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

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
Ambrose O TalisunaUmberto D'Alessandro

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.

References

Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·D J BzikJ Inselburg
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A F CowmanS J Foote
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·T TrigliaA F Cowman
Aug 19, 2000·The Journal of Infectious Diseases·O K DoumboC V Plowe
Jan 5, 2002·Trends in Parasitology·C H SibleyA M Nzila

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Citations

Nov 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jonathan J JulianoSteven R Meshnick
Nov 9, 2007·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Issaka ZongoJean Bosco Ouédraogo
Jan 16, 2007·Clinical Microbiology Reviews·David J Conway
Apr 8, 2006·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Toshihiro MitaAnders Björkman
Apr 25, 2007·Molecular and Biochemical Parasitology·Conner I SandefurCarol Hopkins Sibley
Jul 21, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Piero Olliaro

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