Abstract
BackgroundSulfadoxine–pyrimethamine (SP) is recommended for intermittent preventive treatment of malaria in Africa. However, increasing SP resistance (SPR) affects the therapeutic efficacy of the SP. As molecular markers, Pfdhfr (dihydrofolate reductase) and Pfdhps (dihydropteroate synthase) genes are widely used for SPR surveillance. This study aimed to assess the prevalence of Pfdhfr and Pfdhps genes mutations and haplotypes in Plasmodium falciparum isolates collected from Bioko Island, Equatorial Guinea (EG).MethodsIn total, 180 samples were collected in 2013–2014. The single nucleotide polymorphisms (SNPs) of the Pfdhfr and Pfdhps genes were identified with nested PCR and Sanger sequencing. The genotypes and linkage disequilibrium (LD) tests were also analysed.ResultsSequences of Pfdhfr and Pfdhps genes were obtained from 92.78% (167/180) and 87.78% (158/180) of the samples, respectively. For Pfdhfr, 97.60% (163/167), 87.43% (146/167) and 97.01% (162/167) of the samples carried N51I, C59R and S108N mutant alleles, respectively. The prevalence of the Pfdhps S436A, A437G, K540E, A581G, and A613S mutations were observed in 20.25% (32/158), 90.51% (143/158), 5.06% (8/158), 0.63% (1/158), and 3.16% (5/158) of the samples, respectively. In total, 3 unique haplotypes at the Pfdhfr locus and 8 haplotypes at the Pfdhps locus were identified. A triple mutation (CIRNI) in Pfdhfr was the most prevalent haplotype (86.83%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in Pfdhps. A total of 130 isolates with 12 unique haplotypes were found in the Pfdhfr and Pfdhps combined haplotypes, 65.38% (85/130) of them carried quadruple allele combinations (CIRNI-SGKAA), whereas only one isolate (0.77%, 1/130) was found to carry the wild-type (CNCSI-SAKAA). For LD analysis, the Pfdhfr N51I was significantly associated with the Pfdhps A437G (P < 0.05).ConclusionBioko Island possesses a high prevalence of the Pfdhfr triple mutation (CIRNI) and Pfdhps single mutation (SGKAA), which will undermine the pharmaceutical effect of SP for malaria treatment strategies. To avoid an increase in SPR, continuous molecular monitoring and additional control efforts are urgently needed in Bioko Island, Equatorial Guinea.
Highlights
Sulfadoxine–pyrimethamine (SP) is recommended for intermittent preventive treatment of malaria in Africa
Prevalence of individual point mutations in Pfdhfr and Pfdhps A high prevalence of Pfdhfr mutant alleles was detected in the analysed samples
The C59R mutant allele showed lower prevalence compared to N51I and S108N (χ2 = 6.141, P = 0.013; χ2 = 6.082, P = 0.014)
Summary
Sulfadoxine–pyrimethamine (SP) is recommended for intermittent preventive treatment of malaria in Africa. Pregnant women and children under 5 years old are the main victims of falciparum malaria. To alleviate the global malaria burden in a susceptible population, sulfadoxine–pyrimethamine (SP) is recommended by the World Health Organization (WHO) for use as intermittent preventive treatment in pregnant women (IPTp) and infants (IPTi) in malaria-endemic regions [2]. Recent studies demonstrated P. falciparum parasites are the predominant species in EG, leading to approximately 291,700 cases in 2016; 15% of the deaths from this species were in children under 5 years old [5]. In EG, SP has been used as a second-line treatment in cases of uncomplicated falciparum malaria for several decades. To ensure the prophylactic efficacy of this approach and support the national anti-malarial policy, large-scale screening and surveillance of SP drug resistance is highly recommended [11]
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