Praziquantel Treatment Decreases Schistosoma mansoni Genetic Diversity in Experimental Infections

Background Schistosomiasis has a considerable impact on public health in many tropical and subtropical areas. In the new world, schistosomiasis is caused by the digenetic trematode Schistosoma mansoni. Chemotherapy is the main measure for controlling schistosomiasis, and the current drug of choice for treatment is praziquantel (PZQ). Although PZQ is efficient and safe, its repetitive large-scale use in endemic areas may lead to the selection of resistant strains. Isolates less susceptible to PZQ have been found in the field and selected for in the laboratory. The impact of selecting strains with a decreased susceptibility phenotype on disease dynamics and parasite population genetics is not fully understood. This study addresses the impact of PZQ pressure on the genetics of a laboratory population by analyzing frequency variations of polymorphic genetic markers. Methodology Infected mice were treated with increasing PZQ doses until the highest dose of 3x300 mg/Kg was reached. The effect of PZQ treatment on the parasite population was assessed using five polymorphic microsatellite markers. Parasitological and genetic data were compared with those of the untreated control. After six parasite generations submitted to treatment, it was possible to obtain a S. mansoni population with decreased susceptibility to PZQ. In our experiments we also observed that female worms were more susceptible to PZQ than male worms. Conclusions The selective pressure exerted by PZQ led to decreased genetic variability in S. mansoni and increased endogamy. The understanding of how S. mansoni populations respond to successive drug pressure has important implications on the appearance and maintenance of a PZQ resistance phenotype in endemic regions. Author Summary Schistosomiasis causes severe health problems and economic losses in transmission areas in the Americas, Africa, and Southeast Asia. In regions where treatment is available, such as Brazil, chemotherapy has led to decreased morbidity of the disease. However, parasite resistance to drugs is of general concern. Drug resistance is known in some species of helminths, and there are reports of decreased susceptibility in schistosomes, although such reports are not widespread. The impact of consecutive drug treatment on parasite populations at transmission sites can be evaluated by the genetic makeup of the population. For example, the decrease in the genetic diversity of these populations upon chemotherapy can be interpreted as the selection of less sensitive parasites. In this study, we used a laboratory mouse model of schistosomiasis that was treated with increasing amounts of praziquantel (the drug of choice for human treatment) until we reached the highest dose of 3x300 mg PZQ/kg. Our results clearly indicate that the parasite population showed a decrease in genetic diversity after measuring allelic and genetic diversity. This observation confirms that drug selection occurred in this population. The work highlights the need for genetic monitoring of populations under drug pressure, resistance mechanisms, and the dynamics of parasite populations upon treatment.