Trial reportThe Journal of infectious diseases2009
In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa.
Trial report in The Journal of infectious diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
146 citing papers in PubMed, 3 syntheses or guidelines pooled it, 229 citations in OpenAlex.
- Spatio-temporal trends of the prevalence of Plasmodium falciparum antimalarial drug resistance markers across sub-Saharan Africa from 2010 to 2024: a systematic review and meta-analysis.BMC infectious diseases · 2026Pooled it
- Plasmodium falciparum antimalarial resistance in Angola: a systematic review.Malaria journal · 2026Pooled it
- Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data.Malaria journal · 2011Pooled it
- Trial
- Trial
- Temporal and seasonal changes of genetic polymorphisms associated with altered drug susceptibility to chloroquine, lumefantrine, and quinine in Guinea-Bissau between 2003 and 2012.Antimicrobial agents and chemotherapy · 2015Trial
- Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study.Malaria journal · 2011Trial
- Similar efficacy and tolerability of double-dose chloroquine and artemether-lumefantrine for treatment of Plasmodium falciparum infection in Guinea-Bissau: a randomized trial.The Journal of infectious diseases · 2011Trial
- Article
- Reversal of Chloroquine Resistance inInternational journal of molecular sciences · 2026Article
- Article
- Prevalence of resistance markers of artemisinin, partner drugs, and sulfadoxine-pyrimethamine in Nanyumbu and Masasi Districts, Tanzania between 2020 and 2021.Antimicrobial agents and chemotherapy · 2025Article
- Artemether-Lumefantrine Treatment Selects Plasmodium falciparum Multidrug Resistance 1 (pfmdr1) Increased Copy Number Among African Malaria Infections.The Journal of infectious diseases · 2025Article
- Temporal Patterns of Haplotypic and Allelic Diversity Reflect the Changing Selection Landscape of the Malaria Parasite Plasmodium falciparum.Molecular biology and evolution · 2025Article
- A Narrative Review on the Prevalence ofTropical medicine and infectious disease · 2025Review
- Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.Malaria journal · 2025Review
- Trend of N86Y and Y184F Mutations in Pfmdr1 Gene in Children Under Seasonal Malaria Chemoprevention Coverage in Nanoro, Burkina Faso.Acta parasitologica · 2024Article
- A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants.PLoS pathogens · 2024Article
- Molecular survey of pfmdr-1, pfcrt, and pfk13 gene mutations among patients returning from Plasmodium falciparum endemic areas to Turkey.Malaria journal · 2024Article
- Treatment Failure in a UK Malaria Patient Harboring Genetically Variant Plasmodium falciparum From Uganda With Reduced In Vitro Susceptibility to Artemisinin and Lumefantrine.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundArtemether-lumefantrine (AL) is a major and highly effective artemisinin-based combination therapy that is becoming increasingly important as a new first-line therapy against Plasmodium falciparum malaria. However, recrudescences occurring after AL treatment have been reported. Identification of drug-specific parasite determinants that contribute to treatment failures will provide important tools for the detection and surveillance of AL resistance.
methodsThe findings from a 42-day follow-up efficacy trial in Tanzania that compared AL with sulfadoxine-pyrimethamine (SP) were analyzed to identify candidate markers for lumefantrine tolerance/resistance in the chloroquine resistance transporter gene (pfcrt) and multidrug resistance gene 1 (pfmdr1). The findings were corroborated in vitro with genetically modified isogenic P. falciparum parasite lines.
resultsTreatment with AL selected for the chloroquine-susceptible pfcrt K76 allele (P < .0001) and, to a lesser extent, the pfmdr1 N86 (P = .048) allele among recurrent infections. These genotypes were not selected during SP treatment. No pfmdr1 gene amplifications were observed. Isogenic pfcrt-modified parasite lines demonstrated a 2-fold increase in susceptibility to lumefantrine, which was directly attributable to the K76T mutation.
conclusionsOur findings suggest that the pfcrt K76T mutation is a drug-specific contributor to enhanced P. falciparum susceptibility to lumefantrine in vivo and in vitro, and they highlight the benefit of using AL in areas affected by chloroquine-resistant P. falciparum malaria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.