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Abstract
Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC–MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.
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1 State University of Amazonas (UEA), Manaus, Amazonas, Brazil/Tropical Medicine Foundation-Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil (GRID:grid.412290.c) (ISNI:0000 0000 8024 0602); Federal University Wukari, Department of Microbiology, Wukari, Nigeria (GRID:grid.412290.c)
2 State University of Amazonas (UEA), Manaus, Amazonas, Brazil/Tropical Medicine Foundation-Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil (GRID:grid.412290.c) (ISNI:0000 0000 8024 0602)
3 State University of Campinas (UNICAMP), Institute of Biology, Laboratory of Tropical Diseases-Prof. Dr. Luiz Jacintho da Silva (LDT-LJS), Department of Genetics, Evolution, Microbiology and Immunology, Campinas, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494)
4 State University of Amazonas (UEA), Manaus, Amazonas, Brazil/Tropical Medicine Foundation-Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil (GRID:grid.412290.c) (ISNI:0000 0000 8024 0602); Federal University of Goiás, Institute of Tropical Pathology and Public Health, Goiânia, Brazil (GRID:grid.411195.9) (ISNI:0000 0001 2192 5801); PPGHUEA/HEMOAM), Postgraduate Program in Sciences Applied to Hematology, Manaus, Brazil (GRID:grid.411195.9)
5 Federal University of Goiás, Chromatography and Mass Spectrometry Laboratory, Institute of Chemistry, Goiânia, Brazil (GRID:grid.411195.9) (ISNI:0000 0001 2192 5801)
6 State University of Amazonas (UEA), Manaus, Amazonas, Brazil/Tropical Medicine Foundation-Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil (GRID:grid.412290.c) (ISNI:0000 0000 8024 0602); State University of Amazonas, Metabolomics and Mass Spectrometry Research Group, Manaus, Brazil (GRID:grid.412290.c) (ISNI:0000 0000 8024 0602)
7 Federal University of Goiás, Institute of Tropical Pathology and Public Health, Goiânia, Brazil (GRID:grid.411195.9) (ISNI:0000 0001 2192 5801)
8 State University of Amazonas (UEA), Manaus, Amazonas, Brazil/Tropical Medicine Foundation-Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil (GRID:grid.412290.c) (ISNI:0000 0000 8024 0602); Leônidas & Maria Deane Institute/Oswaldo Cruz Fundation (ILMD/Fiocruz Amazônia), Manaus, Brazil (GRID:grid.412290.c)
9 Department of Maternal and Child Nursing and Public Health, University of São Paulo, Ribeirão Preto School of Nursing, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722)
10 State University of Amazonas (UEA), Manaus, Amazonas, Brazil/Tropical Medicine Foundation-Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil (GRID:grid.412290.c) (ISNI:0000 0000 8024 0602); PPGHUEA/HEMOAM), Postgraduate Program in Sciences Applied to Hematology, Manaus, Brazil (GRID:grid.412290.c)