Register      Login

VOLUME 2 , ISSUE 1 ( January-March, 2023 ) > List of Articles


Congenital Zika Virus Infections

Yahya Ethawi, Gangajal Kasniya, Nibras Al Baiti, Rehab Mohammed, FatimaElzahara Taha Mohammad, Roya Arif Huseynova

Keywords : Congenital Zika syndrome, Newborn, Real-time reverse transcription-polymerase chain reaction, Magnetic resonance imaging, Zika virus infection

Citation Information : Ethawi Y, Kasniya G, Al Baiti N, Mohammed R, Mohammad FT, Huseynova RA. Congenital Zika Virus Infections. 2023; 2 (1):91-101.

DOI: 10.5005/jp-journals-11002-0055

License: CC BY-NC 4.0

Published Online: 07-04-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Zika virus (ZIKV) is an arthropod-borne flavivirus transmitted through bites of the Aedes mosquitoes. Infected mothers can vertically transmit ZIKV to their fetuses, particularly during the first and second trimesters. Infections beginning during early gestation can cause congenital Zika virus syndrome (CZS), which may be marked by arrested development and/or altered healing in the nervous system. There can be microcephaly, craniosynostosis, intracranial calcifications, ventriculomegaly, low brain volume and/or cortical atrophy, and hypoplasia/altered myelination in the corpus callosum, cerebellum, and brainstem. There may also be altered development with polymicrogyria, pachygyria, and lissencephaly. Clinically, infants with CZS may show facial dysmorphism, pulmonary hypoplasia, altered growth and development, hypertonia, hyperreflexia, limb contractures, and arthrogryposis multiplex. Perinatal infections can present with irritability, seizures, eye involvement, and sensorineural hearing loss (SNHL). Congenital zika virus syn and perinatal infections contrast with those acquired after birth, which usually have a relatively milder course. Overall, the mortality rate can reach 4–6%. Laboratory evaluation can include polymerase chain reactions on serum, cerebrospinal fluid, and urine; testing for immunoglobulin M (IgM); and plaque reduction neutralization tests (PRNTs) to confirm the specificity of these Zika virus IgM (ZIKV IgM) antibodies. Unfortunately, no specific treatment is available; most measures are largely supportive.

  1. Dick GW, Kitchen SF, Haddow AJ. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg 1952;46(5):509–520. DOI: 10.1016/0035-9203(52)90042-4.
  2. Grard G, Caron M, Mombo IM, et al. Zika virus in Gabon (Central Africa) – 2007: A new threat from Aedes albopictus? PLoS Negl Trop Dis 2014;8(2):e2681. DOI: 10.1371/journal.pntd.0002681.
  3. Qian X, Qi Z. Mosquito-borne flaviviruses and current therapeutic advances. Viruses 2022;14(6):1226. DOI: 10.3390/v14061226.
  4. Gubler DJ, Vasilakis N, Musso D. History and emergence of Zika virus. J Infect Dis 2017;216(Suppl. 10):S860–S867. DOI: 10.1093/infdis/jix451.
  5. Duffy MR, Chen TH, Hancock WT, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009;360(24):2536–2543. DOI: 10.1056/NEJMoa0805715.
  6. Ikejezie J, Shapiro CN, Kim J, et al. Zika virus transmission – Region of the Americas, May 15, 2015–December 15, 2016. MMWR Morb Mortal Wkly Rep 2017;66(12):329–334. DOI: 10.15585/mmwr.mm6612a4.
  7. Rodriguez–Diaz CE, Garriga–Lopez A, Malave–Rivera SM, et al. Zika virus epidemic in Puerto Rico: Health justice too long delayed. Int J Infect Dis 2017;65:144–147. DOI: 10.1016/j.ijid.2017.07.017.
  8. Morris JK, Dolk H, Duran P, et al. Use of infectious disease surveillance reports to monitor the Zika virus epidemic in Latin America and the Caribbean from 2015 to 2017: Strengths and deficiencies. BMJ Open 2020;10(12):e042869. DOI: 10.1136/bmjopen-2020-042869.
  9. Lowe R, Barcellos C, Brasil P, et al. The Zika virus epidemic in Brazil: From discovery to future implications. Int J Environ Res Public Health 2018;15(1):96. DOI: 10.3390/ijerph15010096.
  10. Yan G, Pang L, Cook AR, et al. Distinguishing Zika and dengue viruses through simple clinical assessment, Singapore. Emerg Infect Dis 2018;24(8):1565–1568. DOI: 10.3201/eid2408.171883.
  11. Chang C, Ortiz K, Ansari A, et al. The Zika outbreak of the 21st century. J Autoimmun 2016;68:1–13. DOI: 10.1016/j.jaut.2016.02.006.
  12. Aubry M, Teissier A, Huart M, et al. Zika virus seroprevalence, French Polynesia, 2014–2015. Emerg Infect Dis 2017;23(4):669–672. DOI: 10.3201/eid2304.161549.
  13. Aliota MT, Bassit L, Bradrick SS, et al. Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network. Antiviral Res 2017;144:223–246. DOI: 10.1016/j.antiviral.2017.06.001.
  14. Bragazzi NL, Alicino C, Trucchi C, et al. Global reaction to the recent outbreaks of Zika virus: Insights from a Big Data analysis. PLoS One 2017;12(9):e0185263. DOI: 10.1371/journal.pone.0185263.
  15. Freitas DA, Souza–Santos R, Carvalho LMA, et al. Congenital Zika syndrome: A systematic review. PLoS One 2020;15(12):e0242367. DOI: 10.1371/journal.pone.0242367.
  16. Paixao ES, Cardim LL, Costa MCN, et al. Mortality from congenital Zika syndrome: Nationwide cohort study in Brazil. N Engl J Med 24 2022;386(8):757–767. DOI: 10.1056/NEJMoa2101195.
  17. Nithiyanantham SF, Badawi A. Maternal infection with Zika virus and prevalence of congenital disorders in infants: systematic review and meta-analysis. Can J Public Health 2019;110(5):638–648. DOI: 10.17269/s41997-019-00215-2.
  18. Curcio AM, Shekhawat P, Reynolds AS, et al. Neurologic infections during pregnancy. Handb Clin Neurol 2020;172:79–104. DOI: 10.1016/B978-0-444-64240-0.00005-2.
  19. Nogueira ML, Nery Junior NRR, Estofolete CF, et al. Adverse birth outcomes associated with Zika virus exposure during pregnancy in Sao Jose do Rio Preto, Brazil. Clin Microbiol Infect 2018;24(6):646–652. DOI: 10.1016/j.cmi.2017.11.004.
  20. Antoniou E, Orovou E, Andronikidi PE, et al. Congenital Zika infection and the risk of neurodevelopmental, neurological, and urinary track disorders in early childhood: A systematic review. Viruses 2021;13(8):1671. DOI: 10.3390/v13081671.
  21. Waldorf KMA, Nelson BR, Stencel–Baerenwald JE, et al. Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain. Nat Med 2018;24(3):368–374. DOI: 10.1038/nm.4485.
  22. Ades AE, Soriano–Arandes A, Alarcon A, et al. Vertical transmission of Zika virus and its outcomes: A Bayesian synthesis of prospective studies. Lancet Infect Dis 2021;21(4):537–545. DOI: 10.1016/S1473-3099(20)30432-1.
  23. Neufeldt CJ, Cortese M, Acosta EG, et al. Rewiring cellular networks by members of the Flaviviridae family. Nat Rev Microbiol 2018;16(3): 125–142. DOI: 10.1038/nrmicro.2017.170.
  24. Mazeaud C, Freppel W, Chatel–Chaix L. The multiples fates of the flavivirus RNA genome during pathogenesis. Front Genet 2018;9:595. DOI: 10.3389/fgene.2018.00595.
  25. Lee H, Halverson S, Ezinwa N. Mosquito-borne diseases. Prim Care 2018;45(3):393–407. DOI: 10.1016/j.pop.2018.05.001.
  26. Bogovic P, Strle F. Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management. World J Clin Cases 2015;3(5):430–441. DOI: 10.12998/wjcc.v3.i5.430.
  27. Petersen LR, Brault AC, Nasci RS. West Nile virus: Review of the literature. JAMA 2013;310(3):308–315. DOI: 10.1001/jama.2013.8042.
  28. Back AT, Lundkvist A. Dengue viruses: An overview. Infect Ecol Epidemiol 2013;3, DOI: 10.3402/iee.v3i0.19839.
  29. Sharma KB, Vrati S, Kalia M. Pathobiology of Japanese encephalitis virus infection. Mol Aspects Med 2021;81:100994. DOI: 10.1016/j.mam.2021.100994.
  30. Barrett AD, Higgs S. Yellow fever: A disease that has yet to be conquered. Annu Rev Entomol 2007;52:209–229. DOI: 10.1146/annurev.ento.52.110405.091454.
  31. Dubrau D, Tortorici MA, Rey FA, et al. A positive-strand RNA virus uses alternative protein–protein interactions within a viral protease/cofactor complex to switch between RNA replication and virion morphogenesis. PLoS Pathog 2017;13(2):e1006134. DOI: 10.1371/journal.ppat.1006134.
  32. Zhang X, Zhang Y, Jia R, et al. Structure and function of capsid protein in flavivirus infection and its applications in the development of vaccines and therapeutics. Vet Res 2021;52(1):98. DOI: 10.1186/s13567-021-00966-2.
  33. Therkelsen MD, Klose T, Vago F, et al. Flaviviruses have imperfect icosahedral symmetry. Proc Natl Acad Sci U S A 2018;115(45):11608–11612. DOI: 10.1073/pnas.1809304115.
  34. Bressanelli S, Stiasny K, Allison SL, et al. Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation. EMBO J 2004;23(4):728–738. DOI: 10.1038/sj.emboj.7600064.
  35. Tan TY, Fibriansah G, Kostyuchenko VA, et al. Capsid protein structure in Zika virus reveals the flavivirus assembly process. Nat Commun 2020;11(1):895. DOI: 10.1038/s41467-020-14647-9.
  36. Shang Z, Song H, Shi Y, et al. Crystal structure of the capsid protein from Zika virus. J Mol Biol 2018;430(7):948–z62. DOI: 10.1016/j.jmb.2018.02.006.
  37. Valente AP, Moraes AH. Zika virus proteins at an atomic scale: How does structural biology help us to understand and develop vaccines and drugs against Zika virus infection? J Venom Anim Toxins Incl Trop Dis 2019;25:e20190013. DOI: 10.1590/1678-9199-JVATITD-2019-0013.
  38. Lee LJ, Komarasamy TV, Adnan NAA, et al. Hide and seek: The interplay between Zika virus and the host immune response. Front Immunol 2021;12:750365. DOI: 10.3389/fimmu.2021.750365.
  39. Sirohi D, Kuhn RJ. Zika virus structure, maturation, and receptors. J Infect Dis 2017;216(Suppl. 10):S935–S944. DOI: 10.1093/infdis/jix515.
  40. Sironi M, Forni D, Clerici M, et al. Nonstructural proteins are preferential positive selection targets in Zika virus and related flaviviruses. PLoS Negl Trop Dis 2016;10(9):e0004978. DOI: 10.1371/journal.pntd.0004978.
  41. Newton ND, Hardy JM, Modhiran N, et al. The structure of an infectious immature flavivirus redefines viral architecture and maturation. Sci Adv 2021;7(20):eabe4507. DOI: 10.1126/sciadv.abe4507.
  42. Moureau G, Cook S, Lemey P, et al. New insights into flavivirus evolution, taxonomy and biogeographic history, extended by analysis of canonical and alternative coding sequences. PLoS One 2015;10(2):e0117849. DOI: 10.1371/journal.pone.0117849.
  43. DiNunno NM, Goetschius DJ, Narayanan A, et al. Identification of a pocket factor that is critical to Zika virus assembly. Nat Commun 2020;11(1):4953. DOI: 10.1038/s41467-020-18747-4.
  44. Sirohi D, Chen Z, Sun L, et al. The 3.8 A resolution cryo-EM structure of Zika virus. Science 2016;352(6284):467–470. DOI: 10.1126/science.aaf5316.
  45. Franca R, Silva JM, Rodrigues LS, et al. New anti-flavivirus fusion loop human antibodies with Zika virus-neutralizing potential. Int J Mol Sci 2022;23(14):7805. DOI: 10.3390/ijms23147805.
  46. Song W, Zhang H, Zhang Y, et al. Identification and characterization of Zika virus NS5 methyltransferase inhibitors. Front Cell Infect Microbiol 2021;11:665379. DOI: 10.3389/fcimb.2021.665379.
  47. Dong S, Xiao MZX, Liang Q. Modulation of cellular machineries by Zika virus-encoded proteins. J Med Virol 2023;95(1):e28243. DOI: 10.1002/jmv.28243.
  48. Roos WH, Ivanovska IL, Evilevitch A, et al. Viral capsids: Mechanical characteristics, genome packaging and delivery mechanisms. Cell Mol Life Sci 2007;64(12):1484–1497. DOI: 10.1007/s00018-007-6451-1.
  49. Yu Y, Gao C, Wen C, et al. Intrinsic features of Zika virus non-structural proteins NS2A and NS4A in the regulation of viral replication. PLoS Negl Trop Dis 2022;16(5):e0010366. DOI: 10.1371/journal.pntd.0010366.
  50. Barnard TR, Abram QH, Lin QF, et al. Molecular determinants of flavivirus virion assembly. Trends Biochem Sci 2021;46(5):378–390. DOI: 10.1016/j.tibs.2020.12.007.
  51. Izaguirre G. The proteolytic regulation of virus cell entry by furin and other proprotein convertases. Viruses 2019;11(9):837. DOI: 10.3390/v11090837.
  52. Braun E, Sauter D. Furin-mediated protein processing in infectious diseases and cancer. Clin Transl Immunology 2019;8(8):e1073. DOI: 10.1002/cti2.1073.
  53. Zhou TF, Lai ZT, Liu S, et al. Susceptibility and interactions between IS mosquitoes and Zika viruses. Insect Sci 2021;28(5):1439–1451. DOI: 10.1111/1744-7917.12858.
  54. Paixao ES, Teixeira MG, Rodrigues LC. Zika, chikungunya and dengue: The causes and threats of new and re-emerging arboviral diseases. BMJ Glob Health 2018;3(Suppl. 1):e000530. DOI: 10.1136/bmjgh-2017-000530.
  55. Chitolina RF, Anjos FA, Lima TS, et al. Raw sewage as breeding site to Aedes (Stegomyia) aegypti (Diptera, culicidae). Acta Trop 2016;164:290–296. DOI: 10.1016/j.actatropica.2016.07.013.
  56. Du S, Liu Y, Liu J, et al. Aedes mosquitoes acquire and transmit Zika virus by breeding in contaminated aquatic environments. Nat Commun 22 2019;10(1):1324. DOI: 10.1038/s41467-019-09256-0.
  57. Zanluca C, de Noronha L, dos Santos CND. Maternal–fetal transmission of the zika virus: An intriguing interplay. Tissue Barriers 2018;6(1):e1402143. DOI: 10.1080/21688370.2017.1402143.
  58. Colt S, Garcia–Casal MN, Pena–Rosas JP, et al. Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: A systematic review. PLoS Negl Trop Dis 2017;11(4):e0005528. DOI: 10.1371/journal.pntd.0005528.
  59. Mann TZ, Haddad LB, Williams TR, et al. Breast milk transmission of flaviviruses in the context of Zika virus: A systematic review. Paediatr Perinat Epidemiol 2018;32(4):358–368. DOI: 10.1111/ppe.12478.
  60. Adams Waldorf KM, Olson EM, Nelson BR, et al. The aftermath of Zika: Need for long-term monitoring of exposed children. Trends Microbiol 2018;26(9):729–732. DOI: 10.1016/j.tim.2018.05.011.
  61. Sampieri CL, Montero H. Breastfeeding in the time of Zika: A systematic literature review. PeerJ 2019;7:e6452. DOI: 10.7717/peerj.6452.
  62. Mead PS, Hills SL, Brooks JT. Zika virus as a sexually transmitted pathogen. Curr Opin Infect Dis 2018;31(1):39–44. DOI: 10.1097/QCO.0000000000000414.
  63. Murray JS. Understanding Zika virus. J Spec Pediatr Nurs 2017;22(1). DOI: 10.1111/jspn.12164.
  64. Counotte MJ, Kim CR, Wang J, et al. Sexual transmission of Zika virus and other flaviviruses: A living systematic review. PLoS Med 2018;15(7):e1002611. DOI: 10.1371/journal.pmed.1002611.
  65. Nicastri E, Castilletti C, Liuzzi G, et al. 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 Surveill 2016;21(32):30314. DOI: 10.2807/1560-7917.ES.2016.21.32.30314.
  66. Vanegas H, Gonzalez F, Reyes Y, et al. Zika RNA and flavivirus-like antigens in the sperm cells of symptomatic and asymptomatic subjects. Viruses 2021;13(2):152. DOI: 10.3390/v13020152.
  67. Magnus MM, Esposito DLA, Costa VAD, et al. Risk of Zika virus transmission by blood donations in Brazil. Hematol Transfus Cell Ther 2018;40(3):250–254. DOI: 10.1016/j.htct.2018.01.011.
  68. Musso D, Nhan T, Robin E, et al. Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014. Euro Surveill 2014;19(14): DOI: 10.2807/1560-7917.es2014.19.14.20761.
  69. Hills SL, Morrison A, Stuck S, et al. Case series of laboratory-associated Zika virus disease, United States, 2016–2019. Emerg Infect Dis 2021;27(5):1296–1300. DOI: 10.3201/eid2705.203602.
  70. Shugart JM, Brown CK. Zika virus presents an ongoing occupational health hazard for laboratory and biomedical research workers. Appl Biosaf 2019;24(1):8–9. DOI: 10.1177/1535676018818562.
  71. Gulland A. Zika virus is a global public health emergency, declares WHO. BMJ 2016;352:i657. DOI: 10.1136/bmj.i657.
  72. Chiu CF, Chu LW, Liao IC, et al. The mechanism of the Zika virus crossing the placental barrier and the blood–brain barrier. Front Microbiol 2020;11:214. DOI: 10.3389/fmicb.2020.00214.
  73. Arruda LV, Salomao NG, Alves FAV, et al. The innate defense in the Zika-infected placenta. Pathogens 2022;11(12): DOI: 10.3390/pathogens11121410.
  74. Rabelo K, de Souza LJ, Salomao NG, et al. Zika induces human placental damage and inflammation. Front Immunol 2020;11:2146. DOI: 10.3389/fimmu.2020.02146.
  75. Ferraris P, Cochet M, Hamel R, et al. Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway. Emerg Microbes Infect 2019;8(1):1003–1016. DOI: 10.1080/22221751.2019.1637283.
  76. King EL, Irigoyen N. Zika virus and neuropathogenesis: The unanswered question of which strain is more prone to causing microcephaly and other neurological defects. Front Cell Neurosci 2021;15:695106. DOI: 10.3389/fncel.2021.695106.
  77. Gurung S, Reuter N, Preno A, et al. Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon. PLoS Pathog 2019;15(1):e1007507. DOI: 10.1371/journal.ppat.1007507.
  78. Zorrilla CD, García IG, Fragoso LG, et al. Zika virus infection in pregnancy: Maternal, fetal, and neonatal considerations. J Infect Dis 2017;216(Suppl. 10):S891–S896. DOI: 10.1093/infdis/jix448.
  79. Shao Q, Herrlinger S, Yang SL, et al. Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage. Development 2016;143(22):4127–4136. DOI: 10.1242/dev.143768.
  80. Wheeler AC. Development of infants with congenital Zika syndrome: What do we know and what can we expect? Pediatrics 2018;141(Suppl. 2):S154–S160. DOI: 10.1542/peds.2017-2038D.
  81. Gazeta RE, Bertozzi A, Dezena R, et al. Three-year clinical follow-up of children intrauterine exposed to Zika virus. Viruses 2021;13(3): DOI: 10.3390/v13030523.
  82. Rothan HA, Fang S, Mahesh M, et al. Zika Virus and the metabolism of neuronal cells. Mol Neurobiol 2019;56(4):2551–2557. DOI: 10.1007/s12035-018-1263-x.
  83. van den Pol AN, Mao G, Yang Y, et al. Zika virus targeting in the developing brain. J Neurosci 2017;37(8):2161–2175. DOI: 10.1523/JNEUROSCI.3124-16.2017.
  84. Alfano C, Gladwyn–Ng I, Couderc T, et al. The unfolded protein response: A key player in Zika virus-associated congenital microcephaly. Front Cell Neurosci 2019;13:94. DOI: 10.3389/fncel.2019.00094.
  85. Beaufrere A, Bessieres B, Bonniere M, et al. A clinical and histopathological study of malformations observed in fetuses infected by the Zika virus. Brain Pathol 2019;29(1):114–125. DOI: 10.1111/bpa.12644.
  86. Melo AS, Aguiar RS, Amorim MM, et al. Congenital Zika virus infection: Beyond neonatal microcephaly. JAMA Neurol 2016;73(12):1407–1416. DOI: 10.1001/jamaneurol.2016.3720.
  87. Li C, Wang Q, Jiang Y, et al. Disruption of glial cell development by Zika virus contributes to severe microcephalic newborn mice. Cell Discov 2018;4:43. DOI: 10.1038/s41421-018-0042-1.
  88. Souza BS, Sampaio GL, Pereira CS, et al. Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells. Sci Rep 23 2016;6:39775. DOI: 10.1038/srep39775.
  89. Wen C, Yu Y, Gao C, et al. RIPK3-dependent necroptosis is induced and restricts viral replication in human astrocytes infected with Zika virus. Front Cell Infect Microbiol 2021;11:637710. DOI: 10.3389/fcimb.2021.637710.
  90. Lin MY, Wang YL, Wu WL, et al. Zika virus infects intermediate progenitor cells and post-mitotic committed neurons in human fetal brain tissues. Sci Rep 2017;7(1):14883. DOI: 10.1038/s41598-017- 13980-2.
  91. Vhp L, Aragao MM, Pinho RS, et al. Congenital zika virus infection: A review with emphasis on the spectrum of brain abnormalities. Curr Neurol Neurosci Rep 2020;20(11):49. DOI: 10.1007/s11910-020-01072-0.
  92. Ferreira LL, Aguilar Ticona JP, Silveira–Mattos PS, et al. Clinical and biochemical features of hypopituitarism among brazilian children with Zika virus-induced microcephaly. JAMA Netw Open 2021;4(5):e219878. DOI: 10.1001/jamanetworkopen.2021.9878.
  93. Enlow W, Bordeleau M, Piret J, et al. Microglia are involved in phagocytosis and extracellular digestion during Zika virus encephalitis in young adult immunodeficient mice. J Neuroinflammation 2021;18(1):178. DOI: 10.1186/s12974-021-02221-z.
  94. Garcez PP, Stolp HB, Sravanam S, et al. Zika virus impairs the development of blood vessels in a mouse model of congenital infection. Sci Rep 2018;8(1):12774. DOI: 10.1038/s41598-018-31149-3.
  95. Merfeld E, Ben–Avi L, Kennon M, et al. Potential mechanisms of Zika-linked microcephaly. Wiley Interdiscip Rev Dev Biol 2017;6(4):e273. DOI: 10.1002/wdev.273.
  96. Sher AA, Glover KKM, Coombs KM. Zika virus infection disrupts astrocytic proteins involved in synapse control and axon guidance. Front Microbiol 2019;10:596. DOI: 10.3389/fmicb.2019.00596.
  97. Brasil P, Pereira JP Jr, Moreira ME, et al. Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 2016;375(24):2321–2334. DOI: 10.1056/NEJMoa1602412.
  98. Krauer F, Riesen M, Reveiz L, et al. Zika virus infection as a cause of congenital brain abnormalities and Guillain–Barre syndrome: Systematic review. PLoS Med 2017;14(1):e1002203. DOI: 10.1371/journal.pmed.1002203.
  99. Schwartz DA. Viral infection, proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection. Arch Gynecol Obstet 2017;295(6):1361–1368. DOI: 10.1007/s00404-017-4361-5.
  100. Rosenberg AZ, Yu W, Hill DA, et al. Placental pathology of Zika virus: Viral infection of the placenta induces villous stromal macrophage (Hofbauer cell) proliferation and hyperplasia. Arch Pathol Lab Med 2017;141(1):43–48. DOI: 10.5858/arpa.2016-0401-OA.
  101. Almeida RDN, Braz-de-Melo HA, Santos IO, et al. The cellular impact of the ZIKA virus on male reproductive tract immunology and physiology. Cells 2020;9(4):1006. DOI: 10.3390/cells9041006.
  102. Walker CL, Merriam AA, Ohuma EO, et al. Femur-sparing pattern of abnormal fetal growth in pregnant women from New York City after maternal Zika virus infection. Am J Obstet Gynecol 2018;219(2):187.e1–187.e20. DOI: 10.1016/j.ajog.2018.04.047.
  103. Cauchemez S, Besnard M, Bompard P, et al. Association between Zika virus and microcephaly in French Polynesia, 2013–15: A retrospective study. Lancet 2016;387(10033):2125–2132. DOI: 10.1016/S0140-6736(16)00651-6.
  104. 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):1343–1348. DOI: 10.15585/mmwr.mm6547e2.
  105. Tang H, Hammack C, Ogden SC, et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell 2016;18(5):587–590. DOI: 10.1016/j.stem.2016.02.016.
  106. Gilmore EC, Walsh CA. Genetic causes of microcephaly and lessons for neuronal development. Wiley Interdiscip Rev Dev Biol 2013;2(4): 461–478. DOI: 10.1002/wdev.89.
  107. Driggers RW, Ho CY, Korhonen EM, et al. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med 2016;374(22):2142–2151. DOI: 10.1056/NEJMoa1601824.
  108. Schuler–Faccini L, Ribeiro EM, Feitosa IM, et al. Possible association between Zika virus infection and microcephaly – Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65(3):59–62. DOI: 10.15585/mmwr.mm6503e2.
  109. Reynolds MR, Jones AM, Petersen EE, et al. Vital signs: Update on Zika virus-associated birth defects and evaluation of all U.S. infants with congenital Zika virus exposure – U.S. Zika Pregnancy Registry, 2016. MMWR Morb Mortal Wkly Rep 2017;66(13):366–373. DOI: 10.15585/mmwr.mm6613e1.
  110. Hoen B, Schaub B, Funk AL, et al. Pregnancy outcomes after ZIKV infection in French territories in the Americas. N Engl J Med 2018;378(11):985–994. DOI: 10.1056/NEJMoa1709481.
  111. Rice ME, Galang RR, Roth NM, et al. Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection – U.S. territories and freely associated states, 2018. MMWR Morb Mortal Wkly Rep 2018;67(31):858–867. DOI: 10.15585/mmwr.mm6731e1.
  112. Jurado KA, Simoni MK, Tang Z, et al. Zika virus productively infects primary human placenta-specific macrophages. JCI Insight 2016;1(13): DOI: 10.1172/jci.insight.88461.
  113. Mlakar J, Korva M, Tul N, et al. Zika virus associated with microcephaly. N Engl J Med 2016;374(10):951–958. DOI: 10.1056/NEJMoa1600651.
  114. Rasmussen SA, Jamieson DJ, Honein MA, et al. Zika virus and birth defects: Reviewing the evidence for causality. N Engl J Med 2016;374(20):1981–1987. DOI: 10.1056/NEJMsr1604338.
  115. Miner JJ, Cao B, Govero J, et al. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell 2016;165(5):1081–1091. DOI: 10.1016/j.cell.2016.05.008.
  116. Moura da Silva AA, Ganz JS, Sousa PD, et al. Early growth and neurologic outcomes of infants with probable congenital Zika virus syndrome. Emerg Infect Dis 2016;22(11):1953–1956. DOI: 10.3201/eid2211.160956.
  117. Miranda–Filho Dde B, Martelli CM, 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.
  118. Calvet G, Aguiar RS, Melo ASO, et al. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: A case study. Lancet Infect Dis 2016;16(6):653–660. DOI: 10.1016/S1473-3099(16)00095-5.
  119. Microcephaly Epidemic Research G. Microcephaly in infants, Pernambuco state, Brazil, 2015. Emerg Infect Dis 2016;22(6):1090–1093. DOI: 10.3201/eid2206.160062.
  120. Martines RB, Bhatnagar J, Keating MK, et al. Notes from the field: Evidence of Zika virus infection in brain and placental tissues from two congenitally infected newborns and two fetal losses – Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65(6):159–160. DOI: 10.15585/mmwr.mm6506e1.
  121. Sarno M, Sacramento GA, Khouri R, et al. Zika virus infection and stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise. PLoS Negl Trop Dis 2016;10(2):e0004517. DOI: 10.1371/journal.pntd.0004517.
  122. WHO. Zika virus and complications: Questions and answers. World Health Organization. 2023. Accessed on: January 2023.
  123. Cordeiro MT, Pena LJ, Brito CA, et al. Positive IgM for Zika virus in the cerebrospinal fluid of 30 neonates with microcephaly in Brazil. Lancet 2016;387(10030):1811–1812. DOI: 10.1016/S0140-6736(16)30253-7.
  124. Villar J, Ismail LC, Victora CG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: The newborn cross-sectional study of the INTERGROWTH-21st project. Lancet 2014;384(9946):857–868. DOI: 10.1016/S0140-6736(14)60932-6.
  125. Meneses JDA, Ishigami AC, de Mello LM, et al. Lessons learned at the epicenter of Brazil's congenital Zika epidemic: Evidence from 87 confirmed cases. Clin Infect Dis 2017;64(10):1302–1308. DOI: 10.1093/cid/cix166.
  126. Chi JG, Dooling EC, Gilles FH. Gyral development of the human brain. Ann Neurol 1977;1(1):86–93. DOI: 10.1002/ana.410010109.
  127. Tsui I, Moreira MEL, Rossetto JD, et al. Eye findings in infants with suspected or confirmed antenatal Zika virus exposure. Pediatrics 2018;142(4): DOI: 10.1542/peds.2018-1104.
  128. Pool KL, Adachi K, Karnezis S, et al. Association between neonatal neuroimaging and clinical outcomes in Zika-exposed infants from Rio de Janeiro, Brazil. JAMA Netw Open 2019;2(7):e198124. DOI: 10.1001/jamanetworkopen.2019.8124.
  129. Adachi K, Romero T, Nielsen–Saines K, et al. Early clinical infancy outcomes for microcephaly and/or small for gestational age Zika-exposed infants. Clin Infect Dis 2020;70(12):2663–2672. DOI: 10.1093/cid/ciz704.
  130. Moore CA, Staples JE, Dobyns WB, et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr 2017;171(3):288–295. DOI: 10.1001/jamapediatrics.2016.3982.
  131. Moreira MEL, Nielsen–Saines K, Brasil P, et al. Neurodevelopment in infants exposed to Zika virus in utero. N Engl J Med 2018;379(24):2377–2379. DOI: 10.1056/NEJMc1800098.
  132. Zin AA, Tsui I, Rossetto J, et al. Screening criteria for ophthalmic manifestations of congenital Zika virus infection. JAMA Pediatr 2017;171(9):847–854. DOI: 10.1001/jamapediatrics.2017.1474.
  133. de Paula Freitas B, de Oliveira Dias JR, Prazeres J, et al. Ocular findings in infants with microcephaly associated with presumed Zika virus congenital infection in Salvador, Brazil. JAMA Ophthalmol 2016;134(5):529–535. DOI: 10.1001/jamaophthalmol.2016.0267.
  134. Moshfeghi DM, de Miranda HA 2nd, Costa MC. Zika virus, microcephaly, and ocular findings. JAMA Ophthalmol 2016;134(8):945. DOI: 10.1001/jamaophthalmol.2016.1303.
  135. Ventura CV, Maia M, Travassos SB, et al. Risk factors associated with the ophthalmoscopic findings identified in infants with presumed Zika virus congenital infection. JAMA Ophthalmol 2016;134(8):912–918. DOI: 10.1001/jamaophthalmol.2016.1784.
  136. Miranda HA II, Costa MC, Frazao MAM, et al. Expanded spectrum of congenital ocular findings in microcephaly with presumed Zika infection. Ophthalmology 2016;123(8):1788–1794. DOI: 10.1016/j.ophtha.2016.05.001.
  137. de Oliveira Dias JR, Ventura CV, Borba PD, et al. Infants with congenital Zika syndrome and ocular findings from Sao Paulo, Brazil: Spread of infection. Retin Cases Brief Rep 2018;12(4):382–386. DOI: 10.1097/ICB.0000000000000518.
  138. Ventura LO, Ventura CV, Lawrence L, et al. Visual impairment in children with congenital Zika syndrome. J AAPOS 2017;21(4):295–299.e2. DOI: 10.1016/j.jaapos.2017.04.003.
  139. Ventura CV, Ventura LO, Bravo–Filho V, et al. Optical coherence tomography of retinal lesions in infants with congenital Zika syndrome. JAMA Ophthalmol016;134(12):1420–1427. DOI: 10.1001/jamaophthalmol.2016.4283.
  140. Ventura CV, Maia M, Bravo–Filho V, et al. Zika virus in Brazil and macular atrophy in a child with microcephaly. Lancet 2016;387(10015):228. DOI: 10.1016/S0140-6736(16)00006-4.
  141. Ventura CV, Maia M, Ventura BV, et al. Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection. Arq Bras Oftalmol 2016;79(1):1–3. DOI: 10.5935/0004-2749.20160002.
  142. de Paula Freitas B, Ko AI, Khouri R, et al. Glaucoma and congenital Zika syndrome. Ophthalmol 2017;124(3):407–408. DOI: 10.1016/j.ophtha.2016.10.004.
  143. Melo ASO, Malinger G, Ximenes R, et al. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: Tip of the iceberg? Ultrasound Obstet Gynecol 2016;47(1):6–7. DOI: 10.1002/uog.15831.
  144. Yepez JB, Murati FA, Pettito M, et al. Ophthalmic manifestations of congenital Zika syndrome in Colombia and Venezuela. JAMA Ophthalmol 2017;135(5):440–445. DOI: 10.1001/jamaophthalmol.2017.0561.
  145. Ventura LO, Ventura CV, Dias NC, et al. Visual impairment evaluation in 119 children with congenital Zika syndrome. J AAPOS 2018;22(3):218.e1–222.e1. DOI: 10.1016/j.jaapos.2018.01.009.
  146. Zin AA, Tsui I, Rossetto JD, et al. Visual function in infants with antenatal Zika virus exposure. J AAPOS 2018;22(6):452.e1–456.e1. DOI: 10.1016/j.jaapos.2018.07.352.
  147. Vercosa I, Carneiro P, Vercosa R, et al. The visual system in infants with microcephaly related to presumed congenital Zika syndrome. J AAPOS 2017;21(4):300.e1–304.e1. DOI: 10.1016/j.jaapos.2017.05.024.
  148. Leal MC, Muniz LF, Ferreira TS, et al. Hearing loss in infants with microcephaly and evidence of congenital Zika virus infection – Brazil, November 2015 – May 2016. MMWR Morb Mortal Wkly Rep 2016;65(34):917–919. DOI: 10.15585/mmwr.mm6534e3.
  149. Franca GV, Schuler–Faccini L, Oliveira WK, et al. Congenital Zika virus syndrome in Brazil: A case series of the first 1501 livebirths with complete investigation. Lancet 27 2016;388(10047):891–897. DOI: 10.1016/S0140-6736(16)30902-3.
  150. Alves LV, Mello MJG, Bezerra PG, Alves JGB. Congenital Zika syndrome and infantile spasms: Case series study. J Child Neurol 2018;33(10):664–666. DOI: 10.1177/0883073818780105.
  151. Cavalcanti DD, Alves LV, Furtado GJ, et al. Echocardiographic findings in infants with presumed congenital Zika syndrome: Retrospective case series study. PLoS One 2017;12(4):e0175065. DOI: 10.1371/journal.pone.0175065.
  152. Besnard M, Eyrolle–Guignot D, Guillemette–Artur P, 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(13). DOI: 10.2807/1560-7917.ES.2016.21.13.30181.
  153. Orofino DHG, Passos SRL, de Oliveira RVC, et al. Cardiac findings in infants with in utero exposure to Zika virus: A cross sectional study. PLoS Negl Trop Dis 2018;12(3):e0006362. DOI: 10.1371/journal.pntd.0006362.
  154. Read JS, Torres–Velasquez B, Lorenzi O, et al. Symptomatic Zika virus infection in infants, children, and adolescents living in Puerto Rico. JAMA Pediatr 2018;172(7):686–693. DOI: 10.1001/jamapediatrics.2018.0870.
  155. Vouga M, Baud D. Imaging of congenital Zika virus infection: The route to identification of prognostic factors. Prenat Diagn 2016;36(9): 799–811. DOI: 10.1002/pd.4880.
  156. Culjat M, Darling SE, Nerurkar VR, et al. Clinical and imaging findings in an infant with Zika embryopathy. Clin Infect Dis 2016;63(6):805–811. DOI: 10.1093/cid/ciw324.
  157. Soares de Oliveira–Szejnfeld P, Levine D, Melo AS, et al. Congenital brain abnormalities and Zika virus: What the radiologist can expect to see prenatally and postnatally. Radiology 2016;281(1):203–218. DOI: 10.1148/radiol.2016161584.
  158. Petribu NCL, Aragao MFV, van der Linden V, et al. Follow-up brain imaging of 37 children with congenital Zika syndrome: Case series study. BMJ 2017;359:j4188. DOI: 10.1136/bmj.j4188.
  159. Adebanjo T, Godfred–Cato S, Viens L, et al. Update: Interim guidance for the diagnosis, evaluation, and management of infants with possible congenital Zika virus infection – United States, October 2017. MMWR Morb Mortal Wkly Rep 2017;66(41):1089–1099. DOI: 10.15585/mmwr.mm6641a1.
  160. World Health Organization. Screening, assessment and management of neonates and infants with complications associated with Zika virus exposure in utero. World Health Organization. 2016. Available at: Accessed on: 2 January 2023.
  161. Petersen LR, Jamieson DJ, Powers AM, et al. Zika Virus. N Engl J Med 2016;374(16):1552–1563. DOI: 10.1056/NEJMra1602113.
  162. Prevention CfDCa. Congenital microcephaly case definitions. Centers for Disease Control and Prevention. Available at: Accessed on: 2 January 2023.
  163. Rabe IB, Staples JE, Villanueva J, et al. Interim guidance for interpretation of Zika virus antibody test results. MMWR Morb Mortal Wkly Rep 2016;65(21):543–546. DOI: 10.15585/mmwr.mm6521e1.
  164. Oliveira DB, Almeida FJ, Durigon EL, et al. Prolonged shedding of Zika virus associated with congenital infection. N Engl J Med 2016;375(12):1202–1204. DOI: 10.1056/NEJMc1607583.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.