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 5526 8-74-1) and a new antischistosomal drug, Ro 15-5458 (10-(2-diethylamino)thy l)-9-acridanone(thiazolidin-2-yl-idene)hydrazone, CAS 92928-47-7) were stud ied in two different strains of Schistosoma mansoni infected mice, namely C D susceptible and SO4 resistant strains. Assessment of cure was performed u sing the following parameters: hepatic and intestinal tissue egg load and d istribution, oogram changes in the small intestine and histopathological ex amination of the mice livers. In this study, a combination was used between 1/3 the curative doses of praziquantel and Po 15-5458. This combination th erapy proved to be beneficial as regards the percentage parasite reduction and hepatic worm shift (99.4 % and 100 %, respectively, in the CD susceptib le mouse strains, compared to 84.1 % and 34.8 % in the SO4 resistant strain s). Treatment with subcurative doses of praziquantel and Ro 15-5458 resulte d 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 SO 4 resistant strains receiving subcurative doses of both drugs was 4-6 and 2 -5, respectively, in five successive low power fields, while in the infecte d untreated control mice, this range reached 8-11 and 5-9, respectively. Hi stopathological sections of the liver revealed a small fibrocellular granul oma with few inflammatory cells and excess fibrous collagen tissue depositi on in animals undergoing the combination therapy. This contrasts with the l arge fibrocellular granulomata seen in the infected untreated control mice. These results may be of value in endemic areas of schistosomiasis, due to t he unexpected emergence of drug resistance against the currently used antis chistosomal drug, praziquantel in these areas.