Temporal and Seasonal Changes of Genetic Polymorphisms Associated with Altered Drug Susceptibility to Chloroquine, Lumefantrine, and Quinine in Guinea-Bissau between 2003 and 2012

摘要: In 2008, artemether-lumefantrine was introduced in Guinea-Bissau, West Africa, but quinine has also been commonly prescribed for the treatment of uncomplicated Plasmodium falciparum malaria. An efficacious high-dose chloroquine regimen used previously. Temporal and seasonal changes genetic polymorphisms associated with altered drug susceptibility to chloroquine, lumefantrine, have described. P. resistance transporter (pfcrt) K76T, pfmdr1 gene copy numbers, N86Y Y184F, sequences 1034 1246 were determined using PCR-based methods. Blood samples came from virtually all (n=1,806) children<15 years age who had monoinfection presented at a health center suburban Bissau (from 2003 2012). The pfcrt K76T frequencies stable, not seen 2007. Since 2007, mean annual increased (P<0.001) 76T (24% 57%), N86 (72% 83%), 76+pfmdr1 86 TN (10% 27%), accumulated during high transmission season (P=0.001). 86+184 NF frequency 39% 66% 2011; P=0.004). One sample two copies. lower parasite density (P<0.001). Following discontinuation an effective regimen, probably highly artemether-lumefantrine-susceptible (with 76T) accumulated, possibly due suboptimal use despite fitness cost linked 76T. (The studies reported here registered ClinicalTrials.gov under registration no. NCT00137514 [PSB-2001-chl-amo], NCT00137566 [PSB-2004-paracetamol], NCT00426439 [PSB-2006-coartem], NCT01157689 [AL-eff 2010], NCT01704508 [Eurartesim 2012].).