Abstract
Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ-susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants.
Highlights
Schistosomiasis is a disease caused by blood fluke trematode, Schistosoma spp., where Schistosoma haematobium, Schistosoma japonicum, and Schistosoma mansoni are the three main species affecting humans (Utzinger and Keiser, 2004; Gryseels et al, 2006; Colley et al, 2014)
Our group in particular had selected, by stepwise drug pressure, a S. mansoni strain that is isogenic to its parental fully susceptible counterpart, except for genetic determinants accounting for the PZQ-drug resistance phenotype, and phenotypically similar to the susceptible strain except in resistance
We took the advantage of the availability of these two strains of S. mansoni and performed a comparative assessment of morphological alterations that the in vitro effect of PZQ can cause on S. mansoni PZQ-resistant parasites
Summary
Schistosomiasis is a disease caused by blood fluke trematode, Schistosoma spp., where Schistosoma haematobium, Schistosoma japonicum, and Schistosoma mansoni are the three main species affecting humans (Utzinger and Keiser, 2004; Gryseels et al, 2006; Colley et al, 2014). The disease registers high rates of morbidity, in about 20 million people and mortality about 280000 deaths annually, especially in tropical and subtropical countries, namely Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname, and other countries such as China, Indonesia and the Philippines [van der Werf et al, 2003; Steinmann et al, 2006; Kamel et al, 2011; World Health Organization (WHO), 2013]. It is a chronic parasitic disease which is considered a neglected disease by the World Health Organization. It has been estimated that approximately 249 million people are infected worldwide, with 780 million being at risk of infection [Steinmann et al, 2006; Caffrey, 2007; World Health Organization (WHO), 2013]
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