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Näsström, Elin
Publications (7 of 7) Show all publications
Näsström, E., Jonsson, P., Johansson, A., Dongol, S., Karkey, A., Basnyat, B., . . . Baker, S. (2018). Diagnostic metabolite biomarkers of chronic typhoid carriage. PLoS Neglected Tropical Diseases, 12(1), Article ID e0006215.
Open this publication in new window or tab >>Diagnostic metabolite biomarkers of chronic typhoid carriage
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2018 (English)In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 12, no 1, article id e0006215Article in journal (Refereed) Published
Abstract [en]

Background: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder.

Methodology/Principal findings: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers.

Conclusions/Significance: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-145618 (URN)10.1371/journal.pntd.0006215 (DOI)000424022700063 ()29373578 (PubMedID)
Funder
Swedish Research Council, VR-U 2015-03442
Available from: 2018-04-17 Created: 2018-04-17 Last updated: 2018-06-09Bibliographically approved
Näsström, E. (2017). Diagnosis of acute and chronic enteric fever using metabolomics. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Diagnosis of acute and chronic enteric fever using metabolomics
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Diagnos av akut och kronisk enterisk feber med hjälp av metabolomik
Abstract [en]

Enteric (or typhoid) fever is a systemic infection mainly caused by Salmonella Typhi and Salmonella Paratyphi A. The disease is common in areas with poor water quality and insufficient sanitation. Humans are the only reservoir for transmission of the disease. The presence of asymptomatic chronic carriers is a complicating factor for the transmission. There are major limitations regarding the current diagnostic methods both for acute infection and chronic carriage. Metabolomics is a methodology studying metabolites in biological systems under influence of environmental or physiological perturbations. It has been applied to study several infectious diseases, with the goal of detecting diagnostic biomarkers. In this thesis, a mass spectrometry-based metabolomics approach, including chemometric bioinformatics techniques for data analysis, has been used to evaluate the potential of metabolite biomarker patterns for diagnosis of enteric fever at different stages of the disease.

In Paper I, metabolite patterns related to acute enteric fever were investigated. Human plasma samples from patients in Nepal with culture-confirmed S. Typhi or S. Paratyphi A infection were compared to afebrile controls. A metabolite pattern discriminating between acute enteric fever and afebrile controls, as well as between the two causative agents of enteric fever was detected. The strength of using a panel of metabolites instead of single metabolites as biomarkers was also highlighted. In Paper II, metabolite patterns for acute enteric fever, this time focusing only on S. Typhi infections, were investigated. Human plasma from patients in Bangladesh with culture-positive or -negative but clinically suspected S. Typhi infection were compared to febrile controls. Differences were found in metabolite patterns between the culture-positive S. Typhi group and the febrile controls with a heterogeneity among the suspected S. Typhi samples. Consistencies in metabolite patterns were found to the results from Paper I. In addition, a validation cohort with culture-positive S. Typhi samples and a control group including patients with malaria and infections caused by other pathogens was analysed. Differences in metabolite patterns were detected between S. Typhi samples and all controls as well as between S. Typhi and malaria. Consistencies in metabolite patterns were found to the primary Bangladeshi cohort and the Nepali cohort from Paper I. Paper III focused on chronic Salmonella carriers. Human plasma samples from patients in Nepal undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage were compared to non-carriage controls. The Salmonella carriage samples were distinguished from the non-carriage controls and differential signatures were also found between the S. Typhi and S. Paratyphi A carriage samples. Comparing metabolites found during chronic carriage and acute enteric fever (in Paper I) resulted in a panel of metabolites significant only during chronic carriage. This work has contributed to highlight the potential of using metabolomics as a tool to find diagnostic biomarker patterns associated with different stages of enteric fever.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2017. p. 76
Keywords
Enteric fever, Salmonella, chronic carriers, metabolomics, diagnosis, biomarkers, multivariate data analysis, GCxGC-MS, GC-MS, LC-MS
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-140188 (URN)978-91-7601-773-9 (ISBN)
Public defence
2017-10-27, KB.E3.03 (Stora hörsalen, Carl Kempe-salen), KBC-huset, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2017-10-06 Created: 2017-10-03 Last updated: 2018-06-09Bibliographically approved
Näsström, E., Parry, C. M., Thieu, N. T., Maude, R. R., de Jong, H. K., Fukushima, M., . . . Baker, S. (2017). Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa. eLIFE, 6, Article ID e15651.
Open this publication in new window or tab >>Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa
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2017 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e15651Article in journal (Refereed) Published
Abstract [en]

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 (Nasstrom 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.

Place, publisher, year, edition, pages
eLife Sciences Publications, 2017
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-135532 (URN)10.7554/eLife.15651 (DOI)000400828100001 ()
Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2018-06-09Bibliographically approved
Östman, M., Fick, J., Näsström, E. & Lindberg, R. (2014). A snapshot of illicit drug use in Sweden acquired through sewage water analysis. Science of the Total Environment, 472, 862-871
Open this publication in new window or tab >>A snapshot of illicit drug use in Sweden acquired through sewage water analysis
2014 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 472, p. 862-871Article in journal (Refereed) Published
Abstract [en]

Analytical measurements of sewage water have been used many times to estimate the consumption of specific drugs in an area. This study measured a large number of illicit drugs and metabolites (>30) at a large number of sewage treatment plants (STPs) distributed across Sweden. Twenty-four illicit and prescription drugs, classified as narcotic substances in Sweden, and seven selected metabolites were included in the study. A 24 hour composite sample of incoming sewage water was collected from 33 different municipalities at various geographic locations across Sweden. Species were analyzed using an on-line solid-phase extraction-liquid chromatography electrospray tandem mass spectrometry method. The method proved to be rapid with minimum need for sample work up and was able to detect 13 compounds above their respective limits of quantification. The results for all compounds were presented as per capita loads. Multivariate data analysis was used to relate drug consumption to geographical location and/or population of cities. The results showed that geographical differences in drug consumption were apparent across the country. For the narcotic pharmaceuticals, the geographical differences suggested by the multivariate model were supported by prescription statistics. (C) 2013 Elsevier B.V. All rights reserved.

Keywords
Illicit drugs, Wastewater, Analysis, LC-MS/MS, Multivariate data analysis, Sweden
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-87410 (URN)10.1016/j.scitotenv.2013.11.081 (DOI)000331916100095 ()
Available from: 2014-04-01 Created: 2014-03-31 Last updated: 2018-06-08Bibliographically approved
Näsström, E., Thieu, N. T., Dongol, S., Karkey, A., Vinh, P. V., Thanh, T. H., . . . Antti, H. (2014). Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever. eLIFE, 3, Article ID e03100.
Open this publication in new window or tab >>Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever
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2014 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 3, article id e03100Article in journal (Refereed) Published
Abstract [en]

The host-pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections.

Keywords
Metabolomics, mass spectrometry, two-dimensional gas chromatography, pattern recognition, chemometrics, enteric fever, typhoid, Salmonella Typhi, Salmonella Paratyphi A, diagnostics, biomarkers
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-90835 (URN)10.7554/eLife.03100 (DOI)000336837500001 ()
Available from: 2014-07-22 Created: 2014-07-01 Last updated: 2018-06-07Bibliographically approved
Antti, H., Fahlgren, A., Näsström, E., Kouremenos, K., Sundén-Cullberg, J., Guo, Y., . . . Fällman, M. (2013). Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance. PLoS ONE, 8(2), Article ID e56971.
Open this publication in new window or tab >>Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2, article id e56971Article in journal (Refereed) Published
Abstract [en]

Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) were used and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6) from severe sepsis (n = 10) and identified treatment responses over time. Combined analysis of human, , and mice samples identified 25 metabolites indicative of effective treatment of sepsis. Taken together, this study provides a proof of concept of the utility of analyzing metabolite patterns in blood for early differentiation between ineffective and effective antibiotic treatment in acute infections.

National Category
Microbiology in the medical area Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-66816 (URN)10.1371/journal.pone.0056971 (DOI)000316849500048 ()23451124 (PubMedID)
Available from: 2013-03-05 Created: 2013-03-05 Last updated: 2018-06-08Bibliographically approved
Näsström, E., Jonsson, P., Johansson, A., Dongol, S., Karkey, A., Basnyat, B., . . . Baker, S. Metabolite biomarkers of typhoid chronic carriage.
Open this publication in new window or tab >>Metabolite biomarkers of typhoid chronic carriage
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(English)Manuscript (preprint) (Other academic)
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-140183 (URN)
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2018-06-09
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