High prevalence of Pfdhfr-Pfdhps quadruple mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea.

Autor: Jiang T; Department of Human Parasitology, School of Basic Medical Sciences, Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, People's Republic of China., Chen J; The Chinese Medical Aid Team To the Republic of Equatorial Guinea; Laboratory Medical Center, Huizhou Municipal Central Hospital, Huizhou, 516001, People's Republic of China., Fu H; Clinical Laboratory, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, People's Republic of China., Wu K; Department of Schistosomiasis and Endemic Diseases, Wuhan City Center for Disease Prevention and Control, Wuhan, People's Republic of China., Yao Y; Department of Human Parasitology, School of Basic Medical Sciences, Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, People's Republic of China., Eyi JUM; Department of Medical Laboratory, Malabo Regional Hospital, Malabo, Equatorial Guinea., Matesa RA; Department of Medical Laboratory, Malabo Regional Hospital, Malabo, Equatorial Guinea., Obono MMO; Department of Medical Laboratory, Malabo Regional Hospital, Malabo, Equatorial Guinea., Du W; Department of Human Parasitology, School of Basic Medical Sciences, Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, People's Republic of China., Tan H; Department of Human Parasitology, School of Basic Medical Sciences, Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, People's Republic of China., Lin M; Department of Histology and Embryology, Shantou University Medical College, Shantou, People's Republic of China. Konfutea@hotmail.com., Li J; Department of Human Parasitology, School of Basic Medical Sciences, Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, People's Republic of China. yxlijian@163.com.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2019 Mar 26; Vol. 18 (1), pp. 101. Date of Electronic Publication: 2019 Mar 26.
DOI: 10.1186/s12936-019-2734-x
Abstrakt: Background: Sulfadoxine-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).
Methods: In 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.
Results: Sequences 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).
Conclusion: Bioko 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.
Databáze: MEDLINE
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