ArticlePloS one2017
Plasma metabolomics reveals membrane lipids, aspartate/asparagine and nucleotide metabolism pathway differences associated with chloroquine resistance in Plasmodium vivax malaria.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 26 citations in OpenAlex.
- 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
- In vitro cultured malaria hypnozoites leave a footprint of specific metabolites.PLoS pathogens · 2025Article
- Host metabolomic responses in recurrent P. vivax malaria.Scientific reports · 2024Article
- Amyloid beta-correlated plasma metabolite dysregulation in Alzheimer's disease: an untargeted metabolism exploration using high-resolution mass spectrometry toward future clinical diagnosis.Frontiers in aging neuroscience · 2023Article
- Recent metabolomic developments for antimalarial drug discovery.Parasitology research · 2022Review
- Multi-Omics Advancements towardsDiagnostics (Basel, Switzerland) · 2021Review
- Insights into malaria pathogenesis gained from host metabolomics.PLoS pathogens · 2020Article
- Review
- Predicting human health from biofluid-based metabolomics using machine learning.Scientific reports · 2020Article
- From Metabolite to Metabolome: Metabolomics Applications inFrontiers in microbiology · 2020Review
- Untargeted metabolomics reveal dysregulations in sugar, methionine, and tyrosine pathways in the prodromal state of AD.Alzheimer's & dementia (Amsterdam, Netherlands) · 2020Article
- Mining the Human Host Metabolome Toward an Improved Understanding of Malaria Transmission.Frontiers in microbiology · 2020Review
- Arginine and Carnitine Metabolites Are Altered in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2019Article
- Distinct amino acid and lipid perturbations characterize acute versus chronic malaria.JCI insight · 2019Article
- Metabolic perturbations in classic galactosemia beyond the Leloir pathway: Insights from an untargeted metabolomic study.Journal of inherited metabolic disease · 2019Article
- Plasma Eicosanoid Profile inFrontiers in immunology · 2019Article
- Malaria in India: The Need for New Targets for Diagnosis and Detection of Plasmodium vivax.Proteomics. Clinical applications · 2018Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundChloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance.
methodsAn untargeted high-resolution metabolomics analysis was performed on plasma samples collected in a malaria clinic in Manaus, Brazil. Male and female patients with Plasmodium vivax were included (n = 46); samples were collected before CQ treatment and followed for 28 days to determine PvCR, defined as the recurrence of parasitemia with detectable plasma concentrations of CQ ≥100 ng/dL. Differentially expressed metabolic features between CQ-Resistant (CQ-R) and CQ-Sensitive (CQ-S) patients were identified using partial least squares discriminant analysis and linear regression after adjusting for covariates and multiple testing correction. Pathway enrichment analysis was performed using Mummichog.
resultsLinear regression and PLS-DA methods yielded 69 discriminatory features between CQ-R and CQ-S groups, with 10-fold cross-validation classification accuracy of 89.6% using a SVM classifier. Pathway enrichment analysis showed significant enrichment (p<0.05) of glycerophospholipid metabolism, glycosphingolipid metabolism, aspartate and asparagine metabolism, purine and pyrimidine metabolism, and xenobiotics metabolism. Glycerophosphocholines levels were significantly lower in the CQ-R group as compared to CQ-S patients and also to independent control samples.
conclusionsThe results show differences in lipid, amino acids, and nucleotide metabolism pathways in the plasma of CQ-R versus CQ-S patients prior to antimalarial treatment. Metabolomics phenotyping of P. vivax samples from patients with well-defined clinical CQ-resistance is promising for the development of new tools to understand the biological process and to identify potential biomarkers of PvCR.
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