ArticleProceedings of the National Academy of Sciences of the United States of America2015
Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in pfcrt.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
99 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- The Global Landscape ofPathogens (Basel, Switzerland) · 2026Pooled it
- Risk of drug resistance in Plasmodium falciparum malaria therapy-a systematic review and meta-analysis.Parasitology research · 2017Pooled it
- Intermittent Preventive Treatment with Dihydroartemisinin-Piperaquine in Ugandan Schoolchildren Selects for Plasmodium falciparum Transporter Polymorphisms That Modify Drug Sensitivity.Antimicrobial agents and chemotherapy · 2016Trial
- Molecular surveillance of antimalarial drug resistance markers in the pfcrt, pfmdr1 and pfmrp1 genes of Plasmodium falciparum isolates from southeastern Iran.Malaria journal · 2026Article
- Genetic diversity and evolutionary perspectives of Pfcrt in Plasmodium falciparum: insights from Indian and global isolates.Malaria journal · 2026Article
- Major features of parasite adaptation revealed by genomes of Plasmodium falciparum population samples archived for over 50 years.Communications biology · 2026Article
- Genomics in Epidemiology and Disease Surveillance: An Exploratory Analysis.Life (Basel, Switzerland) · 2025Review
- Tracking Plasmodium falciparum antimalarial resistance markers during a malaria pre-elimination period in the Pacific coast of South America.Scientific reports · 2025Article
- Tracking Drug Resistance inInternational journal of molecular sciences · 2025Article
- Emerging Plasmodium falciparum K13 gene mutation to artemisinin-based combination therapies and partner drugs among malaria-infected population in sub-Saharan Africa.Parasites, hosts and diseases · 2025Review
- Deletion of theAntimicrobial agents and chemotherapy · 2025Article
- Temporal Patterns of Haplotypic and Allelic Diversity Reflect the Changing Selection Landscape of the Malaria Parasite Plasmodium falciparum.Molecular biology and evolution · 2025Article
- Sensitive and modular amplicon sequencing of Plasmodium falciparum diversity and resistance for research and public health.Scientific reports · 2025Article
- Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023.The Journal of antimicrobial chemotherapy · 2025Article
- Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.Malaria journal · 2025Review
- Sensitive and modular amplicon sequencing ofbioRxiv : the preprint server for biology · 2025Article
- Systematic in vitro evolution inScience (New York, N.Y.) · 2024Article
- Dihydroartemisinin-Piperaquine Combination in the Treatment of UncomplicatedJournal of clinical medicine · 2024Review
- Article
- A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants.PLoS pathogens · 2024Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
In regions with high malaria endemicity, the withdrawal of chloroquine (CQ) as first-line treatment of Plasmodium falciparum infections has typically led to the restoration of CQ susceptibility through the reexpansion of the wild-type (WT) allele K76 of the chloroquine resistance transporter gene (pfcrt) at the expense of less fit mutant alleles carrying the CQ resistance (CQR) marker K76T. In low-transmission settings, such as South America, drug resistance mutations can attain 100% prevalence, thereby precluding the return of WT parasites after the complete removal of drug pressure. In French Guiana, despite the fixation of the K76T allele, the prevalence of CQR isolates progressively dropped from >90% to <30% during 17 y after CQ withdrawal in 1995. Using a genome-wide association study with CQ-sensitive (CQS) and CQR isolates, we have identified a single mutation in pfcrt encoding a C350R substitution that is associated with the restoration of CQ susceptibility. Genome editing of the CQR reference strain 7G8 to incorporate PfCRT C350R caused a complete loss of CQR. A retrospective molecular survey on 580 isolates collected from 1997 to 2012 identified all C350R mutant parasites as being CQS. This mutation emerged in 2002 and rapidly spread throughout the P. falciparum population. The C350R allele is also associated with a significant decrease in piperaquine susceptibility in vitro, suggesting that piperaquine pressure in addition to potential fitness costs associated with the 7G8-type CQR pfcrt allele may have selected for this mutation. These findings have important implications for understanding the evolutionary dynamics of antimalarial drug resistance.
Indexed as
Identifiers
What OpenQuestion holds
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.