Adaptation and evolution of Schistosoma mansoni under chemotherapeutic pressure

• Main Author: Lamberton, Poppy Helen Louise
• Published: Imperial College London 2007
• Subjects: 616.9883
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486652

With the implementation of mass praziquantel (PZQ) treatment for the control of schistosomiasis, knowledge on how the parasite population is affected by these selective pressures could provide vital information for the future success of such control programmes. This thesis aimed to 'monitor and evaluate the effect of PZQ on Schistosoma mansoni infections in Ugandan primary school children, focusing on the clearance and reinfection and associated morbidity in individual children as well elucidating the impact of repeated PZQ exposure on the parasite population genetics using novel techniques for miracidial storage and microsatellite analysis. Epidemiological and molecular data indicated that, although some infections were uncleared by the standard 40mg/kg PZQ dose, widespread PZQ resistance was not observed. Microsatellite data did, however, indicate that the population genetic structure ofparasites from those children with remaining infections or re-infections was altered by PZQ pressure, with reduced allele numbers in treated infections in comparison to PZQnaive infections. Such data could suggest a possible precursor to adaptation for reduced-PZQ susceptibility in these schistosomes. The effect of in vitro PZQ on miracidial larval stages also highlighted differences between miracidia hatched pre- and post-PZQ exposure and of those whose infection intensities were reduced by a single PZQ treatment in comparison to those whose infection intensities were not reduced. Biological costs associated with PZQ-resistance, which could act to slow the rate of spread of any resistant genotypes, were observed at both the defInitive and intermediate host life-cycle stages, with resistant genotypes showing lower adult worm establishment, lower cercarial production and miracidia with potentially reduced ability for dispersal and subsequent host location relative to their susceptible counterparts. The theoretical and applied implications of these results for our understanding of the effects of PZQ treatment and possible suggestions for continuing control programmes were discussed.