Activity of artemether and OZ78 against triclabendazole-resistant Fasciola hepatica

Keiser, Jennifer; Utzinger, Jürg; Vennerstrom, Jonathan L.; Dong, Yuxiang; Brennan, Gerry; Fairweather, Ian

doi:10.1016/j.trstmh.2007.07.012

Cited by 48 publications

(31 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While artemether enters the parasite through oral ingestion and causes substantial disruption to the gut, triclabendazole mainly affects the tegument (29,35). Furthermore, artemether and OZ78 also act against triclabendazole-resistant F. hepatica (22).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

In Vivo and In Vitro Sensitivity of Fasciola hepatica to Triclabendazole Combined with Artesunate, Artemether, or OZ78

Duthaler

Smith

Keiser

2010

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Triclabendazole resistance is continually documented from livestock, and hence new treatment strategies for Fasciola hepatica infections are needed. We investigated the effect of triclabendazole combined with artesunate, artemether, or OZ78 compared to that of monotherapy against adult and juvenile F. hepatica in rats. In vitro experiments with triclabendazole and its sulfoxide and sulfone metabolites, each in combination with the peroxides, complemented our study. F. hepatica-infected rats were subjected to single drugs or drug combinations 3 to 4 weeks (juvenile flukes) and >8 weeks (adult flukes) postinfection. Negative binomial regressions of worm and egg counts were used to analyze dose-response relationships and whether the effects of drug combinations were synergistic or antagonistic. The in vitro assays were evaluated by means of viability scales based on fluke motility. Fifty percent effective dose values of 113.0, 77.7, 22.9, and 2.7 mg/kg of body weight were calculated for monotherapy with artesunate, artemether, OZ78, and triclabendazole, respectively, against adult F. hepatica. Likelihood ratio tests revealed synergistic interactions (P < 0.05) of combinations of triclabendazole (2.5 mg/kg) plus artesunate or artemether on adult worm burden. Antagonistic effects on the adult burden and egg output were observed when a lower triclabendazole dose (1.25 mg/kg) was combined with the artemisinins. No significant interactions (P ‫؍‬ 0.07) were observed for OZ78 and triclabendazole combinations and between the triclabendazole effect and the effects of the other partner drugs on juvenile worms. Our in vitro studies of adult worms agreed with the in vivo results, while the in vitro analysis of juvenile worms revealed greater interactions than observed in vivo. In conclusion, single-agent triclabendazole demonstrated a more potent in vivo and in vitro fasciocidal activity than the experimental drugs artesunate, artemether, and OZ78. When combined, synergistic but also antagonistic effects depending on the doses administered were observed, which should be elucidated in more detail in future studies.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Importantly, artemether and OZ78 cured a triclabendazole-resistant F. hepatica infection in the rat model (22). Contradictory results were obtained in sheep.…”

mentioning

confidence: 90%

In Vivo and In Vitro Sensitivity of Fasciola hepatica to Triclabendazole Combined with Artesunate, Artemether, or OZ78

Duthaler

Smith

Keiser

2010

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…Evidence from animal studies suggests triclabendazole resistance may be overcome by coadministration with the enzyme inhibitor ketonazole (123) . The artemisinins artesunate, artethemer, and OZ78 are active against triclabendazole-resistant Fasciola hepatica (124) , and combination therapy may provide a solution to triclabendazole-resistant flukes, although further work is required (125) .…”

Section: For Clonorchis Sinensis Opisthorchis Viverrini and Opisthormentioning

confidence: 99%

Human liver flukes

Harrington

Lamberton

McGregor

2017

The Lancet Gastroenterology & Hepatology

View full text Add to dashboard Cite

show abstract

“…Other experimental fasciolicides such as artemether and OZ78 also have activity against TCBZ-resistant flukes (Keiser et al 2007). …”

Section: Zoonotic Trematode Infections (A) Fasciolosismentioning

confidence: 99%

Zoonotic helminth infections with particular emphasis on fasciolosis and other trematodiases

Robinson

Dalton

2009

Phil. Trans. R. Soc. B

148

109

View full text Add to dashboard Cite

Zoonotic infections are among the most common on earth and are responsible for .60 per cent of all human infectious diseases. Some of the most important and well-known human zoonoses are caused by worm or helminth parasites, including species of nematodes (trichinellosis), cestodes (cysticercosis, echinococcosis) and trematodes (schistosomiasis). However, along with social, epidemiological and environmental changes, together with improvements in our ability to diagnose helminth infections, several neglected parasite species are now fast-becoming recognized as important zoonotic diseases of humans, e.g. anasakiasis, several fish-borne trematodiasis and fasciolosis. In the present review, we discuss the current disease status of these primary helminth zoonotic infections with particular emphasis on their diagnosis and control. Advances in molecular biology, proteomics and the release of helminth genome-sequencing project data are revolutionizing parasitology research. The use of these powerful experimental approaches, and their potential benefits to helminth biology are also discussed in relation to the future control of helminth infections of animals and humans.

show abstract

Activity of artemether and OZ78 against triclabendazole-resistant Fasciola hepatica

Cited by 48 publications

References 18 publications

In Vivo and In Vitro Sensitivity of Fasciola hepatica to Triclabendazole Combined with Artesunate, Artemether, or OZ78

In Vivo and In Vitro Sensitivity of Fasciola hepatica to Triclabendazole Combined with Artesunate, Artemether, or OZ78

Human liver flukes

Zoonotic helminth infections with particular emphasis on fasciolosis and other trematodiases

Contact Info

Product

Resources

About