Skip to main content

Emerging Causes of Arbovirus Encephalitis in North America: Powassan, Chikungunya, and Zika Viruses

Abstract

Arboviruses are arthropod-borne viruses transmitted by the bite of mosquitoes, ticks, or other arthropods. Arboviruses are a common and an increasing cause of human illness in North America. Powassan virus, Chikungunya virus, and Zika virus are arboviruses that have all recently emerged as increasing causes of neurologic illness. Powassan virus almost exclusively causes encephalitis, but cases are rare, sporadic, and restricted to portions of North America and Russia. Chikungunya virus has spread widely across the world, causing millions of infections. Encephalitis is a rare manifestation of illness but is more common and severe in neonates and older adults. Zika virus has recently spread through much of the Americas and has been associated mostly with microcephaly and other congenital neurologic complications. Encephalitis occurring in infected adults has also been recently reported. This review will discuss the neuropathogenesis of these viruses, their transmission and geographic distribution, the spectrum of their neurologic manifestations, and the appropriate method of diagnosis.

This is a preview of subscription content, access via your institution.

Fig. 1

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    McLean DM, Donohue WL. Powassan virus: isolation of virus from a fatal case of encephalitis. Can Med Assoc J. 1959;80(9):708–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Mandl CW, Holzmann H, Kunz C, Heinz FX. Complete genomic sequence of Powassan virus: evaluation of genetic elements in tick-borne versus mosquito-borne flaviviruses, vol. 194, Virology. Academic Press; 1993. p. 173–84.

  3. 3.

    Gholam BIA, Puksa S, Proviast JP. Powassan encephalitis: a case report with neuropathology and literature review. CMAJ. 1999;161(11):1419–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Tavakoli NP, Wang H, Dupuis M, Hull R, Ebel GD, Gilmore EJ, et al. Brief report: fatal case of deer tick virus encephalitis. N Engl J Med. 2009;360(20):2099–107.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Frolova MP, Isachkova LM, Shestopalova NM, Pogodina VV. Experimental encephalitis in monkeys caused by the Powassan virus. Neurosci Behav Physiol. 1985;15(1):62–9.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Hermance ME, Santos RI, Kelly BC, Valbuena G, Thangamani S. Immune cell targets of infection at the tick-skin interface during Powassan virus transmission. Schneider BS, editor. PLoS ONE 2016 11 Suppl 5:e0155889.

  7. 7.

    Santos R, Hermance M, Gelman B, Thangamani S. Spinal cord ventral horns and lymphoid organ involvement in Powassan virus infection in a mouse model. Viruses. 2016;8(8):E220.

    Article  PubMed  Google Scholar 

  8. 8.

    Kuno G, Artsob H, Karabatsos N, Tsuchiya KR, Chang GJJ. Genomic sequencing of deer tick virus and phylogeny of Powassan-related viruses of North America. Am J Trop Med Hyg. 2001;65(5):671–6.

    CAS  PubMed  Google Scholar 

  9. 9.

    Ebel GD. Update on Powassan virus: emergence of a North American tick-borne flavivirus. Annu Rev Entomol. 2010;55:95–110.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Telford SR, Armstrong PM, Katavolos P, Foppa I, Garcia ASO, Wilson ML, et al. A new tick-borne encephalitis-like virus infecting New England deer ticks, Ixodes dammini. Emerg Infect Dis. 1997;3(2):165–70.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Ebel GD, Campbell EN, Goethert HK, Spielman A, Telford SR. Enzootic transmission of deer tick virus in New England and Wisconsin sites. Am J Trop Med Hyg. 2000;63(1–2):36–42.

    CAS  PubMed  Google Scholar 

  12. 12.

    Ebel GD, Kramer LD. Short report: duration of tick attachment required for transmission of Powassan virus by deer ticks. Am J Trop Med Hyg. 2004;71(3):268–71.

    PubMed  Google Scholar 

  13. 13.

    • El Khoury MY, Camargo JF, White JL, Backenson BP, Dupuis AP, Escuyer KL, et al. Potential role of deer tick virus in Powassan encephalitis cases in Lyme disease-endemic areas of New York, U.S.A. Emerg Infect Dis. 2013;19(12):1926–33. This is the largest case series to date of POWV encephalitis. The authors comprehensively describe the clinical presentation, laboratory and imaging findings, and outcomes of 14 patients from New York.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Hinten SR, Beckett GA, Gensheimer KF, Pritchard E, Courtney TM, Sears SD, et al. Increased recognition of Powassan encephalitis in the United States, 1999–2005. Vector Borne Zoonotic Dis. 2008;8(6):733–40.

    Article  PubMed  Google Scholar 

  15. 15.

    Aliota MT, Dupuis AP, Wilczek MP, Peters RJ, Ostfeld RS, Kramer LD. The prevalence of zoonotic tick-borne pathogens in Ixodes scapularis collected in the Hudson Valley, New York State. Vector-Borne Zoonotic Dis. 2014;14(4):245–50.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Raval M, Singhal M, Guerrero D, Alonto A. Powassan virus infection: case series and literature review from a single institution. BMC Res Notes. 2012;5(1):594.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    • Piantadosi A, Rubin DB, McQuillen DP, Hsu L, Lederer PA, Ashbaugh CD, et al. Emerging cases of Powassan virus encephalitis in New England: clinical presentation, imaging, and review of the literature. Clin Infect Dis. 2015;62(6):707–13. Piantadosi et al. describe 8 cases of POWV encephalitis from Massachusetts and New Hampshire with a particular emphasis on neuroimaging findings.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    CDC. Outbreak of Powassan encephalitis—Maine and Vermont, 1999–2001. MMWR Morb Mortal Wkly Rep. 2001;50(35):761–4.

    Google Scholar 

  19. 19.

    CDC. Powassan virus disease cases and deaths reported to CDC by year and clinical presentation, 2004–2013 [online]. [Internet]. [cited 2016 Sep 22]. Available from: http://www.cdc.gov/powassan/pdf/powv-cases-by-year_2004-2013.pdf.

  20. 20.

    CDC. ArboNET Map Viewer [Internet]. [cited 2016 Sep 22]. Available from: http://diseasemaps.usgs.gov/mapviewer/.

  21. 21.

    Thomas L, Kennedy R, Eklund C. Isolation of a virus closely related to Powassan virus from Dermacentor andersoni collected along north Cache la Poudre River, Colo. Proc Soc Exp Biol Med. 1960;104:355–9.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Leonova GN, Kondratov IG, Ternovoi VA, Romanova EV, Protopopova EV, Chausov EV, et al. Characterization of Powassan viruses from Far Eastern Russia. Arch Virol. 2009;154(5):811–20.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Nofchissey RA, Deardorff ER, Blevins TM, Anishchenko M, Bosco-Lauth A, Berl E, et al. Seroprevalence of Powassan virus in New England deer, 1979–2010. Am J Trop Med Hyg. 2013;88(6):1159–62.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Smith R, Woodall JP, Whitney E, Deibel R, Gross MA, Smith V, et al. Powassan virus infection a report of three human cases of encephalitis. Am J Dis Child. 1974;127:691–3.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Choi EEJ, Taylor RA. A case of Powassan viral hemorrhagic encephalitis involving bilateral thalami. Clin Neurol Neurosurg. 2012;114(2):172–5.

    Article  PubMed  Google Scholar 

  26. 26.

    CDC. Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 Case Definition [Internet]. 2015 [cited 2016 Sep 22]. Available from: https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/.

  27. 27.

    Beasley DWC, Suderman MT, Holbrook MR, Barrett ADT. Nucleotide sequencing and serological evidence that the recently recognized deer tick virus is a genotype of Powassan virus. Virus Res. 2001;79(1–2):81–9.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Sung S, Wurcel AG, Whittier S, Kulas K, Kramer LD, Flam R, et al. Powassan meningoencephalitis, New York, New York, USA. Emerg Infect Dis. 2013;19(9):1504–6.

    Article  Google Scholar 

  29. 29.

    El Khoury MY, Hull RC, Bryant PW, Escuyer KL, St George K, Wong SJ, et al. Diagnosis of acute deer tick virus encephalitis. Clin Infect Dis. 2013;56(4):e40–7.

    Article  PubMed  Google Scholar 

  30. 30.

    Grard G, Moureau G, Charrel RN, Lemasson JJ, Gonzalez JP, Gallian P, et al. Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy. Virology. 2007;361(1):80–92.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Chernokhaeva LL, Rogova YV, Vorovitch MF, Romanova LI, Kozlovskaya LI, Maikova GB, et al. Protective immunity spectrum induced by immunization with a vaccine from the TBEV strain Sofjin. Vaccine. 2016;34(20):2354–61.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Weaver SC, Winegar R, Manger ID, Forrester NL. Alphaviruses: population genetics and determinants of emergence. Antivir Res. 2012;94:242–57.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Lanciotti RS, Valadere AM. Transcontinental movement of Asian genotype Chikungunya virus. Emerg Infect Dis. 2014;20:1400–2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Leparc-Goffart I, Nougairede A, Cassadou S, Prat C, De Lamballerie X. Chikungunya in the Americas. Lancet. 2014;383:514.

    Article  PubMed  Google Scholar 

  35. 35.

    Sourisseau M, Schilte C, Casartelli N, Trouillet C, Guivel-Benhassine F, Rudnicka D, et al. Characterization of reemerging Chikungunya virus. PLoS Pathog. 2007;3(6):804–17.

    CAS  Article  Google Scholar 

  36. 36.

    Leung JYS, Ng MML, Chu JJH. Replication of alphaviruses: a review on the entry process of alphaviruses into cells, Vol. 2011, Adv Virol. Hindawi Publishing Corporation; 2011. p. 1–9.

  37. 37.

    Deeba F, Islam A, Kazim SN, Naqvi IH, Broor S, Ahmed A, et al. Chikungunya virus: recent advances in epidemiology, host pathogen interaction and vaccine strategies. Pathog Dis. 2016;74 Suppl 3.

  38. 38.

    Teo T-H, Her Z, Tan JJL, Lum F-M, Lee WWL, Chan Y-H, et al. Caribbean and La Réunion Chikungunya virus isolates differ in their capacity to induce proinflammatory Th1 and NK cell responses and. Dermody TS, editor. J Virol. 2015;89 Suppl 15:7955–69.

  39. 39.

    Thiberville SD, Moyen N, Dupuis-Maguiraga L, Nougairede A, Gould EA, Roques P, et al. Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy. Antivir Res. 2013;99(3):345–70.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Weger-Lucarelli J, Aliota MT, Wlodarchak N, Kamlangdee A, Swanson R, Osorio JE. Dissecting the role of E2 protein domains on alphavirus pathogenicity. Diamond MS, editor. J Virol. 2016;90 Suppl 5:2418–33.

  41. 41.

    Arpino C, Curatolo P, Rezza G. Chikungunya and the nervous system: what we do and do not know, vol. 19, Rev Med Virol. John Wiley & Sons, Ltd.; 2009. p. 121–9.

  42. 42.

    Wei Chiam C, Fun Chan Y, Chai Ong K, Thong Wong K, Sam I-C. Neurovirulence comparison of chikungunya virus isolates of the Asian and East/Central/South African genotypes from Malaysia. J Gen Virol. 2015;96(11):3243–54.

    Article  Google Scholar 

  43. 43.

    Couderc T, Chretien F, Schilte C, Disson O, Brigitte M, Guivel-Benhassine F, et al. A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog. 2008;4(2):e29.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Inglis FM, Lee KM, Chiu KB, Purcell OM, Didier PJ, Russell-Lodrigue K, et al. Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation. J Neurovirol. 2016;22(2):140–8.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika virus. N Engl J Med. 2016;374(16):1552–63.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Staples JE, Breiman RF, Powers AM. Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis. 2009;49(6):942–8.

    Article  PubMed  Google Scholar 

  47. 47.

    Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L, Vaney MC, et al. Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. IV HV, editor. PLoS Med. 2006;3(7):1058–70.

    CAS  Article  Google Scholar 

  48. 48.

    Vazeille M, Moutailler S, Coudrier D, Rousseaux C, Khun H, Huerre M, et al. Two Chikungunya isolates from the outbreak of La Reunion (Indian Ocean) exhibit different patterns of infection in the mosquito, Aedes albopictus. Montgomery J, editor. PLoS ONE. 2007; 2 Suppl 11:e1168.

  49. 49.

    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):1895–906.

    CAS  Article  Google Scholar 

  50. 50.

    Vega-Rúa A, Zouache K, Girod R, Failloux A-B, Lourenço-de-Oliveira R. High level of vector competence of Aedes aegypti and Aedes albopictus from ten American countries as a crucial factor in the spread of Chikungunya virus. J Virol. 2014;88(11):6294–306.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Rodrigues Faria N, Lourenço J, Marques de Cerqueira E, Maia de Lima M, Pybus O, Carlos Junior Alcantara L. Epidemiology of Chikungunya virus in Bahia, Brazil, 2014–2015. PLoS Curr. 2016.

  52. 52.

    Lorenzi OD, Major C, Acevedo V, Perez-Padilla J, Rivera A, Biggerstaff BJ, et al. Reduced incidence of Chikungunya virus infection in communities with ongoing Aedes aegypti mosquito trap intervention studies—Salinas and Guayama, Puerto Rico, November 2015–February 2016. MMWR Morb Mortal Wkly Rep. 2016;65(18):479–80.

    Article  PubMed  Google Scholar 

  53. 53.

    CDC. Chikungunya virus in the United States [Internet]. [cited 2016 Sep 22]. Available from: https://www.cdc.gov/chikungunya/geo/united-states.html.

  54. 54.

    Manimunda SP, Vijayachari P, Uppoor R, Sugunan AP, Singh SS, Rai SK, et al. Clinical progression of Chikungunya fever during acute and chronic arthritic stages and the changes in joint morphology as revealed by imaging. Trans R Soc Trop Med Hyg. 2010;104(6):392–9.

    Article  PubMed  Google Scholar 

  55. 55.

    Perti T, Lucero-Obusan CA, Schirmer PL, Winters MA, Holodniy M. Chikungunya fever cases identified in the Veterans Health Administration System, 2014. Williams M, editor. PLoS Negl Trop Dis. 2016; 10 Suppl 5:e0004630.

  56. 56.

    Ramful D, Carbonnier M, Pasquet M, Bouhmani B, Ghazouani J, Noormahomed T, et al. Mother-to-child transmission of Chikungunya virus infection. Pediatr Infect Dis J. 2007;26(9):811–5.

    Article  PubMed  Google Scholar 

  57. 57.

    Gerardin P, Barau G, Michault A, Bintner M, Randrianaivo H, Choker G, et al. Multidisciplinary prospective study of mother-to-child Chikungunya virus infections on the island of La Reunion. Chretien J-P, editor. PLoS Med. 2008; 5 Suppl 3:413–23.

  58. 58.

    Borgherini G, Poubeau P, Jossaume A, Gouix A, Cotte L, Michault A, et al. Persistent arthralgia associated with Chikungunya virus: a study of 88 adult patients on Reunion Island. Clin Infect Dis. 2008;47(4):469–75.

    Article  PubMed  Google Scholar 

  59. 59.

    van Genderen FT, Krishnadath I, Sno R, Grunberg MG, Zijlmans W, Adhin MR. First Chikungunya outbreak in Suriname; clinical and epidemiological features. PLoS Negl Trop Dis. 2016;10(4):e0004625.

    Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Kam YW, Simarmata D, Chow A, Her Z, Teng TS, Ong EKS, et al. Early appearance of neutralizing immunoglobulin G3 antibodies is associated with Chikungunya virus clearance and long-term clinical protection. J Infect Dis. 2012;205(7):1147–54.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Rampal L, Sharda MMH. Neurological complications in Chikungunya fever. J Assoc Physicians India. 2007;55:765–9.

    CAS  PubMed  Google Scholar 

  62. 62.

    •• Gérardin P, Couderc T, Bintner M, Tournebize P, Renouil M, Lémant J, et al. Chikungunya virus-associated encephalitis. Neurology. 2016;86(1):94–102. The authors retrospectively analyzed the cases of CHIKV-associated CNS disease, including encephalitis, from a cohort of laboratory-confirmed CHIKV infection during the Réunion outbreak. As the most comprehensive study of CHIKV encephalitis to date, the study offered important assessments of the incidence of CHIKV encephaltis, risk factors, and outcomes.

    Article  PubMed  Google Scholar 

  63. 63.

    • Oehler E, Fournier E, Leparc-Goffart I, Larre P, Cubizolle S, Sookhareea C, et al. Increase in cases of Guillain-Barré syndrome during a Chikungunya outbreak, French Polynesia, 2014 to 2015. Eurosurveillance. 2015; 20 Suppl 48. Oehler et al. demonstrate an epidemiologic link between an increased incidence of GBS and the CHIKV outbreak on French Polynesia, as well as describe the clinical features of nine patients with CHIKV-associated GBS.

  64. 64.

    Lebrun G, Chadda K, Reboux AH, Martinet O, Gaüzère BA. Guillain-Barré syndrome after Chikungunya infection. Emerg Infect Dis. 2009;15:495–6.

    Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Villamil-Gómez W, Silvera LA, Páez-Castellanos J, Rodriguez-Morales AJ. Guillain-Barré syndrome after Chikungunya infection: a case in Colombia. Enferm Infecc Microbiol Clin. 2016;34:140–1.

    Article  PubMed  Google Scholar 

  66. 66.

    Robin S, Ramful D, Le Seach F, Jaffar-Bandjee M-C, Rigou G, Alessandri J-L. Neurologic manifestations of pediatric Chikungunya infection. J Child Neurol. 2008;23(9):1028–35.

    Article  PubMed  Google Scholar 

  67. 67.

    Gauri LA, Ranwa BL, Nagar K, Vyas A, Fatima Q. Post Chikungunya brain stem encephalitis. J Assoc Physicians India. 2012;60(4):68–9.

    CAS  PubMed  Google Scholar 

  68. 68.

    Bank AM, Batra A, Colorado RA, Lyons JL. Myeloradiculopathy associated with Chikungunya virus infection. J Neurovirol. 2016;22(1):125–8.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Renault P, Solet JL, Sissoko D, Balleydier E, Larrieu S, Filleul L, et al. A major epidemic of Chikungunya virus infection on Réunion Island, France, 2005–2006. Am J Trop Med Hyg. 2007;77(4):727–31.

    PubMed  Google Scholar 

  70. 70.

    Chusri S, Siripaitoon P, Hirunpat S, Silpapojakul K. Case reports of neuro-Chikungunya in southern Thailand. Am J Trop Med Hyg. 2011;85(2):386–9.

    Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Crosby L, Perreau C, Madeux B, Cossic J, Armand C, Herrmann-Storke C, et al. Severe manifestations of Chikungunya virus in critically ill patients during the 2013–2014 Caribbean outbreak. Int J Infect Dis. 2016;48:78–80.

    Article  PubMed  Google Scholar 

  72. 72.

    Feldstein LR, Ellis EM, Rowhani-Rahbar A, Halloran EM, Ellis BR. The first reported outbreak of Chikungunya in the U.S. Virgin Islands, 2014–2015. Am J Trop Med Hyg. 2016.

  73. 73.

    Chandak NH, Kashyap RS, Kabra D, Karandikar P, Saha SS, Morey SH, et al. Neurological complications of Chikungunya virus infection. Neurol India. 2009;57(2):177–80.

    Article  PubMed  Google Scholar 

  74. 74.

    Gérardin P, Sampériz S, Ramful D, Boumahni B, Bintner M, Alessandri JL, et al. Neurocognitive outcome of children exposed to perinatal mother-to-child Chikungunya virus infection: the CHIMERE Cohort Study on Reunion Island. Powers AM, editor. PLoS Negl Trop Dis. 2014;8 Suppl 7:e2996.

  75. 75.

    PAHO. Number of reported cases of Chikungunya fever in the Americas—EW 39 [Internet]. 2016 [cited 2016 Oct 5]. Available from: http://www.paho.org/hq/index.php?option=com_topics&view=readall&cid=5927&Itemid=40931Data&lang=en.

  76. 76.

    Tandale BV, Sathe PS, Arankalle VA, Wadia RS, Kulkarni R, Shah SV, et al. Systemic involvements and fatalities during Chikungunya epidemic in India, 2006. J Clin Virol. 2009;46(2):145–9.

    Article  PubMed  Google Scholar 

  77. 77.

    Smalley C, Erasmus JH, Chesson CB, Beasley DWC. Status of research and development of vaccines for Chikungunya. Vaccine. 2016;34(26):2976–81.

    Article  PubMed  Google Scholar 

  78. 78.

    Ndeffo-Mbah ML, Durham DP, Skrip LA, Nsoesie EO, Brownstein JS, Fish D, et al. Evaluating the effectiveness of localized control strategies to curtail Chikungunya. Sci Rep. 2016;6(April):23997.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Kuno G, Chang GJJ. Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses. Arch Virol. 2007;152(4):687–96.

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Beckham JD, Pastula DM, Massey A, Tyler KL, LR P, KD S, et al. Zika virus as an emerging global pathogen. JAMA Neurol. 2016; 73 Suppl 7:875–9.

  81. 81.

    Johnston LJ, Halliday GM, King NJC. Langerhans cells migrate to local lymph nodes following cutaneous infection with an arbovirus. J Invest Dermatol. 2000;114(3):560–8.

    CAS  Article  PubMed  Google Scholar 

  82. 82.

    • Tang H, Hammack C, Ogden SC, Jin P, Wen Z, Qian X, et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell. 2016;18(5):587–90. The authors demonstrate that ZIKV infects human cortical neural progenitors in vitro, offering pathophysiologic support to the causal link between ZIKV congenital infection and microcephaly.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Garcez PP, Loiola EC, Madeiro da Costa R, Higa LM, Trindade P, Delvecchio R, et al. Zika virus impairs growth in human neurospheres and brain organoids. Science (80-). 2016; 352 Suppl 6287:816–8.

  84. 84.

    Hughes BW, Addanki KC, Sriskanda AN, McLean E, Bagasra O. Infectivity of immature neurons to Zika virus: a link to congenital Zika syndrome. EBioMedicine. 2016. doi:10.1016/j.ebiom.2016.06.026.

    Google Scholar 

  85. 85.

    Nowakowski TJ, Pollen AA, Di Lullo E, Sandoval-Espinosa C, Bershteyn M, Kriegstein AR. Expression analysis highlights AXL as a candidate zika virus entry receptor in neural stem cells. Cell Stem Cell. 2016;18(5):591–6.

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Mysorekar IU, Diamond MS. Modeling Zika virus infection in pregnancy. N Engl J Med. 2016;375(5):481–4.

    Article  PubMed  Google Scholar 

  87. 87.

    Martines RB, Bhatnagar J, de Oliveira Ramos AM, Davi HPF, Iglezias SDA, Kanamura CT, et al. Pathology of congenital Zika syndrome in Brazil: a case series. Lancet. 2016;388(10047):898–904.

    CAS  Article  PubMed  Google Scholar 

  88. 88.

    Schuler-Faccini L, Ribeiro EM, Feitosa IML, Horovitz DDG, Cavalcanti DP, Pessoa A, et al. Possible association between Zika virus infection and microcephaly—Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(3):59–62.

    Article  PubMed  Google Scholar 

  89. 89.

    Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M, Mraz J, et al. Zika virus associated with microcephaly. N Engl J Med. 2016;374(10):951–8.

    CAS  Article  PubMed  Google Scholar 

  90. 90.

    Duffy MR, Chen T-H, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360(24):2536–43.

    CAS  Article  PubMed  Google Scholar 

  91. 91.

    Zanluca C, De Melo VCA, Mosimann ALP, Dos Santos GIV, dos Santos CND, Luz K. First report of autochthonous transmission of Zika virus in Brazil. Mem Inst Oswaldo Cruz. 2015;110(4):569–72.

    Article  PubMed  PubMed Central  Google Scholar 

  92. 92.

    WHO. Situation Report: Zika virus, microcephaly, Guillain-Barré syndrome [Internet]. [cited 2016 Sep 22]. Available from: http://apps.who.int/iris/bitstream/10665/250122/1/zikasitrep15Sep16-eng.pdf?ua=1.

  93. 93.

    Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14(8):1232–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  94. 94.

    CDC. Zika virus—case counts in the US [Internet]. [cited 2016 Sep 22]. Available from: http://www.cdc.gov/zika/geo/united-states.html.

  95. 95.

    •• Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects—reviewing the evidence for causality. N Engl J Med. 2016;374(20):1981–7. In this review article, Rasmussen et al. summarize the available evidence supporting the causal link between ZIKV and microcephaly using criteria proposed to assess potential teratogens.

    CAS  Article  PubMed  Google Scholar 

  96. 96.

    Hills SL, Russell K, Hennessey M, Williams C, Oster AM, Fischer M, et al. Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission—continental United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(8):215–6.

    Article  PubMed  Google Scholar 

  97. 97.

    Turmel JM, Abgueguen P, Hubert B, Vandamme YM, Maquart M, Le Guillou-Guillemette H, et al. Late sexual transmission of Zika virus related to persistence in the semen. Lancet. 2016;387:2501.

    Article  PubMed  Google Scholar 

  98. 98.

    Fréour T, Mirallié S, Hubert B, Splingart C, Barrière P, Maquart M, et al. Sexual transmission of Zika virus in an entirely asymptomatic couple returning from a Zika epidemic area, France, April 2016. Eurosurveillance 2016; 21 Suppl 23.

  99. 99.

    Deckard DT, Chung WM, Brooks JT, Smith JC, Woldai S, Hennessey M, et al. Male-to-male sexual transmission of Zika virus—Texas, January 2016. MMWR Morb Mortal Wkly Rep. 2016;65(14):372–4.

    Article  PubMed  Google Scholar 

  100. 100.

    Davidson A, Slavinski S, Komoto K, Rakeman J, Weiss D. Suspected female-to-male sexual transmission of Zika virus—New York City, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(28):716–7.

    Article  PubMed  Google Scholar 

  101. 101.

    Lanteri MC, Kleinman SH, Glynn SA, Musso D, Keith Hoots W, Custer BS, et al. Zika virus: a new threat to the safety of the blood supply with worldwide impact and implications. Transfusion. 2016;56:1907–14.

    Article  PubMed  Google Scholar 

  102. 102.

    Salimi H, Cain MD, Klein RS. Encephalitic arboviruses: emergence, clinical presentation, and neuropathogenesis. Neurotherapeutics. 2016;13(3):514–34.

    Article  PubMed  Google Scholar 

  103. 103.

    •• Brasil P, Pereira, Jr. JP, Raja Gabaglia C, Damasceno L, Wakimoto M, Ribeiro Nogueira RM, et al. Zika virus infection in pregnant women in Rio de Janeiro—preliminary report. N Engl J Med. 2016 NEJMoa1602412. Brasil et al. prospectively followed a cohort of 88 pregnant women who developed rash concerning ZIKV infection during pregnancy. The authors report fetal outcomes in association with the timing of infection; fetal abnormalities were seen on ultrasound in 29% of women who tested positive for ZIKV infection.

  104. 104.

    Cao-Lormeau V-M, Blake A, Mons S, Lastère S, Roche C, Vanhomwegen J, et al. Guillain-Barré syndrome outbreak caused by Zika virus infection in French Polynesia. Lancet. 2016;387:1531–9.

    Article  PubMed  Google Scholar 

  105. 105.

    Oehler E, Watrin L, Larre P, Leparc-Goffart I, Lastere S, Valour F, et al. Zika virus infection complicated by Guillain-Barre syndrome—case report, French Polynesia, December 2013. Euro Surveill. 2014;19(9):7–9.

    Article  Google Scholar 

  106. 106.

    Adams L, Bello-Pagan M, Lozier M, Ryff KR, Espinet C, Torres J, et al. Update: ongoing Zika virus transmission—Puerto Rico, November 1, 2015–July 7, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(30):774–9.

    Article  PubMed  Google Scholar 

  107. 107.

    Mecharles S, Herrmann C, Poullain P, Tran TH, Deschamps N, Mathon G, et al. Acute myelitis due to Zika virus infection. Lancet. 2016;387:1481.

    Article  PubMed  Google Scholar 

  108. 108.

    • Carteaux G, Maquart M, Bedet A, Contou D, Brugieres P, Fourati S, et al. Zika virus associated with meningoencephalitis. NEJM. 2016;374(16):1595–6. This is a detailed summary of the first reported case of ZIKV-associated encephalitis in an adult patient, including the neuroimaging findings.

    Article  PubMed  Google Scholar 

  109. 109.

    Soares CN, Brasil P, Medialdea R, Msc C, Sequeira P, Bispo De Filippis A, et al. Fatal encephalitis associated with Zika virus infection in an adult. J Clin Virol. 2016;83:63–5.

    Article  PubMed  Google Scholar 

  110. 110.

    Rozé B, Najioullah F, Signate A, Apetse K, Brouste Y, Gourgoudou S, et al. Zika virus detection in cerebrospinal fluid from two patients with encephalopathy, Martinique, February 2016. Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull. 2016;21(16):1–4.

    Google Scholar 

  111. 111.

    Besnard M, Eyrolle-Guignot D, Guillemette-Artur P, Lastère S, Bost-Bezeaud F, Marcelis L, et al. Congenital cerebral malformations and dysfunction in fetuses and newborns following the 2013 to 2014 Zika virus epidemic in French Polynesia. Euro Surveill. 2016; 21 Suppl 13.doi:10.2807/1560-7917.ES.2016.21.13.30181.

  112. 112.

    de Fatima Vasco Aragao M, van der Linden V, Brainer-Lima AM, Coeli RR, Rocha MA, Sobral da Silva P, et al. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study. BMJ. 2016;353(2):i1901.

    Article  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Ventura CV, Maia M, Travassos SB, Martins TT, Patriota F, Nunes ME, et al. Risk factors associated with the ophthalmoscopic findings identified in infants with presumed Zika virus congenital infection. JAMA Ophthalmol. 2016;134(8):912–8.

    Article  PubMed  Google Scholar 

  114. 114.

    França GVA, Schuler-Faccini L, Oliveira WK, Henriques CMP, Carmo EH, Pedi VD, et al. Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation. Lancet. 2016;388(10047):891–7.

    Article  PubMed  Google Scholar 

  115. 115.

    Cauchemez S, Besnard M, Bompard P, Dub T, Guillemette-Artur P, Eyrolle-Guignot D, et al. Association between Zika virus and microcephaly in French Polynesia, 2013–15: a retrospective study. Lancet. 2016;387(10033):2125–32.

    Article  PubMed  PubMed Central  Google Scholar 

  116. 116.

    Hazin AN, Poretti A, Di Cavalcanti Souza Cruz D, Tenorio M, van der Linden A, Pena LJ, et al. Computed tomographic findings in microcephaly associated with Zika virus. N Engl J Med. 2016;374(22):2193–5.

    Article  PubMed  Google Scholar 

  117. 117.

    Gourinat AC, O’Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of zika virus in urine. Emerg Infect Dis. 2015;21(1):84–6.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  118. 118.

    Halstead SB, Rohanasuphot S, Sangkawibha N. Original antigenic sin in dengue. Am J Trop Med Hyg. 1983;32(1):154–6.

    CAS  PubMed  Google Scholar 

  119. 119.

    Meaney-Delman D, Rasmussen SA, Staples JE, Oduyebo T, Ellington SR, Petersen EE, et al. Zika virus and pregnancy what obstetric health care providers need to know. Obstet Gynecol. 2016;127(4):642–8.

    Article  PubMed  Google Scholar 

  120. 120.

    Anderson KB, Thomas SJ, Endy TP. The emergence of zika virus a narrative review. Ann Intern Med. 2016;165(3):175–83.

    Article  PubMed  Google Scholar 

  121. 121.

    Petersen EE, Polen KND, Meaney-Delman D, Ellington SR, Oduyebo T, Cohn A, et al. Update: Interim guidance for health care providers caring for women of reproductive age with possible Zika virus exposure—United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(12):315–22.

    Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jennifer Lyons.

Ethics declarations

Conflict of Interest

Christopher T. Doughty, Sigal Yawetz, and Jennifer Lyons declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Infection

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Doughty, C.T., Yawetz, S. & Lyons, J. Emerging Causes of Arbovirus Encephalitis in North America: Powassan, Chikungunya, and Zika Viruses. Curr Neurol Neurosci Rep 17, 12 (2017). https://doi.org/10.1007/s11910-017-0724-3

Download citation

Keywords

  • Arboviruses
  • Encephalitis
  • Zika virus
  • Chikungunya virus
  • Powassan virus