Modeling policy interventions for slowing the spread of artemisinin-resistant pfkelch R561H mutations in Rwanda

被引:15
作者
Zupko, Robert J. [1 ]
Nguyen, Tran Dang [1 ]
Ngabonziza, J. Claude S. [2 ,3 ]
Kabera, Michee [4 ]
Li, Haojun [1 ,5 ]
Tran, Thu Nguyen-Anh [1 ]
Tran, Kien Trung [1 ]
Uwimana, Aline [4 ,6 ]
Boni, Maciej F. [1 ,7 ]
机构
[1] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA
[2] Rwanda Biomed Ctr RBC, Res Innovat & Data Sci Div, Kigali, Rwanda
[3] Univ Rwanda, Dept Clin Biol, Kigali, Rwanda
[4] Rwanda Biomed Ctr RBC, Malaria & Other Parasit Dis Div, Kigali, Rwanda
[5] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA
[6] Univ Catholique Louvain UCLouvain, Louvain Drug Res Inst, B-1200 Brussels, Belgium
[7] Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Med, Oxford, England
基金
美国国家卫生研究院;
关键词
PLASMODIUM-FALCIPARUM MALARIA; COMBINATION THERAPIES; EMERGENCE;
D O I
10.1038/s41591-023-02551-w
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2775 / 2784
页数:28
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