title: Changes in drug sensitivity and anti-malarial drug resistance mutations over time among Plasmodium falciparum parasites in Senegal.
abstract: BACKGROUND
  Malaria treatment efforts are hindered by the rapid emergence and spread of drug resistant parasites. Simple assays to monitor parasite drug response in direct patient samples (ex vivo) can detect drug resistance before it becomes clinically apparent, and can inform changes in treatment policy to prevent the spread of resistance.
  
  
  METHODS
  Parasite drug responses to amodiaquine, artemisinin, chloroquine and mefloquine were tested in approximately 400 Plasmodium falciparum malaria infections in Thiès, Senegal between 2008 and 2011 using a DAPI-based ex vivo drug resistance assay. Drug resistance-associated mutations were also genotyped in pfcrt and pfmdr1.
  
  
  RESULTS
  Parasite drug responses changed between 2008 and 2011, as parasites became less sensitive to amodiaquine, artemisinin and chloroquine over time. The prevalence of known resistance-associated mutations also changed over time. Decreased amodiaquine sensitivity was associated with sustained, highly prevalent mutations in pfcrt, and one mutation in pfmdr1 - Y184F - was associated with decreased parasite sensitivity to artemisinin.
  
  
  CONCLUSIONS
  Directly measuring ex vivo parasite drug response and resistance mutation genotyping over time are useful tools for monitoring parasite drug responses in field samples. Furthermore, these data suggest that the use of amodiaquine and artemisinin derivatives in combination therapies is selecting for increased drug tolerance within this population.
authors: Daria
authors: D
authors: Van Tyne
authors: Baba
authors: B
authors: Dieye
authors: Clarissa
authors: C
authors: Valim
authors: Rachel F
authors: RF
authors: Daniels
authors: Papa Diogoye
authors: PD
authors: Sène
authors: Amanda K
authors: AK
authors: Lukens
authors: Mouhamadou
authors: M
authors: Ndiaye
authors: Amy K
authors: AK
authors: Bei
authors: Yaye Die
authors: YD
authors: Ndiaye
authors: Elizabeth J
authors: EJ
authors: Hamilton
authors: Omar
authors: O
authors: Ndir
authors: Souleymane
authors: S
authors: Mboup
authors: Sarah K
authors: SK
authors: Volkman
authors: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston 02115, USA. dfwirth@hsph.harvard.edu.
authors: Dyann F
authors: DF
authors: Wirth
authors: Daouda
authors: D
authors: Ndiaye
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects* / Q000235:genetics; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D015995:Prevalence; D015203:Reproducibility of Results; D012675:Senegal; D055815:Young Adult
chemical_list: D000962:Antimalarials