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

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...

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Autores principales:	Amy E. Marriott, Hanna Sjoberg, Hayley Tyrer, Joanne Gamble, Emma Murphy, John Archer, Andrew Steven, Mark J. Taylor, Joseph D. Turner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7bc2b8d4bdf1456b87027d72ef7bff3e
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spelling	oai:doaj.org-article:7bc2b8d4bdf1456b87027d72ef7bff3e2021-12-02T15:08:35ZValidation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models10.1038/s41598-018-24294-22045-2322https://doaj.org/article/7bc2b8d4bdf1456b87027d72ef7bff3e2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24294-2https://doaj.org/toc/2045-2322Abstract 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.Amy E. MarriottHanna SjobergHayley TyrerJoanne GambleEmma MurphyJohn ArcherAndrew StevenMark J. TaylorJoseph D. TurnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amy E. Marriott Hanna Sjoberg Hayley Tyrer Joanne Gamble Emma Murphy John Archer Andrew Steven Mark J. Taylor Joseph D. Turner Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models
description	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.
format	article
author	Amy E. Marriott Hanna Sjoberg Hayley Tyrer Joanne Gamble Emma Murphy John Archer Andrew Steven Mark J. Taylor Joseph D. Turner
author_facet	Amy E. Marriott Hanna Sjoberg Hayley Tyrer Joanne Gamble Emma Murphy John Archer Andrew Steven Mark J. Taylor Joseph D. Turner
author_sort	Amy E. Marriott
title	Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models
title_short	Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models
title_full	Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models
title_fullStr	Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models
title_full_unstemmed	Validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models
title_sort	validation of ultrasound bioimaging to predict worm burden and treatment efficacy in preclinical filariasis drug screening models
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7bc2b8d4bdf1456b87027d72ef7bff3e
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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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