title: Praziquantel treatment decreases Schistosoma mansoni genetic diversity in experimental infections.
abstract: 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.
  
  
  METHODS
  Infected mice were treated with increasing PZQ doses until the highest dose of 3 × 300 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.
authors.affiliation: Genomics and Computational Biology Group, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Regina
authors.initials: R
authors.lastname: Coeli
authors.affiliation: Laboratory of Schistosomiasis, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Elio H
authors.initials: EH
authors.lastname: Baba
authors.affiliation: Laboratory of Schistosomiasis, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Neusa
authors.initials: N
authors.lastname: Araujo
authors.affiliation: Laboratory of Schistosomiasis, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Paulo M Z
authors.initials: PM
authors.lastname: Coelho
authors.affiliation: Genomics and Computational Biology Group, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil ; National Institute of Science and Technology in Tropical Diseases, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D014644:Genetic Variation; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats; D011223:Praziquantel / Q000627:therapeutic use*; D012550:Schistosoma mansoni / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology*; D012641:Selection, Genetic
chemical_list: D000871:Anthelmintics; D011223:Praziquantel