Human intestinal flukes (Fasciolopsis buski and Heterophyes heterophyes) were treated with praziquantel in vivo or in vitro and then studied by transmission (TEM) and scanning (SEM) electron microscopy. F. buski worms recovered from patients, which had been cured by oral treatment of 1 × 15, 1 × 25 or 1 × 40 mg praziquantel/kg body weight, showed typical contraction and alterations together with vacuolization and bleb formation of their tegument. H. heterophyes worms recovered from an experimentally infected dog were incubated in media containing 1 μg praziquantel/ml for 5–60 min. Their tegument showed lesions the extent and duration of which increased with exposure time, finally leading to death. The damage observed in vitro was very similar to that found in F. buski recovered from cured patients. The cure rate was very high when using 1 × 15 mg praziquantel/kg.

The effect of praziquantel (Biltricide) on the ultrastructure of trematodes pathogenic to man in Asia was investigated in: Clonorchis sinensis, Opisthorchis viverrini, Schistosoma japonicum, Metagonimus yokogawai, and Paragonimus westermani. The different parasites were isolated from their respective experimental hosts and uniformly incubated for 5, 15, 30 or 60 min at 37 degrees C in medium TC 199 containing 0, 1, 10 or 100 micrograms praziquantel/ml. All parasites exposed to praziquantel were contracted and displayed tegumental alterations. 1. Clonorchis sinensis, Opisthorchis viverrini and Schistosoma japonicum reacted with severe tegumental vacuolisation within 5 min after exposure to 1 microgram praziquantel/ml. The extent of the damage induced increased with exposure time. 2. In vivo treated Opisthorchis viverrini worms had the same damages as in vitro treated ones. 3. Metagonimus yokogawai displayed the same degree of vacuolisation after exposure to all concentrations of praziquantel. Complete destruction of the tegumental surface was not achieved, however, possibly because of the presence of numerous tegumental hooks. 4. Paragonimus westermani was least sensitive to praziquantel. Only very few vacuoles were formed after incubation in 100 micrograms/ml for 60 min. It is assumed that the very dense texture of the thick tegument is responsible for the relative refractoriness to praziquantel in vitro. However, in vivo the parasite is successfully eliminated by praziquantel.

The disintegration of Schistosoma mansoni and their eggs was studied in the liver of mice after termination of the infection by praziquantel. Egg granulomas, which were already present at the time of treatment, attained their maximal diameter of 380 microns after 2-3 weeks. Within the following 5 weeks, granulomas very rapidly regressed in size to only 165 microns. Directly after treatment, worms were trapped in the liver where they were quickly invaded by granulocytes and subsequently phagocytosed within 3 weeks. Worm granulomas measured 700 and 900 microns after 3 and 8 weeks, respectively, but then regressed rapidly to only 550 microns after 12 weeks. Liver lesions appeared to regress more rapidly after praziquantel than after treatment with other schistosomicidal drugs.

14C-praziquantel penetrates the cyst wall of Cysticercus fasciolaris and kills the cysticercus within the cyst, although the uptake of praziquantel by the encysted larva was slower than by an isolated one. This fact is in good agreement with earlier in vitro chemotherapeutic studies. Scanning and transmission electron microscopic studies have shown that praziquantel causes a marked destruction of the tegument along the whole pseudostrobila and the scolex of C. fasciolaris. The type of tegumental damage is identical to that produced in adult tapeworms and trematodes.

The effects of 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) on Schistosoma mansoni was studied in vivo and in vitro by means of electron microscopy. It was found that 1. worms were contracted and became dislodged to the liver; 2. intensive vacuolisation occurred at distinct sites of the tegument within 5 min; 3. the surface coat remained unaffected; 4. host cells of the defense system attached to the tegumental vacuoles and started to penetrate into the interior of the parasites about 4 h after treatment; 5. only oral treatment of mice with a curative dose was lethal for the parasites, whereas worms treated with a subcurative dose recovered from the phenomena described above; 6. worms were fixed by fibroblasts to the walls of blood vessels 17 h after treatment; 7. the interior of the parasites was destroyed by host cells - especially eosinophilic granulocytes - while their exterior structures remained unchanged for some time; 8. worms disintegrated completely in the centre of typical granulomas as seen on days 14 and 18 after treatment; at this time only residues of the parasites were still recognisable within necrotic zones.

The fine structure of the tegument of three trematode species,Schistosoma mansoni, Dicrocoelium dendriticum, andFasciola hepatica, was studied by means of light scanning (SEM) and transmission electron microscopy (TEM) after in vitro exposure to 0, 1,10, and 100 μg/ml of the anthelmintic praziquantel for 5, 15, 30, and 60 min. InS. mansoni andD. dendriticum the resulting vacuolization of the tegument was confined to numerous small areas scattered all over the surface of the parasites and this finally led to the disruption of the apical tegumental layer. No changes were found in the tegument ofF. hepatica after treatment with praziquantel.

AdultHymenolepis diminuta, H. microstoma, H. nana, Echinococcus multilocularis, andTaenia (Hydatigera)taeniaeformis have been exposed in vitro in media containing 0.1 to 100 μg praziquantel/ml. Already after 5 min characteristic tegumental lesions, that were restricted to the growth zone of the neck region, were recognized using both scanning and transmission electron microscopy. Within the tegument numerous vacuoles were formed that released their contents to the exterior and finally caused destruction of the tegument. Proglottides of the central or posterior strobilar portions were never damaged.