Polymorphisms in Plasmodium falciparum K13-propeller in Angola and Mozambique after the introduction of the ACTs.

We report the presence of SNPs in Plasmodium falciparum K13-propeller gene in two African countries, Angola and Mozambique, where malaria is a serious public health problem. Samples were collected before and after ACT introduction as first-line treatment. In each country 50 samples collected before and 50 after ACT introduction were analysed. A total of three different mutations (R471R and R575R in Angola and V494I in Mozambique) were identified in five samples, all collected after the introduction of ACT. The R471R mutation detected in Angola has already been reported in Africa (DR-Congo and Gabon). However, the mutations R575R (Angola) and V494I (Mozambique), have never been reported. V494I is adjacent to the known K13 resistance-associated mutation Y493H, although functional analysis did not predict a deleterious effect on protein function.

Prevalence of pfmdr1 alleles associated with artemether-lumefantrine tolerance/resistance in Maputo before and after the implementation of artemisinin-based combination therapy.

BACKGROUND: Mozambique implemented artemisinin-based combinations therapy (ACT) using artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in 2009. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance. The prevalence of pfmdr1 different alleles in Maputo and Mozambique is not known, either after or before the introduction of ACT. Pfmdr1 molecular markers related to Plasmodium falciparum susceptibility were analysed before and after transition to ACT. METHODS: A first group of samples was collected between June 2003 and June 2005 and a second group in the period between March 2010 and March 2012. Three alleles were analysed by PCR-RFLP: N86Y, Y184F and D1246Y, in the pfmdr1 gene. RESULTS: Alleles N86, 184F and D1246 increased from 19.5, 19.6 and 74.4% in 2003-2005 to 73.2, 22.7 and 96.7% in 2010-2012, respectively. After implementation of ACT (2010-2012), pfmdr1 haplotypes, either two- and three-codon basis, were generally less diverse than before the implementation of ACT (2003-2005). The prevalence of haplotypes N86-184Y, N86-D1246 and 184Y-D1246 increased from 12,2, 27.3 and 71.7% in 2003-2005 to 59.4, 84.3 and 78.6% in 2010-2012. The three-codon basis haplotypes NFD and NYD also increased significantly during the same period. CONCLUSION: The alleles N86 and 184 F and the triple haplotype N86-184 F-D1246 showed a significantly increased prevalence after introduction of ACT.