Synergistic effect of combination chemotherapy with praziquantel and DW-3-15 for Schistosoma japonicum in vitro and in vivo

Zi-Yin Yang,Chao-Ming Xia,Ya-Nan Zhang,Zi-Hao Liu,Shi-Qi Xie,Wen-Jie Pu,Chen Li,Lei Liu,Jing Xu

doi:10.1186/s13071-021-05065-x

Abstract

BackgroundSchistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In our previous studies, we found that the patented compound DW-3-15 (patent no. ZL201110142538.2) displayed significant and stabilized antiparasitic activity through a mechanism that might be distinct from PZQ. Here, we investigated the antischistosomal efficacy of PZQ combined with DW-3-15 against schistosomula and adult worms of Schistosoma japonicum in vitro and in vivo, to verify whether there was a synergistic effect of the two compounds.MethodsThe antischistosomal efficacy of PZQ combined with DW-3-15 in comparison with an untreated control and monotherapy group against schistosomula and adult worms was assessed both in vitro and in vivo. Parasitological studies, scanning electron microscopy, combination index, and histopathological analysis were used for the assessment.ResultsThe results showed significantly reduced viability of schistosomes, achieving 100% viability reduction for juveniles and males by combination chemotherapy using PZQ together with DW-3-15 in vitro. The combination index was 0.28, 0.27, and 0.53 at the higher concentration of PZQ combined with DW-3-15 against juveniles, males, and females, respectively, indicating that the two compounds display strong synergism. Scanning electron microscopy observations also demonstrated that the compound combination induced more severe and extensive alterations to the tegument and subtegument of S. japonicum than those with each compound alone. In vivo, compared with the single-compound-treated group, the group treated with the higher-dose combination demonstrated the best schistosomicidal efficacy, with significantly reduced worm burden, egg burden, and granuloma count and area, which was evident against schistosomula and adult worms.ConclusionsOur study provides a potential novel chemotherapy for schistosomiasis caused by S. japonicum. It would improve the antischistosomal effect on schistosomula and adult worms of S. japonicum, and decrease individual dosages.Graphical

Highlights

Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease
We explored the synergistic effect of combination chemotherapy with PZQ and DW-3-15 against S. japonicum
Effects of individual compounds on the viability of S. japonicum in vitro In order to select the optimal concentration of PZQ and DW-3-15 for combination therapy, the antischistosomal activity of PZQ and DW-3-15 individually was assayed at concentrations of 25–100 μM

Summary

Introduction

Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. We investigated the antischistosomal efficacy of PZQ combined with DW-3-15 against schistosomula and adult worms of Schistosoma japonicum in vitro and in vivo, to verify whether there was a synergistic effect of the two compounds. Whilst PZQ is effective against the adult worms of Schistosoma spp., it displays poor efficacy against schistosome eggs and immature schistosomula [9]. These factors may explain the low cure rates of populations in endemic areas where juveniles and adult worms coexist. Thereafter, the emergence of resistance to PZQ for treatment of schistosomiasis has been reported both clinically and in the laboratory, highlighting the urgent need for alternative drugs against schistosomiasis [11]

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