{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:55:12Z","timestamp":1793087712889,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014016","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000}}],"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008949","name":"Uniscientia Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005688","name":"Gottfried und Julia Bangerter-Rhyner-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030-227438"],"award-info":[{"award-number":["320030-227438"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030-236056"],"award-info":[{"award-number":["320030-236056"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"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>\n                      Echinococcosis is a zoonotic disease caused by cestodes of the genus\n                      <jats:italic>Echinococcus<\/jats:italic>\n                      . Alveolar echinococcosis (AE), caused by\n                      <jats:italic>E. multilocularis<\/jats:italic>\n                      , primarily affects the liver and shows infiltrative, tumor-like growth of the metacestode stage. If untreated, AE is lethal. AE remains a neglected disease with current treatments based on albendazole or mebendazole that are parasitostatic, and not curative, underscoring the need for more effective therapies. Niclosamide is a chlorinated salicylanilide derivative with proven activities against intestinal helminths but is inactive against tissue-dwelling helminths due to poor absorption and limited bioavailability. In this study, we repurposed niclosamide ethanolamine (NEN), a formulation with improved systemic exposure, for the treatment of\n                      <jats:italic>E. multilocularis<\/jats:italic>\n                      infection\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/principal findings<\/jats:title>\n                    <jats:p>\n                      We assessed the\n                      <jats:italic>in vitro<\/jats:italic>\n                      efficacy of niclosamide and NEN against\n                      <jats:italic>E. multilocularis<\/jats:italic>\n                      metacestode vesicles (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009&lt;\u20090.2 \u00b5M) and primary parasite cells (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009&lt;\u20090.3 \u00b5M), with active concentrations largely corresponding to NEN levels reachable in the liver. Metabolic analysis suggested that NEN acts as a mitochondrial uncoupler. Electron microscopy showed that NEN-treatments induced profound structural damage in the metacestode vesicle tissue, but mitochondrial ultrastructure was not notably affected.\n                    <\/jats:p>\n                    <jats:p>\n                      In mice intraperitoneally infected with\n                      <jats:italic>E. multilocularis<\/jats:italic>\n                      , NEN was orally administered during 9 weeks either alone, or in combination with albendazole. Pharmacokinetic analyses showed that NEN reached blood level concentrations above 1 \u00b5M. However, the parasite burden in NEN-treated mice was not significantly reduced under the conditions used in this study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/significance<\/jats:title>\n                    <jats:p>\n                      Although niclosamide and NEN demonstrated potent activity against\n                      <jats:italic>E. multilocularis in vitro<\/jats:italic>\n                      , this efficacy did not translate in the mouse model. The lack of\n                      <jats:italic>in vivo<\/jats:italic>\n                      activity could be attributed to several factors such as infection model, limited drug uptake by the parasite in the animal, or the rapid metabolization of the compound. Future studies should explore novel niclosamide derivatives and formulations to enhance efficacy against AE\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014016","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T17:34:34Z","timestamp":1788197674000},"page":"e0014016","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing niclosamide ethanolamine for alveolar echinococcosis reveals a disconnect between in vitro efficacy and in vivo outcome in the intraperitoneal infection model"],"prefix":"10.1371","volume":"20","author":[{"given":"Mat\u00edas","family":"Preza","sequence":"first","affiliation":[{"name":"University of Bern","place":["Bern, Switzerland"],"department":["Institute of Parasitology, Vetsuisse 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