{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:22:02Z","timestamp":1791908522796,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/210.400\/2019; E-26\/202.003\/2016; E-26\/202.659\/2019; E-26\/202.862\/2018; E-26\/211.565\/2019"],"award-info":[{"award-number":["E-26\/210.400\/2019; E-26\/202.003\/2016; E-26\/202.659\/2019; E-26\/202.862\/2018; E-26\/211.565\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["302462\/2018-0; 307282\/2017-1"],"award-info":[{"award-number":["302462\/2018-0; 307282\/2017-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Departamento de Ci\u00eancia e Tecnologia do Minist\u00e9rio da Sa\u00fade do Brasil","award":["DECIT\/25000.072811\/2016-19."],"award-info":[{"award-number":["DECIT\/25000.072811\/2016-19."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&amp;E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40\u201350 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.<\/jats:p>","DOI":"10.3390\/v13040554","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T21:09:45Z","timestamp":1616706585000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Spontaneous Abortion and Chikungunya Infection: Pathological Findings"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2891-4915","authenticated-orcid":false,"given":"Nat\u00e1lia","family":"Salom\u00e3o","sequence":"first","affiliation":[{"name":"Interdisciplinary Medical Research Laboratory Rio de Janeiro, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Brendolin","sequence":"additional","affiliation":[{"name":"Acute Febrile Diseases Laboratory, Evandro Chagas National Infectiology Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-7788","authenticated-orcid":false,"given":"K\u00edssila","family":"Rabelo","sequence":"additional","affiliation":[{"name":"Ultrastructure and Tissue Biology Laboratory Rio de Janeiro, Rio de Janeiro State University, Rio de Janeiro 20551-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Wakimoto","sequence":"additional","affiliation":[{"name":"Acute Febrile Diseases Laboratory, Evandro Chagas National Infectiology Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"de Filippis","sequence":"additional","affiliation":[{"name":"Flaviviruses Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Viral Immunology Laboratory, Oswaldo Cruz Institute Rio de Janeiro, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2034-0294","authenticated-orcid":false,"given":"Maria Elizabeth","family":"Moreira","sequence":"additional","affiliation":[{"name":"National Institute of Women, Children and Adolescents Health Fernandes Figueira, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alberto","family":"Bas\u00edlio-de-Oliveira","sequence":"additional","affiliation":[{"name":"Pathological Anatomy, Gaffr\u00e9e Guinle University Hospital Rio de Janeiro, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-004, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyzabeth","family":"Avvad-Portari","sequence":"additional","affiliation":[{"name":"National Institute of Women, Children and Adolescents Health Fernandes Figueira, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marciano","family":"Paes","sequence":"additional","affiliation":[{"name":"Interdisciplinary Medical Research Laboratory Rio de Janeiro, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-7976","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Brasil","sequence":"additional","affiliation":[{"name":"Acute Febrile Diseases Laboratory, Evandro Chagas National Infectiology Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"ref_1","first-page":"285","article-title":"Evolutionary influences in arboviral disease","volume":"299","author":"Weaver","year":"2006","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kawashima, K.D., Suarez, L.-A.C., Labayo, H.K.M., Liles, V.R., Salvoza, N.C., Klinzing, D.C., Daroy, M.L.G., Matias, R.R., and Natividad, F.F. (2014). Complete genome sequence of Chikungunya virus isolated in the Philippines. Genome Announc., 2.","DOI":"10.1128\/genomeA.00336-14"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Thiboutot, M.M., Kannan, S., Kawalekar, O.U., Shedlock, D.J., Khan, A.S., Sarangan, G., Srikanth, P., Weiner, D.B., and Muthumani, K. (2010). Chikungunya: A potentially emerging epidemic?. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000623"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrmicro2368","article-title":"Biology and pathogenesis of chikungunya virus","volume":"8","author":"Schwartz","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0255-0857(21)01984-8","article-title":"Chikungunya fever: A re-emerging viral infection","volume":"26","author":"Chhabra","year":"2008","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1086\/517537","article-title":"Outbreak of Chikungunya on Reunion Island: Early clinical and laboratory features in 157 adult patients","volume":"44","author":"Borgherini","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0755-4982(06)74657-7","article-title":"Chikungunya \u00e0 l\u2019\u00eele de la R\u00e9union: Chronique d\u2019une \u00e9pid\u00e9mie annonc\u00e9e","volume":"35","author":"Paganin","year":"2006","journal-title":"Presse M\u00e9dicale"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1097\/INF.0b013e3180616d4f","article-title":"Mother-to-child transmission of Chikungunya virus infection","volume":"26","author":"Ramful","year":"2007","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0755-4982(06)74690-5","article-title":"Vertical maternal fetal transmission of the chikungunya virus. Ten cases among 84 pregnant women","volume":"35","author":"Robillard","year":"2006","journal-title":"Presse Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"G\u00e9rardin, P., Samp\u00e9riz, S., Ramful, D., Boumahni, B., Bintner, M., Alessandri, J.-L., Carbonnier, M., Tiran-Rajaoefera, I., Beullier, G., and Boya, I. (2014). Neurocognitive outcome of children exposed to perinatal mother-to-child Chikungunya virus infection: The CHIMERE Cohort Study on Reunion Island. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002996"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.idcr.2016.07.008","article-title":"Neonatal encephalitis due to Chikungunya vertical transmission: First report in Brazil","volume":"5","author":"Bandeira","year":"2016","journal-title":"IDCases"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"G\u00e9rardin, P., Barau, G., Michault, A., Bintner, M., Randrianaivo, H., Choker, G., Lenglet, Y., Touret, Y., Bouveret, A., and Grivard, P. (2008). Multidisciplinary prospective study of mother-to-child Chikungunya virus infections on the Island of La R\u00e9union. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050060"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"913","DOI":"10.4269\/ajtmh.16-0491","article-title":"Case report: Chikungunya and neonatal immunity: Fatal vertically transmitted chikungunya infection","volume":"96","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1016\/S0755-4982(06)74874-6","article-title":"Early maternal-fetal transmission of the Chikungunya virus","volume":"35","author":"Touret","year":"2006","journal-title":"Presse M\u00e9dicale"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nunes, P., Nogueira, R., Coelho, J., Rodrigues, F., Salom\u00e3o, N., Jos\u00e9, C., De Carvalho, J., Rabelo, K., De Azeredo, E., and Bas\u00edl-io-De-oliveira, R. (2019). A stillborn multiple organs\u2019 investigation from a maternal denv-4 infection: Histopathological and in-flammatory mediators characterization. Viruses, 11.","DOI":"10.3390\/v11040319"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1002\/jmv.24479","article-title":"Detection of dengue NS1 and NS3 proteins in placenta and umbilical cord in fetal and maternal death","volume":"88","author":"Nunes","year":"2016","journal-title":"J. Med. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eaao7090","DOI":"10.1126\/scitranslmed.aao7090","article-title":"Zika virus\u2013related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice","volume":"10","author":"Platt","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.3389\/fimmu.2017.01704","article-title":"Placental histopathology and clinical presentation of severe congenital Zika Syndrome in a human immunodeficiency virus-exposed uninfected infant","volume":"8","author":"Rabelo","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.cell.2016.05.008","article-title":"Zika virus infection during pregnancy in mice causes placental damage and fetal demise","volume":"165","author":"Miner","year":"2016","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0378-1135(88)90037-5","article-title":"Transplacental infection in mice inocu-lated with Getah virus","volume":"16","author":"Kumanomido","year":"1988","journal-title":"Vet. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/0378-1135(91)90162-9","article-title":"Isolation of Getah virus from dead fetuses extracted from a nat-urally infected sow in Japan","volume":"27","author":"Shibata","year":"1991","journal-title":"Vet. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1128\/jvi.50.1.66-72.1984","article-title":"Pathogenesis of in utero infections with abortogenic and non-abortogenic alphaviruses in mice","volume":"50","author":"Milner","year":"1984","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/labinvest.3780334","article-title":"Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta","volume":"81","author":"Tarrade","year":"2001","journal-title":"Lab. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.patbio.2007.07.002","article-title":"Molecular and serological diagnosis of Chikungunya virus infection","volume":"55","author":"Grivard","year":"2007","journal-title":"Pathol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijid.2018.04.4320","article-title":"Co-infection with Zika and Chikungunya viruses associated with fetal death\u2014A case report","volume":"72","author":"Robaina","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"ref_26","unstructured":"Dulay, A.T. (2021, January 15). Spontaneous Abortion. Available online: https:\/\/www.msdmanuals.com\/professional\/gynecology-and-obstetrics\/abnormalities-of-pregnancy\/spontaneous-abortion."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1136\/bmj.320.7251.1708","article-title":"Maternal age and fetal loss: Population based register linkage study","volume":"320","author":"Andersen","year":"2000","journal-title":"BMJ"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/humupd\/dmv041","article-title":"The role of infection in miscarriage","volume":"22","author":"Giakoumelou","year":"2016","journal-title":"Hum. Reprod. Updat."},{"key":"ref_29","first-page":"209","article-title":"Placental villous edema: A possible cause of antenatal hypoxia","volume":"30","author":"Kovalovszki","year":"1990","journal-title":"Acta Paediatr. Hung."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/apm.12847","article-title":"Defense and infection of the human placenta","volume":"126","year":"2018","journal-title":"APMIS"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/j.1471-0528.1965.tb01470.x","article-title":"Placental calcification a study of 3,025 singleton and multiple pregnancies","volume":"72","author":"Tindall","year":"1965","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/uog.7733","article-title":"Exploring the relationship between preterm placental calcification and adverse maternal and fetal outcome","volume":"37","author":"Chen","year":"2011","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s13337-017-0399-z","article-title":"The role of the placenta in prenatally acquired Zika virus infection","volume":"28","author":"Mehrjardi","year":"2017","journal-title":"VirusDisease"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/humrep\/dei456","article-title":"Histological classification of chorionic villous vascularization in early pregnancy","volume":"21","author":"Hakvoort","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/0046-8177(95)90118-3","article-title":"Fetal thrombotic vasculopathy: The clinical significance of extensive avascular villi","volume":"26","author":"Redline","year":"1995","journal-title":"Hum. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.5858\/arpa.2017-0212-RA","article-title":"Fetal vascular malperfusion","volume":"141","author":"Heider","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cohen, M., and Scheimberg, I. (2015). Deaths: Placental and maternal conditions\u2014Pathology. Encyclopedia of Forensic and Legal Medicine, Elsevier. [2nd ed.].","DOI":"10.1016\/B978-0-12-800034-2.00122-1"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/j.ajog.2015.05.056","article-title":"Classification of placental lesions","volume":"213","author":"Redline","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1146\/annurev-virology-092917-043236","article-title":"Congenital viral infection: Traversing the uterine-placental interface","volume":"5","author":"Pereira","year":"2018","journal-title":"Annu. Rev. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.chom.2016.05.015","article-title":"Zika virus infects human placental macrophages","volume":"20","author":"Quicke","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Couderc, T., Chr\u00e9tien, F., Schilte, C., Disson, O., Brigitte, M., Guivel-Benhassine, F., Touret, Y., Barau, G., Cayet, N., and Schuffenecker, I. (2008). A mouse model for Chikungunya: Young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.0040029"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nwabuobi, C., Arlier, S., Schatz, F., Guzeloglu-Kayisli, O., Lockwood, C.J., and Kayisli, U.A. (2017). hCG: Biological functions and clinical applications. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102037"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3389\/fcimb.2018.00345","article-title":"Cellular and Molecular Immune Response to Chikungunya Virus Infection","volume":"8","author":"Tanabe","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jmb.2011.09.045","article-title":"Molecular links between the E2 envelope glycoprotein and nucleocapsid core in Sindbis virus","volume":"414","author":"Tang","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Noranate, N., Takeda, N., Chetanachan, P., Sittisaman, P., A-Nuegoonpipat, A., and Anantapreecha, S. (2014). Characterization of Chikungunya virus-like particles. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108169"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1128\/jvi.51.1.254-258.1984","article-title":"Structural proteins of Chikungunya virus","volume":"51","author":"Simizu","year":"1984","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kantor, A.M., Grant, D.G., Balaraman, V., White, T.A., and Franz, A.W.E. (2018). Ultrastructural analysis of chikungunya virus dissem-ination from the midgut of the yellow fever mosquito, aedes aegypti. Viruses, 10.","DOI":"10.3390\/v10100571"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/4\/554\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:41:17Z","timestamp":1760161277000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/4\/554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["v13040554"],"URL":"https:\/\/doi.org\/10.3390\/v13040554","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,25]]}}}