Five-year surveillance of molecular markers of Plasmodium falciparum antimalarial drug resistance in Korogwe District, Tanzania: accumulation of the 581G mutation in the P. falciparum dihydropteroate synthase gene.
In January 2007, Tanzania replaced sulfadoxine-pyrimethamine (SP) with artemether-lumefantrine for treatment of uncomplicated malaria. This study examined the impact of widespread SP use on molecular markers of Plasmodium falciparum drug resistance in blood samples from persons living in two villages in Korogwe District, Tanzania, from 2003 through 2007. The prevalence of the P. falciparum dihydropteroate synthase (Pfdhps) gene 581G mutation increased from 12% in 2003 to 56% in 2007 (P < 0.001), resulting in an increase in the triple mutant Pfdhps haplotype SGEGA from 8% to 32% (P < 0.001). In contrast, the chloroquine-sensitive P. falciparum chloroquine resistance transporter (Pfcrt) CVMNK haplotype increased from 6% to 30% (P < 0.001). The dramatic increase of the triple Pfdhps mutant SGEGA haplotype may endanger the continued use of SP for intermittent presumptive treatment of pregnant women (IPTp). Further studies are needed to determine the importance of Pfdhps SGEGA haplotype parasites on the efficacy of SP for IPTp.
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark. micali@sund.ku.dk
Michael
M
Alifrangis
John P
JP
Lusingu
Bruno
B
Mmbando
Michael B
MB
Dalgaard
Lasse S
LS
Vestergaard
Deus
D
Ishengoma
Insaf F
IF
Khalil
Thor G
TG
Theander
Martha M
MM
Lemnge
Ib C
IC
Bygbjerg
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004094:Dihydropteroate Synthase / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D011159:Population Surveillance; D013636:Tanzania / Q000453:epidemiology; D013995:Time
D000962:Antimalarials; D005819:Genetic Markers; D004094:Dihydropteroate Synthase