{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T14:03:21Z","timestamp":1784642601809,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012356","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000}}],"reference-count":123,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008054","name":"Fundaci\u00f3n Ram\u00f3n Areces","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008054","name":"Fundaci\u00f3n Ram\u00f3n Areces","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Agency of Science","award":["PGC2018-099424-B-I00"],"award-info":[{"award-number":["PGC2018-099424-B-I00"]}]},{"name":"I+D+i Proyect","award":["A-BIO-350-UGR18"],"award-info":[{"award-number":["A-BIO-350-UGR18"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Chagas disease, once restricted mainly to the Americas, Chagas disease has become a global health problem due to migration from endemic to non-endemic areas. In non-endemic regions, transmission is limited to vertical transmission from infected mothers to newborns or through blood and organ donations. A major challenge in the management of the disease lies in the diagnosis of chronic cases, as blood-borne parasites are often absent and antibodies persist for life, complicating the evaluation of treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology and main findings<\/jats:title>\n<jats:p>This study investigates whether detection of circulating extracellular vesicles (EVs) or their immunocomplexes with host IgGs in the serum of chronic patients with Chagas disease could serve as diagnostic tools and biomarkers of the active presence of the parasite. This method may prove valuable in cases where parasitaemia and other diagnostic tests are inconclusive, especially for assessing treatment efficacy and confirming mother-to-child transmission. Together with exovesicle purification by ultracentrifugation, which is the \u2018gold standard\u2019, an affordable and simplified method for the isolation of EVs or immunocomplexes was tested for use in less well-equipped diagnostic laboratories.<\/jats:p>\n<jats:p>EV detection was performed by enzyme-linked immunosorbent assay (ELISA) targeting Trypanosoma cruzi antigens. Positive results were demonstrated in Bolivian patients in Spain, covering asymptomatic and symptomatic cases (cardiac, gastrointestinal or both). The study also examined infected mothers and their newborns. These findings were further confirmed in Panamanian patients with inconclusive diagnostic results.<\/jats:p>\n<jats:p>Moreover, host IgG isotypes that formed immunocomplexes with parasite exovsicles were identified, with IgG2 and IgG4 being predominant.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our results confirm the usefulness of circulating EVs and their immunocomplexes as markers of metabolically active T. cruzi in chronic infections without detectable parasitaemia, as well as their efficacy in confirming vertical transmission and in cases of inconclusive diagnostic tests.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012356","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T18:40:59Z","timestamp":1732128059000},"page":"e0012356","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Circulating extracellular vesicles in sera of chronic patients as a method for determining active parasitism in Chagas disease"],"prefix":"10.1371","volume":"18","author":[{"given":"Noelia","family":"Lozano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Prescilla-Ledezma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Calabuig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Trelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel Sahuquillo","family":"Arce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"L\u00f3pez Hontangas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Miguel","family":"de Pablos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Gomez-Samblas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-1471","authenticated-orcid":true,"given":"Antonio","family":"Osuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"pntd.0012356.ref001","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0140-6736(17)31612-4","article-title":"Chagas disease","volume":"391","author":"JA P\u00e9rez-Molina","year":"2018","journal-title":"The Lancet"},{"key":"pntd.0012356.ref002","unstructured":"World Health Organization. (2010). Control and prevention of chagas disease in Europe: report of a WHO informal consultation (jointly organized by WHO headquarters and the WHO Regional Office for Europe), Geneva, Switzerland 17\u201318 December 2009. World Health Organization. https:\/\/iris.who.int\/handle\/10665\/95586"},{"key":"pntd.0012356.ref003","first-page":"31","volume":"104","author":"JR Coura","year":"2009","journal-title":"Epidemiology, control and surveillance of Chagas disease: 100 years after its discovery"},{"key":"pntd.0012356.ref004","unstructured":"WHO Expert Committee on the Control of Chagas Disease. Chagas disease (also known as American trypanosomiasis). 2023. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)"},{"key":"pntd.0012356.ref005","doi-asserted-by":"crossref","first-page":"e1136","DOI":"10.1371\/journal.pntd.0001136","article-title":"Chagas Disease Has Now Gone Global","volume":"5","author":"HB Tanowitz","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012356.ref006","doi-asserted-by":"crossref","first-page":"102284","DOI":"10.1016\/j.tmaid.2022.102284","article-title":"Estimating chagas disease prevalence and number of underdiagnosed, and undertreated individuals in Spain","volume":"47","author":"M Navarro","year":"2022","journal-title":"Travel Med Infect Dis"},{"key":"pntd.0012356.ref007","article-title":"Chagas disease: what is known and what is needed\u2014A background article","volume":"112","author":"JR Coura","year":"2007","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pntd.0012356.ref008","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0891-5520(20)30539-0","article-title":"Chagas disease. American trypanosomiasis","volume":"7","author":"L. Kirchhoff","year":"1993","journal-title":"Infect Dis Clin North Am"},{"key":"pntd.0012356.ref009","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/S1473-3099(01)00065-2","article-title":"Clinical and epidemiological aspects of Chagas disease","volume":"1","author":"A Prata","year":"2001","journal-title":"Lancet Infect Dis"},{"key":"pntd.0012356.ref010","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1586\/14787210.2015.1056158","article-title":"Between a bug and a hard place: Trypanosoma cruzi genetic diversity and the clinical outcomes of Chagas disease","volume":"13","author":"LA Messenger","year":"2015","journal-title":"Expert Rev Anti Infect Ther"},{"key":"pntd.0012356.ref011","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1128\/jcm.18.2.327-330.1983","article-title":"Direct micromethod for diagnosis of acute and congenital Chagas\u2019 disease","volume":"18","author":"H Feilij","year":"1983","journal-title":"J Clin Microbiol"},{"key":"pntd.0012356.ref012","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/0035-9203(84)90299-2","article-title":"The use of microhaematocrit tubes for the rapid diagnosis of Chagas\u2019 disease and malaria","volume":"78","author":"C La Fuente","year":"1984","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"pntd.0012356.ref013","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1179\/136485907X241415","article-title":"The PCR-based detection of Trypanosoma cruzi in the faeces of Triatoma infestans fed on patients with chronic American trypanosomiasis gives higher sensitivity and a quicker result than routine xenodiagnosis","volume":"101","author":"I Zulantay","year":"2007","journal-title":"Ann Trop Med Parasitol"},{"key":"pntd.0012356.ref014","doi-asserted-by":"crossref","first-page":"e1881","DOI":"10.1371\/journal.pntd.0001881","article-title":"A Systematic Review of High Quality Diagnostic Tests for Chagas Disease","volume":"6","author":"AM Afonso","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012356.ref015","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1128\/CVI.05289-11","article-title":"Evaluation of a Recombinant Trypanosoma cruzi Mucin-Like Antigen for Serodiagnosis of Chagas\u2019","volume":"18","author":"CR De Marchi","year":"2011","journal-title":"Disease. Clin Vaccine Immunol"},{"key":"pntd.0012356.ref016","doi-asserted-by":"crossref","first-page":"e0106221","DOI":"10.1128\/JCM.01062-21","article-title":"Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection","volume":"59","author":"C Truyens","year":"2021","journal-title":"J Clin Microbiol"},{"key":"pntd.0012356.ref017","first-page":"378","article-title":"Gu\u00edas cl\u00ednicas de la enfermedad de Chagas 2006: Parte V. Diagn\u00f3stico de laboratorio","volume":"25","author":"BW Apt","year":"2008","journal-title":"Rev Chil Infectol"},{"key":"pntd.0012356.ref018","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1001\/jama.298.18.2171","article-title":"Evaluation and Treatment of Chagas Disease in the United StatesA Systematic Review","volume":"298","author":"C Bern","year":"2007","journal-title":"JAMA"},{"issue":"spe","key":"pntd.0012356.ref019","first-page":"7","article-title":"II Consenso Brasileiro em Doen\u00e7a de Chagas, 2015","volume":"25","author":"JC Pinto Dias","year":"2016","journal-title":"Epidemiol Serv Sa\u00fade"},{"key":"pntd.0012356.ref020","unstructured":"World Health Organization (WHO). Control of Chagas disease: second report of the WHO expert committee. Technical Report 109. Geneva: WHO; 2002. http:\/\/whqlibdoc.who.int\/trs\/WHO_TRS_905.pdf"},{"key":"pntd.0012356.ref021","first-page":"11","article-title":"Deposition of immune complexes in experimental Chagas\u2019 disease","volume":"24","author":"J Chaves","year":"1982","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"pntd.0012356.ref022","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1590\/S0036-46651987000100004","article-title":"Specific circulating immune complexes in acute chagas\u2019 disease","volume":"29","author":"R Corral","year":"1987","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"pntd.0012356.ref023","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/0090-1229(91)90152-Z","article-title":"Immune complex-mediated glomerulopathy in experimental Chagas\u2019 disease","volume":"58","author":"RS Costa","year":"1991","journal-title":"Clin Immunol Immunopathol"},{"key":"pntd.0012356.ref024","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/pim.12341","article-title":"Proteomic profile of circulating immune complexes in chronic Chagas disease","volume":"38","author":"K Ohyama","year":"2016","journal-title":"Parasite Immunol"},{"key":"pntd.0012356.ref025","first-page":"141","article-title":"Evaluation of an ELISA technique for detection of antigens and circulating immune complexes of Trypanosoma cruzi by a field study in an endemic zone of Argentina","volume":"34","author":"P Petray","year":"1992","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"pntd.0012356.ref026","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2012.00072","article-title":"Impact of Leishmania metalloprotease GP63 on macrophage signaling","volume":"2","author":"A Isnard","year":"2012","journal-title":"Front Cell Infect Microbiol"},{"key":"pntd.0012356.ref027","doi-asserted-by":"crossref","first-page":"24658","DOI":"10.1074\/jbc.M301451200","article-title":"Expression and Function of the Trypanosoma brucei Major Surface Protease (GP63) Genes","volume":"278","author":"DJ LaCount","year":"2003","journal-title":"J Biol Chem"},{"key":"pntd.0012356.ref028","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1046\/j.1432-1033.2002.02968.x","article-title":"The trans-sialidase from the african trypanosome Trypanosoma brucei","volume":"269","author":"G Montagna","year":"2002","journal-title":"Eur J Biochem"},{"key":"pntd.0012356.ref029","doi-asserted-by":"crossref","first-page":"44451","DOI":"10.1038\/srep44451","article-title":"Immune complexes in chronic Chagas disease patients are formed by exovesicles from Trypanosoma cruzi carrying the conserved MASP N-terminal region","volume":"7","author":"IM D\u00edaz Lozano","year":"2017","journal-title":"Sci Rep"},{"key":"pntd.0012356.ref030","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1093\/nar\/gkp172","article-title":"Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi","volume":"37","author":"DC Bartholomeu","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"pntd.0012356.ref031","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1128\/IAI.05859-11","article-title":"Conserved Regions as Markers of Different Patterns of Expression and Distribution of the Mucin-Associated Surface Proteins of Trypanosoma cruzi","volume":"80","author":"LM De Pablos Torr\u00f3","year":"2012","journal-title":"Infect Immun"},{"key":"pntd.0012356.ref032","doi-asserted-by":"crossref","first-page":"e1779","DOI":"10.1371\/journal.pntd.0001779","article-title":"The MASP Family of Trypanosoma cruzi: Changes in Gene Expression and Antigenic Profile during the Acute Phase of Experimental Infection","volume":"6","author":"SL dos Santos","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012356.ref033","doi-asserted-by":"crossref","first-page":"27293","DOI":"10.1038\/srep27293","article-title":"The C-terminal region of Trypanosoma cruzi MASPs is antigenic and secreted via exovesicles","volume":"6","author":"LM De Pablos Torr\u00f3","year":"2016","journal-title":"Sci Rep"},{"key":"pntd.0012356.ref034","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"C Th\u00e9ry","year":"2018","journal-title":"J Extracell Vesicles"},{"key":"pntd.0012356.ref035","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2018.01190","article-title":"Extracellular Vesicles in Chagas Disease: A New Passenger for an Old Disease","volume":"9","author":"LM De Pablos Torr\u00f3","year":"2018","journal-title":"Front Microbiol"},{"key":"pntd.0012356.ref036","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"G Raposo","year":"2013","journal-title":"J Cell Biol"},{"key":"pntd.0012356.ref037","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1124\/pr.112.005983","article-title":"Classification, Functions, and Clinical Relevance of Extracellular Vesicles","volume":"64","author":"E van der Pol","year":"2012","journal-title":"Pharmacol Rev"},{"key":"pntd.0012356.ref038","first-page":"115","article-title":"Extracellular vesicles: Novel mediator for cell to cell communications in liver pathogenesis","volume":"60","author":"PB Devhare","year":"2018","journal-title":"Mol Asp Extracell Vesicles Dis"},{"key":"pntd.0012356.ref039","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/0005-2736(79)90209-8","article-title":"Plasma membrane vesicles isolated from epimastigote forms of Trypanosoma cruzi","volume":"550","author":"JF Da Silveira","year":"1979","journal-title":"Biochim Biophys Acta"},{"key":"pntd.0012356.ref040","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.micinf.2008.10.003","article-title":"Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response","volume":"11","author":"AC Trocoli Torrecilhas","year":"2009","journal-title":"Microbes Infect"},{"key":"pntd.0012356.ref041","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.4049\/jimmunol.1102053","article-title":"Trypanosoma cruzi Immune Evasion Mediated by Host Cell-Derived Microvesicles","volume":"188","author":"I Cestari","year":"2012","journal-title":"J Immunol"},{"key":"pntd.0012356.ref042","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1021\/pr300947g","article-title":"Proteomic Analysis of Trypanosoma cruzi Secretome: Characterization of Two Populations of Extracellular Vesicles and Soluble Proteins","volume":"12","author":"E Bayer-Santos","year":"2013","journal-title":"J Proteome Res"},{"key":"pntd.0012356.ref043","doi-asserted-by":"crossref","first-page":"e12672","DOI":"10.1111\/cmi.12672","article-title":"Dynamic flux of microvesicles modulate parasite\u2013host cell interaction of Trypanosoma cruzi in eukaryotic cells","volume":"19","author":"MI Ramirez","year":"2017","journal-title":"Cell Microbiol"},{"key":"pntd.0012356.ref044","doi-asserted-by":"crossref","first-page":"e0007163","DOI":"10.1371\/journal.pntd.0007163","article-title":"Extracellular vesicles of Trypanosoma cruzi tissue-culture cell-derived trypomastigotes: Induction of physiological changes in non-parasitized culture cells","volume":"13","author":"L Retana Moreira","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012356.ref045","doi-asserted-by":"crossref","first-page":"7618","DOI":"10.1038\/s41598-023-34820-6","article-title":"Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis","volume":"13","author":"A Cornet Gomez","year":"2023","journal-title":"Sci Rep"},{"key":"pntd.0012356.ref046","doi-asserted-by":"crossref","first-page":"e0006475","DOI":"10.1371\/journal.pntd.0006475","article-title":"The protein family TcTASV-C is a novel Trypanosoma cruzi virulence factor secreted in extracellular vesicles by trypomastigotes and highly expressed in bloodstream forms","volume":"12","author":"LD Caeiro","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012356.ref047","doi-asserted-by":"crossref","first-page":"1463779","DOI":"10.1080\/20013078.2018.1463779","article-title":"Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells","volume":"7","author":"KS Ribeiro","year":"2018","journal-title":"J Extracell Vesicles"},{"key":"pntd.0012356.ref048","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22105183","article-title":"Biophysical and Biochemical Comparison of Extracellular Vesicles Produced by Infective and Non-Infective Stages of Trypanosoma cruzi","volume":"22","author":"L Retana Moreira","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pntd.0012356.ref049","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23137193","article-title":"Molecular Recognition of Surface Trans-Sialidases in Extracellular Vesicles of the Parasite Trypanosoma cruzi Using Atomic Force Microscopy (AFM)","volume":"23","author":"A Prescilla Ledezma","year":"2022","journal-title":"Int J Mol Sci"},{"key":"pntd.0012356.ref050","doi-asserted-by":"crossref","first-page":"e0241921","DOI":"10.1371\/journal.pone.0241921","article-title":"Mixed infections by different Trypanosoma cruzi discrete typing units among Chagas disease patients in an endemic community in Panama","volume":"15","author":"A Prescilla Ledezma","year":"2020","journal-title":"PLOS ONE"},{"key":"pntd.0012356.ref051","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/j.1365-3083.1995.tb03707.x","article-title":"Immunoparasitological Studies of Trypanosoma Cruzi Low Virulence Clones from Panama: Humoral Immune Responses and Antigenic Cross-Reactions with Trypanosoma Rangeli in Experimentally Infected Mice","volume":"42","author":"A Salda\u00f1a","year":"1995","journal-title":"Scand J Immunol"},{"key":"pntd.0012356.ref052","doi-asserted-by":"crossref","first-page":"e0282814","DOI":"10.1371\/journal.pone.0282814","article-title":"Use of sera cell free DNA (cfDNA) and exovesicle-DNA for the molecular diagnosis of chronic Chagas disease","volume":"18","author":"N Lozano","year":"2023","journal-title":"PLOS ONE"},{"key":"pntd.0012356.ref053","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1215913","article-title":"Extracellular vesicles of Trypanosoma cruzi and immune complexes they form with sialylated and non-sialylated IgGs increase small peritoneal macrophage subpopulation and elicit different cytokines profiles","volume":"14","author":"A Cornet Gomez","year":"2023","journal-title":"Front Immunol"},{"key":"pntd.0012356.ref054","first-page":"301","article-title":"Methods for the Isolation and Study of Exovesicle DNA from Trypanosomatid Parasites. Parasite Genomics","volume":"2369","author":"LM Orrego","year":"2021","journal-title":"Methods and Protocols"},{"key":"pntd.0012356.ref055","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1039\/C7NR08360B","article-title":"Technical challenges of working with extracellular vesicles","volume":"10","author":"MI Ramirez","year":"2018","journal-title":"Nanoscale"},{"key":"pntd.0012356.ref056","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01787-7","article-title":"Chagas disease","volume":"403","author":"AS de Sousa","year":"2024","journal-title":"The Lancet"},{"key":"pntd.0012356.ref057","first-page":"115","volume":"104","author":"YM Gomes","year":"2009","journal-title":"Diagnosis of Chagas disease: what has been achieved? What remains to be done with regard to diagnosis and follow up studies?"},{"key":"pntd.0012356.ref058","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.3389\/fmicb.2019.01854","article-title":"Congenital Transmission of Trypanosoma cruzi: A Review About the Interactions Between the Parasite, the Placenta, the Maternal and the Fetal\/Neonatal Immune Responses","volume":"10","author":"U Kemmerling","year":"2019","journal-title":"Front Microbiol"},{"key":"pntd.0012356.ref059","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1128\/CDLI.10.5.826-830.2003","article-title":"Enzyme-Linked Immunoassay Using Recombinant trans-Sialidase of Trypanosoma cruzi Can Be Employed for Monitoring of Patients with Chagas\u2019 Disease after Drug Treatment","volume":"10","author":"VL Pereira Chioccola","year":"2003","journal-title":"Clin Vaccine Immunol"},{"key":"pntd.0012356.ref060","doi-asserted-by":"crossref","first-page":"e0011440","DOI":"10.1371\/journal.pntd.0011440","article-title":"ELISA F29 \u2013A therapeutic efficacy biomarker in Chagas disease: Evaluation in pediatric patients treated with nifurtimox and followed for 4 years post-treatment","volume":"17","author":"R Rivero","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012356.ref061","first-page":"31","article-title":"Chagas\u2019 disease: the hidden enemy around the world","author":"EA Bocchi","year":"2023","journal-title":"Lancet Reg Health\u2013West Pac"},{"key":"pntd.0012356.ref062","doi-asserted-by":"crossref","first-page":"e210193","DOI":"10.1590\/0074-02760210193","article-title":"Trypanosoma cruzi genetic diversity: impact on transmission cycles and Chagas disease","volume":"117","author":"B Zingales","year":"2022","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pntd.0012356.ref063","doi-asserted-by":"crossref","first-page":"2315964","DOI":"10.1080\/22221751.2024.2315964","article-title":"Identification of highly conserved Trypanosoma cruzi antigens for the development of a universal serological diagnostic assay","volume":"13","author":"A Majeau","year":"2024","journal-title":"Emerg Microbes Infect"},{"key":"pntd.0012356.ref064","doi-asserted-by":"crossref","first-page":"e0007694","DOI":"10.1371\/journal.pntd.0007694","article-title":"Congenital Chagas disease: Updated recommendations for prevention, diagnosis, treatment, and follow-up of newborns and siblings, girls, women of childbearing age, and pregnant women","volume":"13","author":"Y Carlier","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012356.ref065","first-page":"111","article-title":"Serological based monitoring of a cohort of patients with chronic Chagas disease treated with benznidazole in a highly endemic area of northern Argentina","author":"LL Niborski","year":"2016","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pntd.0012356.ref066","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4067\/S0717-77122004000300001","article-title":"Enfermedad de Chagas cr\u00f3nica. Ausencia de Triatoma infestans intradomiciliario y persistencia de Trypanosoma cruzi circulante post-terapia","volume":"59","author":"I Zulantay","year":"2004","journal-title":"Parasitol Latinoam"},{"key":"pntd.0012356.ref067","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/14787210.2019.1577731","article-title":"Strategies to enhance access to diagnosis and treatment for Chagas disease patients in Latin America","volume":"17","author":"J Alonso Padilla","year":"2019","journal-title":"Expert Rev Anti Infect Ther"},{"key":"pntd.0012356.ref068","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/TP.0000000000002019","article-title":"Chagas Disease Recommendations for Solid-Organ Transplant Recipients and Donors","volume":"102","author":"LC Pierrotti","year":"2018","journal-title":"Transplantation"},{"key":"pntd.0012356.ref069","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2307\/3275421","article-title":"A method for concentrating hemoflagellates","volume":"48","author":"R. Strout","year":"1962","journal-title":"J Parasitol"},{"key":"pntd.0012356.ref070","doi-asserted-by":"crossref","DOI":"10.1590\/0037-8682-0505-2018","article-title":"Comparison of methodologies for detecting Trypanosoma cruzi parasites by microscopic observation of microhematocrit capillary tubes","volume":"52","author":"M Vera Ku","year":"2019","journal-title":"Rev Soc Bras Med Trop"},{"key":"pntd.0012356.ref071","unstructured":"Directive 2000\/54\/EC of the European Parliament and of the Council of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work."},{"key":"pntd.0012356.ref072","doi-asserted-by":"crossref","first-page":"e34039","DOI":"10.7554\/eLife.34039","article-title":"Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure","volume":"7","author":"FJ S\u00e1nchez Vald\u00e9z","year":"2018","journal-title":"eLife"},{"key":"pntd.0012356.ref073","first-page":"1","article-title":"State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation","volume":"14","author":"J Gabald\u00f3n Figueira","year":"2023","journal-title":"Res Rep Trop Med"},{"key":"pntd.0012356.ref074","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2024.1381357","article-title":"Enhanced secretion of promyogenic exosomes by quiescent muscle cells","volume":"12","author":"P Devan","year":"2024","journal-title":"Front Cell Dev Biol"},{"key":"pntd.0012356.ref075","first-page":"100821","article-title":"Retrospect, advances and challenges in Chagas disease diagnosis: a comprehensive review","volume":"36","author":"AG Schijman","year":"2024","journal-title":"Lancet Reg Health Am"},{"key":"pntd.0012356.ref076","first-page":"346","article-title":"Ant\u00edgenos de excreci\u00f3n\/secreci\u00f3n de tripomastigotes de Trypanosoma cruzi (tesa) como herramientas \u00fatiles para el diagn\u00f3stico de la enfermedad de chagas","volume":"25","author":"M. Berrizbeitia","year":"2013","journal-title":"Saber"},{"key":"pntd.0012356.ref077","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1128\/JCM.44.2.291-296.2006","article-title":"Purified Excreted-Secreted Antigens from Trypanosoma cruzi Trypomastigotes as Tools for Diagnosis of Chagas\u2019 Disease","volume":"44","author":"M Berrizbeitia","year":"2006","journal-title":"J Clin Microbiol"},{"key":"pntd.0012356.ref078","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1128\/CDLI.8.5.1024-1027.2001","article-title":"Excretory-Secretory Antigens of Trypanosoma cruzi Are Potentially Useful for Serodiagnosis of Chronic Chagas\u2019 Disease","volume":"8","author":"M Nakazawa","year":"2001","journal-title":"Clin Diagn Lab Immunol"},{"key":"pntd.0012356.ref079","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1590\/S0074-02761996000100015","article-title":"Trypanosoma cruzi defined antigens in the serological evaluation of an outbreak of acute Chagas disease in Brazil (Catol\u00e9 do Rocha, Para\u00edba)","volume":"91","author":"ES Umezawa","year":"1996","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pntd.0012356.ref080","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0732-8893(01)00216-4","article-title":"Enzyme-linked immunosorbent assay with Trypanosoma cruzi excreted-secreted antigens (TESA-ELISA) for serodiagnosis of acute and chronic Chagas\u2019 disease","volume":"39","author":"ES Umezawa","year":"2001","journal-title":"Diagn Microbiol Infect Dis"},{"key":"pntd.0012356.ref081","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1128\/JCM.01649-16","article-title":"Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells","volume":"55","author":"NL Bautista Lopez","year":"2017","journal-title":"J Clin Microbiol"},{"key":"pntd.0012356.ref082","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1128\/JCM.02353-16","article-title":"A New Development in Trypanosoma cruzi Detection","volume":"55","author":"B Tanowitz Herbert","year":"2017","journal-title":"J Clin Microbiol"},{"key":"pntd.0012356.ref083","doi-asserted-by":"crossref","first-page":"e25914","DOI":"10.1371\/journal.pone.0025914","article-title":"Genomic Analyses, Gene Expression and Antigenic Profile of the Trans-Sialidase Superfamily of Trypanosoma cruzi Reveal an Undetected Level of Complexity","volume":"6","author":"LM Freitas","year":"2011","journal-title":"PLOS ONE"},{"key":"pntd.0012356.ref084","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2016.00348","article-title":"Role of Trypanosoma cruzi Trans-sialidase on the Escape from Host Immune Surveillance","volume":"7","author":"AF Nardy","year":"2016","journal-title":"Front Microbiol"},{"key":"pntd.0012356.ref085","doi-asserted-by":"crossref","first-page":"e0262158","DOI":"10.1371\/journal.pone.0262158","article-title":"The role of Leishmania GP63 in the modulation of innate inflammatory response to Leishmania major infection","volume":"16","author":"A Chan","year":"2022","journal-title":"PLOS ONE"},{"key":"pntd.0012356.ref086","doi-asserted-by":"crossref","first-page":"5739","DOI":"10.1128\/IAI.71.10.5739-5749.2003","article-title":"gp63 Homologues in Trypanosoma cruzi: Surface Antigens with Metalloprotease Activity and a Possible Role in Host Cell Infection","volume":"71","author":"IC Cuevas","year":"2003","journal-title":"Infect Immun"},{"key":"pntd.0012356.ref087","doi-asserted-by":"crossref","first-page":"19591","DOI":"10.1038\/s41598-020-76508-1","article-title":"A novel Trypanosoma cruzi secreted antigen as a potential biomarker of Chagas disease","volume":"10","author":"R Nagarkatti","year":"2020","journal-title":"Sci Rep"},{"key":"pntd.0012356.ref088","doi-asserted-by":"crossref","first-page":"105310","DOI":"10.1016\/j.micinf.2024.105310","article-title":"Extracellular vesicles in parasitic diseases from pathogenesis to future diagnostic tools","volume":"26","author":"SA Menezes","year":"2024","journal-title":"Microbes Infect"},{"key":"pntd.0012356.ref089","doi-asserted-by":"crossref","DOI":"10.1016\/bs.ctm.2024.07.003","article-title":"Extracellular vesicles as biomarkers in parasitic disease diagnosis","author":"B Barnadas Carceller","year":"2024","journal-title":"Current Topics in Membranes"},{"key":"pntd.0012356.ref090","first-page":"e00393","article-title":"Identification of Mycobacterium tuberculosis Peptides in Serum Extracellular Vesicles from Persons with Latent Tuberculosis Infection","volume":"58","author":"Mehaffy Carolina","year":"2020","journal-title":"J Clin Microbiol"},{"key":"pntd.0012356.ref091","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"M Y\u00e1\u00f1ez M\u00f3","year":"2015","journal-title":"J Extracell Vesicles"},{"key":"pntd.0012356.ref092","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1002\/elps.201800526","article-title":"Recent advances and challenges in the recovery and purification of cellular exosomes","volume":"40","author":"S Ayala Mar","year":"2019","journal-title":"Electrophoresis"},{"key":"pntd.0012356.ref093","doi-asserted-by":"crossref","first-page":"e0157566","DOI":"10.1371\/journal.pone.0157566","article-title":"Comparative Study of Extracellular Vesicles from the Urine of Healthy Individuals and Prostate Cancer Patients","volume":"11","author":"OE Bryzgunova","year":"2016","journal-title":"PLOS ONE"},{"key":"pntd.0012356.ref094","first-page":"5764740","article-title":"A Method for the Isolation of Exosomes from Human and Bovine Milk","author":"K Vaswani","year":"2019","journal-title":"J Nutr Metab"},{"key":"pntd.0012356.ref095","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/icb.1989.50","article-title":"IgG subclasses responsible for immune clearance in mice infected with Trypanosoma cruzi","volume":"67","author":"C Brodskyn","year":"1989","journal-title":"Immunol Cell Biol"},{"key":"pntd.0012356.ref096","first-page":"117","article-title":"Chagas disease in the context of the 2030 agenda: global warming and vectors","author":"R Moreira de Souza","year":"2022","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pntd.0012356.ref097","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.anpedi.2017.03.003","article-title":"Seroprevalencia y transmisi\u00f3n vertical de enfermedad de Chagas en una cohorte de gestantes latinoamericanas en un hospital terciario de Madrid","volume":"88","author":"L Francisco Gonz\u00e1lez","year":"2018","journal-title":"An Pediatr\u00eda"},{"key":"pntd.0012356.ref098","doi-asserted-by":"crossref","first-page":"e0218491","DOI":"10.1371\/journal.pone.0218491","article-title":"Congenital transmission of Chagas disease in a non-endemic area, is an early diagnosis possible?","volume":"14","author":"L Francisco Gonz\u00e1lez","year":"2019","journal-title":"PLOS ONE"},{"key":"pntd.0012356.ref099","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1093\/cid\/cis910","article-title":"Risk Factors and Primary Prevention of Congenital Chagas Disease in a Nonendemic Country","volume":"56","author":"L Murcia","year":"2013","journal-title":"Clin Infect Dis"},{"key":"pntd.0012356.ref100","unstructured":"Pan American Health Organization. EMTCT Plus. Framework for elimination of mother-to-child transmission of HIV, Syphilis, Hepatitis B, and Chagas. 2017. https:\/\/iris.paho.org\/handle\/10665.2\/34306"},{"key":"pntd.0012356.ref101","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1093\/trstmh\/trs013","article-title":"Congenital infection by Trypanosoma cruzi in an endemic area of Chile: a multidisciplinary study","volume":"107","author":"W Apt","year":"2013","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"pntd.0012356.ref102","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21124264","article-title":"Exosomes as Messengers between Mother and Fetus in Pregnancy","volume":"21","author":"L Czernek","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pntd.0012356.ref103","doi-asserted-by":"crossref","first-page":"502.e1","DOI":"10.1016\/j.ajog.2019.06.010","article-title":"Cyclic-recombinase-reporter mouse model to determine exosome communication and function during pregnancy","volume":"221","author":"S Sheller Miller","year":"2019","journal-title":"Am J Obstet Gynecol"},{"key":"pntd.0012356.ref104","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.placenta.2016.12.001","article-title":"Fetal-maternal communication via extracellular vesicles\u2013Implications for complications of pregnancies","volume":"54","author":"S Adam","year":"2017","journal-title":"Placenta"},{"key":"pntd.0012356.ref105","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.3390\/ijms21062120","article-title":"Extracellular Vesicles in Feto\u2013Maternal Crosstalk and Pregnancy Disorders","volume":"21","author":"D Buca","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pntd.0012356.ref106","doi-asserted-by":"crossref","first-page":"439","DOI":"10.31486\/toj.20.0049","article-title":"Circulating Placental Extracellular Vesicles and Their Potential Roles During Pregnancy","volume":"20","author":"ACV Nakahara","year":"2020","journal-title":"Ochsner J"},{"key":"pntd.0012356.ref107","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41390-020-01240-5","article-title":"A review of the role of extracellular vesicles in neonatal physiology and pathology","volume":"90","author":"CA Murphy","year":"2021","journal-title":"Pediatric Research"},{"key":"pntd.0012356.ref108","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/blood-2013-03-489732","article-title":"CD169 mediates the capture of exosomes in spleen and lymph node","volume":"123","author":"SC Saunderson","year":"2014","journal-title":"Blood"},{"key":"pntd.0012356.ref109","doi-asserted-by":"crossref","first-page":"5933","DOI":"10.1038\/s41598-017-06288-8","article-title":"Bovine milk-derived exosomes from colostrum are enriched with proteins implicated in immune response and growth","volume":"7","author":"M Samuel","year":"2017","journal-title":"Sci Rep"},{"key":"pntd.0012356.ref110","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"R Kalluri","year":"2020","journal-title":"Science"},{"key":"pntd.0012356.ref111","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/10408363.2016.1190682","article-title":"Extracellular vesicles in blood, milk and body fluids of the female and male urogenital tract and with special regard to reproduction","volume":"53","author":"BP Foster","year":"2016","journal-title":"Crit Rev Clin Lab Sci"},{"key":"pntd.0012356.ref112","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.4049\/jimmunol.179.3.1969","article-title":"Exosomes with Immune Modulatory Features Are Present in Human Breast Milk1","volume":"179","author":"C Admyre","year":"2007","journal-title":"J Immunol"},{"key":"pntd.0012356.ref113","doi-asserted-by":"crossref","first-page":"33862","DOI":"10.1038\/srep33862","article-title":"Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells","volume":"6","author":"T Chen","year":"2016","journal-title":"Sci Rep"},{"key":"pntd.0012356.ref114","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1016\/j.cell.2021.02.031","article-title":"The multifaceted roles of breast milk antibodies","volume":"184","author":"C Atyeo","year":"2021","journal-title":"Cell"},{"key":"pntd.0012356.ref115","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.2353\/ajpath.2006.050482","article-title":"Maternal Antibodies Enhance or Prevent Cytomegalovirus Infection in the Placenta by Neonatal Fc Receptor-Mediated Transcytosis","volume":"168","author":"E Maidji","year":"2006","journal-title":"Am J Pathol"},{"key":"pntd.0012356.ref116","doi-asserted-by":"crossref","first-page":"104796","DOI":"10.1016\/j.cellimm.2023.104796","article-title":"Maternal immune factors involved in the prevention or facilitation of neonatal bacterial infections","volume":"395\u2013396","author":"Y Sereme","year":"2024","journal-title":"Cell Immunol"},{"key":"pntd.0012356.ref117","doi-asserted-by":"crossref","first-page":"e13017","DOI":"10.1111\/sji.13017","article-title":"The neonatal Fc receptor in mucosal immune regulation","volume":"93","author":"KH Aaen","year":"2021","journal-title":"Scand J Immunol"},{"key":"pntd.0012356.ref118","doi-asserted-by":"crossref","first-page":"9698","DOI":"10.1021\/bi000749m","article-title":"Crystal Structure and Immunoglobulin G Binding Properties of the Human Major Histocompatibility Complex-Related Fc Receptor","volume":"39","author":"AP West","year":"2000","journal-title":"Biochemistry"},{"key":"pntd.0012356.ref119","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1046\/j.1365-2567.1997.00326.x","article-title":"Expression of the neonatal Fc receptor, FcRn, on human intestinal epithelial cells","volume":"92","author":"EJ Israel","year":"1997","journal-title":"Immunology"},{"key":"pntd.0012356.ref120","doi-asserted-by":"crossref","first-page":"11076","DOI":"10.1073\/pnas.0402970101","article-title":"Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level","volume":"101","author":"RJ Ober","year":"2004","journal-title":"Proc Natl Acad Sci"},{"key":"pntd.0012356.ref121","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/intimm\/dxg018","article-title":"Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans","volume":"15","author":"ES Ward","year":"2003","journal-title":"Int Immunol"},{"key":"pntd.0012356.ref122","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1111\/j.1365-2222.2012.04043.x","article-title":"FcRn-mediated intestinal absorption of IgG anti-IgE\/IgE immune complexes in mice","volume":"42","author":"S Paveglio","year":"2012","journal-title":"Clin Exp Allergy"},{"key":"pntd.0012356.ref123","doi-asserted-by":"crossref","first-page":"e13331","DOI":"10.1111\/sji.13331","article-title":"IgG exacerbates genital chlamydial pathology in females by enhancing pathogenic CD8+ T cell responses","volume":"99","author":"CW Armitage","year":"2024","journal-title":"Scand J Immunol"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0012356","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T18:44:32Z","timestamp":1733337872000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012356"}},"subtitle":[],"editor":[{"given":"Bradford S","family":"McGwire","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":123,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0012356","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0012356","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}