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Epidemiology, Prevention, and Potential Future Treatments of Sexually Transmitted Zika Virus Infection

  • Davidson H. Hamer
  • Mary E. Wilson
  • Jenny Jean
  • Lin H. Chen
Tropical, Travel and Emerging Infections (L Chen, Section Editor)
First Online:
Part of the following topical collections:
  1. Topical Collection on Tropical, Travel and Emerging Infections

Abstract

Purpose of Review

While mosquitoes have been primarily responsible for outbreaks of Zika virus worldwide, most prominently in the Americas during 2015 and 2016, there has been increased recognition of the importance of sexual transmission. We review human reports and animal model studies of Zika sexual transmission and summarize potential therapeutic candidates.

Recent Findings

Male-to-female, male-to-male, and female-to-male transmission has been reported, among unprotected sexual contacts of returning travelers. Human studies have shown the potential importance of long-term persistence of Zika virus in semen while animal models have begun to yield important insights into pathogenesis of Zika infection of the genital tract.

Summary

Adherence to federal and global guidelines for prevention of sexual transmission of Zika virus from travelers to their sexual partners represents the best strategy for reducing the risk of transmission outside of endemic areas. Active research on potential treatments may soon yield candidates for clinical trials.

Keywords

Zika virus Epidemiology Sexual transmission Semen 
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Notes

Compliance with Ethical Standards

Conflict of Interest

Drs. Hamer, Wilson, Jean, and Chen declare no conflicts of interests

Human and Animal Rights and Informed Consent

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

References

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

  1. 1.
    Dick GWA, Kitchen SF, Haddow A. Zika isolation and serological specificity. Trans R Soc Trop Med Hyg. 1952;46:509–20.CrossRefPubMedGoogle Scholar
  2. 2.
    Chen LH, Hamer DH. Zika virus: rapid spread in the Western hemisphere. Ann Intern Med. 2016;164:613–5. doi: 10.7326/M16-0150.CrossRefPubMedGoogle Scholar
  3. 3.
    Likos A, Griffin I, Bingham AM, Stanek D, Fischer M, White S, et al. Local mosquito-borne transmission of Zika virus—Miami-Dade and Broward Counties, Florida, June–August 2016. Morb Mortal Wkly Rep. 2016;65:1032–8. doi: 10.15585/mmwr.mm6538e1.CrossRefGoogle Scholar
  4. 4.
    CDC. Advice for people living in or traveling to Brownsville, Texas [Internet]. Centers for Disease Control and Prevention. 2016 [cited 2016 Dec 27]. Available from: https://www.cdc.gov/zika/intheus/texas-update.html
  5. 5.
    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;360:2536–43. doi: 10.1056/NEJMoa0805715.CrossRefPubMedGoogle Scholar
  6. 6.
    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;375:2321–34.CrossRefPubMedGoogle Scholar
  7. 7.
    Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects—reviewing the evidence for causality. N Engl J Med. 2016;374:1981–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Cao-Lormeau V, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J, et al. Guillain-Barré syndrome outbreak caused by Zika virus infection in French Polynesia. Lancet. 2016;387:1531–9. doi: 10.1016/S0140-6736(16)00562-6.CrossRefPubMedGoogle Scholar
  9. 9.
    Brasil P, Sequeira PC, Freitas AD, Zogbi H, Calvet GA, de Souza RV, et al. Guillain-Barré syndrome associated with Zika virus infection. Lancet. 2016;387:1482. doi: 10.1016/S0140-6736(16)30058-7.CrossRefPubMedGoogle Scholar
  10. 10.
    Musso D, Gubler DJ. Zika virus. Clin Microbiol Rev. 2016;29:487–524. doi: 10.1128/CMR.00072-15.CrossRefPubMedGoogle Scholar
  11. 11.
    Besnard M, Lastère S, Teissier A, Cao-Lormeau VM, Musso D. Evidence of perinatal transmission of Zika virus. Fr Polynesia Euro Surveill. 2014;19:20751.CrossRefGoogle Scholar
  12. 12.
    Aubry M, Finke J, Teissier A, Roche C, Broult J, Paulous S, et al. Seroprevalence of arboviruses among blood donors in French Polynesia, 2011–2013. Int J Infect Dis. 2015;41:11–2. doi: 10.1016/j.ijid.2015.10.005.CrossRefPubMedGoogle Scholar
  13. 13.
    Barjas-Castro ML, Angerami RN, Cunha MS, Suzuki A, Nogueira JS, Rocco IM, et al. Probable transfusion-transmitted Zika virus in Brazil. Transfusion. 2016;56:1684–8. doi: 10.1111/trf.13681.CrossRefPubMedGoogle Scholar
  14. 14.
    Swaminathan S, Schlaberg R, Lewis J, Hanson KE, Couturier MR. Fatal Zika virus infection with secondary nonsexual transmission. N Engl J Med. 2016;375:1907–9.CrossRefPubMedGoogle Scholar
  15. 15.
    •• World Health Organization. Prevention of sexual transmission of Zika virus—interim guidance update 6 September 2016. (WHO/ZIKV/MOC/16.1 Rev.3) Available at http://www.who.int/csr/resources/publications/zika/sexual-transmission-prevention/en/. Accessed Sep 7, 2016. This document presents a succinct review of sexual transmission of Zika virus and provides detailed recommendations for member countries on strategies for its prevention.
  16. 16.
    Dudley DM, Aliota MT, Mohr EL, Weiler AM, Lehrer-Brey G, Weisgrau KL, et al. A rhesus macaque model of Asian-lineage Zika virus infection. Nat Commun. 2016;7:12204. doi: 10.1038/ncomms12204.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lazear HM, Govero J, Smith AM, Platt DJ, Fernandez E, Miner JJ, et al. A mouse model of Zika virus pathogenesis. Cell Host Microbe. 2016;19:720–30. doi: 10.1016/j.chom.2016.03.010.CrossRefPubMedGoogle Scholar
  18. 18.
    Rossi SL, Tesh RB, Azar SR, Muruato AE, Hanley KA, Auguste AJ, et al. Characterization of a novel murine model to study Zika virus. Am J Trop Med Hyg. 2016;94:1362–9. doi: 10.4269/ajtmh.16-0111.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dowall SD, Graham VA, Rayner E, Atkinson B, Hall G, Watson RJ, et al. A susceptible mouse model for Zika virus infection. PLoS Negl Trop Dis. 2016;10, e0004658. doi: 10.1371/journal.pntd.0004658.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Cugola FR, Fernandes IR, Russo FB, Freitas BC, Dias JLM, Guimarães KP, et al. The Brazilian Zika virus strain causes birth defects in experimental models. Nature. 2016;534:267–71. doi: 10.1038/nature18296.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Ma W, Li S, Ma S, Jia L, Zhang F, Zhang Y, et al. Zika virus causes testis damage and leads to male infertility in mice. Cell. 2016;167:1511–24. doi: 10.1016/j.cell.2016.11.016.CrossRefPubMedGoogle Scholar
  22. 22.
    • Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL, Stutz B, et al. Vaginal exposure to Zika virus during pregnancy leads to fetal brain infection. Cell. 2016;166:1247–56. doi: 10.1016/j.cell.2016.08.004. This mouse model demonstrates how Zika virus can be introduced via the vaginal route, replicate in the vagina, and then spread to infect the fetal brain even in mice with an intact immune system. Notably, Zika virus infection in early pregnancy leads to fetal growth restriction.CrossRefPubMedGoogle Scholar
  23. 23.
    Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A, Haddow AD, et al. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011;17:880–2. doi: 10.3201/eid1705.101939.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau V-M. Potential sexual transmission Zika virus. Emerg Infect Dis. 2015;21:359–62. doi: 10.3201/eid2102.141363.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Venturi G, Zammarchi L, Fortuna C, Remoli ME, Benedetti E, Florentini C, et al. An autochthonous case of Zika due to possible sexual transmission, Florence, Italy, 2014. Euro Surveillance. 2016;21:1–4. doi: 10.2807/1560-7917.ES.2016.21.8.30148.Google Scholar
  26. 26.
    • Russell K, Hills SL, Oster AM, Porse CC, Danyluk G, Cone M, et al. Zika virus sexual transmission male-to-female sexual transmission of Zika virus—United States, Jan–Apr 2016. Clin Infect Dis. 2016 Oct 19. This is a summary of nine cases of male travelers to Latin America and the Caribbean whose female partners became infected within 10 to 19 days after the travelers’ onset of symptoms. Full clinical and laboratory details of these nine cases are provided.Google Scholar
  27. 27.
    • 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. Euro Surveillance. 2016;21:8–10. doi: 10.2807/1560-7917.ES.2016.21.23.30254. This unusual case report describes an asymptomatic couple with the wife identified with Zika virus infection by PCR during routine screening for assisted reproductive treatment. Based on the timing of her illness and their mutual travel to Martinique, her infection most likely occurred 8 to 23 days after return to France.Google Scholar
  28. 28.
    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. doi: 10.1016/S0140-6736(16)30775-9.CrossRefPubMedGoogle Scholar
  29. 29.
    Frank C, Cadar D, Schlaphof A, Neddersen N, Günther S, Schmidt-Chanasit J, et al. Sexual transmission of Zika virus in Germany. Euro Surveillance. 2016;21:2–5. doi: 10.2807/1560-7917.ES.2016.21.23.30252.Google Scholar
  30. 30.
    Arsuaga M, García Bujalance S, Díaz-Menéndez M, Vázquez A, Arribas JR. Probable sexual transmission of Zika virus from a vasectomised man. Lancet Infect Dis. 2016;16:1107–8. doi: 10.1016/S1473-3099(16)30320-6.CrossRefPubMedGoogle Scholar
  31. 31.
    Brooks RB, Carlos MP, Myers RA, White MG, Bobo-Lenoci T, Aplan D, et al. Likely sexual transmission of Zika virus from a man with no symptoms of infection—Maryland, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:915–6. doi: 10.15585/mmwr.mm6534e2.CrossRefPubMedGoogle Scholar
  32. 32.
    D’Ortenzio E, Matheron S, Yazdanpanah Y, de Lamballerie X, Hubert B, Piorkowski G, et al. Evidence of sexual transmission of Zika virus. N Engl J Med. 2016;374:2195–8. doi: 10.1056/NEJMc1604449.CrossRefPubMedGoogle Scholar
  33. 33.
    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;65:372–4. doi: 10.15585/mmwr.mm6514a3.CrossRefPubMedGoogle Scholar
  34. 34.
    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;65:716–7. doi: 10.15585/mmwr.mm6528e2.CrossRefPubMedGoogle Scholar
  35. 35.
    Harrower J, Kiedrzynski T, Baker S, Upton A, Rahnama F, Sherwood J, et al. Sexual transmission of Zika virus and persistence in semen, New Zealand, 2016. Emerg Infect Dis. 2016;22:1855–7. doi: 10.3201/eid2210.160951.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Hills SJ, 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. MMMR Morb Mortal Wkly Rep. 2016;65:1–3. doi: 10.15585/mmwr.mm6508e2.Google Scholar
  37. 37.
    WHO Zika virus infection—disease outbreak news (15/04/2016). http://www.who.int/csr/don/15-april-2016-zika-chile/en/Accessed Jan 3, 2017.
  38. 38.
    Yakob L, Walker T. Zika virus outbreak in the Americas: the need for novel mosquito control methods. Lancet Glob Healt. 2016;4:e148–9. doi: 10.1016/S2214-109X(16)00048-6.CrossRefGoogle Scholar
  39. 39.
    Brasil P, Calvet GA, Siqueira AM, Wakimoto M, de Sequeira PC, Nobre A, et al. Zika virus outbreak in Rio de Janeiro, Brazil: clinical characterization, epidemiological and virological aspects. PLoS Negl Trop Dis. 2016;10, e0004636. doi: 10.1371/journal.pntd.0004636.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hamer DH, Barbre KA, Chen LH, Grobusch MP, Schlagenhauf P, Goorhuis A, et al. Travel-associated Zika virus disease acquired in the Americas through February 2016. A GeoSentinel analysis. Ann Intern Med. 2016. doi: 10.7326/M16-1842.Google Scholar
  41. 41.
    Musso D. Zika virus transmission from French Polynesia to Brazil. Emerg Infect Dis. 2015;21:1887. doi: 10.3201/eid2110.151125.2016;21:2014-6.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Atkinson B, Hearn P, Afrough B, Lumley S, Carter D, Aarons EJ, et al. Detection of Zika virus in semen. Emerg Infect Dis. 2016;22:940. doi: 10.3201/eid2205.160107.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Mansuy JM, Pasquier C, Daudin M, Chapuy-Regaud S, Moinard N, Chevreau C, et al. Zika virus in semen of a patient returning from a non-epidemic area. Lancet Infect Dis. 2016;16(8):894–5. doi: 10.1016/S1473-3099(16)30153-0.CrossRefPubMedGoogle Scholar
  44. 44.
    Barzon L, Pacenti M, Berto A, Sinigaglia A, Franchin E, Lavezzo E, et al. Isolation of infectious Zika virus from saliva and prolonged viral RNA shedding in a traveller returning from the Dominican Republic to Italy, January 2016. Euro Surveillance. 2016;21(10). doi:  10.2807/1560-7917.
  45. 45.
    • Nicastri E, Castilletti C, Liuzzi G, Iannetta M, Capobianchi MR, Ippolito G. Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy February 2016. Euro Surveillance. 2016;21:8–11. doi: 10.2807/1560-7917.ES.2016.21.32.30314. This study demonstrated persistent shedding of Zika virus by PCR for 188 days, the longest duration of shedding yet reported.Google Scholar
  46. 46.
    Barzon L, Pacenti M, Franchin E, Lavezzo E, Trevisan M, Sgarabotto D, et al. Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016. Euro Surveillance. 2016;21:8–11. doi: 10.2807/1560-7917.ES.2016.21.32.30316.Google Scholar
  47. 47.
    Gaskell KM, Houlihan C, Nastouli E, Checkley AM. Persistent Zika virus detection in semen in a traveler returning to the United Kingdom from Brazil, 2016. Emerg Infect Dis. 2017;23:137–9. doi: 10.3201/eid2301.161300.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Reusken C, Pas S, Geurtsvankessel C, Mögling R, van Kampen J, Langerak T, et al. Longitudinal follow-up of Zika virus RNA in semen of a traveller returning from Barbados to the Netherlands with Zika virus disease, March 2016. Euro Surveillance. 2016;21:2–5. doi: 10.2807/1560-7917.ES.2016.21.23.30251.Google Scholar
  49. 49.
    Nicastri E, Castilletti C, Balestra P, Galgani S, Ippolito G. Zika virus infection in the central nervous system and female genital tract. Emerg Infect Dis. 2016;22:2228–30. doi: 10.3201/eid2212.161280.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Prisant N, Bujan L, Benichou H, Hayot P-H, Pavili L, Lurel S, et al. Zika virus in the female genital tract. Lancet Infect Dis. 2016;16:1000–1. doi: 10.1016/S1473-3099(16)30193-1.CrossRefPubMedGoogle Scholar
  51. 51.
    Murray KO, Gorchakov R, Carlson AR, Berry R, Lai L, Natrajan M, et al. Prolonged detection of Zika virus in vaginal secretions and whole blood. Emerg Infect Dis. 2017;23:99–101. doi: 10.3201/eid2301.161394.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Torres JR, Martínez N, Moros Z. Microhematospermia in acute Zika virus infection. Int J Infect Dis. 2016;51:9712. doi: 10.1016/j.ijid.2016.08.025.Google Scholar
  53. 53.
    • Prisant N, Breurec S, Moriniere C, Bujan L, Joguet G. Zika virus genital tract shedding in infected women of child-bearing age. Clin Infect Dis. 2016;64:107–9. The authors reported five women enrolled in a fertility preservation program in Guadeloupe who presented with Zika-like symptoms, with positive Zika PCR, and demonstrated negative Zika PCR in genital samples by the 3rd week.CrossRefPubMedGoogle Scholar
  54. 54.
    Coelho FC, Durovni B, Saraceni V, Lemos C, Codeco CT, Camargo S et al. Higher incidence of Zika in adult women in Rio de Janeiro suggests a significant contribution of sexual transmission from men to women. Int J Infect Dis. 2016;128–132. doi:  10.1016/j.ijid.2016.08.023.
  55. 55.
    Yakob L, Kucharski A, Hue S, Edmunds WJ. Low risk of a sexually-transmitted Zika virus outbreak. Lancet Infect Dis. 2016;16:1100–2. doi: 10.1016/S1473-3099(16)30324-3.CrossRefPubMedGoogle Scholar
  56. 56.
    Althaus CL, Low N. How relevant is sexual transmission of Zika virus? PLoS Med. 2016;13, e1002157. doi: 10.1371/journal.pmed.1002157.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Feranchuk S, Potapova U, Belikov S. Virtual screening of inhibitors for the Zika virus proteins. bioRxiv. 2016. doi: 10.1101/060798.Google Scholar
  58. 58.
    Xu M, Lee EM, Wen Z, Cheng Y, Huang W-K, Qian X, et al. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med. 2016;22:1101–7. doi: 10.1038/nm.4184.CrossRefPubMedGoogle Scholar
  59. 59.
    Eyer L, Nencka R, Huvarova I, Palus M, Alves MJ, Gould EA, et al. Nucleoside inhibitors of ZIka virus. J Infect Dis. 2016 Advance ac:1–21. doi: 10.1093/infdis/jiw226.
  60. 60.
    Zmurko J, Marques RE, Schols D, Verbeken E, Kaptein SJF, Neyts J. The viral polymerase inhibitor 7-deaza-2′-C-methyladenosine Is a potent inhibitor of in vitro Zika virus replication and delays disease progression in a robust mouse infection model. PLoS Negl Trop Dis. 2016;10:1–15. doi: 10.1371/journal.pntd.0004695.CrossRefGoogle Scholar
  61. 61.
    Sacramento CQ, de Melo GR, Rocha N, Hoelz LVB, Mesquita M, Al. E. The clinically approved antiviral drug sofosbuvir impairs Brazilian Zika virus replication. bioRxiv. 2016; Available at http://biorxiv.org/content/early/2016/07/06/061671doi: https://doi.org/10.1101/061671.
  62. 62.
    Delvecchio R, Higa LM, Pezzuto P, Valadao AL, Garcez PP, Monteiro FL, et al. Chloroquine inhibits Zika virus infection in different cellular models. Viruses. 2016;8. (bioRxiv. 2016;51268.)Google Scholar
  63. 63.
    Retallack H, Di Lullo E, Arias C, Knopp KA, Sandoval-Espinosa C, Laurie MT, et al. Zika virus in the human placenta and developing brain: cell tropism and drug inhibition. bioRxiv. 2016;58883.Google Scholar
  64. 64.
    Lin KJ, Mitchell AA, Yau WP, Louik C, Hernández-Díaz S. Safety of macrolides during pregnancy. Am J Obstet Gynecol. 2013;208:221. doi: 10.1016/j.ajog.2012.12.023. e1-8.PubMedGoogle Scholar
  65. 65.
    Carvalho CAM, Casseb SMM, Gonçalves RB, Silva EVP, Gomes AMO, Vasconcelos PFC. Bovine lactoferrin activity against chikungunya and Zika viruses. bioRxiv. 2016;71571.Google Scholar
  66. 66.
    •• Petersen EE, Meaney-Delman D, Neblett-Fanfair R, Havers F, Oduyebo T, Hills SL, 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;65:1077–81. doi: 10.15585/mmwr.mm6539e1. This is a succinct summary of evidence supporting the link between Zika virus infection during pregnancy and the congenital Zika syndrome. The guidelines provide extensive details on strategies for pre- and post-conception prevention of Zika virus infection, and guidance for screening and counselling pregnant women.CrossRefPubMedGoogle Scholar
  67. 67.
    CDC. Infographic: when to test for Zika virus. Available at https://www.cdc.gov/zika/pdfs/when-to-test-zika.pdf. Accessed Dec 19, 2016.

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Davidson H. Hamer
    • 1
    • 2
    • 3
  • Mary E. Wilson
    • 4
    • 5
  • Jenny Jean
    • 6
  • Lin H. Chen
    • 7
    • 8
  1. 1.Center for Global Health and DevelopmentBoston University School of Public HealthBostonUSA
  2. 2.Department of Global HealthBoston University School of Public HealthBostonUSA
  3. 3.Section of Infectious Diseases, Department of MedicineBoston University School of MedicineBostonUSA
  4. 4.University of CaliforniaSan FranciscoUSA
  5. 5.Harvard T. H. Chan School of Public HealthBostonUSA
  6. 6.Boston University School of MedicineBostonUSA
  7. 7.Harvard Medical SchoolBostonUSA
  8. 8.Travel Medicine CenterMount Auburn HospitalCambridgeUSA

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