High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children.
Mombo-Ngoma, G; Oyakhirome, S; Ord, R; Gabor, JJ; Greutélaers, KC; Profanter, K; Greutélaers, B; Kurth, F; Lell, B; Kun, JF; Issifou, S; Roper, C; Kremsner, PG; Grobusch, MP; (2011) High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children. Malar J, 10. p. 123. ISSN 1475-2875 DOI: 10.1186/1475-2875-10-123
- Published Version
Download (313Kb) | Preview
BACKGROUND: Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP). METHODS: 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. RESULTS: 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. CONCLUSIONS: There is a high prevalence of dhfr triple mutant with some dhps point mutations in Gabon, in line with treatment failures observed, and molecular markers of SP resistance should be closely monitored.
|Faculty and Department:||Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology|
|Research Centre:||Antimicrobial Resistance Centre (AMR)
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Actions (login required)