Studies On The Regulation Of Mice Immunity To Prevent Schistosoma Japonicum Infection With Praziquantel

Schistosomiasis japonica presents a serious health threat to both humans and domestic animals.This disease is prevalent in the East Asian countries such as China and the Philippines,and remains one of the most important public health problems in China.Exposure to infected water is the usual route of Schistosoma japonicum(S.japonicum).Praziquantel(PZQ)is the first line drug for the pathogenic treatment of schistosomiasis.A series of studies in recent years confirmed that PZQ can regulate host immunity.In a trail carried out by our laboratory,a reduction over 80 % in the worm development rate(no.of perfused worms / no.of infected cercariae)was found in buffaloes that received two oral administrations of PZQ on days 17 and 18 before infection.In this study,we focused on optimizing the procedure for PZQ administration to most effectively prevent S.japonicum infection.We characterized the effective dose,protection period and onset time of PZQ in preventing S.japonicum infection using a mouse model.To determine the effective dosage,protection period and onset time of PZQ pre-administration,the worm burden,female worm burden and egg burden in the liver were determined in BALB/c mice that had received PZQ administration before infection compared with control mice.In two independent trails,the worm burden,female worm burden and eggs per gram(EPG)in liver from mice pretreated with different dosages of PZQ 15 days before infection were significantly reduced compared with control mice.The effective dose was found to be two oral administrations(interval of 24 h)or one injection at300 mg/kg body weight,which could induce an over 50 % reduction in worm burden,female worm burden and egg burden counts on day 15 post-administration.In mice received administration of effective PZQ dosage,the optimal preventive effect was observed at two days post-administration with a worm reduction rate of more than 92 %,with significant worm reduction being maintained until 21 days after administration.Analyzing of morphological characteristics showed that adult S.japonicum worms recovered from PZQ-pretreated mice were runtish showing a shorter length,smaller organs and fewer eggs in the uteri of females.Detection of cytokines,NO,5-HT and hematological indicators showed that pre-administration of PZQ could induce physiological changes in the host and regulate innate immunity,the higher levels of NO,IFN-γ and IL-2 and lower level of TGF-β might contribute to the reduced number of worms and the maldevelopment of surviving worms in PZQ-pretreated mice.Tests with anti-S.japonicum-specific antibodies revealed that pretreatment with PZQ had no effect on acquired immunity after infection.The plasma PZQ concentration was daily monitored from 24 h to 96 h after the administration using high performance liquid chromatography(HPLC).Furthermore,the plasma PZQ concentrations at 72 h after administration were lower than the detection limit and this demonstrated that the prevention effect may not be caused by a direct effect of PZQ on the worms.Conclusions: Our results confirmed that pretreatment with PZQ can protect hosts against S.japonicum infection for 21 days.This protective effect may be caused by physiological changes in the host induced by PZQ,but not by the direct effect of PZQ on the worms.These findings may guide effective strategies to protect humans(such as fishermen)and livestock(such as cattle,sheep,etc.)who may be exposed to infected water in schistosomiasis endemic areas.They may also provide new insight into the mechanism of action of PZQ in the treatment of schistosomiasis and the development of PZQ as an immunomodulator to prevent infection by other pathogens.