In vivo efficiency of praziquantel treatment of single-sex Schistosoma japonicum aged three months old in mice

Abstract

Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.

Keywords: Praziquantel; S. japonicum; Single-sex infection; Treatment efficiency.

Graphical abstract

Fig. 1

Experimental design for treatment efficiency of single-sex Schistosoma japonicum on mice at total doses of PZQ 0 (Control), 200, or 400 mg/kg. Two experiments were performed. In Experiment one, mice each were first infected with S. japonicum cercariae female only (i.e., exposed to female cercariae for 20 min), and then randomized into three groups (PZQ 0, 200, or 400 mg/kg). Thirteen weeks post primary infection PZQ treatment (at total doses of PZQ 0, 200, or 400 mg/kg in 2% cremophor EL) was orally administered to the mice. Three weeks post treatment the mice each received a second infection with S. japonicum cercariae male only (i.e., exposed to male cercariae for 20 min), which outnumbered cercariae female used in the primary infection. Experiment two was performed at the same time schedule as the first experiment. Mice each were first infected with S. japonicum cercariae male only, then randomized into three groups and administered with PZQ treatment (at total doses of PZQ 0, 200, or 400 mg/kg in 2% cremophor EL), and finally received a second infection with cercariae female only. Five weeks post the second infection, all experimented mice in both experiments were euthanized and dissected, and from each of them paired adult worms were recovered and resultant miracidia quantified.