Ultrastructural changes in the tegument and gut of adult Fasciola hepatica following in vivo treatment with artesunate.

An in vivo study in the laboratory rat model has been carried out to monitor changes to the tegument and gut of adult Fasciola hepatica following treatment with artesunate. Rats infected with the triclabendazole-resistant Oberon isolate were dosed orally with artesunate at a concentration of 200 mg/kg and flukes recovered 24, 48, 72 and 96 h post-treatment (pt). The flukes were processed for scanning and transmission electron microscope examination. Changes to the external surface were limited to swelling and blebbing of the interspinal tegument. There was one exception, a specimen recovered 72 h pt, which had completely lost the syncytium over the posterior region of the fluke. Internal changes to the tegumental syncytium and cell bodies were more severe and were apparent from 48 h pt onwards. Increased numbers of secretory bodies were present in the apical region of the syncytium, the basal infolds were swollen and sloughing of the apical plasma membrane was seen at 96 h pt. In the cell bodies, there was swelling and vesiculation of the cisternae of the granular endoplasmic reticulum (ger), swelling of the mitochondria and a decrease in secretory body production. Changes to the gastrodermal cells were evident from 24 h onwards. They comprised swelling and vesiculation of the ger cisternae, swelling and lysis of the mitochondria and accumulation of autophagic vacuoles and lipid droplets. The nuclei of the cells were karyopyknotic by 96 h pt. The gut was consistently more severely affected than the tegument at all time points pt, pointing to an oral route of uptake for artesunate. This study has provided information on the primary subcellular targets for drug action in the fluke.