ITM Colloquium 'Pathogen Survival Strategies' location:Antwerp date:3-6 December 2012
Schistosomiasis or bilharzia is a major poverty-related disease, caused by parasitic worms of the genus Schistosoma. Praziquantel (PZQ) is the drug of choice to treat schistosomiasis because of the absence of toxicity, low cost and the activity against all schistosome species. Whereas cure rates are usually 78-88%, the observed cure rate at the onset of the epidemic in Senegal reached only 18-32%, indicating the possible existence of PZQ resistance/tolerance. Here we aim to study the impact of treatment with PZQ on the neutral and adaptive evolution of Schistosoma mansoni in Senegal. We hypothesized that treatment will reduce the overall neutral genetic diversity of parasite populations (bottleneck effect) in combination with a selection for drug resistant genotypes that confer parasite survival (adaptive evolution).
This study is part of a larger project where the Senegalese village Nder was treated with PZQ and followed in time to study re-infection rates. We collected schistosome miracidia of individuals at the start of the study and six months after repeated PZQ treatment. First, S. mansoni parasites were genetically characterized using 9 neutral microsatellite DNA markers. In a second step, the same parasites will also be genotyped using a panel of ~50 adaptive SNP markers to identify signatures of selection.
Thorough population genetic analysis of the neutral marker dataset revealed no significant differences in the genetic diversity of, and genetic differentiation between parasite populations before and after repeated treatment. As rapid-reinfection alone cannot explain the sustained high genetic diversity, these results suggest that some strains may survive PZQ treatment. In the following steps, it will be important to test for signatures of selection based on adaptive genetic markers and to conduct larger field studies with short-term follow-up after treatment together with in depth snail surveys.