{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:33:06Z","timestamp":1777491186504,"version":"3.51.4"},"reference-count":112,"publisher":"Cambridge University Press (CUP)","issue":"07","license":[{"start":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T00:00:00Z","timestamp":1550620800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["www.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although leucocytes are targets of renin-angiotensin system (RAS) effector molecules and RAS-modulating drugs exert immunomodulatory effects, their impact on<jats:italic>Trypanosoma cruzi<\/jats:italic>infection remains poorly understood. By using the framework of a systematic review, we integrated the preclinical and clinical evidence to investigate the relevance of angiotensin-inhibiting drugs on<jats:italic>T. cruzi<\/jats:italic>infections. From a comprehensive and structured search in biomedical databases, only original studies were analysed. In preclinical and clinical studies, captopril, enalapril and losartan were RAS-modulating drugs used. The main<jats:italic>in vitro<\/jats:italic>findings indicated that these drugs increased parasite uptake per host cells, IL-12 expression by infected dendritic cells and IFN-<jats:italic>\u03b3<\/jats:italic>by T lymphocytes, in addition to attenuating IL-10 and IL-17 production by CD8 + T cells. In animal models, reduced parasitaemia, tissue parasitism, leucocytes infiltration and mortality were often observed in<jats:italic>T. cruzi<\/jats:italic>-infected animals receiving RAS-modulating drugs. In patients with Chagas\u2019 disease, these drugs exerted a controversial impact on cytokine and hormone levels, and a limited effect on cardiovascular function. Considering a detailed evaluation of reporting and methodological quality, the current preclinical and clinical evidence is at high risk of bias, and we hope that our critical analysis will be useful in mitigating the risk of bias in further studies.<\/jats:p>","DOI":"10.1017\/s003118201900009x","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T10:36:52Z","timestamp":1550659012000},"page":"914-927","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":7,"title":["Could angiotensin-modulating drugs be relevant for the treatment of Trypanosoma cruzi infection? A systematic review of preclinical and clinical evidence"],"prefix":"10.1017","volume":"146","author":[{"given":"Thaiany G.","family":"Souza-Silva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00edvia F.","family":"Diniz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Lia Mazzeti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea A. S.","family":"Mendon\u00e7a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-3590","authenticated-orcid":false,"given":"Reggiani V.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-5328","authenticated-orcid":false,"given":"R\u00f4mulo D.","family":"Novaes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"key":"S003118201900009X_ref39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-1"},{"key":"S003118201900009X_ref38","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.286.6368.832"},{"key":"S003118201900009X_ref37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90521.2008"},{"key":"S003118201900009X_ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2007.07.010"},{"key":"S003118201900009X_ref35","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2018.02.002"},{"key":"S003118201900009X_ref99","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760160334"},{"key":"S003118201900009X_ref34","first-page":"1","volume":"10","year":"2016","journal-title":"PLoS Negligence Tropical Disease"},{"key":"S003118201900009X_ref98","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2012.03.002"},{"key":"S003118201900009X_ref33","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00001"},{"key":"S003118201900009X_ref97","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762009000900021"},{"key":"S003118201900009X_ref95","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2013.09.023"},{"key":"S003118201900009X_ref30","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00779-08"},{"key":"S003118201900009X_ref137a","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.05.010"},{"key":"S003118201900009X_ref93","first-page":"1","volume":"9","year":"2014","journal-title":"PLoS ONE"},{"key":"S003118201900009X_ref91","doi-asserted-by":"publisher","DOI":"10.1590\/S0037-86822008000600011"},{"key":"S003118201900009X_ref90","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2013.04.003"},{"key":"S003118201900009X_ref17a","first-page":"4807","volume":"9","year":"2015","journal-title":"Drug design, development and therapy"},{"key":"S003118201900009X_ref129","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.219279"},{"key":"S003118201900009X_ref128","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00063-10"},{"key":"S003118201900009X_ref127","doi-asserted-by":"publisher","DOI":"10.1086\/381892"},{"key":"S003118201900009X_ref125","first-page":"273","volume":"60","year":"1993","journal-title":"Brazilian Archives of Cardiology"},{"key":"S003118201900009X_ref124","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22940"},{"key":"S003118201900009X_ref123","first-page":"51","volume":"18","year":"2012","journal-title":"Brazilian Journal of Sports Medicine"},{"key":"S003118201900009X_ref122","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61741-5"},{"key":"S003118201900009X_ref120","first-page":"173","volume":"31","year":"2018","journal-title":"International Journal of Cardiovascular Sciences"},{"key":"S003118201900009X_ref49a","first-page":"299","volume-title":"American Trypanosomiasis - Chagas Disease","year":"2017"},{"key":"S003118201900009X_ref33a","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000826"},{"key":"S003118201900009X_ref59","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1128\/IAI.67.1.308-318.1999","volume":"67","year":"1999","journal-title":"Infection and Immunity"},{"key":"S003118201900009X_ref58","doi-asserted-by":"publisher","DOI":"10.1002\/clc.22421"},{"key":"S003118201900009X_ref57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00001"},{"key":"S003118201900009X_ref56","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000195306.61719.64"},{"key":"S003118201900009X_ref54","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000062690.79456.D0"},{"key":"S003118201900009X_ref52","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2017.07.005"},{"key":"S003118201900009X_ref51","first-page":"1","volume":"1","year":"2009","journal-title":"Cold Spring Harbor perspectives in biology"},{"key":"S003118201900009X_ref50","first-page":"1","volume":"18","year":"2018","journal-title":"Microbes and Infection"},{"key":"S003118201900009X_ref123a","doi-asserted-by":"publisher","DOI":"10.1590\/S0036-46651984000600005"},{"key":"S003118201900009X_ref109a","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.8165"},{"key":"S003118201900009X_ref49","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0543"},{"key":"S003118201900009X_ref48","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5273(96)02776-3"},{"key":"S003118201900009X_ref47","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(89)90488-8"},{"key":"S003118201900009X_ref46","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006070707"},{"key":"S003118201900009X_ref45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-1842.2004.00511.x"},{"key":"S003118201900009X_ref43","doi-asserted-by":"publisher","DOI":"10.1111\/tmi.12235"},{"key":"S003118201900009X_ref42","doi-asserted-by":"publisher","DOI":"10.3109\/08037059709086444"},{"key":"S003118201900009X_ref28a","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2018.01.022"},{"key":"S003118201900009X_ref41","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.4049\/jimmunol.158.7.3311","volume":"158","year":"1997","journal-title":"Journal of Immunology"},{"key":"S003118201900009X_ref137","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.10.016"},{"key":"S003118201900009X_ref134","first-page":"1","volume":"2014","year":"2014","journal-title":"Mediators of Inflammation"},{"key":"S003118201900009X_ref133","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-014-0608-1"},{"key":"S003118201900009X_ref131","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(78)90055-3"},{"key":"S003118201900009X_ref7a","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apar.2016.10.001"},{"key":"S003118201900009X_ref29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2012.00333.x"},{"key":"S003118201900009X_ref28","doi-asserted-by":"publisher","DOI":"10.1645\/GE-2396.1"},{"key":"S003118201900009X_ref36a","first-page":"2862","volume":"160","year":"2015","journal-title":"Archives of virology"},{"key":"S003118201900009X_ref26","doi-asserted-by":"publisher","DOI":"10.1136\/jech.52.6.377"},{"key":"S003118201900009X_ref25","first-page":"7","volume":"25","year":"2016","journal-title":"Epidemiology and Health Services: A Review of the Brazilian Unified Health System"},{"key":"S003118201900009X_ref89","first-page":"1","volume":"12","year":"2018","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"S003118201900009X_ref24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2009.01179.x"},{"key":"S003118201900009X_ref88","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182017000634"},{"key":"S003118201900009X_ref23","first-page":"1","volume":"2014","year":"2014","journal-title":"Journal of Immunology Research"},{"key":"S003118201900009X_ref22","first-page":"1","volume":"2014","year":"2014","journal-title":"Mediators of Inflammations"},{"key":"S003118201900009X_ref86","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.15-0237"},{"key":"S003118201900009X_ref21","doi-asserted-by":"publisher","DOI":"10.1042\/bj2900033"},{"key":"S003118201900009X_ref20","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02761988000100016"},{"key":"S003118201900009X_ref84","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1998.00524.x"},{"key":"S003118201900009X_ref81","doi-asserted-by":"publisher","DOI":"10.1042\/cs1040109"},{"key":"S003118201900009X_ref80","first-page":"1","volume":"14","year":"2018","journal-title":"PLoS Pathogens"},{"key":"S003118201900009X_ref65a","doi-asserted-by":"publisher","DOI":"10.2307\/3279787"},{"key":"S003118201900009X_ref118","first-page":"1","volume":"63","year":"2011","journal-title":"Arthritis Care and Research"},{"key":"S003118201900009X_ref116","first-page":"1","volume":"8","year":"2013","journal-title":"PLoS ONE"},{"key":"S003118201900009X_ref115","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2107"},{"key":"S003118201900009X_ref113","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1995.0071"},{"key":"S003118201900009X_ref112","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.9.1289"},{"key":"S003118201900009X_ref111","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2016.08.006"},{"key":"S003118201900009X_ref110","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2010.04270.x"},{"key":"S003118201900009X_ref106a","first-page":"151","volume":"6","year":"2018","journal-title":"Journal of Microbiology e Experimentation"},{"key":"S003118201900009X_ref18","doi-asserted-by":"publisher","DOI":"10.5455\/jeim.070512.or.029"},{"key":"S003118201900009X_ref17","first-page":"1","volume":"73","year":"2015","journal-title":"Pathogens and Disease"},{"key":"S003118201900009X_ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2014.01.002"},{"key":"S003118201900009X_ref14","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.135"},{"key":"S003118201900009X_ref79","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199917040-00012"},{"key":"S003118201900009X_ref13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.27.100173.002023"},{"key":"S003118201900009X_ref78","doi-asserted-by":"publisher","DOI":"10.1051\/vetres\/2009009"},{"key":"S003118201900009X_ref12","first-page":"1","volume":"2013","year":"2013","journal-title":"BioMed Research International"},{"key":"S003118201900009X_ref77","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2018.04.003"},{"key":"S003118201900009X_ref11","first-page":"1","volume":"153","year":"2007","journal-title":"American Heart Journal"},{"key":"S003118201900009X_ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2009.11.008"},{"key":"S003118201900009X_ref75","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7451"},{"key":"S003118201900009X_ref72","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.9.6325"},{"key":"S003118201900009X_ref71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0060001"},{"key":"S003118201900009X_ref70","doi-asserted-by":"publisher","DOI":"10.1590\/0037-8682-0025-2017"},{"key":"S003118201900009X_ref108","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1019"},{"key":"S003118201900009X_ref107","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-009-0776-x"},{"key":"S003118201900009X_ref105","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003845"},{"key":"S003118201900009X_ref104","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a060301"},{"key":"S003118201900009X_ref103","doi-asserted-by":"publisher","DOI":"10.1590\/0037-8682-0324-2018"},{"key":"S003118201900009X_ref102","first-page":"425","volume":"78","year":"2002","journal-title":"Brazilian Cardiology Archives"},{"key":"S003118201900009X_ref101","doi-asserted-by":"crossref","first-page":"8619","DOI":"10.1016\/S0021-9258(18)34171-1","volume":"257","year":"1982","journal-title":"The Journal of Biological Chemistry"},{"key":"S003118201900009X_ref100","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.4049\/jimmunol.153.7.3135","volume":"153","year":"1994","journal-title":"Journal Immunology"},{"key":"S003118201900009X_ref69","first-page":"1","volume":"82","year":"2004","journal-title":"Brazilian Cardiology Archives"},{"key":"S003118201900009X_ref67","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2015.1056158"},{"key":"S003118201900009X_ref66","doi-asserted-by":"publisher","DOI":"10.1006\/expr.2000.4576"},{"key":"S003118201900009X_ref64","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2008.11.012"},{"key":"S003118201900009X_ref62","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"S003118201900009X_ref60","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00183.x"},{"key":"S003118201900009X_ref79a","doi-asserted-by":"publisher","DOI":"10.1590\/S1678-91992012000100005"},{"key":"S003118201900009X_ref9","first-page":"1","volume":"8","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"S003118201900009X_ref8","first-page":"1","volume":"4","year":"2013","journal-title":"Frontiers in Immunology"},{"key":"S003118201900009X_ref5","first-page":"540","volume":"13","year":"2015","journal-title":"Blood Transfusion"},{"key":"S003118201900009X_ref4","first-page":"434","volume":"96","year":"2011","journal-title":"Brazilian Cardiology Archives"},{"key":"S003118201900009X_ref1","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.66838"},{"key":"S003118201900009X_ref63","first-page":"1","volume":"91","year":"2008","journal-title":"Brazilian Cardiology Archives"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S003118201900009X","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T20:13:13Z","timestamp":1694635993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S003118201900009X\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,20]]},"references-count":112,"journal-issue":{"issue":"07","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["S003118201900009X"],"URL":"https:\/\/doi.org\/10.1017\/s003118201900009x","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,20]]},"assertion":[{"value":"Copyright \u00a9 Cambridge University Press 2019\u00a0","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}