PO 8439 EFFECT OF PLASMODIUM FALCIPARUM EXPOSURE ON HUMAN URINARY METABOLOMICS PROFILING

Abstract

BackgroundImmunity against malaria infection is being studied extensively but the underlying mechanisms of protection remain not fully understood. Metabolomics is a post-genomic technology enabling a minimally invasive monitoring of the physiological responses to external and internal stimuli. Here, we present a longitudinal study of the urinary metabolic profiles of healthy individuals before and after intravenous administration of P. falciparum sporozoïtes, aiming at deciphering the metabolic changes observed during malaria infection.MethodsTwenty (20) healthy Gabonese and 5 Europeans were voluntary challenged by live P. falciparum sporozoïtes (3200 PfSPZ) and followed up until they developed symptoms and became thick blood smear-positive. Urine samples were collected before and after challenge at several time points until treatment. Samples were analysed in an untargeted approach using state-of-the-art analytical platforms, namely hydrophilic interaction chromatography-mass spectrometry (HILIC-MS) and nuclear magnetic resonance (NMR) spectroscopy. A combination of the multivariate and univariate data analysis approaches was used for dissecting the metabolic effects of a host response to the infection.ResultsUnlike the Europeans participants, a part of the Gabonese volunteers did not become parasitaemic. Unsupervised data analysis shows sample discrimination between Europeans and Gabonese at baseline, before and after challenge and between Gabonese who controlled their parasitaemia and those who did not.ConclusionThis metabolomics study highlighted the differences in the urinary metabolite profiles during P. falciparum infection. These differences observed between parasitaemic and non-parasitaemic Gabonese after challenge with P. falciparum, may suggest an underlying metabolic mechanism of protection against malaria infection which we will investigate in detail.