Department of Biomedicine and Biotechnology, School of Pharmacy, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Malaria and Neglected Diseases Laboratory, National Centre of Tropical Medicine, Institute of Health Carlos III, Madrid, Spain.
Am J Trop Med Hyg. 2023 Sep 25;109(5):1072-1076. doi: 10.4269/ajtmh.23-0382. Print 2023 Nov 1.
Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.
青蒿素联合疗法是治疗恶性疟原虫疟疾的推荐一线治疗方法，但它们正受到青蒿素耐药性的威胁。pfk13 突变是青蒿素耐药的主要分子标志物。本研究描述了南苏丹西赤道州恶性疟原虫中 pfk13 突变的存在情况。我们分析了来自有症状疟疾病人的 468 个样本，发现了 15 个突变（8 个非同义突变和 7 个同义突变）。每个突变只出现过一次，没有一个是经过验证或候选的抗青蒿素耐药标志物。然而，一些突变出现在经过验证或候选的耐药标志物的相同或后续位置，这表明该基因不稳定，可能导致耐药性。R561L 非同义突变出现在与经过验证的 R561H 突变相同的位置。此外，在非洲广泛存在的 A578S 突变也在本研究中报道。我们发现其他 pfk13 突变的多样性很高，但频率较低。因此，强烈建议常规进行耐药性相关标志物的分子监测，以迅速发现耐药相关突变的出现，并限制其传播。
