Prevalence of Single Nucleotide Polymorphisms in the Plasmodium falciparum Multidrug Resistance Gene (Pfmdr-1) in Korogwe District in Tanzania Before and After Introduction of Artemisinin-Based Combination Therapy

TY - JOUR

T1 - Prevalence of Single Nucleotide Polymorphisms in the Plasmodium falciparum Multidrug Resistance Gene (Pfmdr-1) in Korogwe District in Tanzania Before and After Introduction of Artemisinin-Based Combination Therapy

AU - Thomsen, Thomas T

AU - Ishengoma, Deus S

AU - Mmbando, Bruno P

AU - Lusingu, John P

AU - Vestergaard, Lasse S

AU - Theander, Thor G

AU - Lemnge, Martha M

AU - Bygbjerg, Ib C

AU - Alifrangis, Michael

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Tanzania implemented artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in November of 2006 because of resistance to sulfadoxine-pyrimethamine. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance, which initially may be detected at the molecular level as temporal changes in the frequency of single nucleotide polymorphisms (SNPs) in the Pfmdr-1 gene associated with AL resistance. In Tanzania, 830 Plasmodium falciparum -positive samples collected between 2003 and 2010 were examined for SNPs of Pfmdr-1 at codons 86, 184, and 1246. Both the N86 and 184F increased from 2006 to 2010 (logistic regression; N86: odds ratio [95% confidence interval] = 1.35 [1.07-1.71], P = 0.01; 184F: odds ratio = 1.42 [1.07-1.88], P = 0.02), and no change was found for D1246 (odds ratio = 1.01 [0.80-1.28], P = 0.9). The observed changes may be because of introduction of AL, and if so, this finding gives cause for concern and argues for continued surveillance of these molecular markers.

AB - Tanzania implemented artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in November of 2006 because of resistance to sulfadoxine-pyrimethamine. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance, which initially may be detected at the molecular level as temporal changes in the frequency of single nucleotide polymorphisms (SNPs) in the Pfmdr-1 gene associated with AL resistance. In Tanzania, 830 Plasmodium falciparum -positive samples collected between 2003 and 2010 were examined for SNPs of Pfmdr-1 at codons 86, 184, and 1246. Both the N86 and 184F increased from 2006 to 2010 (logistic regression; N86: odds ratio [95% confidence interval] = 1.35 [1.07-1.71], P = 0.01; 184F: odds ratio = 1.42 [1.07-1.88], P = 0.02), and no change was found for D1246 (odds ratio = 1.01 [0.80-1.28], P = 0.9). The observed changes may be because of introduction of AL, and if so, this finding gives cause for concern and argues for continued surveillance of these molecular markers.

U2 - 10.4269/ajtmh.2011.11-0071

DO - 10.4269/ajtmh.2011.11-0071

M3 - Journal article

C2 - 22144430

SN - 0002-9637

VL - 85

SP - 979

EP - 983

JO - American Journal of Tropical Medicine and Hygiene

JF - American Journal of Tropical Medicine and Hygiene

IS - 6

ER -