{
  "abstract": "Background: Echinococcosis is a zoonotic disease caused by cestodes of the genus Echinococcus. Alveolar echinococcosis (AE), caused by E. multilocularis, 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 E. multilocularis infection in vitro and in vivo. Methodology/principal findings: We assessed the in vitro efficacy of niclosamide and NEN against E. multilocularis metacestode vesicles (IC50 < 0.2 µM) and primary parasite cells (IC50 < 0.3 µM), 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. Conclusions/significance: Although niclosamide and NEN demonstrated potent activity against E. multilocularis in vitro, this efficacy did not translate in the mouse model. The lack of in vivo 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 in vivo. Author summary: Alveolar echinococcosis (AE) is a severe disease caused by the larval stage of the fox tapeworm Echinococcus multilocularis. The parasite forms tumor-like lesions in the liver and can spread to other organs. The currently licensed drugs for the treatment of AE are not always effective, require long-term use, and can cause side effects that frequently require treatment interruption. Therefore, safer and more efficacious treatment options are urgently needed.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Matias Preza"
    },
    {
      "name": "Nicole Dietrich"
    },
    {
      "name": "Pascal Zumstein"
    },
    {
      "name": "Judith Steinmann"
    },
    {
      "name": "Lea Hiller"
    },
    {
      "name": "Trix Zumkehr"
    },
    {
      "name": "Tobias Kampfer"
    },
    {
      "name": "Marylene Chollet-Krugler"
    },
    {
      "name": "Laura Vetter"
    },
    {
      "name": "Andrew Hemphill"
    },
    {
      "name": "Sarah Dion"
    },
    {
      "name": "Britta Lundström-Stadelmann"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d6kjcw5zqyfk2.bib",
  "cited_by": 1,
  "doi": "10.1371/journal.pntd.0014016",
  "fulltext_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014016",
  "id": "d6kjcw5zqyfk2",
  "issns": [
    "1935-2727",
    "1935-2735"
  ],
  "landing_url": "https://hal.science/hal-05767897v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2734|Parasitic infections in humans and animals"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Bioenergetics/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Vesicles"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Electrophysiology/Membrane potential"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Parasitic diseases"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Parasitic diseases/Helminth infections/Echinococcosis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Tropical diseases/Neglected tropical diseases/Echinococcosis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmaceutics/Drug therapy"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Amines/Ethanolamine"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Amines/Ethanolamine"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Mouse models"
    ]
  ],
  "openalex": "W7204849537",
  "pdf_url": "https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014016&type=printable",
  "pmcid": null,
  "pmid": "42672097",
  "published": "2026-08-31",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/d6kjcw5zqyfk2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:42Z",
      "native_id": "hal-05767897",
      "source": "hal",
      "url": "https://hal.science/hal-05767897v1"
    },
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "10.1371/journal.pntd.0014016",
      "source": "plos",
      "url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014016"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "chemistry",
      "origin": "plos:organic chemistry",
      "subfield": "organic"
    },
    {
      "field": "medicine",
      "origin": "plos:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Repurposing niclosamide ethanolamine for alveolar echinococcosis reveals a disconnect between in vitro efficacy and in vivo outcome in the intraperitoneal infection model",
  "title_text": "Repurposing niclosamide ethanolamine for alveolar echinococcosis reveals a disconnect between in vitro efficacy and in vivo outcome in the intraperitoneal infection model",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/d6kjcw5zqyfk2",
  "venue": "PLoS Neglected Tropical Diseases",
  "versions": []
}