Changes in the frequencies of Plasmodium falciparum dhps and dhfr drug-resistant mutations in children from Western Kenya from 2005 to 2018: the rise of Pfdhps S436H.
Changes in the frequencies of Plasmodium falciparum dhps and dhfr drug-resistant mutations in children from Western Kenya from 2005 to 2018: the rise of Pfdhps S436H.
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DOI：
10.1186/s12936-020-03454-8
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发表时间：
2020-10-22
期刊：
影响因子：
3
通讯作者：
Escalante AA
中科院分区：
文献类型：
--
作者：
Pacheco MA;Schneider KA;Cheng Q;Munde EO;Ndege C;Onyango C;Raballah E;Anyona SB;Ouma C;Perkins DJ;Escalante AA
磺胺多辛(SP)是唯一被批准用于妊娠期间歇预防治疗(IPTp)的抗疟疾药物。然而，恶性疟原虫Dhfr(Pfdhfr)和DHps(Pfdhps)基因的突变分别赋予了对乙胺嘧啶和磺胺多辛的耐药性。在这里，比较了2005至2018年间居住在全流行传播地区的肯尼亚疟疾儿童样本中SP耐药性相关突变的频率。从2005年(n = 81)、2010年(n = 95)、2017年(n = 43)和2018年(n = 55)采集的样本中扩增并测序了Pfdhfr和Pfdhps基因的部分序列。对已知的与乙胺嘧啶和磺胺多辛耐药的突变频率进行了估计和比较。由于基于青蒿素的联合疗法(ACT)是目前治疗疟疾的一线疗法，因此在2017/18年度的样本中，研究了恶性疟原虫kelch13基因(Pfk13)螺旋体区域是否存在与ACT延迟的寄生虫清除有关的突变。在其他变化中，Pfdhps S436H的点突变频率从2005年的无法检测增加到2017/18年的28%。三个Pfdhfr突变等位基因(CIRNI)的频率从2005年的84%增加到2017/18年的95%，而Pfdhfr双突变等位基因的频率下降(等位基因CICNI从2005年的29%下降到2017/18年的6%，CNRNI从2005年的9%增加到2010和2017/18年的无法检测)。因此，从2010年到2017/18年，包括Pfdhps S436H在内的具有6个突变(HGEAA/CIRNI)的多位点Pfdhfr/Pfdhps基因型的频率增加。虽然没有观察到与ACT延迟的寄生虫清除相关的突变，但在非洲发现的最普遍的Pfk13 SNP突变A578S的频率很低(2.04%)。SP抗性突变等位基因频率发生了变化，包括Pfdhps S436H的增加。尽管这些模式似乎与药物压力下的定向选择一致，但缺乏信息来确定这种变化的实际原因。这些结果建议将Pfdhfr/Pfdhps突变的分子监测纳入妊娠间歇预防治疗(IPTp)的SP疗效研究的背景下。
Sulfadoxine-pyrimethamine (SP) is the only anti-malarial drug formulation approved for intermittent preventive treatment in pregnancy (IPTp). However, mutations in the Plasmodium falciparum dhfr (Pfdhfr) and dhps (Pfdhps) genes confer resistance to pyrimethamine and sulfadoxine, respectively. Here, the frequencies of SP resistance-associated mutations from 2005 to 2018 were compared in samples from Kenyan children with malaria residing in a holoendemic transmission region. Partial sequences of the Pfdhfr and Pfdhps genes were amplified and sequenced from samples collected in 2005 (n = 81), 2010 (n = 95), 2017 (n = 43), and 2018 (n = 55). The frequency of known mutations conferring resistance to pyrimethamine and sulfadoxine were estimated and compared. Since artemisinin-based combination therapy (ACT) is the current first-line treatment for malaria, the presence of mutations in the propeller domain of P. falciparum kelch13 gene (Pfk13) linked to ACT-delayed parasite clearance was studied in the 2017/18 samples. Among other changes, the point mutation of Pfdhps S436H increased in frequency from undetectable in 2005 to 28% in 2017/18. Triple Pfdhfr mutant allele (CIRNI) increased in frequency from 84% in 2005 to 95% in 2017/18, while the frequency of Pfdhfr double mutant alleles declined (allele CICNI from 29% in 2005 to 6% in 2017/18, and CNRNI from 9% in 2005 to undetectable in 2010 and 2017/18). Thus, a multilocus Pfdhfr/Pfdhps genotype with six mutations (HGEAA/CIRNI), including Pfdhps S436H, increased in frequency from 2010 to 2017/18. Although none of the mutations associated with ACT-delayed parasite clearance was observed, the Pfk13 mutation A578S, the most widespread Pfk13 SNP found in Africa, was detected in low frequency (2.04%). There were changes in SP resistance mutant allele frequencies, including an increase in the Pfdhps S436H. Although these patterns seem consistent with directional selection due to drug pressure, there is a lack of information to determine the actual cause of such changes. These results suggest incorporating molecular surveillance of Pfdhfr/Pfdhps mutations in the context of SP efficacy studies for intermittent preventive treatment in pregnancy (IPTp).
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影响因子：
3
作者：
Mohon AN;Alam MS;Bayih AG;Folefoc A;Shahinas D;Haque R;Pillai DR
通讯作者：
Pillai DR
影响因子：
9.3
作者：
Amaratunga, Chanaki;Andrianaranjaka, Voahangy Hanitriniaina;Woodrow, Charles
通讯作者：
Woodrow, Charles
影响因子：
3.3
作者：
Biswas, S;Escalante, A;Lal, AA
通讯作者：
Lal, AA
DOI：
10.1073/pnas.0905922106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Lozovsky, Elena R.;Chookajorn, Thanat;Hartl, Daniel L.
通讯作者：
Hartl, Daniel L.
DOI：
10.4269/ajtmh.15-0005
发表时间：
2015-09
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Escalante AA;Ferreira MU;Vinetz JM;Volkman SK;Cui L;Gamboa D;Krogstad DJ;Barry AE;Carlton JM;van Eijk AM;Pradhan K;Mueller I;Greenhouse B;Pacheco MA;Vallejo AF;Herrera S;Felger I
通讯作者：
Felger I