Ultrastructural changes to the tegumental system and the gastrodermal cells in adult Fasciola hepatica following in vivo treatment with the experimental fasciolicide, compound alpha

Abstract

Sheep infected with the triclabendazole-susceptible, Cullompton isolate of Fasciola hepatica were dosed with 15 mg/kg of compound alpha at 12 weeks post-infection. Adult flukes were recovered from the bile ducts at 24, 48 and 72 h post-treatment (p.t.). Ultrastructural changes to the flukes were assessed using transmission electron microscopy (TEM), with a view to gathering information on the mechanism(s) of action for compound alpha and on the possible route of its entry into F. hepatica. The tegumental syncytium was more severely affected than the gut at all time-points p.t. with compound alpha, suggesting a predominantly trans-tegumental route of uptake. Disruption to the tegumental system became increasingly severe over time. A stress response was observed at 24 h p.t. and took the form of blebbing and increases in the production and transport of secretory bodies. By 72 h p.t., extensive tegumental loss and degeneration of the tegumental cell bodies had occurred. Degeneration of subtegumental tissues and internal flooding were also observed. Changes in the gastrodermal cells were slow to develop: reduced secretory activity was evident at 72 h p.t.. There was progressive disruption to the somatic muscle layers, with disorganization of the muscle blocks and loss of muscle fibres.

Erratum to: Inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica

“…This is indicative of disruption to the osmoregulatory function of the tegument (Fairweather et al 1999). Similar observations have been made in previous studies involving TCBZ.SO (Stitt and Fairweather 1994;Halferty et al 2009a) and various other fasciolicides (Fairweather et al 1986;Skuce et al 1987;Skuce and Fairweather 1990;Anderson and Fairweather 1995;Meaney et al 2004Meaney et al , 2005Meaney et al , 2007McConville et al 2006McConville et al , 2007McConville et al , 2008McConville et al , 2009McKinstry et al 2007McKinstry et al , 2009Halferty et al 2009b). The severe swelling of the basal infolds would account for the general swelling of the tegument observed in the previous SEM study (Devine et al 2010c); if allowed to continue, this would lead to the sloughing of the tegument.…”

Adult triclabendazole-resistantFasciola hepatica: morphological changes in the tegument and gut followingin vivotreatment with artemether in the rat model

“…The apparent contradiction between drug peaks, drug half-life and drug action has been seen in other drug studies on F. hepatica (e.g. Meaney et al, 2003;McConville et al, 2008McConville et al, , 2009b. For these drugs, which are relatively slow-acting, it may take some time before their action (and the morphological changes they induce) to become apparent; however, the effects are seemingly irreversible, as the drug continues to act following its elimination from the host.…”

Surface changes in adult Fasciola hepatica following treatment in vivo with the experimental fasciolicide, compound alpha

“…The spines (S) are partially obscured by the surrounding tegument. Bar 10 µm McConville et al (2009b), and they can help to explain the disruption visible externally. After 24 h treatment, there was a greater number of secretory bodies in the syncytium, due to accelerated transport from the tegumental cells, and this is part of a generalized stress response by the fluke, as observed in studies on other fasciolicides (Fairweather et al 1987;Skuce and Fairweather 1990;Buchanan et al 2003;McKinstry et al 2003;Meaney et al 2003Meaney et al , 2006Halferty et al 2008Halferty et al , 2009Toner et al 2009).…”

“…The tegument also plays a number of important roles in fluke biology, including protection against immune attack and anthelmintic action (Hanna 1980;Fairweather et al 1999). The present results will be compared with those of a parallel SEM study on juvenile flukes from the same sheep trial ) and with the internal ultrastructural changes observed in adult flukes treated in vivo with compound alpha (McConville et al 2009b). …”

“…The data presented here is of scanning electron microscope (SEM) observations of surface changes in the flukes. Examination of tegumental changes is important because the tegument is the interface between parasite and host and it is the principal route by which compound alpha metabolites enter the fluke (McConville et al 2009b). This is true of TCBZ and other fasciolicides (Mottier et al 2006;Toner et al 2009).…”