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

Robert J. Zupko, Tran Dang Nguyen, J. Claude S. Ngabonziza, Michee Kabera, Haojun Li, Thu Nguyen Anh Tran, Kien Trung Tran, Aline Uwimana, Maciej F. Boni

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2775-2784
Number of pages10
JournalNature Medicine
Volume29
Issue number11
DOIs
StatePublished - Nov 2023

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

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