Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa.

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.