Artemisinin combination therapies (ACTs) are highly effective at treating uncomplicated Plasmodium falciparum malaria, but the emergence of the new pfkelch13 R561H mutation in Rwanda, associated with delayed parasite clearance, suggests that interventions are needed to slow its spread. Using a Rwanda-specific spatial calibration of an individual-based malaria model, we evaluate 26 strategies aimed at minimizing treatment failures and delaying the spread of R561H after 3, 5 and 10 years. Lengthening ACT courses and deploying multiple first-line therapies (MFTs) reduced treatment failures after 5 years when compared to the current approach of a 3-d course of artemether–lumefantrine. The best among these options (an MFT policy) resulted in median treatment failure counts that were 49% lower and a median R561H allele frequency that was 0.15 lower than under baseline. New approaches to resistance management, such as triple ACTs or sequential courses of two different ACTs, were projected to have a larger impact than longer ACT courses or MFT; these were associated with median treatment failure counts in 5 years that were 81–92% lower than the current approach. A policy response to currently circulating artemisinin-resistant genotypes in Africa is urgently needed to prevent a population-wide rise in treatment failures.

青蒿素联合疗法 (ACT) 对于治疗简单的恶性疟原虫疟疾非常有效，但卢旺达出现的新pfkelch13 R561H 突变与寄生虫清除延迟相关，表明需要采取干预措施来减缓其传播。使用基于个体的疟疾模型的卢旺达特定空间校准，我们评估了 26 种策略，旨在最大限度地减少治疗失败并在 3 年、5 年和 10 年后延迟 R561H 的传播。与目前的蒿甲醚-苯芴醇 3 天疗程相比，延长 ACT 疗程和部署多种一线疗法 (MFT) 减少了 5 年后的治疗失败。这些选项中最好的（MFT 政策）导致中位治疗失败计数比基线低 49%，中位 R561H 等位基因频率比基线低 0.15。新的阻力管理方法，例如三重 ACT 或两种不同 ACT 的连续课程，预计将比较长的 ACT 课程或 MFT 产生更大的影响；这些与 5 年内治疗失败中位数相关，比当前方法低 81-92%。迫切需要对非洲目前流行的青蒿素耐药基因型采取政策应对措施，以防止整个人群治疗失败率上升。