Assessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum.
Assessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum.
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评估恶性疟原虫双抗和三抗基因型的出现风险。
DOI：
10.1038/s41467-024-45547-x
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发表时间：
2024
影响因子：
16.6
通讯作者：
Boni,MaciejF
中科院分区：
文献类型：
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作者：
Li,EricZhewen;Nguyen,TranDang;Tran,ThuNguyen-Anh;Zupko,RobertJ;Boni,MaciejF
推迟和减缓抗疟疾药物耐药性的演变是疟疾流行国家的优先事项。在新疗法出现之前，抗疟疾治疗的主流将继续是以青蒿素为基础的联合疗法(ACT)。通过将不同的ACT部署为一组相等的多重一线疗法(MFT)，而不是轮流使用和停止使用，可以对不同ACT的部署进行优化，以将耐药性的进化压力降至最低。在这里，我们考虑了MFT政策的一个潜在的不利因素，即多个ACT的同时部署可以同时驱动不同抗性等位基因的进化，然后这些抗性等位基因可以通过重组成为双重或三重抗性的寄生虫而聚集在一起。使用基于个体的模型，我们比较了疟疾传播环境中从0.1%到50%流行率范围内的MFT和周期政策。我们通过计算双重耐药和三重耐药基因的基因频率曲线(AUC)下的面积来定义多药耐药(MDR)的总风险度量。当流行率≥为1%时，无论耐药性是输入的还是从头产生的，在多药耐药政策下的总体耐多药风险都比在周期政策下低80%。在患病率为0.1%的情况下，MFT和骑自行车之间的MDR风险几乎没有统计学差异。
Delaying and slowing antimalarial drug resistance evolution is a priority for malaria-endemic countries. Until novel therapies become available, the mainstay of antimalarial treatment will continue to be artemisinin-based combination therapy (ACT). Deployment of different ACTs can be optimized to minimize evolutionary pressure for drug resistance by deploying them as a set of co-equal multiple first-line therapies (MFT) rather than rotating therapies in and out of use. Here, we consider one potential detriment of MFT policies, namely, that the simultaneous deployment of multiple ACTs could drive the evolution of different resistance alleles concurrently and that these resistance alleles could then be brought together by recombination into double-resistant or triple-resistant parasites. Using an individual-based model, we compare MFT and cycling policies in malaria transmission settings ranging from 0.1% to 50% prevalence. We define a total risk measure for multi-drug resistance (MDR) by summing the area under the genotype-frequency curves (AUC) of double- and triple-resistant genotypes. When prevalence ≥ 1%, total MDR risk ranges from statistically similar to 80% lower under MFT policies than under cycling policies, irrespective of whether resistance is imported or emerges de novo. At 0.1% prevalence, there is little statistical difference in MDR risk between MFT and cycling.