{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:37:17Z","timestamp":1784590637931,"version":"3.55.0"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malaria is the leading parasitic disease worldwide, with <jats:italic>P. vivax<\/jats:italic> 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 <jats:italic>P. vivax<\/jats:italic> malaria in the Brazilian Amazon. Metabolites extracted from the plasma of <jats:italic>P. vivax<\/jats:italic>-infected patients were subjected to LC\u2013MS 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 \u03b2-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 <jats:italic>P. vivax<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/s41598-024-54231-5","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T11:10:03Z","timestamp":1711537803000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Host metabolomic responses in recurrent P. vivax malaria"],"prefix":"10.1038","volume":"14","author":[{"given":"Michael N.","family":"Yakubu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor I.","family":"Mwangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca L. A.","family":"Netto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria G. C.","family":"Alecrim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R. S.","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C. G.","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel F.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesiane S.","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas S.","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector H. F.","family":"Koolen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago P.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea R.","family":"Chaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boniek G.","family":"Vaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuelton M.","family":"Monteiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio T. M.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus V. G.","family":"Lacerda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz G.","family":"Gardinassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisely C.","family":"de Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"54231_CR1","unstructured":"WHO. World Mal\u00e1ria Report, 2022. (2022)."},{"key":"54231_CR2","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1093\/infdis\/jiy484","volume":"219","author":"J Popovici","year":"2019","unstructured":"Popovici, J. et al. Recrudescence, reinfection, or relapse? A more rigorous framework to assess chloroquine efficacy for Plasmodium vivax malaria. J. Infect. Dis. 219, 315\u2013322 (2019).","journal-title":"J. Infect. Dis."},{"key":"54231_CR3","unstructured":"SIVEP-Malaria e SINAN. O Sistema de Informa\u00e7\u00e3o da Vigil\u00e2ncia Epidemiol\u00f3gica da Malaria (SIVEP) e Sistema de Informa\u00e7\u00e3o de Agravos de Notifica\u00e7\u00e3o (SINAN), Brazil, 2022. (2022)."},{"key":"54231_CR4","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3389\/fcimb.2018.00034","volume":"8","author":"C Bourgard","year":"2018","unstructured":"Bourgard, C., Albrecht, L., Kayano, A. C. A. V., Sunnerhagen, P. & Costa, F. T. M. Plasmodium vivax biology: Insights provided by genomics, transcriptomics and proteomics. Front. Cell. Infect. Microbiol. 8, 34 (2018).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"54231_CR5","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.ijmm.2017.09.002","volume":"307","author":"LG Gardinassi","year":"2017","unstructured":"Gardinassi, L. G. et al. Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria. Int. J. Med. Microbiol. 307, 533\u2013541 (2017).","journal-title":"Int. J. Med. Microbiol."},{"key":"54231_CR6","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1093\/infdis\/jiv142","volume":"212","author":"JT Lin","year":"2015","unstructured":"Lin, J. T. et al. Using amplicon deep sequencing to detect genetic signatures of Plasmodium vivax relapse. J. Infect. Dis. 212, 999\u20131008 (2015).","journal-title":"J. Infect. Dis."},{"key":"54231_CR7","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.pt.2009.12.005","volume":"26","author":"TNC Wells","year":"2010","unstructured":"Wells, T. N. C., Burrows, J. N. & Baird, J. K. Targeting the hypnozoite reservoir of Plasmodium vivax: The hidden obstacle to malaria elimination. Trends Parasitol. 26, 145\u2013151 (2010).","journal-title":"Trends Parasitol."},{"key":"54231_CR8","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/S1473-3099(09)70177-X","volume":"9","author":"I Mueller","year":"2009","unstructured":"Mueller, I. et al. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect. Dis. 9, 555\u2013566 (2009).","journal-title":"Lancet Infect. Dis."},{"key":"54231_CR9","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/1475-2875-13-144","volume":"13","author":"KE Battle","year":"2014","unstructured":"Battle, K. E. et al. Geographical variation in Plasmodium vivax relapse. Malar. J. 13, 144 (2014).","journal-title":"Malar. J."},{"key":"54231_CR10","doi-asserted-by":"publisher","first-page":"4610","DOI":"10.1128\/AAC.00186-16","volume":"60","author":"L Zuluaga-Id\u00e1rraga","year":"2016","unstructured":"Zuluaga-Id\u00e1rraga, L. et al. Prospective study of Plasmodium vivax malaria recurrence after radical treatment with a chloroquine-primaquine standard regimen in Turbo, Colombia. Antimicrob. Agents Chemother. 60, 4610\u20134619 (2016).","journal-title":"Antimicrob. Agents Chemother."},{"key":"54231_CR11","doi-asserted-by":"publisher","first-page":"e105922","DOI":"10.1371\/journal.pone.0105922","volume":"9","author":"GC Melo","year":"2014","unstructured":"Melo, G. C. et al. Expression levels of pvcrt-o and pvmdr-1 are associated with chloroquine resistance and severe Plasmodium vivax malaria in patients of the Brazilian Amazon. PLoS ONE 9, e105922 (2014).","journal-title":"PLoS ONE"},{"key":"54231_CR12","doi-asserted-by":"publisher","first-page":"e0182819","DOI":"10.1371\/journal.pone.0182819","volume":"12","author":"K Uppal","year":"2017","unstructured":"Uppal, K. et al. Plasma metabolomics reveals membrane lipids, aspartate\/asparagine and nucleotide metabolism pathway differences associated with chloroquine resistance in Plasmodium vivax malaria. PLoS ONE 12, e0182819 (2017).","journal-title":"PLoS ONE"},{"key":"54231_CR13","unstructured":"WHO. World malaria report 2009. (2009)."},{"key":"54231_CR14","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3390\/tropicalmed7100263","volume":"7","author":"H Tasman","year":"2022","unstructured":"Tasman, H. et al. Assessing the impact of relapse, reinfection and recrudescence on malaria eradication policy: A bifurcation and optimal control analysis. Trop. Med. Infect. Dis. 7, 263 (2022).","journal-title":"Trop. Med. Infect. Dis."},{"key":"54231_CR15","doi-asserted-by":"publisher","first-page":"e0003595","DOI":"10.1371\/journal.pntd.0003595","volume":"9","author":"AI Adekunle","year":"2015","unstructured":"Adekunle, A. I. et al. Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation in vivo. PLoS Negl. Trop. Dis. 9, e0003595 (2015).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"54231_CR16","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1038\/nbt1207-1383","volume":"25","author":"S-L Tan","year":"2007","unstructured":"Tan, S.-L., Ganji, G., Paeper, B., Proll, S. & Katze, M. G. Systems biology and the host response to viral infection. Nat. Biotechnol. 25, 1383\u20131389 (2007).","journal-title":"Nat. Biotechnol."},{"key":"54231_CR17","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40543-015-0047-4","volume":"6","author":"Y Lee","year":"2015","unstructured":"Lee, Y. et al. Systems biology from virus to humans. J. Anal. Sci. Technol. 6, 3 (2015).","journal-title":"J. Anal. Sci. Technol."},{"key":"54231_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4028\/www.scientific.net\/AMR.995.1","volume":"995","author":"M Rahman","year":"2014","unstructured":"Rahman, M. & Hasan, M. R. Pentose phosphate pathway in disease and therapy. Adv. Mater. Res. 995, 1\u201327 (2014).","journal-title":"Adv. Mater. Res."},{"key":"54231_CR19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1159\/000345607","volume":"16","author":"NW Lucchi","year":"2013","unstructured":"Lucchi, N. W., Oberstaller, J., Kissinger, J. C. & Udhayakumar, V. Malaria diagnostics and surveillance in the post-genomic era. Public Health Genom. 16, 37\u201343 (2013).","journal-title":"Public Health Genom."},{"key":"54231_CR20","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.1038\/s41598-018-37816-9","volume":"9","author":"D Beri","year":"2019","unstructured":"Beri, D. et al. Insights into physiological roles of unique metabolites released from Plasmodium-infected RBCs and their potential as clinical biomarkers for malaria. Sci. Rep. 9, 2875 (2019).","journal-title":"Sci. Rep."},{"key":"54231_CR21","doi-asserted-by":"publisher","first-page":"105570","DOI":"10.1016\/j.phrs.2021.105570","volume":"167","author":"M Zhou","year":"2021","unstructured":"Zhou, M., Varol, A. & Efferth, T. Multi-omics approaches to improve malaria therapy. Pharmacol. Res. 167, 105570 (2021).","journal-title":"Pharmacol. Res."},{"key":"54231_CR22","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1186\/1475-2875-10-384","volume":"10","author":"A Sengupta","year":"2011","unstructured":"Sengupta, A. et al. Global host metabolic response to Plasmodium vivax infection: A 1H NMR based urinary metabonomic study. Malar. J. 10, 384 (2011).","journal-title":"Malar. J."},{"key":"54231_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(99)00208-X","author":"M Kimura","year":"1999","unstructured":"Kimura, M. & Yamaguchi, S. Screening for fatty acid beta oxidation disorders Acylglycine analysis by electron impact ionization gas chromatography\u2013mass spectrometry. J. Chromatogr. B https:\/\/doi.org\/10.1016\/S0378-4347(99)00208-X (1999).","journal-title":"J. Chromatogr. B"},{"key":"54231_CR24","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.brainres.2012.08.039","volume":"1478","author":"LA Knebel","year":"2012","unstructured":"Knebel, L. A. et al. Methylbutyrylglycine induces lipid oxidative damage and decreases the antioxidant defenses in rat brain. Brain Res. 1478, 74\u201382 (2012).","journal-title":"Brain Res."},{"key":"54231_CR25","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/0014-5793(88)80765-8","volume":"232","author":"GN Moll","year":"1988","unstructured":"Moll, G. N. et al. Phospholipid uptake by Plasmodium knowlesi infected erythrocytes. FEBS Lett. 232, 341\u2013346 (1988).","journal-title":"FEBS Lett."},{"key":"54231_CR26","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.molbiopara.2003.07.003","volume":"132","author":"G Krishnegowda","year":"2003","unstructured":"Krishnegowda, G. & Gowda, D. C. Intraerythrocytic Plasmodium falciparum incorporates extraneous fatty acids to its lipids without any structural modification. Mol. Biochem. Parasitol. 132, 55\u201358 (2003).","journal-title":"Mol. Biochem. Parasitol."},{"key":"54231_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/108516","volume":"2014","author":"T Kronenberger","year":"2014","unstructured":"Kronenberger, T. et al. Vitamin B6-dependent enzymes in the human malaria parasite Plasmodium falciparum: A druggable target?. BioMed Res. Int. 2014, 1\u201311 (2014).","journal-title":"BioMed Res. Int."},{"key":"54231_CR28","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.redox.2018.04.011","volume":"17","author":"LG Gardinassi","year":"2018","unstructured":"Gardinassi, L. G. et al. Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling. Redox Biol. 17, 158\u2013170 (2018).","journal-title":"Redox Biol."},{"key":"54231_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/852645","volume":"2014","author":"P Jain","year":"2014","unstructured":"Jain, P., Chakma, B., Patra, S. & Goswami, P. Potential biomarkers and their applications for rapid and reliable detection of malaria. BioMed Res. Int. 2014, 1\u201320 (2014).","journal-title":"BioMed Res. Int."},{"key":"54231_CR30","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1186\/s12967-018-1646-9","volume":"16","author":"H Kaur","year":"2018","unstructured":"Kaur, H. et al. Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria. J Transl Med 16, 272 (2018).","journal-title":"J Transl Med"},{"key":"54231_CR31","doi-asserted-by":"publisher","first-page":"7922","DOI":"10.1038\/s41598-021-86870-3","volume":"11","author":"A Cheda","year":"2021","unstructured":"Cheda, A. et al. A derivative of vitamin B3 applied several days after exposure reduces lethality of severely irradiated mice. Sci. Rep. 11, 7922 (2021).","journal-title":"Sci. Rep."},{"key":"54231_CR32","doi-asserted-by":"publisher","first-page":"626183","DOI":"10.3389\/fmicb.2020.626183","volume":"11","author":"X Yu","year":"2021","unstructured":"Yu, X., Feng, G., Zhang, Q. & Cao, J. From metabolite to metabolome: Metabolomics applications in plasmodium research. Front. Microbiol. 11, 626183 (2021).","journal-title":"Front. Microbiol."},{"key":"54231_CR33","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1590\/0074-0276140043","volume":"109","author":"JL Salinas","year":"2014","unstructured":"Salinas, J. L., Kissinger, J. C., Jones, D. P. & Galinski, M. R. Metabolomics in the fight against malaria. Mem. Inst. Oswaldo Cruz 109, 589\u2013597 (2014).","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"54231_CR34","doi-asserted-by":"publisher","first-page":"e0175686","DOI":"10.1371\/journal.pone.0175686","volume":"12","author":"S Gupta","year":"2017","unstructured":"Gupta, S. et al. Extensive alterations of blood metabolites in pediatric cerebral malaria. PLoS ONE 12, e0175686 (2017).","journal-title":"PLoS ONE"},{"key":"54231_CR35","doi-asserted-by":"publisher","first-page":"768182","DOI":"10.3389\/fcimb.2021.768182","volume":"11","author":"M Vasquez","year":"2021","unstructured":"Vasquez, M., Zuniga, M. & Rodriguez, A. Oxidative stress and pathogenesis in malaria. Front. Cell. Infect. Microbiol. 11, 768182 (2021).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"54231_CR36","doi-asserted-by":"publisher","first-page":"e94061","DOI":"10.1371\/journal.pone.0094061","volume":"9","author":"JK O\u2019Hara","year":"2014","unstructured":"O\u2019Hara, J. K. et al. Targeting NAD+ metabolism in the human malaria parasite plasmodium falciparum. PLoS ONE 9, e94061 (2014).","journal-title":"PLoS ONE"},{"key":"54231_CR37","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.3390\/metabo12121224","volume":"12","author":"ME Betouke Ongwe","year":"2022","unstructured":"Betouke Ongwe, M. E. et al. Urinary metabolic profiling in volunteers undergoing malaria challenge in gabon. Metabolites 12, 1224 (2022).","journal-title":"Metabolites"},{"key":"54231_CR38","doi-asserted-by":"publisher","first-page":"6602","DOI":"10.1038\/s41598-019-43044-6","volume":"9","author":"SJ Leopold","year":"2019","unstructured":"Leopold, S. J. et al. Amino acid derangements in adults with severe falciparum malaria. Sci. Rep. 9, 6602 (2019).","journal-title":"Sci. Rep."},{"key":"54231_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2011\/901854","volume":"2011","author":"A Sengupta","year":"2011","unstructured":"Sengupta, A., Basant, A., Ghosh, S., Sharma, S. & Sonawat, H. M. Liver metabolic alterations and changes in host intercompartmental metabolic correlation during progression of malaria. J. Parasitol. Res. 2011, 1\u201314 (2011).","journal-title":"J. Parasitol. Res."},{"key":"54231_CR40","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12936-020-03174-z","volume":"19","author":"SG Tewari","year":"2020","unstructured":"Tewari, S. G., Swift, R. P., Reifman, J., Prigge, S. T. & Wallqvist, A. Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite. Malar. J. 19, 94 (2020).","journal-title":"Malar. J."},{"key":"54231_CR41","doi-asserted-by":"publisher","first-page":"e1008930","DOI":"10.1371\/journal.ppat.1008930","volume":"16","author":"HN Colvin","year":"2020","unstructured":"Colvin, H. N. & Joice Cordy, R. Insights into malaria pathogenesis gained from host metabolomics. PLoS Pathog. 16, e1008930 (2020).","journal-title":"PLoS Pathog."},{"key":"54231_CR42","doi-asserted-by":"publisher","first-page":"e125156","DOI":"10.1172\/jci.insight.125156","volume":"4","author":"RJ Cordy","year":"2019","unstructured":"Cordy, R. J. et al. Distinct amino acid and lipid perturbations characterize acute versus chronic malaria. JCI Insight 4, e125156 (2019).","journal-title":"JCI Insight"},{"key":"54231_CR43","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1021\/ar2002182","volume":"45","author":"MM Greenberg","year":"2012","unstructured":"Greenberg, M. M. The formamidopyrimidines: Purine lesions formed in competition with 8-oxopurines from oxidative stress. Acc. Chem. Res. 45, 588\u2013597 (2012).","journal-title":"Acc. Chem. Res."},{"key":"54231_CR44","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1098\/rsif.2008.0304.focus","volume":"5","author":"S Jiranusornkul","year":"2008","unstructured":"Jiranusornkul, S. & Laughton, C. A. Destabilization of DNA duplexes by oxidative damage at guanine: Implications for lesion recognition and repair. J. R. Soc. Interface 5, 191\u2013198 (2008).","journal-title":"J. R. Soc. Interface"},{"key":"54231_CR45","doi-asserted-by":"publisher","first-page":"16346","DOI":"10.3390\/ijms131216346","volume":"13","author":"S Perc\u00e1rio","year":"2012","unstructured":"Perc\u00e1rio, S. et al. Oxidative stress in malaria. Int. J. Mol. Sci. 13, 16346\u201316372 (2012).","journal-title":"Int. J. Mol. Sci."},{"key":"54231_CR46","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.imlet.2017.08.016","volume":"192","author":"DC Thomas","year":"2017","unstructured":"Thomas, D. C. The phagocyte respiratory burst: Historical perspectives and recent advances. Immunol. Lett. 192, 88\u201396 (2017).","journal-title":"Immunol. Lett."},{"key":"54231_CR47","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.cotox.2017.11.002","volume":"7","author":"K Lingappan","year":"2018","unstructured":"Lingappan, K. NF-\u03baB in oxidative stress. Curr. Opin. Toxicol. 7, 81\u201386 (2018).","journal-title":"Curr. Opin. Toxicol."},{"key":"54231_CR48","doi-asserted-by":"publisher","first-page":"e02392","DOI":"10.1128\/AAC.02392-20","volume":"65","author":"SG Tewari","year":"2021","unstructured":"Tewari, S. G. et al. Metabolic survival adaptations of plasmodium falciparum exposed to sublethal doses of fosmidomycin. Antimicrob. Agents Chemother. 65, e02392-e2420 (2021).","journal-title":"Antimicrob. Agents Chemother."},{"key":"54231_CR49","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1016\/j.cell.2017.10.020","volume":"171","author":"NMB Brancucci","year":"2017","unstructured":"Brancucci, N. M. B. et al. Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum. Cell 171, 1532-1544.e15 (2017).","journal-title":"Cell"},{"key":"54231_CR50","doi-asserted-by":"publisher","first-page":"e82207","DOI":"10.7554\/eLife.82207","volume":"11","author":"A Ramaprasad","year":"2022","unstructured":"Ramaprasad, A. et al. A choline-releasing glycerophosphodiesterase essential for phosphatidylcholine biosynthesis and blood stage development in the malaria parasite. eLife 11, e82207 (2022).","journal-title":"eLife"},{"key":"54231_CR51","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1186\/1475-2875-11-337","volume":"11","author":"MA Ambele","year":"2012","unstructured":"Ambele, M. A. & Egan, T. J. Neutral lipids associated with haemozoin mediate efficient and rapid \u03b2-haematin formation at physiological pH, temperature and ionic composition. Malar. J. 11, 337 (2012).","journal-title":"Malar. J."},{"key":"54231_CR52","doi-asserted-by":"publisher","first-page":"13","DOI":"10.25011\/cim.v32i1.5082","volume":"32","author":"Y Cao","year":"2009","unstructured":"Cao, Y. et al. Comparison of pharmacokinetics of L-carnitine, Acetyl-L-carnitine and Propionyl-Lcarnitine after single oral administration of L-carnitine in healthy volunteers. Clin. Investig. Med. 32, 13 (2009).","journal-title":"Clin. Investig. Med."},{"key":"54231_CR53","doi-asserted-by":"publisher","first-page":"13075","DOI":"10.1073\/pnas.1516544112","volume":"112","author":"EB Gordon","year":"2015","unstructured":"Gordon, E. B. et al. Targeting glutamine metabolism rescues mice from late-stage cerebral malaria. Proc. Natl. Acad. Sci. U. S. A. 112, 13075\u201313080 (2015).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"54231_CR54","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1186\/s12936-015-1036-1","volume":"14","author":"V Pappa","year":"2015","unstructured":"Pappa, V. et al. Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria. Malar. J. 14, 513 (2015).","journal-title":"Malar. J."},{"key":"54231_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-9-110","author":"A Basant","year":"2010","unstructured":"Basant, A., Rege, M., Sharma, S. & Sonawat, H. M. RAesletaercrhations in urine, serum and brain metabolomic profiles exhibit sexual dimorphism during malaria disease progression. Malar. J. https:\/\/doi.org\/10.1186\/1475-2875-9-110 (2010).","journal-title":"Malar. J."},{"key":"54231_CR56","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1038\/s41591-020-1084-0","volume":"26","author":"CM Andrade","year":"2020","unstructured":"Andrade, C. M. et al. Increased circulation time of Plasmodium falciparum underlies persistent asymptomatic infection in the dry season. Nat. Med. 26, 1929\u20131940 (2020).","journal-title":"Nat. Med."},{"key":"54231_CR57","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s12936-017-1875-z","volume":"16","author":"S Abdelrazig","year":"2017","unstructured":"Abdelrazig, S. et al. A metabolomic analytical approach permits identification of urinary biomarkers for Plasmodium falciparum infection: A case\u2013control study. Malar. J. 16, 229 (2017).","journal-title":"Malar. J."},{"key":"54231_CR58","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0378-4347(97)00343-5","volume":"701","author":"H He","year":"1997","unstructured":"He, H., Stein, C. M., Christman, B. & Wood, A. J. J. Determination of catecholamines in sheep plasma by high-performance liquid chromatography with electrochemical detection: Comparison of deoxyepinephrine and 3,4-dihydroxybenzylamine as internal standard. J. Chromatogr. B Biomed. Sci. Appl. 701, 115\u2013119 (1997).","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"54231_CR59","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.tips.2020.11.006","volume":"42","author":"M Modoux","year":"2021","unstructured":"Modoux, M., Rolhion, N., Mani, S. & Sokol, H. Tryptophan metabolism as a pharmacological target. Trends Pharmacol. Sci. 42, 60\u201373 (2021).","journal-title":"Trends Pharmacol. Sci."},{"key":"54231_CR60","doi-asserted-by":"publisher","first-page":"1058926","DOI":"10.3389\/fcimb.2022.1058926","volume":"12","author":"DN Farinella","year":"2023","unstructured":"Farinella, D. N. et al. Malaria disrupts the rhesus macaque gut microbiome. Front. Cell. Infect. Microbiol. 12, 1058926 (2023).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"54231_CR61","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","volume":"31","author":"E Ricciotti","year":"2011","unstructured":"Ricciotti, E. & FitzGerald, G. A. Prostaglandins and inflammation. Alter. Thromb. Vasc. Boil 31, 986\u20131000 (2011).","journal-title":"Alter. Thromb. Vasc. Boil"},{"key":"54231_CR62","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.4049\/jimmunol.0904179","volume":"185","author":"BB Andrade","year":"2010","unstructured":"Andrade, B. B. et al. Heme impairs prostaglandin E2 and TGF-\u03b2 production by human mononuclear cells via Cu\/Zn superoxide dismutase: Insight into the pathogenesis of severe malaria. J. Immunol. 185, 1196\u20131204 (2010).","journal-title":"J. Immunol."},{"issue":"10","key":"54231_CR63","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1086\/503047","volume":"193","author":"CC Keller","year":"2006","unstructured":"Keller, C. C. et al. Suppression of prostaglandin E2 by malaria parasite products and antipyretics promotes overproduction of tumor necrosis factor\u2013a: Association with the pathogenesis of childhood malarial anemia. J. Infect. Dis. 193(10), 1384\u201393 (2006).","journal-title":"J. Infect. Dis."},{"key":"54231_CR64","doi-asserted-by":"publisher","first-page":"e1004667","DOI":"10.1371\/journal.ppat.1004667","volume":"11","author":"TW Yeo","year":"2015","unstructured":"Yeo, T. W. et al. Impaired systemic tetrahydrobiopterin bioavailability and increased dihydrobiopterin in adult falciparum malaria: Association with disease severity, impaired microvascular function and increased endothelial activation. PLoS Pathog. 11, e1004667 (2015).","journal-title":"PLoS Pathog."},{"key":"54231_CR65","doi-asserted-by":"publisher","first-page":"e1004655","DOI":"10.1371\/journal.ppat.1004655","volume":"11","author":"MP Rubach","year":"2015","unstructured":"Rubach, M. P. et al. Impaired systemic tetrahydrobiopterin bioavailability and increased oxidized biopterins in pediatric falciparum malaria: Association with disease severity. PLoS Pathog. 11, e1004655 (2015).","journal-title":"PLoS Pathog."},{"key":"54231_CR66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/595694","volume":"2012","author":"AP Rogerio","year":"2012","unstructured":"Rogerio, A. P. & Anibal, F. F. Role of leukotrienes on protozoan and Helminth infections. Mediat. Inflamm. 2012, 1\u201313 (2012).","journal-title":"Mediat. Inflamm."},{"key":"54231_CR67","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1126\/science.abn0611","volume":"376","author":"SC Xie","year":"2022","unstructured":"Xie, S. C. et al. Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy. Science 376, 1074\u20131079 (2022).","journal-title":"Science"},{"key":"54231_CR68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0242372","volume":"15","author":"K Kesely","year":"2020","unstructured":"Kesely, K. et al. Identification of tyrosine kinase inhibitors that halt Plasmodium falciparum parasitemia. PLoS ONE 15, e0242372 (2020).","journal-title":"PLoS ONE"},{"key":"54231_CR69","first-page":"1","volume":"2020","author":"PF Uzor","year":"2020","unstructured":"Uzor, P. F. Alkaloids from plants with antimalarial activity: A review of recent studies. Evid.-Based Complement. Altern. Med. 2020, 1\u201317 (2020).","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"54231_CR70","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","volume":"3","author":"LW Sumner","year":"2007","unstructured":"Sumner, L. W. et al. Proposed minimum reporting standards for chemical analysis: Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics 3, 211\u2013221 (2007).","journal-title":"Metabolomics"},{"key":"54231_CR71","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s13071-018-2787-7","volume":"11","author":"ACG Almeida","year":"2018","unstructured":"Almeida, A. C. G. et al. High proportions of asymptomatic and submicroscopic Plasmodium vivax infections in a peri-urban area of low transmission in the Brazilian Amazon. Parasites Vectors 11, 194 (2018).","journal-title":"Parasites Vectors"},{"key":"54231_CR72","doi-asserted-by":"publisher","first-page":"e02194","DOI":"10.1128\/spectrum.02194-22","volume":"11","author":"LG Gardinassi","year":"2023","unstructured":"Gardinassi, L. G. et al. Integrated metabolic and inflammatory signatures associated with severity of, fatality of, and recovery from COVID-19. Microbiol. Spectr. 11, e02194-e2222 (2023).","journal-title":"Microbiol. Spectr."},{"key":"54231_CR73","doi-asserted-by":"publisher","first-page":"e00726","DOI":"10.1128\/msystems.00726-23","volume":"8","author":"VI Mwangi","year":"2023","unstructured":"Mwangi, V. I. et al. Methylprednisolone therapy induces differential metabolic trajectories in severe COVID-19 patients. mSystems 8, e00726-23. https:\/\/doi.org\/10.1128\/msystems.00726-23 (2023).","journal-title":"mSystems"},{"key":"54231_CR74","doi-asserted-by":"publisher","first-page":"4113","DOI":"10.1038\/s41467-023-39889-1","volume":"14","author":"S Li","year":"2023","unstructured":"Li, S., Siddiqa, A., Thapa, M., Chi, Y. & Zheng, S. Trackable and scalable LC-MS metabolomics data processing using asari. Nat. Commun. 14, 4113 (2023).","journal-title":"Nat. Commun."},{"key":"54231_CR75","doi-asserted-by":"publisher","first-page":"e1003123","DOI":"10.1371\/journal.pcbi.1003123","volume":"9","author":"S Li","year":"2013","unstructured":"Li, S. et al. Predicting network activity from high throughput metabolomics. PLoS Comput. Biol. 9, e1003123 (2013).","journal-title":"PLoS Comput. Biol."},{"key":"54231_CR76","doi-asserted-by":"publisher","first-page":"5811","DOI":"10.1038\/s41467-019-13680-7","volume":"10","author":"X Domingo-Almenara","year":"2019","unstructured":"Domingo-Almenara, X. et al. The METLIN small molecule dataset for machine learning-based retention time prediction. Nat. Commun. 10, 5811 (2019).","journal-title":"Nat. Commun."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-54231-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-54231-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-54231-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T11:28:25Z","timestamp":1711538905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-54231-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":76,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["54231"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-54231-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,27]]},"assertion":[{"value":"10 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7249"}}