Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaounde, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles
Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaounde, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles
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DOI：
10.1093/jac/dkv160
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发表时间：
2015-09-01
影响因子：
5.2
通讯作者：
Berry, Antoine
中科院分区：
文献类型：
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作者：
Chauvin, Pamela;Menard, Sandie;Berry, Antoine
目的：确定喀麦隆采用磺胺多辛/乙胺嘧啶(IPTp-SP)对孕妇进行间歇预防治疗6年后，(I)恶性疟原虫二氢叶酸还原酶(Pfdhfr)和二氢蝶形酸合成酶(Pfdhps)基因突变与磺胺/乙胺嘧啶耐药相关的多态和流行情况以及(Ii)磺胺/乙胺嘧啶使用对恶性疟原虫pfdhfr/pfdhps等位基因选择的影响。方法：从喀麦隆雅温德采集的恶性疟原虫分离株在服用IPTp-SP[SP2组(对照组)(n=51)]或之后[SP+组(n=49)]的pfdhfr和pfdhps基因S108N三重突变的发生率接近100%(96/100)，在两组中均未检测到密码子50和164的突变。SP2组最常见的pfdhps基因突变为A437G，发生率为76.5%(39/51)，服用磺胺多辛/乙胺的孕妇中A437G突变发生率为95.9%(47/49)，差异有统计学意义(P=0.012)。我们的研究证实了在喀麦隆存在pfdhps K540E突变，但仍然很少见。自2005年的上一次研究以来，pfdhps A581G和A613S突变的患病率增加了[对照组中分别为5.9%(3/51)和11.8%(6/51)]。令人惊讶的是，发现了新的pfdhps I431V突变，发生率为9.8%(5/51)，并与其他pfdhfr/pfdhps等位基因相关联，形成了N51I、C59R、S108N/I431V、S436A、A437G、A581G、A613S突变。特别是，我们观察到几种寄生虫携带pfdhfr/pfdhps基因的八个突变，这些寄生虫对磺胺多辛/乙胺嘧啶具有高水平的耐药性。
Objectives: To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles.Methods: pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaounde (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP2 group (control) (n = 51)] or afterwards [SP+ group (n = 49)] were sequenced.Results: The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP2 group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P = 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant.Conclusions: Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.