Trends in Molecular Markers Associated with Resistance to Sulfadoxine-Pyrimethamine (SP) Among Plasmodium falciparum Isolates on Bioko Island, Equatorial Guinea: 2011-2017
Trends in Molecular Markers Associated with Resistance to Sulfadoxine-Pyrimethamine (SP) Among Plasmodium falciparum Isolates on Bioko Island, Equatorial Guinea: 2011-2017
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赤道几内亚比奥科岛恶性疟原虫分离株中与磺胺多辛-乙胺嘧啶 (SP) 耐药性相关的分子标记趋势：2011-2017 年
DOI：
10.2147/idr.s236898
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Lin, Min
中科院分区：
文献类型：
--
作者：
Lin, Li-Yun;Li, Jian;Lin, Min
目的：抗疟药物耐药性是全球控制和消除疟疾努力的主要挑战之一。2006年，在赤道几内亚的比奥科岛，磺胺嘧啶-乙胺嘧啶（SP）被青蒿素为基础的联合疗法（ACT）取代，以应对SP耐药性的增加，SP耐药性与二氢叶酸还原酶（Pfdhfr）和二氢蝶酸合酶（Pfdhps）基因的突变有关。为了评估2011年至2017年比奥科岛与SP耐药相关的分子标记的趋势，通过PCR和DNA测序分析了在活动病例检测期间收集的179份样本。Pfdhfr和Pfdhps基因序列的获得率分别为90.5%（162/179）和77.1%（138/179）。Pfdhfr的N51 I、C59 R和S108 N突变型等位基因的检出率分别为97.5%（158/162）、95.7%（155/162）和98.1%（159/162）。Pfdhps S436 A、A437 G、K540 E、A581 G和A613 S突变分别占25.4%（35/138）、88.4%（122/138）、5.1%（7/138）、1.4%（2/138）和7.2%（10/138）。鉴定了两类先前描述的与SP抗性相关的Pfdhfr-Pfdhps单倍型及其频率：部分抗性（IRNI-SGKAA，59.4%）和完全抗性（IRNI-SGEAA，5.5%）。虽然没有显着差异，观察到在不同的时间段（p>0.05），我们的研究证实了一个缓慢增加的趋势，这些SP耐药标记的频率在比奥科岛的寄生虫在7年investigated.Conclusion：研究结果揭示了SP耐药标记的普遍存在，即使在取代SP作为一线治疗简单的疟疾。迫切需要在该地区进行持续的分子监测和额外的控制努力。
Purpose: Antimalarial drug resistance is one of the major challenges in global efforts to control and eliminate malaria. In 2006, sulfadoxine-pyrimethamine (SP) replaced with artemisinin-based combination therapy (ACT) on Bioko Island, Equatorial Guinea, in response to increasing SP resistance, which is associated with mutations in the dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes.Patients and Methods: To evaluate the trend of molecular markers associated with SP resistance on Bioko Island from 2011 to 2017, 179 samples collected during active case detection were analysed by PCR and DNA sequencing.Results: Pfdhfr and Pfdhps gene sequences were obtained for 90.5% (162/179) and 77.1% (138/179) of the samples, respectively. For Pfdhfr, 97.5% (158/162), 95.7% (155/162) and 98.1% (159/162) of the samples contained N51I, C59R and S108N mutant alleles, respectively. And Pfdhps S436A, A437G, K540E, A581G, and A613S mutations were observed in 25.4% (35/138), 88.4% (122/138), 5.1% (7/138), 1.4% (2/138), and 7.2% (10/138) of the samples, respectively. Two classes of previously described Pfdhfr-Pfdhps haplotypes associated with SP resistance and their frequencies were identified: partial (IRNI-SGKAA, 59.4%) and full (IRNI-SGEAA, 5.5%) resistance. Although no significant difference was observed in different time periods (p>0.05), our study confirmed a slowly increasing trend of the frequencies of these SP-resistance markers in Bioko parasites over the 7 years investigated.Conclusion: The findings reveal the general existence of SP-resistance markers on Bioko Island even after the replacement of SP as a first-line treatment for uncomplicated malaria. Continuous molecular monitoring and additional control efforts in the region are urgently needed.