Abstract
BackgroundMalaria is a major parasitic disease, affecting millions of people in endemic areas. Plasmodium falciparum parasites are responsible for the most severe cases and its resistance to anti-malarial drugs is notorious. This is a possible obstacle to the effectiveness of intermittent preventive treatment (IPT) based on sulfadoxine–pyrimethamine (SP) cures administrated to pregnant women (IPTp) during their pregnancy. As this intervention is recommended in Angola since 2006, it has assessed, in this country, the molecular profiles in P. falciparumdhfr and dhps, two polymorphic genes associated to pyrimethamine and sulfadoxine resistance, respectively.MethodsBlood samples from 52 falciparum patients were collected in Lubango, Angola and pfdhfr and pfdhps polymorphisms were analysed using nested-PCR and DNA sequencing.ResultsIn the pfdhfr gene, the 108N mutation was almost fixed (98 %), followed by 59R (63 %), 51I (46 %), 50R and 164L (2 %, respectively). No 16V/S mutations were found. The most common double mutant genotype was CNRN (59 + 108; 46 %), followed by CICN (51 + 108; 29 %) whereas IRN (51 + 59 + 108; 15 %), CNRNVL (59 + 108 + 164; 2 %) and RICN (50 + 51 + 108; 2 %) triple mutant genotypes were detected. Investigations of the pfdhps gene showed that the 437G mutation was the most prevalent (97 %). Only two and one samples disclosed the 540E (7 %) and the 436A (3 %), respectively. Single mutant SGKAA (437; 86 %) was higher than SGEAA (437 + 540; 7 %) or AGKAA (436 + 437; 3 %) double mutants genotypes. No polymorphism was detected at codons 581G and 613T/S. Combining pfdhfr and pfdhps alleles two triple mutant haplotypes (double mutant in dhfr and single mutant in dhps) were observed: the ACICNVI/SGKAA in 14 (56 %) samples and the ACNRNVI/SGKAA in five (20 %) samples. One quadruple mutant haplotype was detected (ACIRNVI/SGKAA) in six (24 %) P. falciparum samples. No quintuple pfdhfr–pfdhps mutant was noted.Conclusionpfdhfr and pfdhps gene mutations in isolates from Lubango are suggestive of a low-grade SP resistance and IPT for pregnant women and infant based on SP treatment could be effective. Routine molecular studies targeting polymorphism in these two genes need to be routinely conducted at country level.
Highlights
Malaria is a major parasitic disease, affecting millions of people in endemic areas
sulfadoxine–pyrimeth‐ amine (SP) acts by inhibiting the P. falciparum dihydrofolate reductase and dihydropteroate synthetase, two fundamental enzymes involved in the folate biosynthesis pathway [4]
The objective of this study was to investigate the polymorphism at codons A16V/S, C50R, N51I, C59R, S108N, V140L and I164L in the pfdhfr gene and at codons S436A/F/C, A437G, K540E, A581G and A613T/S in the pfdhps gene, in order to provide baseline data regarding the proportion of P. falciparum pfdhfr and pfdhps mutations, before SP-IPTi introduction in Lubango, an Angolan malaria stable transmission region
Summary
Plasmodium falciparum parasites are responsible for the most severe cases and its resistance to anti-malarial drugs is notorious This is a possible obstacle to the effectiveness of intermittent preventive treatment (IPT) based on sulfadoxine–pyrimeth‐ amine (SP) cures administrated to pregnant women (IPTp) during their pregnancy. As this intervention is recom‐ mended in Angola since 2006, it has assessed, in this country, the molecular profiles in P. falciparum dhfr and dhps, two polymorphic genes associated to pyrimethamine and sulfadoxine resistance, respectively. To inform current policy makers when recommending the use of SP in IPT, dhfr and dhps molecular markers are used to differentiate high and low grade SP resistance areas and to define its geographical distribution [5]
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