Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola.

Abstract

BACKGROUND:

Plasmodium falciparum malaria remains a leading health problem in Africa and its control is seriously challenged by drug resistance. Although resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination remains an important component of malaria control programmes as intermittent preventive therapy (IPT) for pregnant women and children. In Angola, resistance patterns have been poorly characterized, and IPT has been employed for pregnant women since 2006. The aim of this study was to assess the prevalence of key antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in P. falciparum samples from Angola.

METHODS:

Plasmodium falciparum samples collected in Luanda, in 2007, were genotyped by amplification and DNA forward and reverse sequencing of the pfdhfr and pfdhps genes.

RESULTS:

The most prevalent polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps 437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed in West Africa were also identified (540E in 10%, 581G in 7% of samples).

CONCLUSION:

This study documents an important prevalence of 4 P. falciparum polymorphisms that predicts an antifolate resistance in Luanda. Further, some samples presented additional mutations associated to high-level resistance. These results suggest that the use of SP for IPT may no longer be warranted in Angola.

• Authors: Bianca E Gama, Guilhermina A L Pereira-Carvalho, Florbela J I Lutucuta Kosi, Natália K Almeida de Oliveira, Filomeno Fortes, Philip J Rosenthal, Virgílio E do Rosário, Cláudio Tadeu Daniel-Ribeiro, Maria de Fátima Ferreira-da-Cruz
• Journal: Malaria journal (Malar J) Vol. 10 Pg. 248 (Aug 24 2011) ISSN: 1475-2875 [Electronic] England
• PMID: 21864379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Folic Acid Antagonists
• Genetic Markers
• Protozoan Proteins
• Tetrahydrofolate Dehydrogenase
• Dihydropteroate Synthase

Topics

• Adult
• Angola
• Antimalarials (pharmacology)
• Child
• Child, Preschool
• Dihydropteroate Synthase (genetics)
• Drug Resistance
• Female
• Folic Acid Antagonists (pharmacology)
• Gene Frequency
• Genetic Markers
• Genotype
• Humans
• Malaria, Falciparum (parasitology)
• Plasmodium falciparum (drug effects, genetics, isolation & purification)
• Polymorphism, Genetic
• Pregnancy
• Protozoan Proteins (genetics)
• Sequence Analysis, DNA
• Tetrahydrofolate Dehydrogenase (genetics)