Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection

Author summaryAccording to WHO, more than 290.8 million people required preventive treatment against schistosomiasis in 2018. The pathology caused by the tissue-embolized eggs laid by adult worms is associated with symptoms such as anemia, tissue injuries, and severe fibrosis. Despite efforts to control this disease, it remains a public health problem in many tropical countries. One of the main challenges for managing this disease is to set up an efficient treatment at the early stage of the infection. Unfortunately, there is no appropriate therapeutic regimen for this purpose to the best of our knowledge. In this study, we propose an efficient praziquantel-based regimen that prevents the installation of the pathology in a mouse model of schistosomiasis. We found that praziquantel administration at the early stage of the infection prevents Schistosoma mansoni-infected mice from liver and intestine injuries, anemia, chronic inflammation, and severe fibrosis by reducing parasitic burden. Firstly, this study offers a reference treatment for further experimental investigations. Secondly, it could be a starting point for developing new protocols for preventive chemotherapy in endemic areas. BackgroundOne of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice. Methodology/Principal findingsTwo months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56(th) day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-gamma, TNF-alpha, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-beta gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2. Conclusion/SignificanceThis study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.