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  • Title: Two mutations in dihydrofolate reductase combined with one in the dihydropteroate synthase gene predict sulphadoxine-pyrimethamine parasitological failure in Ugandan children with uncomplicated falciparum malaria.
    Author: Talisuna AO, Nalunkuma-Kazibwe A, Langi P, Mutabingwa TK, Watkins WW, Van Marck E, Egwang TG, D'Alessandro U.
    Journal: Infect Genet Evol; 2004 Dec; 4(4):321-7. PubMed ID: 15374529.
    Abstract:
    The point mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) and the dihydropteroate synthase (dhps) genes that are linked to sulphadoxine-pyrimethamine (SP) resistance in vitro have been well characterised. To determine whether a few of these mutations could predict SP treatment failure in vivo, two mutations (Asn-108 and Arg-59) in the dhfr gene and one (Glu-540) in the dhps gene were analysed according to the risk of SP parasitological failure (RI-RIII) at day 28 in pre-treatment isolates in 79 Ugandan children aged 6-59 (mean = 18.4, S.D. = 8.8) months with uncomplicated falciparum malaria. Neither the dhfr-108 (P = 0.3) nor the dhps-540 (P = 0.6) or dhfr-108 + dhps-540 (P = 0.04) mutations were significantly associated with SP parasitological failure. However, the dhfr-108 + dhfr-59 (P = 0.04), the dhfr-59 + dhps-540 (P = 0.04) and the dhfr-108 + dhfr-59 + dhps-540 (P = 0.02) mutations significantly increased the risk for SP parasitological failure. Our findings confirm an earlier report that the dhfr-59 and the dhps-540 mutations could be useful genetic markers for rapid screening of populations at high risk of SP resistance.
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