ArticleMalaria journal2018
CYP2D6 activity and the risk of recurrence of Plasmodium vivax malaria in the Brazilian Amazon: a prospective cohort study.
Article in Malaria journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 3 of them syntheses 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
39 citing papers in PubMed, 3 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Automated reporting of primaquine dose efficacy, tolerability and safety for Plasmodium vivax malaria using a systematic review and individual patient data meta-analysis.Malaria journal · 2025Pooled it
- Primaquine for uncomplicated Plasmodium vivax malaria in children younger than 15 years: a systematic review and individual patient data meta-analysis.The Lancet. Child & adolescent health · 2024Pooled it
- Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.Malaria journal · 2023Pooled 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
- Effects of MAO-A and CYP450 on primaquine metabolism in healthy volunteers.Parasitology research · 2019Trial
- Differential impact of Tafenoquine and Primaquine onAntimicrobial agents and chemotherapy · 2026Article
- Reduced cytochrome P-450 (CYP) 2D6 activity and Plasmodium vivax malaria risk in Amazonians: A retrospective, population-based cohort study.PLoS neglected tropical diseases · 2026Article
- Haplo2D6: a web-based tool for automatedBioinformatics advances · 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
- 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
- Perspectives of healthcare professionals on training for quantitative G6PD testing during implementation of tafenoquine in Brazil (QualiTRuST Study).PLoS neglected tropical diseases · 2024Article
- Operational effectiveness of tafenoquine and primaquine for the prevention of Plasmodium vivax recurrence in Brazil: a retrospective observational study.The Lancet. Infectious diseases · 2024Observational
- Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients.Malaria journal · 2022Article
- Prevalence of glucose 6-phosphate dehydrogenase deficiency in highly malaria-endemic municipalities in the Brazilian Amazon: A region-wide screening study.Lancet regional health. Americas · 2022Article
- Measurements of 5,6-Orthoquinone, a Surrogate for the Presumed Active Primaquine Metabolite 5-Hydroxyprimaquine, in the Urine of Cambodian Adults.Antimicrobial agents and chemotherapy · 2022Article
- Global perspectives onFrontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCYP2D6 pathway mediates the activation of primaquine into active metabolite(s) in hepatocytes. CYP2D6 is highly polymorphic, encoding CYP2D6 isoforms with normal, reduced, null or increased activity. It is hypothesized that Plasmodium vivax malaria patients with defective CYP2D6 function would be at increased risk for primaquine failure to prevent recurrence. The aim of this study was to investigate the association of CYP2D6 polymorphisms and inferred CYP2D6 phenotypes with malaria recurrence in patients from the Western Brazilian Amazon, following chloroquine/primaquine combined therapy.
methodsThe prospective cohort consisted of P. vivax malaria patients who were followed for 6 months after completion of the chloroquine/primaquine therapy. Recurrence was defined as one or more malaria episodes, 28-180 days after the initial episode. Genotyping for nine CYP2D6 SNPs and copy number variation was performed using TaqMan assays in a Fast 7500 Real-Time System. CYP2D6 star alleles (haplotypes), diplotypes and CYP2D6 phenotypes were inferred, and the activity score system was used to define the functionality of the CYP2D6 diplotypes. CYP2D6 activity scores (AS) were dichotomized at ≤ 1 (gPM, gIM and gNM-S phenotypes) and ≥ 1.5 (gNM-F and gUM phenotypes).
resultsGenotyping was successfully performed in 190 patients (44 with recurrence and 146 without recurrences). Recurrence incidence was higher in individuals presenting reduced activity CYP2D6 phenotypes (adjusted relative risk = 1.89, 95% CI 1.01-3.70; p = 0.049). Attributable risk and population attributable fraction were 11.5 and 9.9%, respectively. The time elapsed from the first P. vivax malaria episode until the recurrence did not differ between patients with AS of ≤ 1 versus ≥ 1.5 (p = 0.917).
conclusionsThe results suggest that CYP2D6 polymorphisms are associated with increased risk of recurrence of vivax malaria, following chloroquine-primaquine combined therapy. This association is interpreted as the result of reduced conversion of primaquine into its active metabolites in patients with reduced CYP2D6 enzymatic activity.
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