Frequency Distribution of Antimalarial Drug-Resistant Alleles Among Isolates of Plasmodium Falciparum in Bangui, Central African Republic

Abstract

We determined the baseline frequency distribution of mutant alleles of genes associated with resistance to chloroquine and sulfadoxine-pyrimethamine in Plasmodium falciparum isolates in Bangui, Central African Republic. Mutant alleles of the P. falciparum chloroquine resistance transporter (pfcrt) gene were found in all samples and the frequency of the deduced CIET pfcrt haplotype was high (45%). The most common allele of the P. falciparum multidrug resistance 1 (pfmdr1) gene among the field isolates of P. falciparum was 86Y (21.9%). The 1246Y allele was also common (18.0%). Of the 167 P. falciparum isolates in which the dihydrofolate reductase gene was studied, only 11 carried the wild-type allele (6.6%) whereas many (50.3%) were quadruple mutants (50R, 51I, 59R, 108N). The frequency of the 436A mutant allele of the dihydropteroate synthase gene was high (74.3%), but the frequencies of the 437G (18.6%) and 540E (5.2%) mutant alleles were low. Molecular analyses of antimalarial drug-resistant alleles of P. falciparum isolates in Bangui strongly suggest the widespread distribution of chloroquine and pyrimethamine resistance and to a lesser extent sulfadoxine resistance.

In Vitro Activity of Antifolate and Polymorphism in Dihydrofolate Reductase ofPlasmodium falciparumIsolates from the Kenyan Coast: Emergence of Parasites with Ile-164-Leu Mutation

“…Recently, this mutation has been found in Malawi, in parasites from human immunodeficiency virus-positive pregnant women, by using a real-time PCR method and a heteroduplex tracking assay (1, 26); however, this has not been confirmed in a subsequent study in the same area (42). This Ile-164-Leu mutation has also been reported in Uganda and the Central African Republic (16,35,51), and a recent study showed prevalences of 4 to 14% at two sites in Uganda where P. falciparum is endemic (31). Interestingly, this mutation has been found in the western part of Kenya by using standard PCR methods and cloning; surprisingly, its presence was not associated with reduced PM-SD efficacy (21,34), questioning its clinical relevance.…”

Molecular Correlates of High-Level Antifolate Resistance in Rwandan Children with Plasmodium falciparum Malaria

“…Of relevance, the only other place in Africa where a high frequency on May 10, 2018 by guest http://aac.asm.org/ (14%) of the genotype with a polymorphism at position 164 in pfdhfr has been reported is Kabale in Uganda (16), which is close to the eastern Rwanda border. The genotype with a polymorphism at position 164 in pfdhfr has been reported at lower frequencies in Kenya (18), Malawi (1), and Central Africa (19) and from travelers returning from Ghana and Kenya (9). The quadruple mutant is prevalent at higher frequencies in Southeast Asia and South America, where SP is no longer effective.…”

Pfcrt mutant haplotypes may not correspond with chloroquine resistance

“…In recent years, in addition to the conventional in vivo and in vitro methods, the molecular markersbased approach to study and elucidate antimalarial drug resistance has proved useful [22][23][24][25][26]29,30,32]. In this study, we described the distribution of pfcrt K76T and pfmdr1 N86Y mutations in the study area and attempted to evaluate the correlation of these mutations with in vivo clinical outcomes.…”