Disruption of egg formation by Fasciola hepatica following treatment in vivo with triclabendazole in the sheep host

A comparative study on the impact of two artemisinin derivatives, artemether and artesunate, on the female reproductive system of Fasciola hepatica

“…This phenomenon is more likely to be pH-related than due to any disruption of Ca ++ homeostasis, as it was not observed after treatment with the calcium ionophore, lasalocid (Colhoun et al, 1998). The population shift of cell types within the vitelline follicles with time pt, towards a predominance of mature cells, was similar to that observed with flukes treated in vivo with TCBZ and in vitro with its sulphoxide metabolite (Stitt and Fairweather, 1996;Toner et al, 2011). However, in TCBZ-treated flukes this shift became apparent more rapidly (by 48 h) than with the artemisinins and was attributed to the role of TCBZ as a microtubule disrupter and inhibitor of mitosis.…”

“…That only the vitellaria among the female reproductive organs was affected is unusual, as in studies on other flukicides all tissues have been seen to be affected: e.g. TCBZ, compound alpha, closantel, nitroxynil and rafoxanide (Stammers, 1975(Stammers, , 1976Hanna et al, 2006Hanna et al, , 2010Hanna et al, , 2012Hanna et al, , 2013Toner et al, 2011;McConville et al, 2012). However, in bithionol-treated flukes, the ovary was unaffected, whilst the vitellaria and egg formation were disrupted (Dawes, 1966a(Dawes, ,b, 1967.…”

“…The main focus of the paper will be on the vitelline cells, which provide shell protein and energy reserves for egg formation. They have a very high level of secretory activity and rapid turnover, are very sensitive to drug action and previously have been good models for studies on drug action against F. hepatica Skuce and Fairweather, 1990;Stitt and Fairweather, 1996;Colhoun et al, 1998;Halferty et al, 2009;Toner et al, 2011;McConville et al, 2012). Additional histological observations on changes induced by artemether in other female tissues will provide a more complete picture of drug action and the downstream impact on egg production.…”

Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy?

“…The loss of motility and the degeneration of the gastrodermal cells (seen by 72 h pt) (Toner et al, 2010b) would prevent the fluke from feeding and this would exacerbate the general disruption of the fluke. Changes to the reproductive system took place earlier: for example, the testis was severely affected by 48 h pt (Toner et al, 2011b) and no eggs were present in the uterus at this time (Toner et al, 2011a). The latter was due to the disruption of the ovary, vitelline follicles and Mehlis' gland, which provide the components for egg formation in the ootype (Toner et al, 2011a).…”

“…Changes to the reproductive system took place earlier: for example, the testis was severely affected by 48 h pt (Toner et al, 2011b) and no eggs were present in the uterus at this time (Toner et al, 2011a). The latter was due to the disruption of the ovary, vitelline follicles and Mehlis' gland, which provide the components for egg formation in the ootype (Toner et al, 2011a). The diagnosis of drug efficacy is often based on faecal egg counts, so the observation of such a rapid cessation of egg production would imply that any eggs recovered after successful treatment would be due to the storage and release of eggs from the gall bladder and not to eggs produced by any surviving flukes themselves.…”