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

• Published in: eLife Vol. 6
• Main Authors: Näsström, Elin, Parry, Christopher M, Vu Thieu, Nga Tran, Maude, Rapeephan R, de Jong, Hanna K, Fukushima, Masako, Rzhepishevska, Olena, Marks, Florian, Panzner, Ursula, Im, Justin, Jeon, Hyonjin, Park, Seeun, Chaudhury, Zabeen, Ghose, Aniruddha, Samad, Rasheda, Van, Tan Trinh, Johansson, Anders, Dondorp, Arjen M, Thwaites, Guy E, Faiz, Abul, Antti, Henrik, Baker, Stephen
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 09.05.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Bangladesh; Biochemistry; Biomarkers; Blood culture; Blood plasma; Chromatography; diagnostics; Discriminant analysis; Disease; Fever; Health aspects; Humans; Infections; Malaria; Mass Spectrometry; Mass spectroscopy; Medical diagnosis; Medicine; Metabolites; Metabolomics; Metabolomics - methods; Microbiology and Infectious Disease; Patients; Pattern recognition; Physiological aspects; Plasma - chemistry; Research Advance; Salmonella; Salmonella typhi - growth & development; Salmonella typhi - metabolism; Scientific imaging; Senegal; Tropical diseases; two-dimensional gas chromatography; Typhoid; Typhoid fever; Typhoid Fever - diagnosis; Typhoid Fever - pathology; Urine; Senegal; Bangladesh; Metabolomics; diagnostics; infectious disease; biomarkers; biochemistry; microbiology; typhoid fever; S. enterica serovar typhi; mass spectrometry; two-dimensional gas chromatography
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.15651

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.