Surface changes in adult Fasciola hepatica following treatment in vivo 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 postinfection. Adult flukes were recovered from the bile ducts at 24, 48, and 72 h post-treatment (p.t.). Changes to the surface morphology of the flukes were assessed using scanning electron microscopy (SEM). Flukes were still active at 24 h p.t. and displayed limited areas of disruption, which were restricted to the oral cone region. At 48 h p.t., a reduced level of motility was observed in approximately 50% of the flukes recovered. Swelling of the tegument was more widespread and was accompanied by blebbing and partial loss of the tegumental covering of the spines. By 72 h p.t., the reduction in motility was greater, and approximately one quarter of the flukes recovered were inactive. In the majority of the flukes examined, the midbody region was marked by a discoloration of the flukes' tissues. This was seen to be due to the loss of the tegumental syncytium. Sloughing extended into the tail region in some specimens and, in the more badly-affected specimens, the basal lamina was breached to expose the underlying musculature. Elsewhere on the body, the tegument that remained was relatively normal, although areas of swelling and blebbing were present. Overall, the results provided information on the time-scale of changes to the surface morphology of the fluke that underpin the efficacy of compound alpha.

Effects of Mirazid® and myrrh volatile oil on adult Fasciola gigantica under laboratory conditions

“…These changes consisted of swelling, blebbing, which was later disrupted, leading to erosion and desquamation of the tegument, resulting in the lesion, and finally the exposure and disruption of basal lamina and the dislodging of spines. Swelling and blebbing were characteristic of a stress response by the fluke; they had been seen in the present study with TCBZ-SO and in previous studies with other drugs (clorsulon, albendazole, closantel, nitroxynil, compound alpha, and artemether) [9,10,[21][22][23][24]. Also, they were similar to changes on the surface of, a closely related trematode, Schistosoma mansoni treated with Mirazid襅 oleoresin [25] .…”

“…Stock solutions of Mirazid襅 oleoresin and myrrh volatile oil at 10 mg/mL were prepared in Cremiphore EL 10%. The flukes were incubated with 10,30 and 60 毺g/mL of Mirazid襅 oleoresin and myrrh volatile oil for 24 h at 37 曟 in an atmosphere of 5% CO 2 . A positive control group was prepared by incubating whole flukes for 24 h in RPMI 1640 culture medium containing 15 毺g/mL TCBZ-SO.…”

“…The emergence of resistance has prompted the search for new compounds or for better use of existing drugs. Alternative drugs tested include nitazoxanide, artemisinin derivatives, the TCBZ derivative, compound alpha and Mirazid襅 [10] .…”

“…On the other hand, the fluke's tegument is the interface between parasite and host, and it is the principal route by which drug metabolites enter the fluke [10] . It also plays a number of important roles in fluke biology, including protection against immune attack and anthelmintic action [18] .…”

Electron microscopical study to assess thein vitroeffects of the synthetic trioxolane OZ78 against the liver fluke,Fasciola hepatica

“…Female Wistar rats (purchased from RCC, Itingen, Switzerland) were experimentally infected with metacercarial cysts of the Cullompton isolate, shown in previous experiments to be susceptible to TCBZ in vivo and to its sulphoxide metabolite in vitro (Robinson et al 2002 ;McCoy et al 2005 ;Halferty et al 2008Halferty et al , 2009McConville et al 2006McConville et al , 2009Meaney et al 2006Meaney et al , 2007Devine et al 2009 ;Toner et al 2009). All animals were housed in environmentally-controlled conditions in groups of 4 and afforded 1 week to acclimatize.…”