Schistosomiasis is a major health burden, infecting over 207 million people and over 20 million suffering from severe disease. There is one drug available for mass chemotherapy, praziquantel (PZQ). This Project (P2) is motivated by the lack of information on the effect of sequential PZQ treatment on the genetic makeup of the parasite population, especially in South America where a distinct schema of mass treatment is employed. Furthermore, there is virtually no information on the level of polymorphism existing in genes of interest for the development of control measures. The objective of this project is to determine the impact of PZQ treatment on Schistosoma mansoni population dynamics and adaptive potenfial. The information generated by P2 will be used in modeling of schistosomiasis transmission and in the selection of biomarkers, diagnosfic or vaccine purposes. P2 has two main aims.
In aim 1 we will study the genetic diversity of the parasite populations and how they relate to the many variables studied in other projects of this proposal.
In aim 2 we will evaluate polymorphisms present or selected and how they relate to the development of resistance after treatment. The approach will be to genotype infrapopulations of infected individuals. As sampling the adult worm is not a possibility in human infections, we will collect eggs from fecal samples and hatch the eggs. Miracidia obtained will be preserved. For genotyping pools of miracidia from one infected individual will be submitted to whole genome amplification, in order to generate sufficient DNA for genotyping. Genotyping will be accomplished by SNP typing or by deep sequencing. The information produced will be uploaded into SchistoDB genome database for wide use of the research community. P2 will interact with Project 1 by enabling the correlation of polymorphisms in genes coding the proteins coded in the arrays with the reaction profile observed with the different groups. It will also provide information that will enable the comparison of distinct antigen recognition patterns with parasite genetic profiles. Project 3 provides the material to be used for genotyping. At the same time data generated by P2, both polymorphism and genetic makeup of the population, will inform the mathematical models of transmission .
The molecular population genetic approach we propose will provide additional insights into transmission and control of parasites that complement information gleaned from traditional epidemiological surveys using egg counts, and can be used to parameterize mathematical models. The models will provide insight into control of schistosomiasis in Brazil and other endemic countries.
|Andrade, Gisele; Bertsch, David J; Gazzinelli, Andrea et al. (2017) Decline in infection-related morbidities following drug-mediated reductions in the intensity of Schistosoma infection: A systematic review and meta-analysis. PLoS Negl Trop Dis 11:e0005372|
|Chevalier, Frédéric D; Le Clec'h, Winka; Eng, Nina et al. (2016) Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population. Int J Parasitol 46:417-24|
|Chevalier, Frédéric D; Le Clec'h, Winka; Alves de Mattos, Ana Carolina et al. (2016) Real-time PCR for sexing Schistosoma mansoni cercariae. Mol Biochem Parasitol 205:35-8|
|de Assis, Rafael Ramiro; Ludolf, Fernanda; Nakajima, Rie et al. (2016) A next-generation proteome array for Schistosoma mansoni. Int J Parasitol 46:411-5|
|Gazzinelli, Maria Flávia; Lobato, Lucas; Andrade, Gisele et al. (2016) Improving the understanding of schistosomiasis among adolescents in endemic areas in Brazil: A comparison of educational methods. Patient Educ Couns 99:1657-62|
|Bonin, Camila P; Baccarin, Raquel Y A; Nostell, Katarina et al. (2013) Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NF?B binding sites. Biochem Biophys Res Commun 432:256-61|