Luiz Gustavo Gardinassi1, Regina Joice Cordy2, Marcus V G Lacerda3, Jorge L Salinas4, Wuelton M Monteiro5, Gisely C Melo5, André M Siqueira6, Fernando F Val5, ViLinh Tran7, Dean P Jones7, Mary R Galinski8, Shuzhao Li9. 1. Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, Emory University, Atlanta, GA, USA; Malaria Host-Pathogen Interaction Center, Atlanta, GA, USA. 2. Malaria Host-Pathogen Interaction Center, Atlanta, GA, USA; International Center for Malaria Research, Education and Development, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA. 3. Gerência de Malária, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, AM, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, AM, Brazil; Instituto Leônidas & Maria Deane (FIOCRUZ), Manaus, AM, Brazil. 4. Rollins School of Public Health, Emory University, GA, USA. 5. Gerência de Malária, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, AM, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, AM, Brazil. 6. Instituto Nacional de Infectologia Evandro Chagas (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. 7. Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, Emory University, Atlanta, GA, USA; Malaria Host-Pathogen Interaction Center, Atlanta, GA, USA; Clinical Biomarkers Laboratory, Department of Medicine, Emory University, Atlanta, GA, USA. 8. Malaria Host-Pathogen Interaction Center, Atlanta, GA, USA; International Center for Malaria Research, Education and Development, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA; Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA, USA. 9. Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, Emory University, Atlanta, GA, USA; Malaria Host-Pathogen Interaction Center, Atlanta, GA, USA; Clinical Biomarkers Laboratory, Department of Medicine, Emory University, Atlanta, GA, USA. Electronic address: sli49@emory.edu.
Abstract
BACKGROUND: Plasmodium vivax is one of the leading causes of malaria worldwide. Infections with this parasite cause diverse clinical manifestations, and recent studies revealed that infections with P. vivax can result in severe and fatal disease. Despite these facts, biological traits of the host response and parasite metabolism during P. vivax malaria are still largely underexplored. Parasitemia is clearly related to progression and severity of malaria caused by P. falciparum, however the effects of parasitemia during infections with P. vivax are not well understood. RESULTS: We conducted an exploratory study using a high-resolution metabolomics platform that uncovered significant associations between parasitemia levels and plasma metabolites from 150 patients with P. vivax malaria. Most plasma metabolites were inversely associated with higher levels of parasitemia. Top predicted metabolites are implicated into pathways of heme and lipid metabolism, which include biliverdin, bilirubin, palmitoylcarnitine, stearoylcarnitine, phosphocholine, glycerophosphocholine, oleic acid and omega-carboxy-trinor-leukotriene B4. CONCLUSIONS: The abundance of several plasma metabolites varies according to the levels of parasitemia in patients with P. vivax malaria. Moreover, our data suggest that the host response and/or parasite survival might be affected by metabolites involved in the degradation of heme and metabolism of several lipids. Importantly, these data highlight metabolic pathways that may serve as targets for the development of new antimalarial compounds.
BACKGROUND:Plasmodium vivax is one of the leading causes of malaria worldwide. Infections with this parasite cause diverse clinical manifestations, and recent studies revealed that infections with P. vivax can result in severe and fatal disease. Despite these facts, biological traits of the host response and parasite metabolism during P. vivax malaria are still largely underexplored. Parasitemia is clearly related to progression and severity of malaria caused by P. falciparum, however the effects of parasitemia during infections with P. vivax are not well understood. RESULTS: We conducted an exploratory study using a high-resolution metabolomics platform that uncovered significant associations between parasitemia levels and plasma metabolites from 150 patients with P. vivax malaria. Most plasma metabolites were inversely associated with higher levels of parasitemia. Top predicted metabolites are implicated into pathways of heme and lipid metabolism, which include biliverdin, bilirubin, palmitoylcarnitine, stearoylcarnitine, phosphocholine, glycerophosphocholine, oleic acid and omega-carboxy-trinor-leukotriene B4. CONCLUSIONS: The abundance of several plasma metabolites varies according to the levels of parasitemia in patients with P. vivax malaria. Moreover, our data suggest that the host response and/or parasite survival might be affected by metabolites involved in the degradation of heme and metabolism of several lipids. Importantly, these data highlight metabolic pathways that may serve as targets for the development of new antimalarial compounds.
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