A comparative study of the effects of chloroquine and praziquantel on splenomegaly in experimental Schistosomiasis mansoni

Abstract

Background Splenomegaly is a major morbid sequela of schistosomiasis. Praziquantel (PZQ) is the only recommended schistosomicidal drug despite its erratic bioavailability and growing resistance. Moreover, neglecting early treatment of splenomegaly eventually necessitates splenectomy. With drug repurposing, the antimalarial drug chloroquine (CLQ) has gained much interest because of its anti-inflammatory effect. Additionally, CLQ inhibits hemozoin formation essential for in vivo survival of blood-feeding parasites.Aim To investigate the schistosomicidal effect of CLQ and its role in splenomegaly modification, with or without PZQ in an experimental model.Patients and methods The study was conducted on 180 mice equally divided into three groups: control; infected and early treated with CLQ, PZQ, or both drugs; and infected and late treated. In group II, each drug was given in its optimum time of action to study the effect on worm eradication/reproductivity and pathology development. In group III, repeated drug regimens were applied to study the effect on the already established splenomegaly. Mice were euthanized 7 weeks P.I. to calculate the parasitic load and 15 weeks post infection (P.I.) to assess tissue pathology by hematoxylin and eosin staining.Results Combined CLQ and PZQ administration produced a significant reduction of parasitic load compared with CLQ alone. A highly significant decrease (P<0.001) in hepatic granulomas mean number and splenic index was also recorded in early combined subgroup, with improved structure. With late treatment, the combined rather than single therapy showed an overall less pathology; however, early therapy showed better outcome.Conclusions CLQ combined with PZQ has a synergistic schistosomicidal, has a valuable anti-inflammatory effect, and restrains the effect on splenomegaly, especially with early administration.