A. Flisser

Praziquantel treatment of porcine brain and muscle Taenia solium cysticercosis. 1. Radiological, physiological and histopathological studies.

PorcineTaenia solium cysticercosis, recognized as a model of the human disease, was used to analyze the effect of the anthelminthic drug praziquantel on hosts and parasites. The drug (50 mg/kg daily) was given over 15 days in the feed of 13 cysticercotic and 9 control pigs. Changes in the number, size and appearance of brain parasites were seen by computerized tomography immediately after the last dose of praziquantel, although not all cysticerci had disappeared by day 47 following the end of the treatment. Muscle parasites became small and hyperdense shortly after treatment and disappeared from tomographic images afterwards. No alterations were found in EEGs or in brain-stem auditory and somatosensory evoked potentials. Muscle cysticerci showed increasing degrees of degeneration with time after treatment, and an augmented inflammatory reaction was concomitantly observed. In contrast, more heterogeneous results were obtained in parasites lodged in the brain, since viable cysts and less intense inflammatory reactions were found in the brain at different times after treatment. Physiological evaluation of the parasites showed that evagination was inhibited immediately after treatment and that oxygen consumption decreased with time. The results of this investigation suggest that praziquantel damages cysticerci and that the inflammatory reaction destroys and eliminates them.Porcine Taenia solium cysticercosis, recognized as a model of the human disease, was used to analyze the effect of the anthelminthic drug praziquantel on hosts and parasites. The drug (50 mg/kg daily) was given over 15 days in the feed of 13 cysticercotic and 9 control pigs. Changes in the number, size and appearance of brain parasites were seen by computerized tomography immediately after the last dose of praziquantel, although not all cysticerci had disappeared by day 47 following the end of the treatment. Muscle parasites became small and hyperdense shortly after treatment and disappeared from tomographic images afterwards. No alterations were found in EEGs or in brain-stem auditory and somatosensory evoked potentials. Muscle cysticerci showed increasing degrees of degeneration with time after treatment, and an augmented inflammatory reaction was concomitantly observed. In contrast, more heterogeneous results were obtained in parasites lodged in the brain, since viable cysts and less intense inflammatory reactions were found in the brain at different times after treatment. Physiological evaluation of the parasites showed that evagination was inhibited immediately after treatment and that oxygen consumption decreased with time. The results of this investigation suggest that praziquantel damages cysticerci and that the inflammatory reaction destroys and eliminates them.

Praziquantel treatment of brain and muscle porcine Taenia solium cysticercosis. 2. Immunological and cytogenetic studies.

Praziquantel (Pzq) is widely used for the treatment of human neurocysticercosis (Flisser 1988; Groll 1984). Nevertheless, there are few studies that analyze the effect of the drug on the humoral immune response of patients (Markwalder et al. 1984; Sotelo et al. 1984). The objective of this study was to monitor changes in the anticysticercus antibody response due to Pzq treatment as well as possible effects of the drug on the chromosomes of the hosts lymphocytes. For this purpose, ten hybrid pigs with naturally acquired cysticercosis, diagnosed by palpation of cysticerci in their tongues, were purchased in a market and kept in corrals. Five non-cysticercotic pigs from the same market were used as controls. Most animals were undernourished and had respiratory or intestinal infections. After purchase, pigs were submitted to a shower against ectoparasites and vaccinated against porcine cholera, and their bacterial infections were cured with several antibiotics. At 4 weeks after acquisition, all pigs were treated with pure Pzq (donated by E. Groll, E. Merck, Darmstadt) at a dose of 50 mg/kg t.i.d, for 15 days. The drug was mixed with a small amount of the pigs food. Heparinised and non-heparinised blood samples were obtained immediately before and at various times after treatment. The enzyme-linked immunosorbent assay (ELISA) was performed using 10 lag/ml Taenia sotium cysticercal antigenic extract (prepared as described by Flisser et al. 1980), serum samples diluted 1:100, anti-pig immunoglobulins conjugated to horseradish peroxidase diluted 1:2000 and 2-h incubations at 37 ~ C. Cysticercal antigens recognised by the sera were identified by immunoelectrophoresis (IEP) carried out with the antigenic extract as previously described (Flisser et al. 1980). Ali-

Characterization of GP39-42 and GP24 antigens from Taenia solium cysticerci and of their antigenic GP10 subunit

Abstract Diagnosis of neurocysticercosis is performed by Western blotting with an enriched fraction of glycoproteins (LLGP). GP39-42 and GP24 are immunodominant antigens. These antigens were electroeluted and characterized by biochemical methods. When GP39-42 or GP24 were reduced, a band of 10u2009kDa (named GP10) appeared; this band was also analyzed. The most abundant amino acids in the three GPs were lysine, phenylalanine, asparagine, glycine, and leucine. The amino terminal portion was sequenced, and the following order was obtained for the three GPs: EKNKPKNVAXSTKKGYEYVXEF. The glycan portion was 8.4%, 18.2%, and 18.3% in GP39-42, GP24, and GP10, respectively. The three GPs contained mannose, N-acetyl-D-glucosamine, and galactose. GP39-42 and GP24 seem to be oligomeric forms of GP10. When reduced LLGP was reacted with samples obtained from patients with neurocysticercosis or pigs with cysticercosis, a band corresponding to GP10 was always observed. Furthermore, hyperimmune serum from rabbits immunized with GP39-42 or with GP24 recognized GP10 as well as GP39-42 and GP24. The data obtained in this paper suggest that GP10 might be a useful tool for diagnosis.

Praziquantel treatment of muscleTaenia solium cysticercosis

The in vitro effect of Praziquantel (PZQ) onTaenia solium cysticerci was analyzed. The oxygen consumption rate of the parasites was inhibited and the release of proteins was enhanced, but no statistically significant differences were found between the control group and the experimental groups. The drug had a significant, dose-dependent negative effect on the evagination ability of the larvae; 50% effect was seen at concentrations of between 10−9 and 10−8M PZQ. The drug also induced morphological disturbances in the tegument of the worm and of the bladder wall. Finally, a very drastic effect was the induction of spastic paralysis in evaginated cysticerci at high drug doses and of flaccid paralysis at lower PZQ concentrations. The dose inducing these effects was various orders of magnitude lower than that inhibiting the evagination ability of intact cysts. Moreover, the latter effect was reversible after had been washed out the drug and the parasites had been cultured. We suggest that PZQ alters the Ca2+ flux inT. solium as it does in other helminths. Furthermore, we corroborated the protective role of the bladder for the invaginated worm. Finally, we think that in vivo the drug must act synergistically with the immune system components so as to eliminate the parasite.