ArticlePloS one2016
Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses.
Article in PloS one, 2016. 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 44 papers, 1 of them a synthesis that pooled it.
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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
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Assessment of copy number variation in genes related to drug resistance in Plasmodium vivax and Plasmodium falciparum isolates from the Brazilian Amazon and a systematic review of the literature.Malaria journal · 2017Pooled it
- Pharmacokinetics/pharmacodynamics of chloroquine and artemisinin-based combination therapy with primaquine.Malaria journal · 2019Trial
- Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil.Antimicrobial agents and chemotherapy · 2019Trial
- Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.The New England journal of medicine · 2019Trial
- Differential impact of Tafenoquine and Primaquine onAntimicrobial agents and chemotherapy · 2026Article
- The Landscape of Malaria in a Five-Decade Institution in the State of Amazonas: Historical Trends, Scientific Contributions, and Research Priorities.Revista da Sociedade Brasileira de Medicina Tropical · 2026Review
- How CYP2D6 Polymorphism Modulates the Community-Wide Risk of Plasmodium vivax Infection: A Panel Study in Amazonian Brazil.The Journal of infectious diseases · 2025Article
- Enhancing CYP2D6 genotyping with nanopore sequencing to address allele diversity P. vivax malaria elimination.Scientific reports · 2025Article
- Efficacy of Primaquine for the Radical Cure of Plasmodium vivax Malaria in Northeast Myanmar and the Impact of Cytochrome P450 2D6 Genotypes.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon.Scientific reports · 2025Article
- Review
- Monoamine oxidase-A (MAO-A) low-expression variants and increased risk of Plasmodium vivax malaria relapses.The Journal of antimicrobial chemotherapy · 2024Article
- A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver.Antimicrobial agents and chemotherapy · 2024Article
- Pharmacogenomic variation in the Malagasy population: implications for the antimalarial drug primaquine metabolism.Pharmacogenomics · 2023Article
- Using Graph-Based Signatures to Guide Rational Antibody Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Individual variation in Plasmodium vivax malaria risk: Are repeatedly infected people just unlucky?PLoS neglected tropical diseases · 2023Review
- Systematic evaluation of computational tools to predict the effects of mutations on protein stability in the absence of experimental structures.Briefings in bioinformatics · 2022Article
- Global perspectives onFrontiers in pharmacology · 2022Review
- Prediction of the CYP2D6 enzymatic activity based on investigating of the CYP2D6 genotypes around the vivax malaria patients in Yunnan Province, China.Malaria journal · 2021Article
- Increased primaquine total dose prevents Plasmodium vivax relapses in patients with impaired CYP2D6 activity: report of three cases.Malaria journal · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although Plasmodium vivax relapses are classically associated with hypnozoite activation, it has been proposed that a proportion of these cases are due to primaquine (PQ) treatment failure caused by polymorphisms in cytochrome P-450 2D6 (CYP2D6). Here, we present evidence that CYP2D6 polymorphisms are implicated in PQ failure, which was reinforced by findings in genetically similar parasites, and may explain a number of vivax relapses. Using a computational approach, these polymorphisms were predicted to affect the activity of CYP2D6 through changes in the structural stability that could lead to disruption of the PQ-enzyme interactions. Furthermore, because PQ is co-administered with chloroquine (CQ), we investigated whether CQ-impaired metabolism by cytochrome P-450 2C8 (CYP2C8) could also contribute to vivax recurrences. Our results show that CYP2C8-mutated patients frequently relapsed early (<42 days) and had a higher proportion of genetically similar parasites, suggesting the possibility of recrudescence due to CQ therapeutic failure. These results highlight the importance of pharmacogenetic studies as a tool to monitor the efficacy of antimalarial therapy.
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