Proellochs Nicholas I, Andolina Chiara, Ramjith Jordache, Stoter Rianne, van Gemert Geert-Jan, Graumans Wouter, Campino Susana, Vanheer Leen N, Okitwi Martin, Tumwebaze Patrick K, Conrad Melissa D, Clark Taane G, Fidock David A, Menard Didier, Mok Sachel, Bousema Teun
bioRxiv. 2025 Mar 11:2024.12.23.630038. doi: 10.1101/2024.12.23.630038.
The emergence of parasites partially resistant to artemisinins (ART-R) poses a significant threat to recent gains in malaria control. ART-R has been associated with PfKelch13 (K13) mutations, which differ in fitness costs. This study investigates the gametocyte production and transmission fitness of African and Asian isolates with different K13 genotypes across multiple mosquito species. We tested three ART-sensitive (ART-S) isolates (NF54, NF135, NF180) and three ART-R isolates (ARN1G, 3815, PAT-023) for sexual conversion and transmission to and . ART-R levels were quantified using the Ring-stage Survival Assay (RSA), and the transmission-reducing effects of dihydroartemisinin (DHA) on mature gametocytes were assessed. Results showed that ART-S parasite lines consistently produced gametocytes and transmitted effectively in all three mosquito species. ART-R isolates showed variability: ARN1G maintained high transmission levels, whereas 3815 showed limited transmission potential despite higher sporozoite loads in . The African ART-R isolate PAT-023 demonstrated low gametocyte commitment but was transmitted efficiently in both and . DHA exposure reduced mosquito infectivity for all isolates, regardless of K13 genotype. These findings, based on a limited number of field isolates, suggest that ART-R parasites remain transmissible across different species. However, ART-R does not appear to confer a direct transmission advantage. This study highlights the complexity of ART-R dynamics and underscores the need for further research to inform malaria control strategies in regions where ART-R parasites are circulating.
对青蒿素产生部分抗性的寄生虫（ART-R）的出现对疟疾控制方面最近取得的成果构成了重大威胁。ART-R与PfKelch13（K13）突变有关，这些突变在适合度代价方面存在差异。本研究调查了具有不同K13基因型的非洲和亚洲分离株在多种蚊种中的配子体产生和传播适合度。我们测试了三种青蒿素敏感（ART-S）分离株（NF54、NF135、NF180）和三种ART-R分离株（ARN1G、3815、PAT-023）的有性转化以及向按蚊和库蚊的传播情况。使用环期存活试验（RSA）对ART-R水平进行定量，并评估双氢青蒿素（DHA）对成熟配子体的传播减少作用。结果表明，ART-S寄生虫株在所有三种蚊种中均持续产生配子体并能有效传播。ART-R分离株表现出变异性：ARN1G保持高传播水平，而3815尽管在按蚊中孢子体载量较高，但传播潜力有限。非洲ART-R分离株PAT-023配子体形成率低，但在按蚊和库蚊中均能有效传播。DHA处理降低了所有分离株对蚊子的感染性，无论其K13基因型如何。这些基于有限数量现场分离株的研究结果表明，ART-R寄生虫在不同蚊种中仍具有传播能力。然而，ART-R似乎并未赋予直接的传播优势。本研究突出了ART-R动态的复杂性，并强调需要进一步开展研究，为ART-R寄生虫传播地区的疟疾控制策略提供依据。
