{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:37:23Z","timestamp":1791596243149,"version":"4.3.4"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Nifurtimox is a recommended treatment for Chagas disease, but data from treated children are limited. We investigated the efficacy, safety and tolerability of nifurtimox administered as divisible, dispersible 30 mg and 120 mg tablets in children with Chagas disease. In this blinded, controlled study conducted January 2016\u2013July 2018, 330 patients aged &lt;18 years from 25 medical centres across three South American countries were randomised 2:1 to nifurtimox 10\u201320 mg\/kg\/day (aged &lt;12 years) or 8\u201310 mg\/kg\/day (aged \u226512 years) for 60 days (n = 219), or for 30 days plus placebo for 30 days (n = 111) (ClinicalTrials.gov NCT02625974). The primary outcome was anti-<jats:italic>Trypanosoma cruzi<\/jats:italic> serological response (negative seroconversion or seroreduction \u226520% in mean optical density from baseline determined by two conventional enzyme-linked immunosorbent assays) at 12 months in the 60-day treatment group versus historical placebo controls. Nifurtimox for 60 days achieved negative seroconversion (n = 10) and seroreduction (n = 62) in 72 patients (serological response 32.9%; 95% confidence interval [CI] 26.4%, 39.3%, of all treated patients), confirming superiority relative to the upper 95% CI of 16% for controls. In patients aged &lt;8 months, 10\/12 treated for 60 days (83.3%) and 5\/7 treated for 30 days (71.4%) achieved negative seroconversion. Overall serological response was lower for 30-day than for 60-day nifurtimox (between-treatment difference 14.0% [95% CI 3.7%, 24.2%]). The frequency of <jats:italic>T<\/jats:italic>. <jats:italic>cruzi-<\/jats:italic>positive quantitative polymerase chain reactions decreased substantially from baseline levels (60-day regimen 53.4% versus 1.4%; 30-day regimen 51.4% versus 4.5%). Study drug-related treatment-emergent adverse events (TEAEs), which were observed in 62 patients (28.3%) treated for 60 days and 29 patients (26.1%) treated for 30 days, were generally mild or moderate and resolved without sequelae; 4.2% of all TEAEs led to nifurtimox discontinuation. Age- and weight-adjusted nifurtimox for 60 days achieved a serological response at 12 months post-treatment that was superior to historical placebo, was well tolerated and had a favourable safety profile in children with Chagas disease. Although, at 1 year serological follow-up, efficacy of the shorter nifurtimox treatment was not comparable to the 60-day treatment regimen for the overall study population, further long-term follow-up of the patients will provide important information about the progress of serological conversion in children treated with nifurtimox, as well as the potential efficacy difference between the two regimens over time.<\/jats:p>","DOI":"10.1371\/journal.pntd.0008912","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:02:43Z","timestamp":1610064163000},"page":"e0008912","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":48,"title":["Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO)"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5865-7991","authenticated-orcid":true,"given":"Jaime","family":"Altcheh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6040-5438","authenticated-orcid":true,"given":"Luis","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Dib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-0561","authenticated-orcid":true,"given":"Ulrike","family":"Grossmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erya","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Moscatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6884-4379","authenticated-orcid":true,"given":"Jimy Jos\u00e9","family":"Pinto Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa Estela","family":"Ram\u00edrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the CHICO Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"pntd.0008912.ref001","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/S1473-3099(13)70002-1","article-title":"Global economic burden of Chagas disease: a computational simulation model","volume":"13","author":"BY Lee","year":"2013","journal-title":"Lancet Infect Dis"},{"key":"pntd.0008912.ref002","article-title":"Chagas disease (American trypanosomiasis)","author":"World Health Organization","year":"2020","journal-title":"Epidemiology"},{"key":"pntd.0008912.ref003","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1128\/CMR.00005-11","article-title":"Trypanosoma cruzi and Chagas\u2019 disease in the United States","volume":"24","author":"C Bern","year":"2011","journal-title":"Clin Microbiol Rev"},{"key":"pntd.0008912.ref004","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1056\/NEJMra1410150","article-title":"Chagas\u2019 disease","volume":"373","author":"C Bern","year":"2015","journal-title":"N Engl J Med"},{"key":"pntd.0008912.ref005","first-page":"154","article-title":"Chagas disease: current perspectives on a forgotten disease","volume":"81","author":"D-A \u00c1lvarez-Hern\u00e1ndez","year":"2018","journal-title":"Rev Med Hosp Gen M\u00e9x"},{"key":"pntd.0008912.ref006","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/S0140-6736(10)60061-X","article-title":"Chagas disease","volume":"375","author":"A Rassi","year":"2010","journal-title":"Lancet"},{"key":"pntd.0008912.ref007","volume-title":"Expert Committee on the Control of Chagas Disease","author":"World Health Organization","year":"2002"},{"key":"pntd.0008912.ref008","first-page":"1","volume-title":"Subdirecci\u00f3n de Vigilancia y Controlen Salud P\u00fablica","author":"Instituto Nacional de Salud","year":"2010"},{"key":"pntd.0008912.ref009","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s40506-018-0170-z","article-title":"Treatment of Chagas disease in the United States","volume":"10","author":"S Meymandi","year":"2018","journal-title":"Curr Treat Options Infect Dis"},{"key":"pntd.0008912.ref010","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/IPC.0000000000000512","article-title":"Addressing the challenges of Chagas disease. 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