprinted from reference with permission.

Citation: Smith D, Mackenzie J, Frolov I, Weaver S. 2017. Alphaviruses, p 1347-1379. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch55
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References

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1. Strauss JH, Strauss EG. 1994. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58:491562.[PubMed]
2. Weaver SC, Frey TK, Huang HV, Kinney RM, Rice CM, Roehrig JT, Shope RE, Strauss EG,. 2005. Family Togaviridae, p 9991008. In Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA (ed), Virus Taxonomy: Classification and Nomenclature of Viruses. Eighth Report of the International Committee on Taxonomy of Viruses. Academic Press, San Diego, CA.
3. Weaver SC, Lecuit M. 2015. Chikungunya virus and the global spread of a mosquito-borne disease. N Engl J Med 372:12311239.[PubMed]
4. Weaver SC, Reisen WK. 2010. Present and future arboviral threats. Antiviral Res 85:328345.[PubMed]
5. Calisher CH. 1994. Medically important arboviruses of the United States and Canada. Clin Microbiol Rev 7:89116.[PubMed]
6. Wolstenholme J. 1993. Ross River virus disease—the first recorded outbreak? Aust N Z J Med 23:417418.[PubMed]
7. Nasar F, Palacios G, Gorchakov RV, Guzman H, Da Rosa AP, Savji N, Popov VL, Sherman MB, Lipkin WI, Tesh RB, Weaver SC. 2012. Eilat virus, a unique alphavirus with host range restricted to insects by RNA replication. Proc Natl Acad Sci USA 109:1462214627.[PubMed]
8. Forrester NL, Palacios G, Tesh RB, Savji N, Guzman H, Sherman M, Weaver SC, Lipkin WI. 2012. Genome-scale phylogeny of the alphavirus genus suggests a marine origin. J Virol 86:27292738.[PubMed]
9. Pisano MB, Oria G, Beskow G, Aguilar J, Konigheim B, Cacace ML, Aguirre L, Stein M, Contigiani MS. 2013. Venezuelan equine encephalitis viruses (VEEV) in Argentina: serological evidence of human infection. PLoS Negl Trop Dis 7:e2551.[PubMed]
10. Weaver SC, Brault AC, Kang W, Holland JJ. 1999. Genetic and fitness changes accompanying adaptation of an arbovirus to vertebrate and invertebrate cells. J Virol 73:43164326.[PubMed]
11. Gould EA, Coutard B, Malet H, Morin B, Jamal S, Weaver S, Gorbalenya A, Moureau G, Baronti C, Delogu I, Forrester N, Khasnatinov M, Gritsun T, de Lamballerie X, Canard B. 2010. Understanding the alphaviruses: recent research on important emerging pathogens and progress towards their control. Antiviral Res 87:111124.[PubMed]
12. Weaver SC, Kang W, Shirako Y, Rumenapf T, Strauss EG, Strauss JH. 1997. Recombinational history and molecular evolution of western equine encephalomyelitis complex alphaviruses. J Virol 71:613623.[PubMed]
13. Allison AB, Stallknecht DE, Holmes EC. 2015. Evolutionary genetics and vector adaptation of recombinant viruses of the western equine encephalitis antigenic complex provides new insights into alphavirus diversity and host switching. Virology 474:154162.[PubMed]
14. Bolling BG, Weaver SC, Tesh RB, Vasilakis N. 2015. Insect-specific virus discovery: significance for the arbovirus community. Viruses 7:49114928.[PubMed]
15. Arrigo NC, Adams AP, Weaver SC. 2010. Evolutionary patterns of eastern equine encephalitis virus in North versus South America suggest ecological differences and taxonomic revision. J Virol 84:10141025.[PubMed]
16. 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 369:732744.[PubMed]
17. Aguilar PV, Paessler S, Carrara AS, Baron S, Poast J, Wang E, Moncayo AC, Anishchenko M, Watts D, Tesh RB, Weaver SC. 2005. Variation in interferon sensitivity and induction among strains of eastern equine encephalitis virus. J Virol 79:1130011310.[PubMed]
18. Wang E, Barrera R, Boshell J, Ferro C, Freier JE, Navarro JC, Salas R, Vasquez C, Weaver SC. 1999. Genetic and phenotypic changes accompanying the emergence of epizootic subtype IC Venezuelan equine encephalitis viruses from an enzootic subtype ID progenitor. J Virol 73:42664271.[PubMed]
19. Weaver SC, Pfeffer M, Marriott K, Kang W, Kinney RM. 1999. Genetic evidence for the origins of Venezuelan equine encephalitis virus subtype IAB outbreaks. Am J Trop Med Hyg 60:441448.[PubMed]
20. Voss JE, Vaney MC, Duquerroy S, Vonrhein C, Girard-Blanc C, Crublet E, Thompson A, Bricogne G, Rey FA. 2010. Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature 468:709712.[PubMed]
21. Lescar J, Roussel A, Wien MW, Navaza J, Fuller SD, Wengler G, Wengler G, Rey FA. 2001. The Fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH. Cell 105:137148.[PubMed]
22. Zhang R, Hryc CF, Cong Y, Liu X, Jakana J, Gorchakov R, Baker ML, Weaver SC, Chiu W. 2011. 4.4 Å cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus. EMBO J 30:38543863.[PubMed]
23. Griffin DE, Levine B, Ubol S, Hardwick JM. 1994. The effects of alphavirus infection on neurons. Ann Neurol 35(Suppl):S23S27.[PubMed]
24. Griffin DE, Hardwick JM. 1997. Regulators of apoptosis on the road to persistent alphavirus infection. Annu Rev Microbiol 51:565592.[PubMed]
25. La Linn M, Eble JA, Lübken C, Slade RW, Heino J, Davies J, Suhrbier A. 2005. An arthritogenic alphavirus uses the alpha1beta1 integrin collagen receptor. Virology 336:229239.[PubMed]
26. van Duijl-Richter MKS, Hoornweg TE, Rodenhuis-Zybert IA, Smit JM. 2015. Early events in chikungunya virus infection—from virus cell binding to membrane fusion. Viruses 7:36473674.[PubMed]
27. Heil ML, Albee A, Strauss JH, Kuhn RJ. 2001. An amino acid substitution in the coding region of the E2 glycoprotein adapts Ross River virus to utilize heparan sulfate as an attachment moiety. J Virol 75:63036309.[PubMed]
28. Aguilar PV, Robich RM, Turell MJ, O'Guinn ML, Klein TA, Huaman A, Guevara C, Rios Z, Tesh RB, Watts DM, Olson J, Weaver SC. 2007. Endemic eastern equine encephalitis in the Amazon region of Peru. Am J Trop Med Hyg 76:293298.[PubMed]
29. Anderson BA. 1984. Focal neurologic signs in western equine encephalitis. Can Med Assoc J 130:10191021.[PubMed]
30. Anderson CR, Downs WG, Wattley GH, Ahin NW, Reese AA. 1957. Mayaro virus: a new human disease agent. II. Isolation from blood of patients in Trinidad, B.W.I. Am J Trop Med Hyg 6:10121016.[PubMed]
31. Tsetsarkin KA, Weaver SC. 2011. Sequential adaptive mutations enhance efficient vector switching by Chikungunya virus and its epidemic emergence. PLoS Pathog 7:e1002412.[PubMed]
32. Tsetsarkin KA, Chen R, Yun R, Rossi SL, Plante KS, Guerbois M, Forrester N, Perng GC, Sreekumar E, Leal G, Huang J, Mukhopadhyay S, Weaver SC. 2014. Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes albopictus mosquitoes. Nat Commun 5:4084.[PubMed]
33. Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S. 2007. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog 3:e201.[PubMed]
34. Tsetsarkin KA, Chen R, Sherman MB, Weaver SC. 2011. Chikungunya virus: evolution and genetic determinants of emergence. Curr Opin Virol 1:310317.[PubMed]
35. Uemura Y, Yang YH, Heldebrant CM, Takechi K, Yokoyama K. 1994. Inactivation and elimination of viruses during preparation of human intravenous immunoglobulin. Vox Sang 67:246254.[PubMed]
36. Harley D, Sleigh A, Ritchie S. 2001. Ross River virus transmission, infection, and disease: a cross-disciplinary review. Clin Microbiol Rev 14:909932.[PubMed]
37. de la Monte S, Castro F, Bonilla NJ, Gaskin de Urdaneta A, Hutchins GM. 1985. The systemic pathology of Venezuelan equine encephalitis virus infection in humans. Am J Trop Med Hyg 34:194202.[PubMed]
38. Trobaugh DW, Gardner CL, Sun C, Haddow AD, Wang E, Chapnik E, Mildner A, Weaver SC, Ryman KD, Klimstra WB. 2014. RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. Nature 506:245248.[PubMed]
39. Reynaud JM, Kim DY, Atasheva S, Rasalouskaya A, White JP, Diamond MS, Weaver SC, Frolova EI, Frolov I. 2015. IFIT1 Differentially interferes with translation and replication of alphavirus genomes and promotes induction of type I interferon. PLoS Pathog 11:e1004863.[PubMed]
40. Hyde JL, Gardner CL, Kimura T, White JP, Liu G, Trobaugh DW, Huang C, Tonelli M, Paessler S, Takeda K, Klimstra WB, Amarasinghe GK, Diamond MS. 2014. A viral RNA structural element alters host recognition of nonself RNA. Science 343:783787.[PubMed]
41. Griffin D, Levine B, Tyor W, Ubol S, Desprès P. 1997. The role of antibody in recovery from alphavirus encephalitis. Immunol Rev 159:155161.[PubMed]
42. Chen W, Foo SS, Sims NA, Herrero LJ, Walsh NC, Mahalingam S. 2015. Arthritogenic alphaviruses: new insights into arthritis and bone pathology. Trends Microbiol 23:3543.[PubMed]
43. Suhrbier A, Jaffar-Bandjee MC, Gasque P. 2012. Arthritogenic alphaviruses—an overview. Nat Rev Rheumatol 8:420429.[PubMed]
44. Fraser JR, Ratnamohan VM, Dowling JP, Becker GJ, Varigos GA. 1983. The exanthem of Ross River virus infection: histology, location of virus antigen and nature of inflammatory infiltrate. J Clin Pathol 36:12561263.[PubMed]
45. Hörling J, Vene S, Franzén C, Niklasson B. 1993. Detection of Ockelbo virus RNA in skin biopsies by polymerase chain reaction. J Clin Microbiol 31:20042009.[PubMed]
46. Clarris BJ, Doherty RL, Fraser JR, French EL, Muirden KD. 1975. Epidemic polyarthritis: a cytological, virological and immunochemical study. Aust N Z J Med 5:450457.[PubMed]
47. Suhrbier A, La Linn M. 2004. Clinical and pathologic aspects of arthritis due to Ross River virus and other alphaviruses. Curr Opin Rheumatol 16:374379.[PubMed]
48. Fraser JR. 1986. Epidemic polyarthritis and Ross River virus disease. Clin Rheum Dis 12:369388.[PubMed]
49. Sane J, Kurkela S, Lokki ML, Miettinen A, Helve T, Vaheri A, Vapalahti O. 2012. Clinical Sindbis alphavirus infection is associated with HLA-DRB1*01 allele and production of autoantibodies. Clin Infect Dis 55:358363.[PubMed]
50. Lidbury BA, Rulli NE, Musso CM, Cossetto SB, Zaid A, Suhrbier A, Rothenfluh HS, Rolph MS, Mahalingam S. 2011. Identification and characterization of a Ross River virus variant that grows persistently in macrophages, shows altered disease kinetics in a mouse model, and exhibits resistance to type I interferon. J Virol 85:56515663.[PubMed]
51. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, and National Institutes of Health. 2009. Biosafety in Microbiological and Biomedical Laboratories (BMBL), 5th ed. U.S. Government Printing Office, Washington, DC. http://www.cdc.gov/OD/ohs/biosfty/bmbl4/bmbl4toc.htm.
52. Scherer WF, Eddy GA, Monath TP The Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod-Borne Viruses. 1980. Laboratory safety for arboviruses and certain other viruses of vertebrates. Am J Trop Med Hyg 29:13591381.[PubMed]
53. Hall-Mendelin S, Ritchie SA, Johansen CA, Zborowski P, Cortis G, Dandridge S, Hall RA, van den Hurk AF. 2010. Exploiting mosquito sugar feeding to detect mosquito-borne pathogens. Proc Natl Acad Sci USA 107:1125511259.[PubMed]
54. Selvey LA, Donnelly JA, Lindsay MD, PottumarthyBoddu S, D'Abrera VC, Smith DW. 2014. Ross River virus infection surveillance in the Greater Perth Metropolitan area—has there been an increase in cases in the winter months? Commun Dis Intell Q Rep 38:E114E122.[PubMed]
55. Cashman P, Hueston L, Durrheim D, Massey P, Doggett S, Russell RC. 2008. Barmah Forest virus serology; implications for diagnosis and public health action. Commun Dis Intell Q Rep 32:263266.[PubMed]
56. Jardine A, Neville PJ, Lindsay MD. 2015. Proximity to mosquito breeding habitat and Ross River virus risk in the Peel region of Western Australia. Vector Borne Zoonotic Dis 15:141146.[PubMed]
57. Hoffmann AA, Ross PA, Rašić G. 2015. Wolbachia strains for disease control: ecological and evolutionary considerations. Evol Appl 8:751768.[PubMed]
58. Nasci RS, Wirtz RA, Brogdon WG,. 2016. Protection against mosquitoes, ticks, & other arthropods. p 9599. In Brunette GW (ed), CDC Health Information for International Travel 2016. Oxford University Press. New York, NY. 9599.
59. Brault AC, Powers AM, Chavez CL, Lopez RN, Cachón MF, Gutierrez LF, Kang W, Tesh RB, Shope RE, Weaver SC. 1999. Genetic and antigenic diversity among eastern equine encephalitis viruses from North, Central, and South America. Am J Trop Med Hyg 61:579586.[PubMed]
60. Grady GF, Maxfield HK, Hildreth SW, Timperi RJ Jr, Gilfillan RF, Rosenau BJ, Francy DB, Calisher CH, Marcus LC, Madoff MA. 1978. Eastern equine encephalitis in Massachusetts, 1957–1976. A prospective study centered upon analyses of mosquitoes. Am J Epidemiol 107:170178.[PubMed]
61. Centers for Disease Control and Prevention (CDC). 2006. Eastern equine encephalitis—New Hampshire and Massachusetts, August–September 2005. MMWR Morb Mortal Wkly Rep 55:697700.[PubMed]
62. Centers for Disease Control and Prevention. Arbonet: Eastern equine encephalitis. http://www.cdc.gov/EasternEquineEncephalitis/. Accessed 16 March 2016.
63. Goldfield M, Welsh JN, Taylor BF. 1968. The 1959 outbreak of Eastern encephalitis in New Jersey. 5. The inapparent infection:disease ratio. Am J Epidemiol 87:3233.[PubMed]
64. Bigler WJ, Lassing EB, Buff EE, Prather EC, Beck EC, Hoff GL. 1976. Endemic eastern equine encephalomyelitis in Florida: a twenty-year analysis, 1955–1974. Am J Trop Med Hyg 25:884890.[PubMed]
65. US Geological Survey. Disease maps. http://diseasemaps.usgs.gov. Accessed 21 March 2016.
66. Letson GW, Bailey RE, Pearson J, Tsai TF. 1993. Eastern equine encephalitis (EEE): a description of the 1989 outbreak, recent epidemiologic trends, and the association of rainfall with EEE occurrence. Am J Trop Med Hyg 49:677685.[PubMed]
67. Getting VA. 1941. Equine encephalomyelitis in Massachusetts. N Engl J Med 224:9991006.
68. Komar N, Spielman A. 1994. Emergence of eastern encephalitis in Massachusetts. Ann N Y Acad Sci 740(1 Disease in Ev):157168.[PubMed]
69. Hart KL, Keen D, Belle EA. 1964. An outbreak of eastern equine encephalomyelitis in Jamaica, West Indies. I. Description of human cases. Am J Trop Med Hyg 13:331334.[PubMed]
70. Federal Select Agent Program. http://www.selectagents.gov. Accessed 16 March 2016.
71. Bastian FO, Wende RD, Singer DB, Zeller RS. 1975. Eastern equine encephalomyelitis. Histopathologic and ultrastructural changes with isolation of the virus in a human case. Am J Clin Pathol 64:1013.[PubMed]
72. Garen PD, Tsai TF, Powers JM. 1999. Human eastern equine encephalitis: immunohistochemistry and ultrastructure. Mod Pathol 12:646652.[PubMed]
73. Jordan RA, Wagner JA, McCrumb FR. 1965. Eastern equine encephalitis: report of a case with autopsy. Am J Trop Med Hyg 14:470474.[PubMed]
74. Wesselhoeft C, Smith EC, Branch CF. 1938. Human encephalitis: eight fatal cases with four due to virus of equine encephalomyelitis. JAMA 111:17351741.
75. Przelomski MM, O'Rourke E, Grady GF, Berardi VP, Markley HG. 1988. Eastern equine encephalitis in Massachusetts: a report of 16 cases, 1970–1984. Neurology 38:736739.[PubMed]
76. Clarke DH. 1961. Two nonfatal human infections with the virus of eastern encephalitis. Am J Trop Med Hyg 10:6770.[PubMed]
77. Deresiewicz RL, Thaler SJ, Hsu L, Zamani AA. 1997. Clinical and neuroradiographic manifestations of eastern equine encephalitis. N Engl J Med 336:18671874.[PubMed]
78. Lambert AJ, Martin DA, Lanciotti RS. 2003. Detection of North American eastern and western equine encephalitis viruses by nucleic acid amplification assays. J Clin Microbiol 41:379385.[PubMed]
79. Wendell LC, Potter NS, Roth JL, Salloway SP, Thompson BB. 2013. Successful management of severe neuroinvasive eastern equine encephalitis. Neurocrit Care 19:111115.[PubMed]
80. Mukerji SS, Lam AD, Wilson MR. 2016. Eastern equine encephalitis treated with intravenous immunoglobulins. Neurohospitalist 6:2931.[PubMed]
81. Dickerman RW, Pinheiro FP, Oliva OF, Travassos da Rosa JF, Calisher CH. 1980. Eastern encephalitis virus from virgin forests of Northern Brazil. Bull Pan Am Health Organ 14:1521.[PubMed]
82. Silva ML, Galiza GJ, Dantas AF, Oliveira RN, Iamamoto K, Achkar SM, Riet-Correa F. 2011. Outbreaks of Eastern equine encephalitis in northeastern Brazil. J Vet Diagn Invest 23:570575.[PubMed]
83. Tikasingh ES, Ardoin P, Everard CO, Davies JB. 1973. Eastern equine encephalitis in Trinidad. Epidemiological investigations following two human cases of South American strain in Santa Cruz. Trop Geogr Med 25:355361.[PubMed]
84. Luciani K, Abadía I, Martínez-Torres AO, Cisneros J, Guerra I, García M, Estripeaut D, Carrera JP. 2015. Madariaga virus infection associated with a case of acute disseminated encephalomyelitis. Am J Trop Med Hyg 92:11301132.[PubMed]
85. Nolen-Walston R, Bedenice D, Rodriguez C, Rushton S, Bright A, Fecteau ME, Short D, Majdalany R, Tewari D, Pedersen D, Kiupel M, Maes R, Del Piero F. 2007. Eastern equine encephalitis in 9 South American camelids. J Vet Intern Med 21:846852.[PubMed]
86. Bianchi TI, Aviles G, Monath TP, Sabattini MS. 1993. Western equine encephalomyelitis: virulence markers and their epidemiologic significance. Am J Trop Med Hyg 49:322328.[PubMed]
87. Meehan PJ, Wells DL, Paul W, Buff E, Lewis A, Muth D, Hopkins R, Karabatsos N, Tsai TF. 2000. Epidemiological features of and public health response to a St. Louis encephalitis epidemic in Florida, 1990–1. Epidemiol Infect 125:181188.[PubMed]
88. Centers for Disease Control (CDC). 1988. Arboviral infections of the central nervous system—United States, 1987. MMWR Morb Mortal Wkly Rep 37:506508, 513–515.[PubMed]
89. Eklund CM. 1946. Human encephalitis of the Western equine type in Minnesota in 1941; clinical and epidemiological study of serologically positive cases. Am J Hyg 43:171193.[PubMed]
90. Leech RW, Harris JC, Johnson RM. 1981. 1975 encephalitis epidemic in North Dakota and western Minnesota. An epidemiologic, clinical, and neuropathologic study. Minn Med 64:545548.[PubMed]
91. Medovy H. 1976. The history of Western encephalomyelitis in Manitoba. Can J Public Health 67(Suppl 1):1314.[PubMed]
92. Fothergill LD, Holden M, Wyckoff RWG. 1939. Western equine encephalomyelitis in a laboratory worker. JAMA 113:206207.
93. Gold H, Hampil B. 1942. Equine encephalomyelitis in laboratory technician with recovery. Ann Intern Med 16:556559.
94. Davis JH. 1940. Equine encephalomyelitis (western type) in children: report of cases with residual atrophy of the brain. J Pediatr 16:591595.
95. Noran HH, Baker AB. 1943. Sequels of equine encephalomyelitis. Arch Neurol Psychiatry 49:398413.
96. Rozdilsky B, Robertson HE, Chorney J. 1968. Western encephalitis: report of eight fatal cases. Saskatchewan epidemic, 1965. Can Med Assoc J 98:7986.[PubMed]
97. Palmer RJ, Finley KH. 1956. Sequelae of encephalitis: report of a study after the California epidemic. Calif Med 84:98100.[PubMed]
98. Shinefield HR, Townsend TE. 1953. Transplacental transmission of western equine encephalomyelitis. J Pediatr 43:2125.[PubMed]
99. Mulder DW, Parrott M, Thaler M. 1951. Sequelae of western equine encephalitis. Neurology 1:318327.[PubMed]
100. Copps SC, Giddings LE. 1959. Transplacental transmission of western equine encephalitis; report of a case. Pediatrics 24:3133.[PubMed]
101. Sciple GW, Ray G, LaMotte LC, Holden P, Gardner P, Crane G, Bublis MD. 1967. Western encephalitis with recovery of virus from cerebrospinal fluid. Neurology 17:169171.[PubMed]
102. Bia FJ, Thornton GF, Main AJ, Fong CK, Hsiung GD. 1980. Western equine encephalitis mimicking herpes simplex encephalitis. JAMA 244:367369.[PubMed]
103. Schultz DR, Barthal JS, Garrett G. 1977. Western equine encephalitis with rapid onset of parkinsonism. Neurology 27:10951096.[PubMed]
104. Somekh E, Glode MP, Reiley TT, Tsai TF. 1991. Multiple intracranial calcifications after western equine encephalitis. Pediatr Infect Dis J 10:408409.[PubMed]
105. Kokernot RH, Shinefield HR, Longshore WA Jr. 1953. The 1952 outbreak of encephalitis in California; differential diagnosis. Calif Med 79:7377.[PubMed]
106. Julander JG, Smee DF, Morrey JD, Furuta Y. 2009. Effect of T-705 treatment on western equine encephalitis in a mouse model. Antiviral Res 82:169171.[PubMed]
107. Delekta PC, Dobry CJ, Sindac JA, Barraza SJ, Blakely PK, Xiang J, Kirchhoff PD, Keep RF, Irani DN, Larsen SD, Miller DJ. 2014. Novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo. J Virol 88:1119911214.[PubMed]
108. Dietz WH Jr, Alvarez O Jr, Martin DH, Walton TE, Ackerman LJ, Johnson KM. 1978. Enzootic and epizootic Venezuelan equine encephalomyelitis virus in horses infected by peripheral and intrathecal routes. J Infect Dis 137:227237.[PubMed]
109. Young NA, Johnson KM. 1969. Antigenic variants of Venezuelan equine encephalitis virus: their geographic distribution and epidemiologic significance. Am J Epidemiol 89:286307.[PubMed]
110. Weaver SC, Salas R, Rico-Hesse R, Ludwig GV, Oberste MS, Boshell J, Tesh RB VEE Study Group. 1996. Re-emergence of epidemic Venezuelan equine encephalomyelitis in South America. Lancet 348:436440.[PubMed]
111. Powers AM, Oberste MS, Brault AC, Rico-Hesse R, Schmura SM, Smith JF, Kang W, Sweeney WP, Weaver SC. 1997. Repeated emergence of epidemic/epizootic Venezuelan equine encephalitis from a single genotype of enzootic subtype ID virus. J Virol 71:66976705.[PubMed]
112. Rivas F, Diaz LA, Cardenas VM, Daza E, Bruzon L, Alcala A, De la Hoz O, Caceres FM, Aristizabal G, Martinez JW, Revelo D, De la Hoz F, Boshell J, Camacho T, Calderon L, Olano VA, Villarreal LI, Roselli D, Alvarez G, Ludwig G, Tsai T. 1997. Epidemic Venezuelan equine encephalitis in La Guajira, Colombia, 1995. J Infect Dis 175:828832.[PubMed]
113. Oberste MS, Fraire M, Navarro R, Zepeda C, Zarate ML, Ludwig GV, Kondig JF, Weaver SC, Smith JF, Rico-Hesse R. 1998. Association of Venezuelan equine encephalitis virus subtype IE with two equine epizootics in Mexico. Am J Trop Med Hyg 59:100107.[PubMed]
114. Monath TP, Calisher CH, Davis M, Bowen GS, White J. 1974. Experimental studies of rhesus monkeys infected with epizootic and enzootic subtypes of Venezuelan equine encephalitis virus. J Infect Dis 129:194200.[PubMed]
115. Gutierrev E, Monath TP, Alava A, Uriguen D, Arzube M, Chamberlain RW. 1975. Epidemiologic investigations of the 1969 epidemic of Venezuelan encephalitis in Ecuador. Am J Epidemiol 102:400413.[PubMed]
116. Koprowski H, Cox HR. 1947. Human laboratory infection with Venezuelan equine encephalomyelitis virus: report of four cases. N Engl J Med 236:647654.[PubMed]
117. Bowen GS, Fashinell TR, Dean PB, Gregg MB. 1976. Clinical aspects of human Venezuelan equine encephalitis in Texas. Bull Pan Am Health Organ 10:4657.[PubMed]
118. Dietz WH Jr, Peralta PH, Johnson KM. 1979. Ten clinical cases of human infection with Venezuelan equine encephalomyelitis virus, subtype I-D. Am J Trop Med Hyg 28:329334.[PubMed]
119. Oberste MS, Weaver SC, Watts DM, Smith JF. 1998. Identification and genetic analysis of Panama-genotype Venezuelan equine encephalitis virus subtype ID in Peru. Am J Trop Med Hyg 58:4146.[PubMed]
120. Sanchez JL, Takafuji ET, Lednar WM, LeDuc JW, Macasaet FF, Mangiafico JA, Rosato RR, Driggers DP, Haecker JC. 1984. Venezuelan equine encephalomyelitis: report of an outbreak associated with jungle exposure. Mil Med 149:618621.[PubMed]
121. Watts DM, Callahan J, Rossi C, Oberste MS, Roehrig JT, Wooster MT, Smith JF, Cropp CB, Gentrau EM, Karabatsos N, Gübler D, Hayes CG. 1998. Venezuelan equine encephalitis febrile cases among humans in the Peruvian Amazon River region. Am J Trop Med Hyg 58:3540.[PubMed]
122. Rossi AL. 1967. Rural epidemic encephalitis in Venezuela caused by a group A arbovirus (VEE). Prog Med Virol 9:176203.[PubMed]
123. Bowen GS, Calisher CH. 1976. Virological and serological studies of Venezuelan equine encephalomyelitis in humans. J Clin Microbiol 4:2227.[PubMed]
124. Wenger F. 1977. Venezuelan equine encephalitis. Teratology 16:359362.[PubMed]
125. Molina OM, Morales MC, Soto ID, Peña JA, Haack RS, Cardozo DP, Cardozo JJ. 1999. Venezuelan equine encephalitis. 1995 outbreak: clinical profile of the case with neurologic involvement. Rev Neurol 29:296298.[PubMed]
126. León CA, Jaramillo R, Martinez S, Fernandez F, Téllez H, Lasso B, De Guzmán R. 1975. Sequelae of Venezuelan equine encephalitis in humans: a four year follow-up. Int J Epidemiol 4:131140.[PubMed]
127. Hommel D, Heraud JM, Hulin A, Talarmin A. 2000. Association of Tonate virus (subtype IIIB of the Venezuelan equine encephalitis complex) with encephalitis in a human. Clin Infect Dis 30:188190.[PubMed]
128. Linssen B, Kinney RM, Aguilar P, Russell KL, Watts DM, Kaaden OR, Pfeffer M. 2000. Development of reverse transcription-PCR assays specific for detection of equine encephalitis viruses. J Clin Microbiol 38:15271535.[PubMed]
129. Rosato RR, Macasaet FF, Jahrling PB. 1988. Enzyme-linked immunosorbent assay detection of immunoglobulins G and M to Venezuelan equine encephalomyelitis virus in vaccinated and naturally infected humans. J Clin Microbiol 26:421425.[PubMed]
130. Wang E, Paessler S, Aguilar PV, Smith DR, Coffey LL, Kang W, Pfeffer M, Olson J, Blair PJ, Guevara C, Estrada-Franco J, Weaver SC. 2005. A novel, rapid assay for detection and differentiation of serotype-specific antibodies to Venezuelan equine encephalitis complex alphaviruses. Am J Trop Med Hyg 72:805810.[PubMed]
131. Pittman PR, Makuch RS, Mangiafico JA, Cannon TL, Gibbs PH, Peters CJ. 1996. Long-term duration of detectable neutralizing antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine. Vaccine 14:337343.[PubMed]
132. Paessler S, Weaver SC. 2009. Vaccines for Venezuelan equine encephalitis. Vaccine 27(Suppl 4):D80D85.[PubMed]
133. Engler RJ, Mangiafico JA, Jahrling P, Ksiazek TG, Pedrotti-Krueger M, Peters CJ. 1992. Venezuelan equine encephalitis-specific immunoglobulin responses: live attenuated TC-83 versus inactivated C-84 vaccine. J Med Virol 38:305310.[PubMed]
134. McClain DJ, Pittman PR, Ramsburg HH, Nelson GO, Rossi CA, Mangiafico JA, Schmaljohn AL, Malinoski FJ. 1998. Immunologic interference from sequential administration of live attenuated alphavirus vaccines. J Infect Dis 177:634641.[PubMed]
135. Lumsden WHR. 1955. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–1953. II. General description and epidemiology. Trans R Soc Trop Med Hyg 49:3357.[PubMed]
136. Powers AM, Brault AC, Tesh RB, Weaver SC. 2000. Re-emergence of Chikungunya and O'nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships. J Gen Virol 81:471479.[PubMed]
137. Blackburn NK, Besselaar TG, Gibson G. 1995. Antigenic relationship between chikungunya virus strains and o'nyong nyong virus using monoclonal antibodies. Res Virol 146:6973.[PubMed]
138. Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L, Vaney MC, Lavenir R, Pardigon N, Reynes JM, Pettinelli F, Biscornet L, Diancourt L, Michel S, Duquerroy S, Guigon G, Frenkiel MP, Bréhin AC, Cubito N, Desprès P, Kunst F, Rey FA, Zeller H, Brisse S. 2006. Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. PLoS Med 3:e263.[PubMed]
139. Halstead SB. 2015. Reappearance of chikungunya, formerly called dengue, in the Americas. Emerg Infect Dis 21:557561.[PubMed]
140. Pialoux G, Gaüzère B-A, Jauréguiberry S, Strobel M. 2007. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis 7:319327.[PubMed]
141. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M, Cordioli P, Fortuna C, Boros S, Magurano F, Silvi G, Angelini P, Dottori M, Ciufolini MG, Majori GC, Cassone A CHIKV study group. 2007. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 370:18401846.[PubMed]
142. Diallo M, Thonnon J, Traore-Lamizana M, Fontenille D. 1999. Vectors of chikungunya virus in Senegal: current data and transmission cycles. Am J Trop Med Hyg 60:281286.[PubMed]
143. Pan American Health Organization. Number of reported cases of chikungunya fever in the Americas, by Country or Territory 2016. http://www.paho.org. Accessed 22 March 2016.
144. Kennedy AC, Fleming J, Solomon L. 1980. Chikungunya viral arthropathy: a clinical description. J Rheumatol 7:231236.[PubMed]
145. Jadhav M, Namboodripad M, Carman RH, Carey DE, Myers RM. 1965. Chikungunya disease in infants and children in Vellore: a report of clinical and haematological features of virologically proved cases. Indian J Med Res 53:764776.[PubMed]
146. Gérardin P, Couderc T, Bintner M, Tournebize P, Renouil M, Lémant J, Boisson V, Borgherini G, Staikowsky F, Schramm F, Lecuit M, Michault A Encephalchik Study Group. 2016. Chikungunya virus-associated encephalitis: a cohort study on La Réunion Island, 2005–2009. Neurology 86:94102.[PubMed]
147. Thiruvengadam KV, Kalyanasundaram V, Rajgopal J. 1965. Clinical and pathological studies on chikungunya fever in Madras city. Indian J Med Res 53:729744.[PubMed]
148. Gérardin P, Sampériz S, Ramful D, Boumahni B, Bintner M, Alessandri JL, Carbonnier M, Tiran-Rajaoefera I, Beullier G, Boya I, Noormahomed T, Okoï J, Rollot O, Cotte L, Jaffar-Bandjee MC, Michault A, Favier F, Kaminski M, Fourmaintraux A, Fritel X. 2014. Neurocognitive outcome of children exposed to perinatal mother-to-child chikungunya virus infection: the CHIMERE cohort study on Réunion Island. PLoS Negl Trop Dis 8:e2996.[PubMed]
149. Torres JR, Córdova LG, Saravia V, Arvelaez J, Castro JS. 2016. Nasal skin necrosis: an unexpected new finding in severe chikungunya fever. Clin Infect Dis 62:7881.[PubMed]
150. Brighton SW, Prozesky OW, de la Harpe AL. 1983. Chikungunya virus infection: a retrospective study of 107 cases. S Afr Med J 63:313315.[PubMed]
151. Fourie ED, Morrison JG. 1979. Rheumatoid arthritic syndrome after chikungunya fever. S Afr Med J 56:130132.[PubMed]
152. Carey DE, Myers RM, DeRanitz CM, Jadhav M, Reuben R. 1969. The 1964 chikungunya epidemic at Vellore, South India, including observations on concurrent dengue. Trans R Soc Trop Med Hyg 63:434445.[PubMed]
153. Riswari SF, Ma'roef CN, Djauhari H, Kosasih H, Perkasa A, Yudhaputri FA, Artika IM, Williams M, van der Ven A, Myint KS, Alisjahbana B, Ledermann JP, Powers AM, Jaya UA. 2016. Study of viremic profile in febrile specimens of chikungunya in Bandung, Indonesia. J Clin Virol 74:6165.[PubMed]
154. Lam SK, Chua KB, Hooi PS, Rahimah MA, Kumari S, Tharmaratnam M, Chuah SK, Smith DW, Sampson IA. 2001. Chikungunya infection—an emerging disease in Malaysia. Southeast Asian J Trop Med Public Health 32:447451.[PubMed]
155. Jacobsen S, Patel P, Schmidt-Chanasit J, Leparc-Goffart I, Teichmann A, Zeller H, Niedrig M. 2016. External quality assessment studies for laboratory performance of molecular and serological diagnosis of chikungunya virus infection. J Clin Virol 76:5565.[PubMed]
156. Carvalho DO, McKemey AR, Garziera L, Lacroix R, Donnelly CA, Alphey L, Malavasi A, Capurro ML. 2015. Suppression of a field population of Aedes aegypti in Brazil by sustained release of transgenic male mosquitoes. PLoS Negl Trop Dis 9:e0003864.[PubMed]
157. Abdelnabi R, Neyts J, Delang L. 2015. Towards antivirals against chikungunya virus. Antiviral Res 121:5968.[PubMed]
158. Williams MC, Woodall JP, Gillett JD. 1965. O'nyong-nyong fever: an epidemic virus disease in East Africa. VII. Virus isolations from man and serological studies up to July 1961. Trans R Soc Trop Med Hyg 59:186197.[PubMed]
159. Kiwanuka N, Sanders EJ, Rwaguma EB, Kawamata J, Ssengooba FP, Najjemba R, Were WA, Lamunu M, Bagambisa G, Burkot TR, Dunster L, Lutwama JJ, Martin DA, Cropp CB, Karabatsos N, Lanciotti RS, Tsai TF, Campbell GL. 1999. O'nyong-nyong fever in south-central Uganda, 1996–1997: clinical features and validation of a clinical case definition for surveillance purposes. Clin Infect Dis 29:12431250.[PubMed]