{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:06:31Z","timestamp":1760241991035,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303999\/2016-0","439971\/2016-0","440405\/2016-5"],"award-info":[{"award-number":["303999\/2016-0","439971\/2016-0","440405\/2016-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: The recent Zika virus(ZIKV) epidemic in Brazil was characterized by a range of different clinical presentations, particularly microcephaly, Guillain-Barr\u00e9 syndrome, and death. In this context, we determined the causal relationship between fatal microcephaly cases and ZIKV infection. Methods: Twelve fatal cases of neonates, whose mothers were infected with ZIKV during pregnancy, were examined; cases included nine neonatal deaths due to microcephaly, one miscarriage, and two stillbirths. Tissue samples were obtained from all cases at necropsy and were submitted for virological investigation (RT-qPCR and virus isolation) and\/or histopathology (hematoxylin and eosin staining) and immunohistochemical assay for the detection of ZIKV antigens. Results: ZIKV antigens and\/or ZIKV RNA were detected in tissue samples of all 12 cases examined. ZIKV was recovered in one case. Results of the virological and immunohistochemical analyses, as well as the anatomic abnormalities and histopathologic changes observed at necropsy on the 12 fatal cases, are presented. Conclusions: Data from these 12 cases provide strong evidence of the causal relationship between ZIKV and congenital disease in fetuses of women who were infected with the virus during pregnancy.<\/jats:p>","DOI":"10.3390\/jcm7120496","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T11:43:44Z","timestamp":1543405424000},"page":"496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Zika Virus Epidemic in Brazil. II. Post-Mortem Analyses of Neonates with Microcephaly, Stillbirths, and Miscarriage"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1932-9976","authenticated-orcid":false,"given":"Raimunda","family":"Azevedo","sequence":"first","affiliation":[{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, Minist\u00e9rio da Sa\u00fade, Rodovia BR-316, km-07, Ananindeua 67030-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marialva","family":"Araujo","sequence":"additional","affiliation":[{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, Minist\u00e9rio da Sa\u00fade, Rodovia BR-316, km-07, Ananindeua 67030-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Consuelo","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, 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Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Henriques","sequence":"additional","affiliation":[{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, Minist\u00e9rio da Sa\u00fade, Rodovia BR-316, km-07, Ananindeua 67030-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana","family":"Silva","sequence":"additional","affiliation":[{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, Minist\u00e9rio da Sa\u00fade, Rodovia BR-316, km-07, Ananindeua 67030-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9ria","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Se\u00e7\u00e3o de Arbovirologia e Febres Hemorr\u00e1gicas, Instituto Evandro Chagas, Minist\u00e9rio da Sa\u00fade, Rodovia BR-316, km-07, Ananindeua 67030-000, 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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":"1347","DOI":"10.3201\/eid1509.090442","article-title":"Zika Virus Outside Africa","volume":"15","author":"Hayes","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2807\/1560-7917.ES2014.19.9.20720","article-title":"Zika virus infection complicated by Guillain-Barre syndrome\u2014Case report, French Polynesia, December 2013","volume":"19","author":"Oehler","year":"2014","journal-title":"Euro Surveill."},{"key":"ref_4","unstructured":"Pan American Health Organization (PAHO)\/World Health Organization (WHO) (2017). Zika\u2014Epidemiological Update, 25 August 2017, PAHO\/WHO."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.3201\/eid2110.150847","article-title":"Zika Virus Outbreak, Bahia, Brazil","volume":"21","author":"Campos","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1590\/0074-02760150192","article-title":"First report of autochthonous transmission of Zika virus in Brazil","volume":"110","author":"Zanluca","year":"2015","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1126\/science.aaf5036","article-title":"Zika virus in the Americas: Early epidemiological and genetic findings","volume":"352","author":"Faria","year":"2016","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jcv.2016.10.024","article-title":"Zika virus epidemic in Brazil. I. Fatal disease in adults: Clinical and laboratorial aspects","volume":"85","author":"Azevedo","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_9","unstructured":"Pan American Health Organization (PAHO)\/World Health Organization (WHO) (2015). Epidemiological Alert\u2014Neurological Syndrome, Congenital Malformations, and Zika Virus Infection. Implications for Public Health in the Americas\u20141 December 2015, PAHO\/WHO."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.4269\/ajtmh.1979.28.1053","article-title":"A method for the isolation and identification of dengue viruses, using mosquito cell cultures","volume":"28","author":"Tesh","year":"1979","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jcv.2008.05.005","article-title":"One-step RT-PCR for detection of Zika virus","volume":"43","author":"Faye","year":"2008","journal-title":"J. Clin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3201\/eid1408.080287","article-title":"Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007","volume":"14","author":"Lanciotti","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S0140-6736(16)30883-2","article-title":"Pathology of congenital Zika syndrome in Brazil: A case series","volume":"388","author":"Martines","year":"2016","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s00401-017-1699-5","article-title":"The spectrum of neuropathological changes associated with congenital Zika virus infection","volume":"133","author":"Chimelli","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-17765-5","article-title":"In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus","volume":"8","author":"Azevedo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"de Sousa, J.R., Azevedo, R.S.S., Martins Filho, A.J., de Araujo, M.T.F., Moutinho, E.R.C., Baldez Vasconcelos, B.C., Cruz, A.C.R., Oliveira, C.S., Martins, L.C., and Baldez Vasconcelos, B.H. (2018). Correlation between apoptosis and in situ immune response in fatal cases of microcephaly caused by Zika virus. Am. J. Pathol., 188.","DOI":"10.1016\/j.ajpath.2018.07.009"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.cyto.2018.08.008","article-title":"In situ inflammasome activation results in severe damage to the central nervous system in fatal Zika virus microcephaly cases","volume":"111","author":"Cruz","year":"2018","journal-title":"Cytokine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/cjp2.84","article-title":"Optimization of commercially available Zika virus antibodies for use in a laboratory-developed immunohistochemical assay","volume":"4","author":"Bollweg","year":"2017","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_19","unstructured":"Pan American Health Organization (PAHO)\/World Health Organization (WHO) (2016). Zika\u2014Epidemiological Update, 8 April 2016, PAHO\/WHO."},{"key":"ref_20","unstructured":"PAHO\/WHO-Case Definitions (2018, September 20). Zika Resources: Case Definitions. Available online: https:\/\/www.paho.org\/hq\/index.php?option = com_content&view = article&id = 11117:zika-resources-case-definitions&Itemid = 41532&lang = en."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Moore, C.A., Staples, J.E., Dobyns, W.B., Pessoa, A., Ventura, C.V., da Fonseca, E.B., Ribeiro, E.M., Ventura, L.O., Neto, N.N., and Arena, J.F. (2016). Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians. JAMA Pediatr.","DOI":"10.1001\/jamapediatrics.2016.3982"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"598","DOI":"10.2105\/AJPH.2016.303115","article-title":"Initial Description of the Presumed Congenital Zika Syndrome","volume":"106","author":"Martelli","year":"2016","journal-title":"Am. J. Public Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0140-6736(16)00320-2","article-title":"Zika virus and microcephaly: Why is this situation a PHEIC?","volume":"387","author":"Heymann","year":"2016","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1473-3099(16)00095-5","article-title":"Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: A case study","volume":"16","author":"Calvet","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/uog.15831","article-title":"Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: Tip of the iceberg?","volume":"47","author":"Malinger","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1056\/NEJMoa1600651","article-title":"Zika Virus Associated with Microcephaly","volume":"374","author":"Mlakar","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"925","DOI":"10.3201\/eid2205.151934","article-title":"Fatal Sickle Cell Disease and Zika Virus Infection in Girl from Colombia","volume":"22","author":"Polo","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jcv.2014.08.030","article-title":"Yellow fever","volume":"64","author":"Monath","year":"2015","journal-title":"J. Clin. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.actatropica.2005.03.003","article-title":"Reconsideration of histopathology and ultrastructural aspects of the human liver in yellow fever","volume":"94","author":"Quaresma","year":"2005","journal-title":"Acta Trop."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/jmv.23758","article-title":"Immunopathogenesis of dengue hemorrhagic fever: Contribution to the study of human liver lesions","volume":"86","author":"Pagliari","year":"2014","journal-title":"J. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jcv.2015.12.005","article-title":"Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17","volume":"75","author":"Pagliari","year":"2016","journal-title":"J. Clin. Virol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/7\/12\/496\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:33:12Z","timestamp":1760196792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/7\/12\/496"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,28]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["jcm7120496"],"URL":"https:\/\/doi.org\/10.3390\/jcm7120496","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2018,11,28]]}}}