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

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

doi:10.7554/elife.15651

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.

Highlights

Typhoid is a systemic infection caused by the bacterium Salmonella Typhi
We aimed to identify metabolite profiles that could distinguish between patients with S
We hypothesized that metabolite profiles might differentiate clinically indistinguishable infections caused by these genetically related pathogens (Didelot et al, 2007; Maskey et al, 2006); asymptomatic individuals constituted the control group

Summary

Introduction

Typhoid is a systemic infection caused by the bacterium Salmonella Typhi Isolating the organism from the bloodstream is the mainstay of typhoid diagnostics (Gilman et al, 1975; Parry et al, 2011), but this method lacks sensitivity and researchers are aiming to discover biomarkers that may become a more reliable and rapid approach to diagnosing disease (Baker et al, 2010). We found that a combination of six metabolites could define the infecting pathogen in the blood of febrile patients. These data represented a major step forward in the discovery of biomarkers with the potential to be future typhoid diagnostics. We have applied a similar approach with plasma samples collected from febrile patients in Bangladesh and Senegal to further investigate and validate our previous findings

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Conclusion