<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Studies on evolution of drug resistance in P. falciparum malaria in vivo and in vitro"^^ . "The global burden of Malaria remains high with a 2.2 billion people estimated to live in endemic areas (Snow et al, 2005). Prompt and efficacious chemotherapy remains an important cornerstone in the fight against malaria. Development of resistance is the parasite’s mechanisms to respond to massive drug pressure. In this study I analysed drug-parasites interactions in vivo and in vitro using discreet experimental approaches. I started by studying parasite survival in vivo, 7 days after treatment intervention. In the following, I analysed parasites isolates in vitro that had been exposed to various drugs over the last years in the community. In the final part of the project, I attempted to gain insight in the evolution of drug resistance in vitro. For this work, I set up induction of resistance experiments in vitro and analysed in a time course mechanisms of resistance. Of particular interest was here the relationship between gene amplification and the emergence of single nucleotide polymorphisms. The results presented in this work show that 7 days after start of treatment (artemisinin combination therapy or amodiaquine) subpatent parasite populations were detected in 64/156 patients (41%) with high sensitivity. However, persistence of parasites was not associated with recrudescent infection at the individual level but showed instead correlation with initial parasite density in potentially less immune patients. Analysis of field isolates revealed high prevalence of anti-folate resistance due to triple and double mutant Pfdhfr. In theses parasites, no gene copy number variations were detected for genes involved in the folate pathway. However, induction of pyrimethamine resistance in vitro, lead to Pfdhfr amplification in two laboratory strains 3D7 (31 fold) and FCR3 (9 fold) associated with high cross-resistance to cycloguanil and trimethoprim but not to chloroquine. Further, I was able to identify gene amplification as a mechanism for acquisition of S108N in Pfdhfr. My findings of persistent subpatent parasitaemia after treatment underline the need of understanding clearance rate, persistence and elimination of parasites after anti- malarial treatment, particularly in regard to recent reports of emerging artemisinin resistance in western Cambodia (Dondorp et al, 2009), My results also suggest that resistant phenotypes may persist in parasite populations, once introduced. And finally, my data suggest gene amplification as an intermediate step in the acquisition of resistance conferring point mutations in P. falciparum."^^ . "2010" . . . . . . . . "Judith"^^ . "Straimer"^^ . "Judith Straimer"^^ . . . . . . "Studies on evolution of drug resistance in P. falciparum malaria in vivo and in vitro (PDF)"^^ . . . "Phd_Judith_Straimer.pdf"^^ . . . "Studies on evolution of drug resistance in P. falciparum malaria in vivo and in vitro (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Studies on evolution of drug resistance in P. falciparum malaria in vivo and in vitro (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Studies on evolution of drug resistance in P. falciparum malaria in vivo and in vitro (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Studies on evolution of drug resistance in P. falciparum malaria in vivo and in vitro (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Studies on evolution of drug resistance in P. falciparum malaria in vivo and in vitro (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #10576 \n\nStudies on evolution of drug resistance in P. falciparum malaria in vivo and in vitro\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .