{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:00:55Z","timestamp":1791378055071,"version":"4.3.2"},"reference-count":223,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Congenital transmission of Zika virus (ZIKV) and\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    (\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    ) remains a major public health concern in the Americas. Both pathogens cross the placental barrier and cause severe neonatal outcomes, yet no confirmed congenital co-infections have been reported, and their combined effects on maternal\u2013fetal health are unknown. Critical gaps persist regarding placental immunopathology, fetal immune programming, and long-term consequences of prenatal exposure. This review synthesizes current evidence on the routes and mechanisms of placental transmission of ZIKV and\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    , their tropism for placental and fetal tissues, and their distinct immunological footprints. We summarize how congenital infection perturbs fetal immune maturation, including dysregulation of type I\/type III interferons, Th1-skewed inflammation, altered immune-tolerance pathways involving HLA-G and PD-1\/PD-L1 signaling, and early innate imprinting. We review advances in vaccine development (spanning inactivated, DNA, mRNA, subunit, and viral vector platforms) and highlight barriers such as antibody-dependent enhancement in ZIKV vaccines and the scarcity of pregnancy-relevant preclinical models for\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    . Promising candidates with evidence of fetal or maternal protection in animal studies are described. Therapeutic approaches, including antiviral discovery, immunomodulatory strategies, and emerging anti-\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    compounds are also examined. A detailed understanding of the immunopathology of congenital ZIKV and\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infections is essential to improve diagnostic accuracy, preventive strategies, and maternal\u2013fetal clinical care. Integrated mechanistic and translational research is urgently needed to assess the plausibility of co-infection, identify biomarkers of fetal risk, and guide the development of pregnancy-safe vaccines and therapeutics, particularly in resource-limited, endemic settings.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1824065","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:09:17Z","timestamp":1791374957000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Placental immunopathology and congenital transmission of Zika virus and Trypanosoma cruzi: comparative mechanisms, immune disturbances, and potential co-infection scenarios"],"prefix":"10.3389","volume":"17","author":[{"given":"Carlos Andres","family":"Rodriguez-Salazar","sequence":"first","affiliation":[{"name":"Molecular Biology and Virology Laboratory, Faculty of Medicine and Health Sciences, Corporaci\u00f3n Universitaria Empresarial Alexander von Humboldt","place":["Armenia, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia Piedad","family":"Recalde-Reyes","sequence":"additional","affiliation":[{"name":"Molecular Biology and Virology Laboratory, Faculty of Medicine and Health Sciences, Corporaci\u00f3n Universitaria Empresarial Alexander von Humboldt","place":["Armenia, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha J.","family":"Garg","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch (UTMB)","place":["Galveston, TX, United States"]},{"name":"Institute for Human Infections and Immunity (IHII), UTMB","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Giraldo","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch (UTMB)","place":["Galveston, TX, United States"]},{"name":"Institute for Human Infections and Immunity (IHII), UTMB","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.actatropica.2011.10.018","article-title":"Congenital parasitic infections: a review","volume":"121","author":"Carlier","year":"2012","journal-title":"Acta Trop"},{"key":"B2","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.clp.2021.05.004","article-title":"The term newborn: congenital infections","volume":"48","author":"Moodley","year":"2021","journal-title":"Clin Perinatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1709481","article-title":"Pregnancy outcomes after ZIKV infection in French territories in the Americas","volume":"378","author":"Hoen","year":"2018","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1602412","article-title":"Zika virus infection in pregnant women in Rio de Janeiro","volume":"375","author":"Brasil","year":"2016","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3201\/eid1705.101939","article-title":"Probable non-vector-borne transmission of Zika virus, Colorado, USA","volume":"17","author":"Foy","year":"2011","journal-title":"Emerg Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000000525","article-title":"The recent resurgence of Zika virus: current outbreak, epidemiology, transmission, diagnostic, prevention, treatment and complications \u2013 correspondent","volume":"85","author":"Islam","year":"2023","journal-title":"Ann Med Surg"},{"key":"B7","doi-asserted-by":"publisher","first-page":"100946","DOI":"10.1016\/j.lanmic.2024.07.009","article-title":"Climate change and Trypanosoma cruzi transmission in North and central America","volume":"5","author":"Forsyth","year":"2024","journal-title":"Lancet Microbe"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.24875\/bmhim.22000110","article-title":"Congenital zika syndrome","volume":"80","author":"Crisanto-Lopez","year":"2023","journal-title":"Bol Med Hosp Infant Mex"},{"key":"B9","doi-asserted-by":"publisher","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 - 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