Lin Li-Yun, Li Jian, Huang Hui-Ying, Liang Xue-Yan, Jiang Ting-Ting, Chen Jiang-Tao, Ehapo Carlos Salas, Eyi Urbano Monsuy, Zheng Yu-Zhong, Zha Guang-Cai, Xie Dong-De, Wang Yu-Ling, Chen Wei-Zhong, Liu Xiang-Zhi, Lin Min
School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong Province, People's Republic of China.
University of Chinese Academy of Sciences, Beijing, People's Republic of China.
Infect Drug Resist. 2020 Apr 28;13:1203-1212. doi: 10.2147/IDR.S236898. eCollection 2020.
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 () and dihydropteroate synthase () genes.
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.
and gene sequences were obtained for 90.5% (162/179) and 77.1% (138/179) of the samples, respectively. For , 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 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 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 (>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.
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.
抗疟药物耐药性是全球疟疾防控和消除工作面临的主要挑战之一。2006年,由于磺胺多辛-乙胺嘧啶(SP)耐药性增加,赤道几内亚的比奥科岛将其替换为以青蒿素为基础的联合疗法(ACT),SP耐药性与二氢叶酸还原酶(DHFR)和二氢蝶酸合酶(DHPS)基因的突变有关。
为评估2011年至2017年比奥科岛与SP耐药性相关分子标志物的变化趋势,对主动病例检测期间收集的179份样本进行了PCR和DNA测序分析。
分别从90.5%(162/179)和77.1%(138/179)的样本中获得了DHFR和DHPS基因序列。对于DHFR,97.5%(158/162)、95.7%(155/162)和98.1%(159/162)的样本分别含有N51I、C59R和S108N突变等位基因。并且在25.4%(35/138)、88.4%(122/138)、5.1%(7/138)、1.4%(2/138)和7.2%(10/138)的样本中分别观察到DHPS的S436A、A437G、K540E、A581G和A613S突变。鉴定出两类先前描述的与SP耐药性相关的DHPS单倍型及其频率:部分(IRNI-SGKAA,59.4%)和完全(IRNI-SGEAA,5.5%)耐药。尽管在不同时间段未观察到显著差异(P>0.05),但我们的研究证实,在调查的7年中,比奥科疟原虫中这些SP耐药性标志物的频率呈缓慢上升趋势。
研究结果表明,即使在将SP替换为非复杂性疟疾的一线治疗药物后,比奥科岛仍普遍存在SP耐药性标志物。该地区迫切需要持续的分子监测和额外的防控措施。