Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa
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
Affiliations
Elin Näsström
Department of Chemistry, Computational Life Science Cluster, Umeå University, Umeå, Sweden
Christopher M Parry
Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
Nga Tran Vu Thieu
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University, Oxford, United Kingdom; Clinical Research Unit, Ho Chi Minh City, Vietnam
Rapeephan R Maude
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Hanna K de Jong
Department of Internal Medicine, Division of Infectious Diseases and Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, the Netherlands; Center for Experimental Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Masako Fukushima
Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Olena Rzhepishevska
Department of Chemistry, Computational Life Science Cluster, Umeå University, Umeå, Sweden
Florian Marks
The International Vaccine Institute, Seoul, South Korea
Ursula Panzner
The International Vaccine Institute, Seoul, South Korea
Justin Im
The International Vaccine Institute, Seoul, South Korea
Hyonjin Jeon
The International Vaccine Institute, Seoul, South Korea
Seeun Park
The International Vaccine Institute, Seoul, South Korea
Zabeen Chaudhury
The International Vaccine Institute, Seoul, South Korea
Aniruddha Ghose
Chittagong Medical College Hospital, Chittagong, Bangladesh
Rasheda Samad
Chittagong Medical College Hospital, Chittagong, Bangladesh
Tan Trinh Van
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University, Oxford, United Kingdom
Anders Johansson
Department of Clinical Microbiology, Umeå University, Umeå, Sweden
Arjen M Dondorp
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Guy E Thwaites
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University, Oxford, United Kingdom; Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom
Abul Faiz
Malaria Research Group and Dev Care Foundation, Dhaka, Bangladesh
Henrik Antti
Department of Chemistry, Computational Life Science Cluster, Umeå University, Umeå, Sweden
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University, Oxford, United Kingdom; Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom; Department of Medicine, The University of Cambridge, Cambridge, United Kingdom
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.
