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Published in: Malaria Journal 1/2017

Open Access 01-12-2017 | Research

A metabolomic analytical approach permits identification of urinary biomarkers for Plasmodium falciparum infection: a case–control study

Authors: Salah Abdelrazig, Catharine A. Ortori, Gail Davey, Wakgari Deressa, Dhaba Mulleta, David A. Barrett, Alemayehu Amberbir, Andrew W. Fogarty

Published in: Malaria Journal | Issue 1/2017

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Abstract

Background

Currently available diagnostic techniques of Plasmodium falciparum infection are not optimal for non-invasive, population-based screening for malaria. It was hypothesized that a mass spectrometry-based metabolomics approach could identify urinary biomarkers of falciparum malaria.

Methods

The study used a case–control design, with cases consisting of 21 adults in central Ethiopia with a diagnosis of P. falciparum infection confirmed with microscopy, and 25 controls of adults with negative blood smears for malaria matched on age and sex. Urinary samples were collected from these individuals during presentation at the clinic, and a second sample was collected from both cases and controls 4 weeks later, after the cases had received anti-malarial medication. The urine samples were screened for small molecule urinary biomarkers, using mass spectrometry-based metabolomics analyses followed by multivariate analysis using principal component analysis and orthogonal partial least square-discriminant analysis. The chemical identity of statistically significant malaria biomarkers was confirmed using tandem mass spectrometry.

Results

The urinary metabolic profiles of cases with P. falciparum infection were distinct from healthy controls. After treatment with anti-malarial medication, the metabolomic profile of cases resembled that of healthy controls. Significantly altered levels of 29 urinary metabolites were found. Elevated levels of urinary pipecolic acid, taurine, N-acetylspermidine, N-acetylputrescine and 1,3-diacetylpropane were identified as potential biomarkers of falciparum malaria.

Conclusion

The urinary biomarkers of malaria identified have potential for the development of non-invasive and rapid diagnostic test of P. falciparum infection.
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Literature
1.
go back to reference Gething P, Patil A, Smith D, Guerra C, Elyazar I, Johnston G, et al. A new world malaria map: Plasmodium falciparum endemicity in 2010. Malar J. 2011;10:378.CrossRefPubMedPubMedCentral Gething P, Patil A, Smith D, Guerra C, Elyazar I, Johnston G, et al. A new world malaria map: Plasmodium falciparum endemicity in 2010. Malar J. 2011;10:378.CrossRefPubMedPubMedCentral
2.
go back to reference WHO. World malaria report. Geneva: World Health Organization; 2013. WHO. World malaria report. Geneva: World Health Organization; 2013.
3.
go back to reference Katzung B, Masters S, Trevor A. Basic and clinical pharmacology. 12th ed. New York: McGraw-Hill Education; 2012. Katzung B, Masters S, Trevor A. Basic and clinical pharmacology. 12th ed. New York: McGraw-Hill Education; 2012.
4.
go back to reference Björkman A, Mårtensson A. risks and benefits of targeted malaria treatment based on rapid diagnostic test results. Clin Infect Dis. 2010;51:512–4.CrossRefPubMed Björkman A, Mårtensson A. risks and benefits of targeted malaria treatment based on rapid diagnostic test results. Clin Infect Dis. 2010;51:512–4.CrossRefPubMed
5.
go back to reference Jain P, Chakma B, Patra S, Goswami P. Potential biomarkers and their applications for rapid and reliable detection of malaria. Biomed Res Int. 2014;2014:852645.CrossRefPubMedPubMedCentral Jain P, Chakma B, Patra S, Goswami P. Potential biomarkers and their applications for rapid and reliable detection of malaria. Biomed Res Int. 2014;2014:852645.CrossRefPubMedPubMedCentral
6.
go back to reference Haji Y, Deressa W, Davey G, Fogarty A. Concerns about covert HIV testing are associated with delayed presentation of suspected malaria in Ethiopian children: a cross-sectional study. Malar J. 2014;13:310.CrossRef Haji Y, Deressa W, Davey G, Fogarty A. Concerns about covert HIV testing are associated with delayed presentation of suspected malaria in Ethiopian children: a cross-sectional study. Malar J. 2014;13:310.CrossRef
7.
go back to reference Tadesse F, Deressa W, Fogarty A. Concerns about covert HIV testing are associated with delayed presentation in Ethiopian adults with suspected malaria: a cross-sectional study. BMC Public Health. 2016;16:102.CrossRefPubMedPubMedCentral Tadesse F, Deressa W, Fogarty A. Concerns about covert HIV testing are associated with delayed presentation in Ethiopian adults with suspected malaria: a cross-sectional study. BMC Public Health. 2016;16:102.CrossRefPubMedPubMedCentral
8.
go back to reference Want EJ, Wilson ID, Gika H, Theodoridis G, Plumb RS, Shockcor J, et al. Global metabolic profiling procedures for urine using UPLC-MS. Nat Protoc. 2010;5:1005–18.CrossRefPubMed Want EJ, Wilson ID, Gika H, Theodoridis G, Plumb RS, Shockcor J, et al. Global metabolic profiling procedures for urine using UPLC-MS. Nat Protoc. 2010;5:1005–18.CrossRefPubMed
9.
go back to reference Xia J, Broadhurst D, Wilson M, Wishart D. Translational biomarker discovery in clinical metabolomics: an introductory tutorial. Metabolomics. 2013;9:280–99.CrossRefPubMed Xia J, Broadhurst D, Wilson M, Wishart D. Translational biomarker discovery in clinical metabolomics: an introductory tutorial. Metabolomics. 2013;9:280–99.CrossRefPubMed
10.
go back to reference Sengupta A, Ghosh S, Pathak S, Gogtay N, Thatte U, Doshi M, et al. Metabolomic analysis of urine samples of vivax malaria in-patients for biomarker identification. Metabolomics. 2015;11:1351–62.CrossRef Sengupta A, Ghosh S, Pathak S, Gogtay N, Thatte U, Doshi M, et al. Metabolomic analysis of urine samples of vivax malaria in-patients for biomarker identification. Metabolomics. 2015;11:1351–62.CrossRef
11.
go back to reference Sengupta A, Ghosh S, Basant A, Malusare S, Johri P, Pathak S, et al. Global host metabolic response to Plasmodium vivax infection: a 1H NMR based urinary metabonomic study. Malar J. 2011;10:384.CrossRefPubMedPubMedCentral Sengupta A, Ghosh S, Basant A, Malusare S, Johri P, Pathak S, et al. Global host metabolic response to Plasmodium vivax infection: a 1H NMR based urinary metabonomic study. Malar J. 2011;10:384.CrossRefPubMedPubMedCentral
12.
go back to reference Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002;419:498–511.CrossRefPubMed Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002;419:498–511.CrossRefPubMed
13.
go back to reference Li J, Wang Y, Saric J, Nicholson J, Dirnhofer S, Singer B, et al. Global metabolic responses of NMRI mice to an experimental Plasmodium berghei infection. J Proteome Res. 2008;7:3948–56.CrossRefPubMed Li J, Wang Y, Saric J, Nicholson J, Dirnhofer S, Singer B, et al. Global metabolic responses of NMRI mice to an experimental Plasmodium berghei infection. J Proteome Res. 2008;7:3948–56.CrossRefPubMed
14.
go back to reference Tritten L, Keiser J, Godejohann M, Utzinger J, Vargas M, Beckonert O, et al. Metabolic profiling framework for discovery of candidate diagnostic markers of malaria. Sci Rep. 2013;3:2769.CrossRefPubMed Tritten L, Keiser J, Godejohann M, Utzinger J, Vargas M, Beckonert O, et al. Metabolic profiling framework for discovery of candidate diagnostic markers of malaria. Sci Rep. 2013;3:2769.CrossRefPubMed
15.
go back to reference Dinarello CA. Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med. 1984;311:1413–8.CrossRefPubMed Dinarello CA. Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med. 1984;311:1413–8.CrossRefPubMed
17.
go back to reference Surowiec I, Orikiiriza J, Karlsson E, Nelson M, Bonde M, Kyamanwa P, et al. Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria. Open Forum Infect Dis. 2015;2:62.CrossRef Surowiec I, Orikiiriza J, Karlsson E, Nelson M, Bonde M, Kyamanwa P, et al. Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria. Open Forum Infect Dis. 2015;2:62.CrossRef
18.
go back to reference Sana TR, Gordon DB, Fischer SM, Tichy SE, Kitagawa N, Lai C, et al. Global mass spectrometry based metabolomics profiling of erythrocytes infected with Plasmodium falciparum. PLoS ONE. 2013;8:e60840.CrossRefPubMedPubMedCentral Sana TR, Gordon DB, Fischer SM, Tichy SE, Kitagawa N, Lai C, et al. Global mass spectrometry based metabolomics profiling of erythrocytes infected with Plasmodium falciparum. PLoS ONE. 2013;8:e60840.CrossRefPubMedPubMedCentral
19.
go back to reference Teng R, Junankar PR, Bubb WA, Rae C, Mercier P, Kirk K. Metabolite profiling of the intraerythrocytic malaria parasite Plasmodium falciparum by 1H NMR spectroscopy. NMR Biomed. 2009;22:292–302.CrossRefPubMed Teng R, Junankar PR, Bubb WA, Rae C, Mercier P, Kirk K. Metabolite profiling of the intraerythrocytic malaria parasite Plasmodium falciparum by 1H NMR spectroscopy. NMR Biomed. 2009;22:292–302.CrossRefPubMed
20.
go back to reference Delic D, Warskulat U, Borsch E, Al-Qahtani S, Al-Quraishi S, Häussinger D, et al. Loss of ability to self-heal malaria upon taurine transporter deletion. Infect Immun. 2010;78:1642–9.CrossRefPubMedPubMedCentral Delic D, Warskulat U, Borsch E, Al-Qahtani S, Al-Quraishi S, Häussinger D, et al. Loss of ability to self-heal malaria upon taurine transporter deletion. Infect Immun. 2010;78:1642–9.CrossRefPubMedPubMedCentral
21.
go back to reference Day NPJ, Hien TT, Schollaardt T, Loc PP, Chuong LV, Hong Chau TT, et al. The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. J Infect Dis. 1999;180:1288–97.CrossRefPubMed Day NPJ, Hien TT, Schollaardt T, Loc PP, Chuong LV, Hong Chau TT, et al. The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. J Infect Dis. 1999;180:1288–97.CrossRefPubMed
Metadata
Title
A metabolomic analytical approach permits identification of urinary biomarkers for Plasmodium falciparum infection: a case–control study
Authors
Salah Abdelrazig
Catharine A. Ortori
Gail Davey
Wakgari Deressa
Dhaba Mulleta
David A. Barrett
Alemayehu Amberbir
Andrew W. Fogarty
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2017
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-017-1875-z

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