Increased prevalence of the pfdhfr/phdhps quintuple mutant and rapid emergence of pfdhps resistance mutations at codons 581 and 613 in Kisumu, Kenya

• Published in: Malaria Journal
• Main Authors: Prigge Sean T, Bedno Sheryl A, Akala Hoseah M, Eyase Fredrick L, Spalding Maroya D, Coldren Rodney L, Moss William J, Waters Norman C
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2010
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-9-338; https://doaj.org/article/8961d69b008a45e18923db0c87283f36

Abstract Background Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP in 2004. Two cross-sectional studies were conducted to monitor changes in the prevalence of molecular markers of drug resistance over the period in which SP was used as the first-line anti-malarial. The baseline study was carried out from 1999-2000, shortly after implementation of SP, and the follow-up study occurred from 2003-2005, during the transition to AL. Materials and methods Blood was collected from malaria smear-positive, symptomatic patients presenting to outpatient centers in Kisumu, Kenya, during the baseline and follow-up studies. Isolates were genotyped at codons associated with SP and CQ resistance. In vitro IC 50 values for antifolates and quinolones were determined for isolates from the follow-up study. Results The prevalence of isolates containing the pfdhfr N51I/C59R/S108N/ pfdhps A437G/K540E quintuple mutant associated with SP-resistance rose from 21% in the baseline study to 53% in the follow-up study (p < 0.001). Isolates containing the pfdhfr I164L mutation were absent from both studies. The pfdhps mutations A581G and A613S/T were absent from the baseline study but were present in 85% and 61%, respectively, of isolates from the follow-up study. At follow-up, parasites with mutations at five pfdhps codons, 436, 437, 540, 581, and 613, accounted for 39% of isolates. The CQ resistance-associated mutations pfcrt K76T and pfmdr1 N86Y rose from 82% to 97% (p = 0.001) and 44% to 76% (p < 0.001), respectively, from baseline to follow-up. Conclusions During the period in which SP was the first-line anti-malarial in Kenya, highly SP-resistant parasites emerged, including isolates harboring pfdhps mutations not previously observed there. SP continues to be widely used in Kenya; however, given the highly resistant genotypes observed in this study, ...