Profile of molecular mutations in pfdhfr, pfdhps, pfmdr1, and pfcrt genes of Plasmodium falciparum related to resistance to different anti-malarial drugs in the Bata District (Equatorial Guinea).
Profile of molecular mutations in pfdhfr, pfdhps, pfmdr1, and pfcrt genes of Plasmodium falciparum related to resistance to different anti-malarial drugs in the Bata District (Equatorial Guinea).
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DOI：
10.1186/s12936-016-1672-0
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发表时间：
2017-01-13
期刊：
影响因子：
3
通讯作者：
Benito A
中科院分区：
文献类型：
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作者：
Berzosa P;Esteban-Cantos A;García L;González V;Navarro M;Fernández T;Romay-Barja M;Herrador Z;Rubio JM;Ncogo P;Santana-Morales M;Valladares B;Riloha M;Benito A
恶性疟原虫耐药性的出现是造成全球疟疾负担的一个主要原因。耐药性使治疗变得复杂，是疟疾控制中最重要的问题之一。这项研究评估了赤道几内亚大陆地区在采用青蒿琥酯联合疗法作为一线治疗 8 年后，恶性疟原虫基因 pfdhfr、pfdhps、pfmdr1 和 pfcrt 的突变水平，这些基因与不同抗疟疾药物的耐药性相关。在 78% 的农村样本中发现了 pfdhfr 三重突变体 (51I/59R/108N)，该突变体对磺胺多辛/乙胺嘧啶 (SP) 具有抗性；其频率在城市和农村环境中存在显着差异 (p = 0.007)。 164L 突变首次在该地区的农村地区被发现（1.4%）。我们还确定了三类先前描述的突变体及其频率：部分耐药（pfdhfr 51I/59R/108N + pfdhps 437G），发现率为 54%（95% CI 47.75–60.25）；完全耐药 (pfdhfr 51I/59R/108N + pfdhps 437G/540E)，发现率为 28% (95% CI 7.07–14.93)；和超级耐药 (pfdhfr 51I/59R/108N + pfdhps 437G/540E/581G)，发现率为 6% (95% CI 0.48–4.32)。 pfmdr1 (86Y + 1246Y) 的双突变以 2% (95% CI 0.24–3.76) 的频率检测到，分布在城市和农村样本中。该地区 22% (95% CI 16.8–27.2) 的样本中检测到 pfmdr1 和 pfcrt 基因 (86Y + 76T) 的单一突变组合，该突变与氯喹和阿莫地喹耐药相关。在恶性疟原虫中检测到的与 SP 抗性相关的高水平突变可能与该地区 SP 治疗的不成功撤消有关。耐药性会降低 5 岁以下儿童和孕妇使用 SP 进行间歇性预防性治疗的效果。尽管检测到大量突变，但一线治疗药物青蒿素/阿莫地喹的疗效并未受到影响。为了避免突变数量、发生和传播的增加，并保护人口，卫生部应确保向卫生中心和医院提供适当的疟疾一线治疗。
The emergence of drug resistance in Plasmodium falciparum has been a major contributor to the global burden of malaria. Drug resistance complicates treatment, and it is one of the most important problems in malaria control. This study assessed the level of mutations in P. falciparum genes, pfdhfr, pfdhps, pfmdr1, and pfcrt, related to resistance to different anti-malarial drugs, in the Continental Region of Equatorial Guinea, after 8 years of implementing artesunate combination therapies as the first-line treatment. A triple mutant of pfdhfr (51I/59R/108N), which conferred resistance to sulfadoxine/pyrimethamine (SP), was found in 78% of samples from rural settings; its frequency was significantly different between urban and rural settings (p = 0.007). The 164L mutation was detected for the first time in this area, in rural settings (1.4%). We also identified three classes of previously described mutants and their frequencies: the partially resistant (pfdhfr 51I/59R/108N + pfdhps 437G), found at 54% (95% CI 47.75–60.25); the fully resistant (pfdhfr 51I/59R/108N + pfdhps 437G/540E), found at 28% (95% CI 7.07–14.93); and the super resistant (pfdhfr 51I/59R/108N + pfdhps 437G/540E/581G), found at 6% (95% CI 0.48–4.32). A double mutation in pfmdr1 (86Y + 1246Y) was detected at 2% (95% CI 0.24–3.76) frequency, distributed in both urban and rural samples. A combination of single mutations in the pfmdr1 and pfcrt genes (86Y + 76T), which was related to resistance to chloroquine and amodiaquine, was detected in 22% (95% CI 16.8–27.2) of samples from the area. The high level of mutations detected in P. falciparum genes related to SP resistance could be linked to the unsuccessful withdrawal of SP treatment in this area. Drug resistance can reduce the efficacy of intermittent prophylactic treatment with SP for children under 5 years old and for pregnant women. Although a high number of mutations was detected, the efficacy of the first-line treatment, artemisinin/amodiaquine, was not affected. To avoid increases in the numbers, occurrence, and spread of mutations, and to protect the population, the Ministry of Health should ensure that health centres and hospitals are supplied with appropriate first-line treatments for malaria.