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

AUTHORS

Elin Näsström, Christopher M Parry, Nga Tran Vu Thieu, Rapeephan R Maude, Hanna K de Jong, Masako Fukushima, Olena Rzhepishevska, Florian Marks, Ursula Panzner, Justin Im, Hyonjin Jeon, Seeun Park, Zabeen Chaudhury, Aniruddha Ghose, Rasheda Samad, Tan Trinh Van, Anders Johansson, Arjen M Dondorp, Guy E Thwaites, Abul Faiz, Henrik Antti, Stephen Baker

ABSTRACT

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.

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