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Peer reviewedOpen accessEchinococcosis

Repurposing niclosamide ethanolamine for alveolar echinococcosis reveals a disconnect between in vitro efficacy and in vivo outcome in the intraperitoneal infection model

PLOS Neglected Tropical Diseases·

Matías Preza, Nicole Dietrich, Pascal Zumstein, Judith Steinmann, Lea Hiller, Trix Zumkehr, Tobias Kämpfer, Marylène Chollet-Krugler, Laura Vetter, Andrew Hemphill, Sarah Dion, Britta Lundström-Stadelmann

DOI
10.1371/journal.pntd.0014016
PMID
42672097
PMCID
OpenAlex
W7204849537
Study type
Journal article
Publisher
Public Library of Science (PLoS)
Article type
journal-article
Integrity
current

Why this research matters now

Alveolar echinococcosis is a lethal neglected disease when untreated, and current therapies with albendazole or mebendazole are parasitostatic rather than curative. The findings underscore ongoing challenges in developing effective treatments and highlight the importance of bridging in vitro promise with in vivo performance.

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Structured evidence summary

Research question

The study evaluated whether niclosamide ethanolamine, a formulation with improved systemic exposure, could effectively treat Echinococcus multilocularis infection both in laboratory cultures and in a mouse model of alveolar echinococcosis.

Study design

The investigators conducted in vitro assays using E. multilocularis metacestode vesicles to measure drug efficacy, followed by in vivo testing in a mouse model using intraperitoneal infection.

Population and setting

The study used E. multilocularis metacestode vesicles in laboratory culture and experimentally infected mice with intraperitoneal E. multilocularis infection.

Main findings

Niclosamide and niclosamide ethanolamine showed potent activity against E. multilocularis metacestode vesicles in vitro, with IC50 values below 1 micromolar. However, this laboratory efficacy did not translate to the mouse infection model, where no meaningful anti-parasitic activity was observed.

Public-health relevance

Alveolar echinococcosis is a lethal neglected disease when untreated, and current therapies with albendazole or mebendazole are parasitostatic rather than curative. The findings underscore ongoing challenges in developing effective treatments and highlight the importance of bridging in vitro promise with in vivo performance.

Important limitations

The authors attribute the lack of in vivo activity to potential factors including the infection model used, limited drug uptake by the parasite in the animal, or rapid metabolization of the compound.

GIDS interpretation

This article is discoverable through disease classifier links for echinococcosis and topic links for One Health and Treatment. It represents peer-reviewed research on experimental therapeutics for a neglected parasitic disease and does not report surveillance data or outbreak investigations.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 7 auditable classifier relationships to diseases, places, topics, and study design.

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