No abstract

The possible additive or synergistic effects of both praziquantel (CAS 55268-74-1) and a new antischistosomal drug, Ro 15-5458 (10-(2-diethylamino)thyl)-9-acridanone(thiazolidin-2-yl-i dene)hydrazone, CAS 92928-47-7) were studied in two different strains of Schistosoma mansoni infected mice, namely CD susceptible and SO4 resistant strains. Assessment of cure was performed using the following parameters: hepatic and intestinal tissue egg load and distribution, oogram changes in the small intestine and histopathological examination of the mice livers. In this study, a combination was used between 1/3 the curative doses of praziquantel and Ro 15-5458. This combination therapy proved to be beneficial as regards the percentage parasite reduction and hepatic worm shift (99.4% and 100%, respectively, in the CD susceptible mouse strains, compared to 84.1% and 34.8% in the SO4 resistant strains). Treatment with subcurative doses of praziquantel and Ro 15-5458 resulted in 78.6% intestinal dead ova and 21.4% mature ones. This score shifted to 98.6% and 1.4% dead and mature ova, respectively, in the SO4 resistant strains. Again the range of liver granulomata in the CD susceptible and SO4 resistant strains receiving subcurative doses of both drugs was 4-6 and 2-5, respectively, in five successive low power fields, while in the infected untreated control mice, this range reached 8-11 and 5-9, respectively. Histopathological sections of the liver revealed a small fibrocellular granuloma with few inflammatory cells and excess fibrous collagen tissue deposition in animals undergoing the combination therapy. This contrasts with the large fibrocellular granulomata seen in the infected untreated control mice. These results may be of value in endemic areas of schistosomiasis, due to the unexpected emergence of drug resistance against the currently used antischistosomal drug, praziquantel in these areas.

This study is a trial to demonstrate the effect of the broad spectrum anthelmintic drug flubendazole (methyl 5-(p-fluoro-benzoyl)-2-benzimidazolecarbamate, CAS 31430-15-6), a mebendazole derivative, together with praziquantel (CAS 55268-74-1, EMBAY 8440, Biltricide) in murine schistosomiasis mansoni. Moreover, the relationship between the posttreatment worm burden, oogram pattern, tissue egg load and hepatic granuloma volume was also investigated. Three main groups of Swiss albino mice infected with Schistosoma mansoni cercariae were used in the experiment. Group I included infected untreated control mice. Group II: Subgroup II (a): Animals received 1/3 the dose of praziquantel 25 days post infection. Subgroup II (b): Mice were given 1/3 dose of flubendazole 25 days post infection. Subgroup II (c): Animals received the combination (1/3 dose of flubendazole + 1/3 the dose of praziquantel 25 days post infection. Group III: Subgroup III (a): Mice were given 1/3 the dose of praziquantel 7 weeks post infection. Subgroup III (b): Mice received 1/3 dose of flubendazole 25 days post infection. 24 days later, 1/3 the dose of praziquantel was given. Mice given the consecutive drug regimen (flubendazole 1/3 single oral dose 25 days post infection, then praziquantel 1/3 oral dose for two successive days 24 days later, revealed a significant reduction in the recovery of adult schistosomes after portal perfusion (95.9%), absence of immature stages of ova development, a higher level of dead ova in the oogram and the smallest granuloma mean diameter. These data were less conspicuous in mice given the simultaneous drug regimen.

The efficacy of Ro 15-5458 ([10-(2-diethylamino)ethyl)-9-acridanone(thiazolidin-2-ylidene)hydrazone, CAS 92928-47-7) as a new antischistosomal drug was studied in hamsters using a dose of 20 mg/kg body weight against an Egyptian strain of Schistosoma haematobium, in comparison with praziquantel (PZQ, CAS 55268-74-1) (full dose 1000 mg/kg body weight). This was carried out at 4, 8 and 12 weeks post cercarial exposure of hamsters. The criteria used for the assessment of drug efficacy were the worm load, oogram pattern and number of ova/g liver and intestine. Results revealed that in earlier stages of infection (4 weeks post cercarial exposure), Ro 15-5458 proved to be more effective than PZO, the worm load was reduced by 83.2% and 55.6% from the untreated control group, respectively. At the same time, treatment with Ro 15-5458 increased the ratio of dead ova, while treatment with PZQ showed no change in the oogram pattern compared with the untreated control group. The reduction of eggs/g liver and intestine was higher in the group treated with Ro 15-5458, being 95.7% and 98.2%, compared to 65.3% and 79.2% in the PZQ group, respectively. However, in older infection (at 8 and 12 weeks post cercarial exposure) both drugs produced similar positive results regarding worm load, oogram pattern and the number of eggs/g liver and intestinal tissues. Consequently, Ro 15-5458 proved to be as efficient a drug as PZQ in the treatment of mature infection of schistosomiasis haematobium. Furthermore it showed much better effect in immature cases of infection.