1 Department of Mathematical and Physical Sciences, Concordia University of Edmonton, Edmonton, Alberta, Canada.
2 National Reference Centre for Parasitology, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.
3 Infectious Diseases and Immunity in Global Health (IDIGH) Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.
4 Drugs for Neglected Diseases initiative, Geneva, Switzerland.
5 Division of Primary Care Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
6 Chemistry Department, Université du Québec à Montréal, Montreal, Quebec, Canada.
7 Center for Excellence in Research on Orphan Diseases - Fondation Courtois (CERMO-FC), Montreal, Quebec, Canada.
8 Chemistry Department, Regional Centre for Mass Spectrometry, Université de Montréal, Montreal, Quebec, Canada.
9 Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
10 Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.

The causative agent of Chagas disease (CD), Trypanosoma cruzi, claims thousands of lives each year. Current diagnostic tools are insufficient to ensure parasitological detection in chronically infected patients has been achieved. A host-derived metabolic signature able to distinguish CD patients from uninfected individuals and assess antiparasitic treatment efficiency is introduced. Serum samples were collected from chronic CD patients, prior to and three years after treatment, and subjected to untargeted metabolomics analysis against demographically matched CD-negative controls. Five metabolites were confirmed by high-resolution tandem mass spectrometry. Several database matches for sex steroids were significantly altered in CD patients. A murine experiment corroborated sex steroid perturbation in T. cruzi-infected mice, particularly in male animals. Proteomics analysis also found increased steroidogenesis in the testes of infected mice. Metabolic alterations identified in this study shed light on the pathogenesis and provide the basis for developing novel assays for the diagnosis and screening of CD patients.