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dc.contributor.authorArtimovich, Elena M.*
dc.date.accessioned2015-01-21T17:25:56Z
dc.date.available2015-01-21T17:25:56Z
dc.date.issued2014
dc.identifier.urihttp://hdl.handle.net/10713/4368
dc.descriptionUniversity of Maryland, Baltimore. Human Genetics. Ph.D. 2014en_US
dc.description.abstractBackground: The continued expansion of resistance to anti-malarial chemotherapies is a threat to public health, and to malaria control and elimination. The reexpansion of drug sensitive parasites after the removal of drug pressure has renewed interest in epidemiological factors affecting resistance haplotype dynamics, in the hopes that previously abandoned drugs might once again find clinical utility. Objectives: Estimate the effect of changes in drug pressure and different malaria transmission settings on sulfadoxine-pyrimethamine (SP)-resistant haplotype prevalence and characteristics of selective sweeps. Methods: DNA was extracted from dried blood spots representing malaria infections from three time periods (high-SP use 1999-2001, transition-period 2007-2008, low-SP use 2012) of drug pressure in Malawi and three transmission settings (urban-low, rural-moderate, rural-high). Pyrosequencing and microsatellite genotyping were performed on all samples to determine haplotype prevalence and sweep characteristics. Changes in haplotype prevalence were assessed via Chi-squared tests and changes in sweep characteristics via permutation. Results: We observed the persistence of the DHFR 51I/59R/108N and DHPS 437G/540E haplotypes, five years after reduction in SP pressure as well as an increase in the prevalence of DHPS 437G/540E/581G haplotype. Selective sweeps indicated little to no fitness cost to the DHFR 51I/59R/108N and DHPS 437G/540E haplotypes in the absence of strong SP pressure. A decline in polyclonal infections was found across the three time periods. No significant difference in haplotype prevalence was found between transmission settings. Sweep characteristics could suggest divergent evolutionary history in the rural-moderate transmission setting. Conclusions: There is little to no fitness cost of SP-resistance in the absence of strong SP pressure in these three transmission settings within Malawi. The reexpansion of SP sensitive parasites in the region is not expected under current epidemiological conditions. Reduction in the amount of malaria in the region could further reduce the likelihood of reexpansion through the elimination of rare haplotypes due to genetic drift.en_US
dc.language.isoen_USen_US
dc.subjectDHFRen_US
dc.subjectDHPSen_US
dc.subjectselective sweepen_US
dc.subject.meshDrug Resistanceen_US
dc.subject.meshMalariaen_US
dc.subject.meshMalawien_US
dc.titleThe Effect of Drug Pressure and Transmission Setting on Sulfadoxine-Pyrimethamine Resistant Plasmodium falciparum Haplotype Prevalence and Selective Sweep Characteristics, in Malawien_US
dc.typedissertationen_US
dc.contributor.advisorTakala-Harrison, Shannon
refterms.dateFOA2019-02-21T02:01:25Z


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