High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children.

Malaria Journal
Ghyslain Mombo-NgomaMartin P Grobusch

Abstract

Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP). The study assessed the frequency of SP resistance-conferring polymorphisms in Plasmodium falciparum-positive samples from two clinical studies in Lambaréné. Their role on treatment responses and transmission potential was studied in an efficacy open-label clinical trial with a 28-day follow-up in 29 children under five with uncomplicated malaria. SP was well tolerated by all subjects in vivo. Three subjects were excluded from per-protocol analysis. PCR-corrected, 12/26 (46%) achieved an adequate clinical and parasitological response, 13/26 (50%) were late parasitological failures, while 1/26 (4%) had an early treatment failure, resulting in early trial discontinuation. Of 106 isolates, 98 (92%) carried the triple mutant dhfr haplotype. Three point mutations were found in dhps in a variety of haplotypic configurations. The 437G + 540E double mutant allele was found for the first time in Gabon. There is a high prevalence of dhfr triple mutant with some dhps point mutations in Gabon, in line with treatment failures obse...Continue Reading

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Citations

Feb 18, 2014·International Journal for Parasitology. Drugs and Drug Resistance·Daouda NdiayeSarah Volkman
May 3, 2015·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Felix Koukouikila-KoussoundaFrancine Ntoumi
Jan 3, 2018·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ghyslain Mombo-NgomaPeter G Kremsner
Aug 13, 2014·Antimicrobial Agents and Chemotherapy·Jana HeldBenjamin Mordmüller
Nov 21, 2018·Antimicrobial Agents and Chemotherapy·Michael RamharterThorsten Lehr
Jun 19, 2019·Malaria Research and Treatment·Jeanne Vanessa Koumba LengongoDenise Patricia Mawili-Mboumba

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Methods Mentioned

BETA
genotyping
PCR
electrophoresis
dot-blot

Clinical Trials Mentioned

NCT00167843
NCT00453856

Software Mentioned

Stata
IPTi
SP

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