[Point mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum from three endemic malaria regions in Colombia].
BACKGROUND
Plasmodium falciparum has the ability to counter the antiparasitic activity of sulphadoxine-pyrimethamine by progressively accumulating mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes. These mutations gradually increase the resistance of the parasite to these drugs and lead to therapeutic failure.


OBJECTIVE
To determine the frequency of mutations associated with resistance to sulphadoxine and pyrimethamine in the dhfr and dhps genes of P. falciparum in samples from patients in three endemic zones of Colombia -La Carpa, Guaviare; Casuarito, Vichada; and Tierralta and Puerto Libertador, Córdoba.


METHODS
Forty samples were selected from patients with uncomplicated P. falciparum malaria. The frequency profiles of the 108, 59 and 164 alleles of dhfr were obtained by application of an allele-specific polymerase chain reaction, whereas the other alleles (alleles 51 of the dhfr gene and 436, 437 and 540 of dhps) were obtained by polymerase chain reaction and restriction fragment length polymorphism.


RESULTS
The 108N and 51I mutations in the dhfr gene were found in all of the 40 samples. No mutant alleles were found in the 59 and 164 codons of the dhfr gene, or in the 436 codon of the dhps gene. The 437G mutation was observed in 36 samples and the wild-type allele was present in 3 from Tierralta and one from La Carpa. The 540E mutation was only detected in two samples from Casuarito.


CONCLUSIONS
The 108N, 51I and 437G mutations prevail in the populations of P. falciparum, indicating a cumulative effect of mutations and the need to continue surveillance for other changes which can lead to the total loss of the efficacy of sulphadoxine-pyrimethamine.
Galindo
John Alexander
JA
Grupo de Bioquímica y Biología Celular, Instituto Nacional de Salud, Bogotá, DC, Colombia.
Cristiano
Fabio Aníbal
FA
Knudson
Angélica
A
Nicholls
Rubén Santiago
RS
Guerra
Angela Patricia
AP
D003105:Colombia / Q000453:epidemiology; D004094:Dihydropteroate Synthase / Q000235:genetics*; D019353:Endemic Diseases; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics*; D017354:Point Mutation; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase