Increased Prevalence of the pfdhfr/phdhps Quintuple Mutant and Rapid Emergence of pfdhps Eesistance Mutations at Codons 581 and 613 in Kisumu, Kenya
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF PREVENTIVE MEDICINE AND BIOMETRICS
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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 N51IC59RS108Npfdhps A437GK540E quintuple mutant associated with SP-resistance rose from 21 in the baseline study to 53 in the follow-up study p0.001. Isolates containing the pfdhfr I164L mutation were absent from both studies. The pfdhps mutations A581G and A613ST 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 p0.001 and 44 to 76 p0.001, 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.
- Medicine and Medical Research