Increased Prevalence of the pfdhfr/phdhps Quintuple Mutant and Rapid Emergence of pfdhps Eesistance Mutations at Codons 581 and 613 in Kisumu, Kenya
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 IC50 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 followup 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 followup. 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 24, 2010
- Accession Number
- ADA532981
Entities
People
- Fredrick L. Eyase
- Hoseah M. Akala
- Maroya D. Spalding
- Norman C. Waters
- Rodney L. Coldren
- Sean T Prigge
- Sheryl A. Bedno
- William J. Moss
Organizations
- Uniformed Services University of the Health Sciences