Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon

Area of Science:

• Parasitology
• Metabolomics
• Immunology

Background:

• The host-parasite interaction in malaria is complex.
• Urinary metabolite profiles during Plasmodium falciparum (P. falciparum) infection and their link to immunity are not well understood.

Purpose of the Study:

• To investigate longitudinal urinary metabolite profiles in response to P. falciparum sporozoite (PfSPZ) challenge.
• To compare metabolic changes between malaria-naïve Europeans and Africans with lifelong exposure.
• To identify potential biomarkers for parasitaemia control.

Main Methods:

• Longitudinal study involving direct venous inoculation of PfSPZ in 20 Africans and 5 Europeans.
• Urine sample collection pre-challenge and at multiple time points post-challenge (days 2, 5, 9, 11).
• Analysis of urinary metabolite profiles using metabolomics.

Main Results:

• Distinct urinary metabolite alterations were observed between Europeans and Africans post-infection, more pronounced in Europeans.
• Africans with lifelong exposure exhibited delayed or controlled parasitaemia compared to Europeans.
• Specific metabolites (e.g., formate, urea, choline) were elevated in infected Africans, while others (e.g., pyruvate, 3-methylhistidine) were lower in those controlling infection.
• Pre-infection levels of phenylacetylglutamine may predict parasitaemia control in Africans.

Conclusions:

• Lifelong exposure to malaria significantly influences urinary metabolic responses to P. falciparum infection.
• Urinary metabolomics can differentiate responses based on malaria exposure history.
• Pre-infection metabolic profiles may offer predictive value for parasitaemia control in malaria-endemic regions.