{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:43Z","timestamp":1787030143928,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>A decade has elapsed since the first recognized cluster of congenital anomalies associated with Zika virus (ZIKV) was reported in Brazil in 2015, culminating in the formal delineation of Congenital Zika Syndrome (CZS) as a specific pattern of birth defects. This narrative review examines the ten-year trajectory of CZS as a tropical infectious disease, from its initial emergence and public health emergency declaration by the World Health Organization (WHO) in February 2016, through evolving epidemiological, clinical, and scientific understanding. CZS is characterized by a spectrum of severe neurological manifestations\u2014including microcephaly, subcortical calcifications, malformations of cortical development, ventriculomegaly, and corpus callosum abnormalities\u2014alongside ophthalmic, auditory, and musculoskeletal complications. Transmitted primarily by Aedes aegypti mosquitoes in tropical and subtropical regions, ZIKV disproportionately affects low- and middle-income countries in Latin America, Africa, and Southeast Asia, underscoring its nature as a quintessential tropical disease linked to poverty, inadequate vector control, and health inequity. Over ten years, substantial advances have been made in understanding ZIKV pathogenesis, neurodevelopmental outcomes, diagnostic criteria, and multidisciplinary clinical management of affected children. In the therapeutic and preventive domain, over 45 vaccine candidates have been identified, with 16 reaching Phase 1 or 2 clinical trials by late 2025, though no licensed vaccine or specific antiviral therapy yet exists. This review contextualizes CZS within the broader framework of neglected tropical diseases, evaluates its global and family-level burden, and critically appraises progress and remaining gaps in clinical care, vaccination, and vector control over the past ten years.<\/jats:p>","DOI":"10.3390\/tropicalmed11050124","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:30:22Z","timestamp":1778059822000},"page":"124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ten Years of Congenital Zika Syndrome: From Outbreak to a Decade of Clinical, Therapeutic, and Preventive Advances in a Tropical Disease Context"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-0238","authenticated-orcid":false,"given":"Fabr\u00edcio Silva","family":"Pessoa","sequence":"first","affiliation":[{"name":"Pediatric Infectious Diseases Department, UFMA University Hospital, Bar\u00e3o de Itapary, 227, Centro, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus (I). Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0035-9203(54)90006-1","article-title":"Zika virus: A report on three cases of human infection during an epidemic of jaundice in Nigeria","volume":"48","author":"MacNamara","year":"1954","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1056\/NEJMoa0805715","article-title":"Zika virus outbreak on Yap Island, Federated States of Micronesia","volume":"360","author":"Duffy","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3201\/eid2006.140138","article-title":"Zika virus, French Polynesia, South Pacific, 2013","volume":"20","author":"Roche","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0140-6736(16)30902-3","article-title":"Congenital Zika virus syndrome in Brazil: A case series of the first 1501 livebirths with complete investigation","volume":"388","author":"Oliveira","year":"2016","journal-title":"Lancet"},{"key":"ref_6","unstructured":"World Health Organization (2016). WHO Statement on the First Meeting of the International Health Regulations (2005) Emergency Committee on Zika Virus and Observed Increase in Neurological Disorders and Neonatal Malformations, WHO."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/jamapediatrics.2016.3982","article-title":"Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians","volume":"171","author":"Moore","year":"2017","journal-title":"JAMA Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1128\/CMR.00072-15","article-title":"Zika virus","volume":"29","author":"Musso","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1126\/science.aaf5316","article-title":"The 3.8 \u00c5 resolution cryo-EM structure of Zika virus","volume":"352","author":"Sirohi","year":"2016","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMra1602113","article-title":"Zika virus","volume":"374","author":"Petersen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMc1604449","article-title":"Evidence of sexual transmission of Zika virus","volume":"374","author":"Matheron","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_13","first-page":"1555","article-title":"Zika virus shedding in vaginal secretions among asymptomatic women","volume":"379","author":"Mead","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2471\/BLT.16.178608","article-title":"Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016","volume":"95","author":"Jaenisch","year":"2017","journal-title":"Bull. World Health Organ."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/S0140-6736(16)00651-6","article-title":"Association between Zika virus and microcephaly in French Polynesia, 2013\u20132015: A retrospective study","volume":"387","author":"Cauchemez","year":"2016","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.15585\/mmwr.mm6547e2","article-title":"Description of 13 infants born during October 2015\u2013January 2016 with congenital Zika virus infection without microcephaly at birth\u2014Brazil","volume":"65","author":"Pessoa","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_17","unstructured":"Pan American Health Organization, and World Health Organization (2023). Epidemiological Update: Zika Virus Infection, WHO."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1126\/science.abb4218","article-title":"The effect of human mobility and control measures on the COVID-19 epidemic in China","volume":"368","author":"Kraemer","year":"2020","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hotez, P.J., Alvarado, M., Bas\u00e1\u00f1ez, M.G., Bolliger, I., Bourne, R., Boussinesq, M., Brooker, S.J., Brown, A.S., Buckle, G., and Budke, C.M. (2014). The global burden of disease study 2010: Interpretation and implications for the neglected tropical diseases. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002865"},{"key":"ref_20","first-page":"i1901","article-title":"Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: Retrospective case series study","volume":"353","author":"Coeli","year":"2016","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1056\/NEJMc1603617","article-title":"Computed tomographic findings in microcephaly associated with Zika virus","volume":"374","author":"Hazin","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.aaf6116","article-title":"Zika virus impairs growth in human neurospheres and brain organoids","volume":"352","author":"Garcez","year":"2016","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1126\/science.aam7120","article-title":"A single mutation in the prM protein of Zika virus contributes to fetal microcephaly","volume":"358","author":"Yuan","year":"2017","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1056\/NEJMc1716070","article-title":"Epilepsy profile in infants with congenital Zika virus infection","volume":"379","author":"Carvalho","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e021304","DOI":"10.1136\/bmjopen-2017-021304","article-title":"Neurodevelopment of 24 children born in Brazil with congenital Zika syndrome in 2015: A case series study","volume":"8","author":"Alves","year":"2018","journal-title":"BMJ Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1001\/jamapediatrics.2019.5204","article-title":"Neurodevelopmental abnormalities in children with in utero Zika virus exposure without congenital Zika syndrome","volume":"174","author":"Mulkey","year":"2020","journal-title":"JAMA Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"59","DOI":"10.15585\/mmwr.mm6503e2","article-title":"Possible association between Zika virus infection and microcephaly\u2014Brazil, 2015","volume":"65","author":"Ribeiro","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5935\/0004-2749.20160002","article-title":"Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection","volume":"79","author":"Ventura","year":"2016","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"917","DOI":"10.15585\/mmwr.mm6534e3","article-title":"Hearing loss in infants with microcephaly and evidence of congenital Zika virus infection\u2014Brazil, November 2015\u2013May 2016","volume":"65","author":"Leal","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1001\/jama.2016.19006","article-title":"Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy","volume":"317","author":"Honein","year":"2017","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S167","DOI":"10.1542\/peds.2017-2038F","article-title":"Motor abnormalities and epilepsy in infants and children with evidence of congenital Zika virus infection","volume":"141","author":"Pessoa","year":"2018","journal-title":"Pediatrics"},{"key":"ref_32","first-page":"124","article-title":"Children born to mothers with rash during Zika virus epidemic in Brazil: First 18 months of life","volume":"66","author":"Vianna","year":"2020","journal-title":"J. Trop. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"372","DOI":"10.15585\/mmwr.mm6514a3","article-title":"Male-to-male sexual transmission of Zika virus\u2014Texas, January 2016","volume":"65","author":"Deckard","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"739","DOI":"10.15585\/mmwr.mm6529e1","article-title":"Update: Interim guidance for health care providers caring for pregnant women with possible Zika virus exposure\u2014United States, July 2016","volume":"65","author":"Oduyebo","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_35","first-page":"438","article-title":"Accuracy of dengue reporting by national surveillance system, Brazil","volume":"27","author":"Kikuti","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1001\/jamaneurol.2016.3720","article-title":"Congenital Zika virus infection: Beyond neonatal microcephaly","volume":"73","author":"Melo","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_37","unstructured":"Centers for Disease Control and Prevention (2016). Interim guidance for the evaluation and management of infants with possible congenital Zika virus infection. MMWR Morb. Mortal. Wkly. Rep., 65, 1047\u20131055."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/dmcn.15067","article-title":"Physical therapy in children with cerebral palsy in Brazil: A scoping review","volume":"64","author":"Furtado","year":"2022","journal-title":"Dev. Med. Child. Neurol."},{"key":"ref_39","first-page":"1425","article-title":"Congenital Zika syndrome and family impacts: An integrative review","volume":"28","author":"Melo","year":"2023","journal-title":"Ci\u00eancia Sa\u00fade Coletiva"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"40920","DOI":"10.1038\/srep40920","article-title":"The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication","volume":"7","author":"Sacramento","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature20564","article-title":"Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice","volume":"540","author":"Sapparapu","year":"2016","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cell.2017.09.002","article-title":"A human bi-specific antibody against Zika virus with high therapeutic potential","volume":"171","author":"Wang","year":"2017","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"National Institute of Allergy and Infectious Diseases (NIAID) (2024). Continuing development of vaccines and monoclonal antibodies against Zika virus: Workshop proceedings. npj Vaccines, 9, 91.","DOI":"10.1038\/s41541-024-00889-x"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"ftad036","DOI":"10.1093\/femspd\/ftad036","article-title":"A review on Zika vaccine development","volume":"82","author":"Peng","year":"2024","journal-title":"Pathog. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1126\/science.aai9137","article-title":"Rapid development of a DNA vaccine for Zika virus","volume":"354","author":"Dowd","year":"2016","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.cell.2017.02.017","article-title":"Modified mRNA vaccines protect against Zika virus infection","volume":"168","author":"Richner","year":"2017","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature21428","article-title":"Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination","volume":"543","author":"Pardi","year":"2017","journal-title":"Nature"},{"key":"ref_48","unstructured":"Valneva SE (2026, February 10). VLA1601 Zika Vaccine Candidate Phase 1 Clinical Trial Update, November 2025. Available online: https:\/\/valneva.com."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1126\/science.aan6836","article-title":"Antibody-dependent enhancement of severe dengue disease in humans","volume":"358","author":"Katzelnick","year":"2017","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection","volume":"353","author":"Stettler","year":"2016","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Moyes, C.L., Vontas, J., Martins, A.J., Ng, L.C., Koou, S.Y., Dusfour, I., Raghavendra, K., Pinto, J., Corbel, V., and David, J.P. (2017). Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005625"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1056\/NEJMoa2030243","article-title":"Efficacy of Wolbachia-infected mosquito deployments for the control of dengue","volume":"384","author":"Utarini","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_53","unstructured":"Oxitec Ltd. (2020). Open field trials of OX513A Aedes aegypti in Brazil: A summary. Reg. Toxicol. Pharmacol., 114, 104652."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Brady, O.J., Gething, P.W., Bhatt, S., Messina, J.P., Brownstein, J.S., Hoen, A.G., Moyes, C.L., Farlow, A.W., Scott, T.W., and Hay, S.I. (2012). Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001760"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mordecai, E.A., Cohen, J.M., Evans, M.V., Gudapati, P., Johnson, L.R., Lippi, C.A., Miazgowicz, K., Murdock, C.C., Rohr, J.R., and Ryan, S.J. (2017). Detecting the impact of temperature on transmission of Zika, dengue, and chikungunya using mechanistic models. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005568"}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/11\/5\/124\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T10:18:28Z","timestamp":1778062708000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/11\/5\/124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["tropicalmed11050124"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed11050124","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]}}}