Epidemiology, Prevention, and Potential Future Treatments of Sexually Transmitted Zika Virus Infection
- 948 Downloads
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.
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.
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.
KeywordsZika virus Epidemiology Sexual transmission Semen
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.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 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
- 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.
- 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
- 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.• 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
- 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.
- 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
- 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.• 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.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
- 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
- 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.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.
- 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.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.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.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.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
- 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.•• 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.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.