ArticleThe Lancet. Microbe2022
Pre-existing partner-drug resistance to artemisinin combination therapies facilitates the emergence and spread of artemisinin resistance: a consensus modelling study.
Article in The Lancet. Microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- A systematic review of epidemiological models for malaria transmission in Sub-Saharan Africa.Malaria journal · 2026Pooled it
- Structure-Activity Relationship Study of Antimalarial Asparagine-Derived Proteasome Inhibitors.ACS omega · 2026Article
- Discovery of Potent Antimalarial Agents Targeting Plasmodium falciparum DNA Gyrase B by Integrating Computational and Experimental Approaches.Chemical biology & drug design · 2026Article
- Slowing the spread of treatment failure to artemisinin-based combination therapies in Uganda.Nature communications · 2026Article
- Indigenous knowledge and plant species used as mosquito repellents in the West Nile Subregion, Uganda.Tropical medicine and health · 2025Article
- A Review on Phytochemistry, Ethnopharmacology, and Antiparasitic Potential ofPharmaceuticals (Basel, Switzerland) · 2025Review
- Global risk of selection and spread of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions.Nature medicine · 2025Article
- Effects of recombination on multi-drug resistance evolution in Plasmodium falciparum malaria.PLoS computational biology · 2025Article
- Artemether-Lumefantrine Treatment Selects Plasmodium falciparum Multidrug Resistance 1 (pfmdr1) Increased Copy Number Among African Malaria Infections.The Journal of infectious diseases · 2025Article
- Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment.Malaria journal · 2025Article
- Selection of Plasmodium falciparum kelch13 mutations in Uganda in comparison with southeast Asia: a modelling study.The Lancet. Microbe · 2025Article
- Recurrent Plasmodium falciparum Malaria in U.S. Travelers Treated with Artemether-Lumefantrine.The American journal of tropical medicine and hygiene · 2025Article
- Bridging the Gap from Molecular Surveillance to Programmatic Decisions for Malaria Control and Elimination.The American journal of tropical medicine and hygiene · 2025Review
- Risk of selection and timelines for the continued spread of artemisinin and partner drug resistance in Africa.medRxiv : the preprint server for health sciences · 2024Article
- Combating antimicrobial resistance in malaria, HIV and tuberculosis.Nature reviews. Drug discovery · 2024Review
- Evaluation of Segmentation, Rotation, and Geographic Delivery Approaches for Deployment of Multiple First-Line Treatment (MFT) to Respond to Antimalarial Drug Resistance in Africa: A Qualitative Study in Seven Sub-Sahara Countries.Tropical medicine and infectious disease · 2024Article
- Role of seasonal importation and genetic drift on selection for drug-resistant genotypes ofJournal of the Royal Society, Interface · 2024Article
- Article
- Assessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum.Nature communications · 2024Article
- Antigenic strain diversity predicts different biogeographic patterns of maintenance and decline of anti-malarial drug resistance.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundArtemisinin-resistant genotypes of Plasmodium falciparum have now emerged a minimum of six times on three continents despite recommendations that all artemisinins be deployed as artemisinin combination therapies (ACTs). Widespread resistance to the non-artemisinin partner drugs in ACTs has the potential to limit the clinical and resistance benefits provided by combination therapy. We aimed to model and evaluate the long-term effects of high levels of partner-drug resistance on the early emergence of artemisinin-resistant genotypes.
methodsUsing a consensus modelling approach, we used three individual-based mathematical models of Plasmodium falciparum transmission to evaluate the effects of pre-existing partner-drug resistance and ACT deployment on the evolution of artemisinin resistance. Each model simulates 100 000 individuals in a particular transmission setting (malaria prevalence of 1%, 5%, 10%, or 20%) with a daily time step that updates individuals' infection status, treatment status, immunity, genotype-specific parasite densities, and clinical state. We modelled varying access to antimalarial drugs if febrile (coverage of 20%, 40%, or 60%) with one primary ACT used as first-line therapy: dihydroartemisinin-piperaquine (DHA-PPQ), artesunate-amodiaquine (ASAQ), or artemether-lumefantrine (AL). The primary outcome was time until 0·25 580Y allele frequency for artemisinin resistance (the establishment time).
findingsHigher frequencies of pre-existing partner-drug resistant genotypes lead to earlier establishment of artemisinin resistance. Across all models, a 10-fold increase in the frequency of partner-drug resistance genotypes on average corresponded to loss of artemisinin efficacy 2-12 years earlier. Most reductions in time to artemisinin resistance establishment were observed after an increase in frequency of the partner-drug resistance genotype from 0·0 to 0·10.
interpretationPartner-drug resistance in ACTs facilitates the early emergence of artemisinin resistance and is a major public health concern. Higher-grade partner-drug resistance has the largest effect, with piperaquine resistance accelerating the early emergence of artemisinin-resistant alleles the most. Continued investment in molecular surveillance of partner-drug resistant genotypes to guide choice of first-line ACT is paramount.
fundingSchmidt Science Fellowship in partnership with the Rhodes Trust; Bill & Melinda Gates Foundation; Wellcome Trust.
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