Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models

Marriott, Amy E, Sjoberg, Hanna, Tyrer, Hayley, Gamble, Joanne ORCID: 0000-0001-7302-3412, Murphy, Emma, Archer, John, Steven, Andrew, Taylor, Mark J and Turner, Joseph D (2018) Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models. SCIENTIFIC REPORTS, 8 (1). 5910-.

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Official URL: http://dx.doi.org/10.1038/s41598-018-24294-2

Abstract

Filariasis is a global health problem targeted for elimination. Curative drugs (macrofilaricides) are required to accelerate elimination. Candidate macrofilaricides require testing in preclinical models of filariasis. The incidence of infection failures and high intra-group variation means that large group sizes are required for drug testing. Further, a lack of accurate, quantitative adult biomarkers results in protracted timeframes or multiple groups for endpoint analyses. Here we evaluate intra-vital ultrasonography (USG) to identify B. malayi in the peritonea of gerbils and CB.17 SCID mice and assess prognostic value in determining drug efficacy. USG operators, blinded to infection status, could detect intra-peritoneal filarial dance sign (ipFDS) with 100% specificity and sensitivity, when >5 B. malayi worms were present in SCID mice. USG ipFDS was predictive of macrofilaricidal activity in randomized, blinded studies comparing flubendazole, albendazole and vehicle-treated SCID mice. Semi-quantification of ipFDS could predict worm burden >10 with 87-100% accuracy in SCID mice or gerbils. We estimate that pre-assessment of worm burden by USG could reduce intra-group variation, obviate the need for surgical implantations in gerbils, and reduce total SCID mouse use by 40%. Thus, implementation of USG may reduce animal use, refine endpoints and negate invasive techniques for assessing anti-filarial drug efficacy.

Item Type:	Article
Uncontrolled Keywords:	Animals, Mice, Mice, SCID, Brugia malayi, Filariasis, Albendazole, Filaricides, Ultrasonography, Treatment Outcome, Drug Evaluation, Preclinical
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	12 Oct 2022 08:27
Last Modified:	18 Jan 2023 20:37
DOI:	10.1038/s41598-018-24294-2
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3165352