{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:02:16Z","timestamp":1791640936332,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Oropouche virus (OROV) is an emerging arbovirus endemic in Latin America and the Caribbean that causes Oropouche fever, a febrile illness that clinically resembles some other arboviral infections. It is currently spreading through Brazil and surrounding countries, where, from 1 January to 1 August 2024, more than 8000 cases have been identified in Bolivia, Brazil, Columbia, and Peru and for the first time in Cuba. Travelers with Oropouche fever have been identified in the United States and Europe. A significant occurrence during this epidemic has been the report of pregnant women infected with OROV who have had miscarriages and stillborn fetuses with placental, umbilical blood and fetal somatic organ samples that were RT-PCR positive for OROV and negative for other arboviruses. In addition, there have been four cases of newborn infants having microcephaly, in which the cerebrospinal fluid tested positive for IgM antibodies to OROV and negative for other arboviruses. This communication examines the biology, epidemiology, and clinical features of OROV, summarizes the 2023\u20132024 Oropouche virus epidemic, and describes the reported cases of vertical transmission and congenital infection, fetal death, and microcephaly in pregnant women with Oropouche fever, addresses experimental animal infections and potential placental pathology findings of OROV, and reviews other bunyavirus agents that can cause vertical transmission. Recommendations are made for pregnant women travelling to the regions affected by the epidemic.<\/jats:p>","DOI":"10.3390\/v16091435","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T03:04:18Z","timestamp":1725851058000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Oropouche Virus (OROV) in Pregnancy: An Emerging Cause of Placental and Fetal Infection Associated with Stillbirth and Microcephaly following Vertical Transmission"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7486-8545","authenticated-orcid":false,"given":"David A.","family":"Schwartz","sequence":"first","affiliation":[{"name":"Perinatal Pathology Consulting, 490 Dogwood Valley Drive, Atlanta, GA 30342, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-3186","authenticated-orcid":false,"given":"Pradip","family":"Dashraath","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9914-6496","authenticated-orcid":false,"given":"David","family":"Baud","sequence":"additional","affiliation":[{"name":"Materno-Fetal & Obstetrics Research Unit, Department Woman-Mother-Child, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"746","DOI":"10.5858\/arpa.2022-0520-SA","article-title":"Mpox virus in pregnancy, the placenta, and newborn","volume":"147","author":"Schwartz","year":"2023","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.placenta.2022.10.002","article-title":"Common pathways targeted by viral hemorrhagic fever viruses to infect the placenta and increase the risk of stillbirth","volume":"141","author":"Coler","year":"2023","journal-title":"Placenta"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Masmejan, S., Musso, D., Vouga, M., Pomar, L., Dashraath, P., Stojanov, M., Panchaud, A., and Baud, D. (2020). Zika virus. Pathogens, 9.","DOI":"10.3390\/pathogens9110898"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/uog.21936","article-title":"Placental infection by Zika virus in French Guiana","volume":"56","author":"Pomar","year":"2020","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ajog.2022.10.001","article-title":"SARS-CoV-2 placentitis, stillbirth, and maternal COVID-19 vaccination: Clinical-pathologic correlations","volume":"228","author":"Schwartz","year":"2023","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"529","DOI":"10.5858\/arpa.2021-0586-SA","article-title":"Fetal deaths in Ireland due to SARS-CoV-2 placentitis caused by SARS-CoV-2 alpha","volume":"146","author":"Fitzgerald","year":"2022","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Schwartz, D.A. (2024). High rates of miscarriage and stillbirth among pregnant women with clade I mpox (monkeypox) are confirmed during 2023-2024 DR Congo outbreak in South Kivu province. Viruses, 16.","DOI":"10.3390\/v16071123"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.3201\/eid2911.230606","article-title":"Congenital mpox syndrome (clade I) in stillborn fetus after placental infection and intrauterine transmission, Democratic Republic of the Congo, 2008","volume":"29","author":"Schwartz","year":"2023","journal-title":"Emerg. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.micinf.2017.11.013","article-title":"Oropouche fever, an emergent disease from the Americas","volume":"20","author":"Escobar","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e29897","DOI":"10.1002\/jmv.29897","article-title":"Epidemiological and clinical overview of the 2024 Oropouche virus disease outbreaks, an emerging\/re-emerging neurotropic arboviral disease and global public health threat","volume":"96","author":"Liu","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41541-022-00456-2","article-title":"Baseline mapping of Oropouche virology, epidemiology, therapeutics, and vaccine research and development","volume":"7","author":"Files","year":"2022","journal-title":"NPJ Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"574","DOI":"10.4269\/ajtmh.1961.10.574","article-title":"Oropouche virus: A new human disease agent from Trinidad, West Indies","volume":"10","author":"Anderson","year":"1961","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Naveca, F.G., Pires de Almeida, T.A., Souza, V., Nascimento, V., Silva, D., Nascimento, F., Mej\u00eda, M., Silva de Oliveira, Y., Rocha, L., and Xavier, N. (2024). Emergence of a novel reassortant Oropouche virus drives persistent human outbreaks in the Brazilian Amazon region from 2022 to 2024. medRxiv, medRxiv:07.23.24310415.","DOI":"10.1101\/2024.07.23.24310415"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"The Lancet Infectious Diseases (2024). Oropouche fever, the mysterious threat. Lancet Infect. Dis., 24, 935.","DOI":"10.1016\/S1473-3099(24)00516-4"},{"key":"ref_15","unstructured":"Centers for Disease Control and Prevention (2024, September 02). Clinical Overview of Oropouche Virus Disease. 22 August 2024, Available online: https:\/\/www.cdc.gov\/oropouche\/hcp\/clinical-overview\/index.html."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Moreira, H.M., Sgorlon, G., Queiroz, J.A.S., Roca, T.P., Ribeiro, J., Teixeira, K.S., Passos-Silva, A.M., Ara\u00fajo, A., Gasparelo, N.W.F., and Dos Santos, A.dO. (2024). Outbreak of Oropouche virus in frontier regions in western Amazon. Microbiol. Spectr., 12.","DOI":"10.1128\/spectrum.01629-23"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"800","DOI":"10.3201\/eid1705.101333","article-title":"Molecular epidemiology of Oropouche virus, Brazil","volume":"17","author":"Vasconcelos","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_18","unstructured":"Moutinho, S. (2024). Virus spreading in Latin America may cause stillbirths and birth defects. Science, 20, Available online: https:\/\/www.science.org\/content\/article\/virus-spreading-in-latin-america-may-cause-stillbirths-and-birth-defects."},{"key":"ref_19","unstructured":"Centers for Disease Control and Prevention (2024, August 30). Increased Oropouche Virus Activity and Associated Risk to Travelers. 16 August 2024, Available online: https:\/\/emergency.cdc.gov\/han\/2024\/han00515.asp."},{"key":"ref_20","unstructured":"World Health Organization (2024, September 03). Oropouche Virus Disease\u2014Cuba. 11 June 2024, Available online: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/2024-DON521."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"769","DOI":"10.15585\/mmwr.mm7335e1","article-title":"Oropouche virus disease among U.S. travelers\u2014United States, 2024","volume":"73","author":"Morrison","year":"2024","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_22","unstructured":"European Centre for Disease Prevention and Control (ECDC) (2024, September 02). Threat Assessment Brief: Oropouche Virus Disease Cases Imported to the European Union, Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/threat-assessment-brief-oropouche-virus-disease-cases-imported-european-union."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.3201\/eid1512.090917","article-title":"Oropouche fever outbreak, Manaus, Brazil, 2007\u20132008","volume":"15","author":"Bastos","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s13365-021-00987-9","article-title":"Neurological disease caused by Oropouche virus in northern Brazil: Should it be included in the scope of clinical neurological diseases?","volume":"27","author":"Chiang","year":"2021","journal-title":"J. Neurovirol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sakkas, H., Bozidis, P., Franks, A., and Papadopoulou, C. (2018). Oropouche fever: A review. Viruses, 10.","DOI":"10.3390\/v10040175"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.4269\/ajtmh.16-0672","article-title":"Oropouche virus: Clinical, epidemiological, and molecular aspects of a neglected orthobunyavirus","volume":"96","author":"Pinheiro","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"732","DOI":"10.4269\/ajtmh.2012.11-0485","article-title":"deS.; Figueiredo, L.T.; Naveca, F.G.; Monte, R.L.; Lessa, N.; Pinto de Figueiredo, R.M.; Gimaque, J.B.; Pivoto Jo\u00e3o, G.; Ramasawmy, R.; Mour\u00e3o, M.P. Identification of Oropouche orthobunyavirus in the cerebrospinal fluid of three patients in the Amazonas, Brazil","volume":"86","author":"Bastos","year":"2012","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1590\/0074-02760150123","article-title":"Detection of Oropouche virus segment S in patients and in Culex quinquefasciatus in the state of Mato Grosso, Brazil","volume":"110","author":"Cardoso","year":"2015","journal-title":"Mem. Inst. Oswaldo Cruz."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Martins-Filho, P.R., Carvalho, T.A., and Dos Santos, C.A. (2024). Oropouche fever: Reports of vertical transmission and deaths in Brazil. Lancet Infect. Dis.","DOI":"10.1016\/S1473-3099(24)00557-7"},{"key":"ref_30","unstructured":"Pan American Health Organization (2024, September 03). Q&A\u2014Oropouche Fever. 24 July 2024. Available online: https:\/\/www.paho.org\/en\/news\/24-7-2024-qa-oropouche-fever."},{"key":"ref_31","unstructured":"Science Media Center (2024, September 01). Expert Reaction to the Oropouche Virus in South America and Some Imported Cases in Europe from Travellers to Cuba or Brazil. 14 August 2024. Available online: https:\/\/www.sciencemediacentre.org\/expert-reaction-to-the-oropouche-virus-in-south-america-and-some-imported-cases-in-europe-from-travellers-to-cuba-or-brazil\/."},{"key":"ref_32","unstructured":"Pan American Health Organization\/World Health Organization (2024, September 02). Epidemiological Alert: Oropouche in the Region of the Americas: Vertical Transmission Event under Investigation in Brazil. 17 July 2024. Available online: https:\/\/www.paho.org\/en\/documents\/epidemiological-alert-oropouche-region-americas-vertical-transmission-event-under."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Schwartz, D.A., and Pittman, P.R. (2023). Mpox (monkeypox) in pregnancy: Viral clade differences and their associations with varying obstetrical and fetal outcomes. Viruses, 15.","DOI":"10.3390\/v15081649"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pittman, P.R., Martin, J.W., Kingebeni, P.M., Tamfum, J.M., Mwema, G., Wan, Q., Ewala, P., Alonga, J., Bilulu, G., and Reynolds, M.G. (2023). Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo. PLoS Negl. Trop. Dis., 17.","DOI":"10.1371\/journal.pntd.0010384"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"660","DOI":"10.5858\/arpa.2022-0029-SA","article-title":"Placental tissue destruction and insufficiency from COVID-19 causes stillbirth and neonatal death from hypoxic-ischemic injury","volume":"146","author":"Schwartz","year":"2022","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Schwartz, D.A. (2022). Stillbirth after COVID-19 in unvaccinated mothers can result from SARS-CoV-2 placentitis, placental insufficiency, and hypoxic ischemic fetal demise, not direct fetal infection: Potential role of maternal vaccination in pregnancy. Viruses, 14.","DOI":"10.3390\/v14030458"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"151919","DOI":"10.1016\/j.semperi.2024.151919","article-title":"Impact of SARS-CoV-2 infection during pregnancy on the placenta and fetus","volume":"48","author":"Li","year":"2024","journal-title":"Semin. Perinatol."},{"key":"ref_38","unstructured":"Dashraath, P., Nielsen-Saines, K., Schwartz, D.A., Musso, D., and Baud, D. Vertical transmission potential of Oropouche virus infection in human pregnancies, in submission."},{"key":"ref_39","unstructured":"Minist\u00e9rio da Sa\u00fade Brazil (2024, September 01). Minist\u00e9rio da Sa\u00fade Informa Caso de Anomalia Cong\u00eanita Associada \u00e0 Oropouche. 8 August 2024, Available online: https:\/\/www.gov.br\/saude\/pt-br\/canais-de-atendimento\/sala-de-imprensa\/notas-a-imprensa\/2024\/ministerio-da-saude-informa-caso-de-anomalia-congenita-associada-a-oropouche."},{"key":"ref_40","unstructured":"Centers for Disease Control and Prevention (2024, September 03). Interim Clinical Considerations for Pregnant People with Confirmed or Probable Oropouche Virus Disease. 27 August 2024, Available online: https:\/\/www.cdc.gov\/oropouche\/hcp\/clinical-care\/pregnancy.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Foropouche%2Fhcp%2Fclinical-care-pregnancy%2Findex.html."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13028-015-0145-8","article-title":"Virus-induced congenital malformations in cattle","volume":"57","author":"Agerholm","year":"2015","journal-title":"Acta Vet. Scand."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Dutuze, M.F., Nzayirambaho, M., Mores, C.N., and Christofferson, R.C. (2018). A review of Bunyamwera, Batai, and Ngari viruses: Understudied Orthobunyaviruses with potential One Health implications. Front. Vet. Sci., 5.","DOI":"10.3389\/fvets.2018.00069"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5586","DOI":"10.1128\/JVI.01821-12","article-title":"Ovine fetal immune response to Cache Valley virus infection","volume":"87","author":"Dorniak","year":"2013","journal-title":"J. Virol."},{"key":"ref_44","unstructured":"Centers for Disease Control and Prevention (2024, September 02). Cache Valley: Causes and How It Spreads. 15 May 2024, Available online: https:\/\/www.cdc.gov\/cache-valley\/causes-and-spread\/index.html."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.virusres.2010.08.009","article-title":"Oropouche virus experimental infection in the golden hamster (Mesocrisetus auratus)","volume":"155","author":"Rodrigues","year":"2011","journal-title":"Virus Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.virusres.2012.07.006","article-title":"Experimental infection of suckling mice by subcutaneous inoculation with Oropouche virus","volume":"170","author":"Santos","year":"2012","journal-title":"Virus Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e225345","DOI":"10.1001\/jamanetworkopen.2022.5345","article-title":"SARS-CoV-2 Placentitis and intraparenchymal thrombohematomas among COVID-19 infections in pregnancy","volume":"5","author":"Huynh","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1007\/s00404-017-4361-5","article-title":"Viral infection, proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection","volume":"295","author":"Schwartz","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/infdis\/jiw206","article-title":"Ebola virus disease in pregnancy: Clinical, histopathologic, and immunohistochemical findings","volume":"215","author":"Muehlenbachs","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12985-024-02323-z","article-title":"Development of monoclonal antibodies against oropouche virus and its applicability to immunohistochemical diagnosis","volume":"21","author":"Andreolla","year":"2024","journal-title":"Virol. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"490","DOI":"10.3201\/eid2702.200684","article-title":"Prolonged maternal Zika viremia as a marker of adverse perinatal outcomes","volume":"27","author":"Pomar","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_52","unstructured":"The American College of Obstetricians and Gynecologists (2024, September 01). Update on Oropouche Virus and Potential Effects on Pregnancy. August 2024., Available online: https:\/\/www.acog.org\/clinical\/clinical-guidance\/practice-advisory\/articles\/2024\/08\/update-on-oropouche-virus-and-potential-effects-on-pregnancy."},{"key":"ref_53","unstructured":"Society of Maternal-Fetal Medicine (2024, September 02). Oropouche Virus Disease in Pregnancy. 23 August 2024. Available online: https:\/\/www.smfm.org\/oropouche-fever."},{"key":"ref_54","unstructured":"Centers for Disease Control and Prevention (2024, September 06). Interim Guidance for Evaluating and Managing Infants Born to Pregnant People with Confirmed or Probable Oropouche Virus Disease. 27 August 2024, Available online: https:\/\/www.cdc.gov\/oropouche\/hcp\/clinical-care\/infants.html."},{"key":"ref_55","unstructured":"Centers for Disease Control and Prevention (2024, September 06). Interim Guidance for Health Departments on Testing and Reporting for Oropouche Virus Disease. 27 August 2024, Available online: https:\/\/www.cdc.gov\/oropouche\/php\/reporting\/index.html."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40249-023-01091-2","article-title":"Transmission risk of Oropouche fever across the Americas","volume":"12","author":"Escobar","year":"2023","journal-title":"Infect. Dis. 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