Five-year surveillance of molecular markers of Plasmodium falciparum antimalarial drug resistance in Korogwe district, Tanzania - Accumulation of the 581G mutation in the Pfdhps gene

Description

Antimalarial drug resistance has forced most malaria-endemic countries to change first-line malaria treatment from various monotherapies to artemisinin-based combination therapies (ACTs). In January 2007, Tanzania replaced sulfadoxine-pyrimethamine (SP) with artemether-lumefantrine (Coartem®) as first-line treatment against uncomplicated malaria.

To examine the prevalence of molecular markers of resistance to SP and other antimalarials during and after widespread use of SP, we measured the frequency and prevalence of single nucleotide polymorphisms (SNPs) in the genes Pfdhps, Pfdhfr, and Pfcrt causing sulfadoxine, pyrimethamine and chloroquine/amodiaquine resistance, respectively, in parasite-positive blood samples from asymptomatic individuals between 6 months and 20 years of age. The samples were collected as part of longitudinal epidemiological and malariometric studies from 2003 to 2007 in two villages in Korogwe District in north-eastern Tanzania. The samples were analyzed by PCR, followed by a sequence-specific oligonucleotide probe (SSOP)-ELISA-based method.  

The frequency of the triple mutated Pfdhps haplotype, SGEGA, increased significantly from 8% in 2003 to 32% in 2007 (P<0.001), and the prevalence of  the 581G mutation  from 12% in 2003, to 56% in 2007. The triple Pfdhfr haplotype, CIRNI remained at approximately 90% throughout with only marginal differences from year to year. In contrast, the frequency of the sensitive Pfcrt CVMNK haplotype increased significantly from 6% to 30% (P<0.001) during the observation period.

The dramatic increase of the Pfdhps-581G mutation resulting in triple Pfdhps mutant SGEGA haplotype indicate that sulfadoxine and/or other sulfonamide drugs still may exert a significant pressure on the parasite population. Further studies are needed to determine whether such changes in Pfdhps are endangering the continued use of SP for intermittent presumptive treatment of pregnant women (IPTp).