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

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Marriott, Amy, Sjoberg, Hanna, Tyrer, Hayley, Gamble, Jo, Murphy, Emma ORCID: https://orcid.org/0000-0001-9421-7777, Archer, John, Steven, Andrew, Taylor, Mark and Turner, Joseph (2018) 'Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models.'. Scientific Reports, Vol 8, Issue 1, p. 5910.

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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
Subjects: QX Parasitology > Helminths. Annelida > QX 200 Helminths
QX Parasitology > Helminths. Annelida > QX 301 Filarioidea
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WN Radiology. Diagnostic imaging > WN 180 Diagnostic imaging (General)
WN Radiology. Diagnostic imaging > WN 20 Research (General)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1038/s41598-018-24294-2
SWORD Depositor: JISC Pubrouter
Depositing User: Stacy Murtagh
Date Deposited: 24 Apr 2018 10:30
Last Modified: 15 Nov 2018 12:35
URI: http://archive.lstmed.ac.uk/id/eprint/8524

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