title: The effect of local variation in malaria transmission on the prevalence of sulfadoxine-pyrimethamine resistant haplotypes and selective sweep characteristics in Malawi.
abstract: BACKGROUND
  Persistence of sulfadoxine-pyrimethamine (SP) resistance has been described in an urban setting in Malawi where malaria transmission is relatively low. Higher malaria transmission is associated with greater genetic diversity and more frequent genetic recombination, which could lead to a more rapid re-emergence of SP-sensitive parasites, as well as more rapid degradation of selective sweeps. In this study, the impact of local variation in malaria transmission on the prevalence of SP-resistant haplotypes and selective sweep characteristics was investigated at an urban site with low parasite prevalence and two rural sites with moderate and high parasite prevalence.
  
  
  METHODS
  Samples from three sites with different parasite prevalence were genotyped for resistance markers within pfdhfr-ts and pfdhps and at microsatellites flanking these genes. Expected heterozygosity (He) was estimated to evaluate genetic diversity.
  
  
  RESULTS
  No difference in the prevalence of highly resistant DHFR 51I/59R/108N and DHPS 437G/540E was found between sites. Small differences in He flanking pfdhfr-ts and pfdhps were seen between rural-moderate and the other sites, as well as some shared haplotypes between the rural-high and urban-low sites.
  
  
  CONCLUSIONS
  The results do not show an effect of local variation in malaria transmission, as inferred from parasite prevalence, on SP-resistant haplotype prevalence.
authors.affiliation: Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF1-480, Baltimore, MD, 21201, USA. earti001@umaryland.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Artimovich
authors.affiliation: Malaria Alert Center, Blantyre, Malawi. atupelekapito@gmail.com.
authors.forename: Atupele
authors.initials: A
authors.lastname: Kapito-Tembo
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi. paulpensulo@gmail.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Pensulo
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi. omnyirenda@gmail.com.
authors.forename: Osward
authors.initials: O
authors.lastname: Nyirenda
authors.affiliation: University of Maryland, Baltimore County, Baltimore, MD, USA. bro6@umbc.edu.
authors.forename: Sarah
authors.initials: S
authors.lastname: Brown
authors.affiliation: Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF1-480, Baltimore, MD, 21201, USA. sjoshi@medicine.umaryland.edu.
authors.forename: Sudhaunshu
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi. ttmalawi@msu.edu.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.affiliation: Malaria Alert Center, Blantyre, Malawi. dmathang@mac.medcol.mw.
authors.forename: Don
authors.initials: D
authors.lastname: Mathanga
authors.affiliation: Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, USA. ananias.escalante@asu.edu.
authors.forename: Ananias A
authors.initials: AA
authors.lastname: Escalante
authors.affiliation: Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF1-480, Baltimore, MD, 21201, USA. mlaufer@medicine.umaryland.edu.
authors.forename: Miriam K
authors.initials: MK
authors.lastname: Laufer
authors.affiliation: Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF1-480, Baltimore, MD, 21201, USA. stakala@medicine.umaryland.edu.
authors.forename: Shannon
authors.initials: S
authors.lastname: Takala-Harrison
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000235:genetics; D018562:Disease Transmission, Infectious; D004338:Drug Combinations; D004351:Drug Resistance; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008288:Malaria / Q000453:epidemiology / Q000635:transmission*; D008295:Malawi / Q000453:epidemiology; D018895:Microsatellite Repeats; D010453:Peptide Synthases / Q000235:genetics; D010961:Plasmodium / Q000187:drug effects* / Q000302:isolation & purification; D015995:Prevalence; D011739:Pyrimethamine / Q000494:pharmacology*; D012424:Rural Population; D012641:Selection, Genetic; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014505:Urban Population
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D010453:Peptide Synthases; C020041:dihydrofolate synthetase; D011739:Pyrimethamine