{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:34:36Z","timestamp":1791934476699,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009269","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011749","name":"Pontificia Universidad Cat\u00f3lica del Ecuador","doi-asserted-by":"publisher","award":["O13066"],"award-info":[{"award-number":["O13066"]}],"id":[{"id":"10.13039\/501100011749","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ParaFrap","award":["PhD South Program 2017-2020"],"award-info":[{"award-number":["PhD South Program 2017-2020"]}]},{"name":"Institut de recherche pour le developpement"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Chagas disease, a neglected tropical disease endemic to Latin America caused by the parasite<jats:italic>Trypanosoma cruzi<\/jats:italic>, currently affects 6\u20137 million people and is responsible for 12,500 deaths each year. No vaccine exists at present and the only two drugs currently approved for the treatment (benznidazole and nifurtimox), possess serious limitations, including long treatment regimes, undesirable side effects, and frequent clinical failures. A link between parasite genetic variability and drug sensibility\/efficacy has been suggested, but remains unclear. Therefore, we investigated associations between<jats:italic>T<\/jats:italic>.<jats:italic>cruzi<\/jats:italic>genetic variability and<jats:italic>in vitro<\/jats:italic>benznidazole susceptibility via a systematic article review and meta-analysis.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methodology\/Principal findings<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic>normalized benznidazole susceptibility indices (LC<jats:sub>50<\/jats:sub>and IC<jats:sub>50<\/jats:sub>) for epimastigote, trypomastigote and amastigote stages of different<jats:italic>T<\/jats:italic>.<jats:italic>cruzi<\/jats:italic>strains were recorded from articles in the scientific literature. A total of 60 articles, which include 189 assays, met the selection criteria for the meta-analysis. Mean values for each discrete typing unit (DTU) were estimated using the meta and metaphor packages through R software, and presented in a rainforest plot. Subsequently, a meta-regression analysis was performed to determine differences between estimated mean values by DTU\/parasite stage\/drug incubation times. For each parasite stage, some DTU mean values were significantly different, e.g. at 24h of drug incubation, a lower sensitivity to benznidazole of TcI vs. TcII trypomastigotes was noteworthy. Nevertheless, funnel plots detected high heterogeneity of the data within each DTU and even for a single strain.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Conclusions\/Significance<\/jats:title><jats:p>Several limitations of the study prevent assigning DTUs to different<jats:italic>in vitro<\/jats:italic>benznidazole sensitivity groups; however, ignoring the parasite\u2019s genetic variability during drug development and evaluation would not be advisable. Our findings highlight the need for establishment of uniform experimental conditions as well as a screening of different DTUs during the optimization of new drug candidates for Chagas disease treatment.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pntd.0009269","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T17:29:17Z","timestamp":1616434157000},"page":"e0009269","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":58,"title":["In vitro susceptibility of Trypanosoma cruzi discrete typing units (DTUs) to benznidazole: A systematic review and 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