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J Antimicrob Chemother ; 73(10): 2704-2715, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30053021

ABSTRACT

Background: In 2005, the Democratic Republic of the Congo (DRC) switched to artesunate/amodiaquine as the first-line antimalarial in response to increasing sulfadoxine/pyrimethamine resistance and adopted intermittent preventive treatment using sulfadoxine/pyrimethamine in pregnancy. Objectives: To determine the prevalence of molecular markers of sulfadoxine/pyrimethamine resistance in southwestern DRC 10 years after the new policy was instituted. Methods: From March 2014 to December 2015, blood samples were collected from symptomatic patients presenting to outpatient centres in urban and rural areas. A total of 2030 confirmed Plasmodium falciparum isolates were genotyped at codons associated with sulfadoxine/pyrimethamine resistance. Results: The prevalence of pfdhfr-N51I, C59R and S108N and pfdhps-A437G mutations was consistently high; the prevalence of the pfdhps-K540E mutation was low but increased since its first report in 2008 in the same region, reaching 17.6% by 2015. The pfdhps-A581G mutation increased from ∼4.5% in 2014 to ∼14.0% in 2015 at urban sites while in rural areas it remained low (∼4.0%). The mutations pfdhfr-I164L and pfdhps-A613S were detected for the first time in DRC. Also, 11 (0.8%) isolates revealed the presence of the newly described pfdhps-I431V mutation. Combining pfdhfr and pfdhps alleles, quintuple and sextuple mutations were observed, with the emergence of septuple (IRNI/IAGEGA)- and octuple (IRNI/VAGKGS)-mutant genotypes. Conclusions: Intermittent preventive treatment using sulfadoxine/pyrimethamine during pregnancy remains warranted in southwestern DRC. However, the expansion of pfdhps-K540E mutation and emergence of mutants that cause higher levels of sulfadoxine/pyrimethamine resistance is concerning and may present a challenge for future preventive interventions in the country.


Subject(s)
Antimalarials/pharmacology , Drug Resistance, Multiple/genetics , Plasmodium falciparum/drug effects , Protozoan Proteins/genetics , Pyrimethamine/pharmacology , Sulfadoxine/pharmacology , Tetrahydrofolate Dehydrogenase/genetics , Adolescent , Adult , Alleles , Ambulatory Care Facilities/statistics & numerical data , Child , Child, Preschool , Democratic Republic of the Congo , Female , Genotype , Humans , Malaria, Falciparum/blood , Malaria, Falciparum/drug therapy , Male , Mutation , Polymorphism, Genetic , Prevalence , Young Adult
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