Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria

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.