Pregnancy and Zika virus

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the Flaviviridae family. In 1947 and 1948 ZIKV was first isolated from a nonhuman primate as well as from mosquitoes in Africa, respectively. For half a century, ZIKV infections in human were sporadic prior to 2015–2016 pandemic spreading. Transmission of ZIKV from mother to fetus can occur in any trimester of pregnancy, even if mother was an asymptomatic carrier. The clinical signs of ZIKV infection are nonspecific and can be misdiagnosed as some other infectious diseases, especially those caused by arboviruses such as Dengue and Chikungunya. ZIKV infection was solely associated with mild illness prior to the large French Polynesian and Brazil outbreaks, when severe neurological complications, Guillain–Barre syndrome and dramatically increased rate of severe congenital malformations (including microcephaly) were reported. The adaptation of ZIKV to an urban cycle in endemic areas suggests that the incidence of ZIKV infections may be underestimated. The pandemic of novel coronavirus infection (COVID-19) demonstrates that lessons from ZIKV pandemic propagation has not been learned properly.

1. Musso D., Gubler D.J. Zika virus. Clin Microbiol Rev. 2016;29(3):487–524. DOI: 10.1128/CMR.00072-15.

2. Petersen L.R., Jamieson D.J., Powers A.M., Honein M.A. Zika virus. N Engl J Med. 2016;374(16):1552–63. DOI: 10.1056/NEJMra1602113.

3. de Oliveira W.K., de França G.V.A., Carmo E.H. et al. Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: a surveillance-based analysis. Lancet. 2017;390(10097):861–70. DOI: 10.1016/S0140-6736(17)31368-5.

4. Krow-Lucal E.R., de Andrade M.R., Cananéa J.N.A. et al. Association and birth prevalence of microcephaly attributable to Zika virus infection among infants in Paraíba, Brazil, in 2015-16: a case-control study. Lancet Child Adolesc Health. 2018;2(3):205–13. DOI: 10.1016/S2352-4642(18)30020-8.

5. Grubaugh N.D., Ishtiaq F., Setoh Y.X., Ko A.I. Misperceived risks of Zika-related microcephaly in India. Trends Microbiol. 2019;27(5):381–3. DOI: 10.1016/j.tim.2019.02.004.

6. Liu Z.Y., Shi W.F., Qin C.F. The evolution of Zika virus from Asia to the Americas. Nat Rev Microbiol. 2019;17(3):131–9. DOI: 10.1038/s41579-018-0134-9.

7. Dick G.W., Kitchen S.F., Haddow A.J. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46(5):509–20. DOI: 10.1016/0035-9203(52)90042-4.

8. Faria N.R., Azevedo R.D.S.D.S., Kraemer M.U.G. et al. Zika virus in the Americas: early epidemiological and genetic findings. Science. 2016;352(6283):345–9. DOI: 10.1126/science.aaf5036.

9. Weaver S.C., Costa F., Garcia-Blanco M.A. et al. Zika virus: history, emergence, biology, and prospects for control. Antiviral Res. 2016;130:69–80. DOI: 10.1016/j.antiviral.2016.03.010.

10. Heang V., Yasuda C.Y., Sovann L. et al. Zika virus infection, Cambodia, 2010. Emerg Infect Dis. 2012;18(2):349–51. DOI: 10.3201/eid1802.111224.

11. Duffy M.R., Chen T.H., Hancock W.T. et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360(24):2536–43. DOI: 10.1056/NEJMoa0805715.

12. Musso D., Bossin H., Mallet H.P. et al. Zika virus in French Polynesia 2013–14: anatomy of a completed outbreak. Lancet Infect Dis. 2018;18(5):e172–e182. DOI: 10.1016/S1473-3099(17)30446-2.

13. Baud D., Gubler D.J., Schaub B. et al. An update on Zika virus infection. Lancet. 2017;390(10107):2099–109. DOI: 10.1016/S0140-6736(17)31450-2.

14. Rossi S.L., Ebel G.D., Shan C. et al. Did Zika virus mutate to cause severe outbreaks? Trends Microbiol. 2018;26(10):877–85. DOI: 10.1016/j.tim.2018.05.007.

15. Rodriguez-Barraquer I., Costa F., Nascimento E.J.M. et al. Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region. Science. 2019;363(6427):607–10. DOI: 10.1126/science.aav6618

16. Cao-Lormeau V.M., Blake A., Mons S. et al. Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016;387(10027):1531–9. DOI: 10.1016/S0140-6736(16)00562-6.

17. deAraújo T.V.B., Rodrigues L.C., de Alencar Ximenes R.A. et al. Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study. Lancet Infect Dis. 2016;16(12):1356–63. DOI: 10.1016/S1473-3099(16)30318-8.

18. Rasmussen S.A., Jamieson D.J., Honein M.A., Petersen LR. Zika virus and birth defects — reviewing the evidence for causality. N Engl J Med. 2016;374(20):1981–7. DOI: 10.1056/NEJMsr1604338.

19. Victora C.G., Schuler-Faccini L., Matijasevich A. et al. Microcephaly in Brazil: how to interpret reported numbers? Lancet. 2016;387():621–4. DOI: 10.1016/S0140-6736(16)00273-7.

20. Hay J.A., Nouvellet P., Donnelly C.A., Riley S. Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy. PLoS Negl Trop Dis. 2018;12(12):e0006991. DOI: 10.1371/journal.pntd.0006991.

21. Liu Y., Liu J., Du S. et al. Evolutionary enhancement of Zika virus infectivity in Aedesaegypti mosquitoes. Nature. 2017;545(7655):482–6. DOI: 10.1038/nature22365.

22. Yuan L., Huang X.Y., Liu Z.Y. et al. A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science. 2017;358(6365):933–6. DOI: 10.1126/science.aam7120.

23. Swanstrom J.A., Plante J.A., Plante K.S. et al. Dengue virus envelope dimer epitope monoclonal antibodies isolated from dengue patients are protective against Zika virus. MBio. 2016;7(4). pii: e01123-16. DOI: 10.1128/mBio.01123-16.

24. Bardina S.V., Bunduc P., Tripathi S. et al. Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity. Science. 2017;356(6334):175–80. DOI: 10.1126/science.aal4365.

25. Gordon A., Gresh L., Ojeda S. et al. Prior dengue virus infection and risk of Zika: a pediatric cohort in Nicaragua. PLoS Med. 2019;16(1):e100272. DOI: 10.1371/journal.pmed.1002726.

26. Ferguson N.M., Cucunubá Z.M., Dorigatti I. et al. Epidemiology: countering the Zika epidemic in Latin America. Science. 2016;353(6297):353–4. DOI: 10.1126/science.aag0219.

27. Grubaugh N.D., Saraf S., Gangavarapu K. et al. Travel surveillance and genomics uncover a hidden Zika outbreak during the waning epidemic. Cell. 2019;178(5):1057–71.e11. DOI: 10.1016/j.cell.2019.07.018.

28. Favoretto S.R., Araujo D.B., Duarte N.F.H. et al. Zika virus in peridomesticneotropical primates, northeast Brazil. Ecohealth. 2019;16(1):61–9. DOI: 10.1007/s10393-019-01394-7.

29. Duong V., Dussart P., Buchy P. Zika virus in Asia. Int J Infect Dis. 2017;54:121–8. DOI: 10.1016/j.ijid.2016.11.420.

30. Gutiérrez-Bugallo G., Piedra L.A., Rodriguez M. et al. Vector-borne transmission and evolution of Zika virus. Nat Ecol Evol. 2019;3(4):561–9. DOI: 10.1038/s41559-019-0836-z.

31. Bloch E.M., Ness P.M., Tobian A.A.R., Sugarman J. Revisiting blood safety practices given emerging data about Zika virus. N Engl J Med. 2018;378(19):1837–41. DOI: 10.1056/NEJMsb1704752.

32. Polen K.D., Gilboa S.M., Hills S. et al. Update: interim guidance for preconception counseling and prevention of sexual transmission of Zika virus for men with possible Zika virus exposure – United States, August 2018. MMWR Morb Mortal Wkly Rep. 2018;67(31):868–71. DOI: 10.15585/mmwr.mm6731e2.

33. Wilder-Smith A., Chang C.R., Leong W.Y. Zika in travellers 1947–2017: a systematic review. J Travel Med. 2018;25(1). DOI: 10.1093/jtm/tay044.

34. Mead P.S., Duggal N.K., Hook S.A. et al. Zika virus shedding in semen of symptomatic infected men. N Engl J Med. 2018;378(15):1377–85. DOI: 10.1056/NEJMoa1711038.

35. Joguet G., Mansuy J-M., Matusali G. et al. Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study. Lancet Infect Dis. 2017;17(11):1200–8. DOI: 10.1016/S1473-3099(17)30444-9.

36. Hoen B., Schaub B., Funk A.L. et al. Pregnancy outcomes after ZIKV infection in French territories in the Americas. N Engl J Med. 2018;378(11):985–94. DOI: 10.1056/NEJMoa1709481.

37. Shapiro-Mendoza C.K., Rice M.E., Galang R.R. et al. Pregnancy outcomes after maternal Zika virus infection during pregnancy – U.S. territories, January 1, 2016–April 25, 2017. MMWR Morb Mortal Wkly Rep. 2017;66(23):615–21. DOI: 10.15585/mmwr.mm6623e1. 38. Reynolds M.R., Jones A.M., Petersen E.E. et al; U.S. Zika Pregnancy Registry Collaboration. Vital signs: update on Zika virus-associated birth defects and evaluation of all U.S. infants with

38. congenital Zika virus exposure – U.S. Zika Pregnancy Registry, 2016. MMWR Morb Mortal Wkly Rep. 2017;66(13):366–73. DOI: 10.15585/mmwr.mm6613e1.

39. Pomar L., Vouga M., Lambert V. et al. Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana. BMJ. 2018;363:k4431. DOI:10.1136/bmj.k4431.

40. Mann T.Z., Haddad L.B., Williams T.R. et al. Breast milk transmission of flaviviruses in the context of Zika virus: a systematic review. Paediatr Perinat Epidemiol. 2018;32(4):358–68. DOI: 10.1111/ppe.12478.

41. Miner J.J., Diamond M.S. Zika virus pathogenesis and tissue tropism. Cell Host Microbe. 2017;21(2):134–42. DOI: 10.1016/j.chom.2017.01.004.

42. Mier-Y-Teran-Romero L., Delorey M.J., Sejvar J.J., Johansson M.A. Guillain-Barré syndrome risk among individuals infected with Zika virus: a multi-country assessment. BMC Med. 2018;16(1):67. DOI: 10.1186/s12916-018-1052-4.

43. Halpin A.L., Gu W., Wise M.E. et al. Post-Campylobacter Guillain Barré syndrome in the USA: secondary analysis of surveillance data collected during the 2009–2010 novel influenza A (H1N1) vaccination campaign. Epidemiol Infect. 2018;146(13):1740–5. DOI: 10.1017/S0950268818001802.

44. Muñoz L.S., Parra B., Pardo C.A. Neurological implications of Zika virus infection in adults. J Infect Dis. 2017;216(Suppl 10):S897–S905. DOI: 10.1017/S0950268818001802.

45. Dirlikov E., Major C.G., Medina NA, et al. Clinical features of Guillain-Barré syndrome with vs without Zika virus infection, Puerto Rico, 2016. JAMA Neurol. 2018;75(9):1089–97. DOI: 10.1001/jamaneurol.2018.1058.

46. Costa F., Sarno M., Khouri R. et al. Emergence of congenital Zika syndrome: viewpoint from the front lines. Ann Intern Med. 2016;164(10):689–91. DOI: 10.7326/M16-0332.

47. Miranda-Filho D. de B., Martelli C.M., Ximenes RA. et al. Initial description of the presumed congenital Zika syndrome. Am J Public Health. 2016;106(4):598–600. DOI: 10.2105/AJPH.2016.303115.

48. Moore C.A., Staples J.E., Dobyns W.B. et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr. 2017;171(3):288–95. DOI: 10.1001/jamapediatrics.2016.3982. 49. Honein M.A., Dawson A.L., Petersen E.E. et al; US Zika Pregnancy Registry Collaboration. Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy. JAMA. 2017;317(1):59–68. DOI: 10.1001/jama.2016.19006.

49. Rice M.E., Galang R.R., Roth N.M. et al. Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection – U.S.

50. territories and freely associated states, 2018. MMWR Morb Mortal Wkly Rep. 2018;67(31):858–67. DOI: 10.15585/mmwr.mm6731e1.

51. Ventura C.V., Ventura L.O. Ophthalmologic manifestations associated with Zika virus infection. Pediatrics. 2018;141(Suppl 2):S161–S166. DOI: 10.1542/peds.2017-2038E.

52. van der Linden V., Pessoa A., Dobyns W. et al. Description of 13 infants born during October 2015–January 2016 with congenital Zika virus infection without microcephaly at Birth – Brazil. MMWR Morb Mortal Wkly Rep. 2016;65(47):1343–8. DOI: 10.15585/mmwr.mm6547e2.

53. Paz-Bailey G., Rosenberg E.S., Doyle K. et al. Persistence of Zika virus in body fluids – final report. N Engl J Med. 2017;379(13):1234–43. DOI: 10.1056/NEJMoa16.

54. Schaub B., Vouga M., Najioullah F. et al. Analysis of blood from Zika virus-infected fetuses: a prospective case series. Lancet Infect Dis. 2017;17(5):520–7. DOI: 10.1016/S1473-3099(17)30102-0.

55. Schaub B., Gueneret M., Jolivet E. et al. Ultrasound imaging for identification of cerebral damage in congenital Zika virus syndrome: a case series. Lancet Child Adolesc Health. 2017;1(1):45–55. DOI: 10.1016/S2352-4642(17)30001-9.

56. Masmejan S., Baud D., Musso D., Panchaud A. Zika virus, vaccines, and antiviral strategies. Expert Rev Anti Infect Ther. 2018;16(6):471–83. DOI: 10.1080/14787210.2018.1483239.

57. Wilder-Smith A., Vannice K., Durbin A. et al. Zika vaccines and therapeutics: landscape analysis and challenges ahead. BMC Med. 2018;16(1):84. DOI: 10.1186/s12916-018-1067-x.

58. Vannice K.S., Cassetti M.C., Eisinger R.W. et al. Demonstrating vaccine effectiveness during a waning epidemic: a WHO/NIH meeting report on approaches to development and licensure of Zika vaccine candidates. Vaccine. 2019;37(6):863–8. DOI: 10.1016/j.vaccine.2018.12.040.

59. Morain S.R., Wootton S.H., Eppes C. A devastating delay – Zika and the implementation gap. N Engl J Med. 2017;377(16):1505–7. DOI: 10.1056/NEJMp1707273.

60. Aiken A.R., Scott J.G., Gomperts R. et al. Requests for abortion in Latin America related to concern about Zika virus exposure. N Engl J Med. 2016;375(4):396–8. DOI: 10.1056/NEJMc1605389.

61. Castro M.C., Han Q.C., Carvalho L.R. et al. Implications of Zika virus and congenital Zika syndrome for the number of live births in Brazil. Proc Natl Acad Sci U S A. 2018;115(24):6177–82. DOI: 10.1073/pnas.1718476115.

62. von Seidlein L., Kekulé A.S., Strickman D. Novel vector control approaches: the future for prevention of Zika virus transmission? PLoS Med. 2017;14(1):e1002219. DOI: 10.1371/journal.pmed.1002219.

63. Rice M.E., Galang R.R., Roth N.M. et al. Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zikavirus infection – U.S. territories and freely associated states, 2018. MMWR Morb Mortal Wkly Rep. 2018;67(31):858–67. DOI: 10.15585/mmwr.mm6731e1.