Effect of a combination of the new antischistosomal drug Ro 15-5458 and praziquantel on different strains of Schistosoma mansoni infected mice.

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.