Metabolomic-Based Methods in Diagnosis and Monitoring Infection Progression

  • Miguel Fernández-García
  • David Rojo
  • Fernanda Rey-Stolle
  • Antonia García
  • Coral Barbas
Part of the Experientia Supplementum book series (EXS, volume 109)


A robust biomarker screening and validation is crucial for overcoming the current limits in the clinical management of infectious diseases. In this chapter, a general workflow for metabolomics is summarized. Subsequently, an overview of the major contributions of this omics science to the field of biomarkers of infectious diseases is discussed. Different approaches using a variety of analytical platforms can be distinguished to unveil the key metabolites for the diagnosis, prognosis, response to treatment and susceptibility for infectious diseases. To allow the implementation of such biomarkers into the clinics, the performance of large-scale studies employing solid validation criteria becomes essential. Focusing on the etiological agents and after an extensive review of the field, we present a comprehensive revision of the main metabolic biomarkers of viral, bacterial, fungal, and parasitic diseases. Finally, we discussed several articles which show the strongest validation criteria. Following these research avenues, precious clinical resources will be revealed, allowing for reduced misdiagnosis, more efficient therapies, and affordable costs, ultimately leading to a better patient management.


Metabolomics Infectious diseases Diagnostics Biomarkers Biomarker discovery 


Funding Statement

The co-authors would like to acknowledge funding from the Spanish Ministry of Economy and Competitiveness (CTQ2014-55279-R). Author M. F.-G. acknowledges Fundación Universitaria San Pablo CEU for his PhD fellowship.


  1. Allegretti JR, Kearney S, Li N, Bogart E, Bullock K, Gerber GK, Bry L, Clish CB, Alm E, Korzenik JR (2016) Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles. Aliment Pharmacol Ther 43(11):1142–1153. Scholar
  2. Autino B, Corbett Y, Castelli F, Taramelli D (2012) Pathogenesis of malaria in tissues and blood. Mediterr J Hematol Infect Dis.
  3. Badiee P, Hashemizadeh Z (2014) Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J Med Res 139(2):195–204PubMedPubMedCentralGoogle Scholar
  4. Bahr NC, Boulware DR (2014) Methods of rapid diagnosis for the etiology of meningitis in adults. Biomark Med 8(9):1085–1103. Scholar
  5. Bedossa P, Poynard T (1996) An algorithm for the grading of activity in chronic hepatitis C. Hepatology 24(2):289–293. Scholar
  6. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GRW, Simmons CP, Scott TW, Farrar JJ, Hay SI (2013) The global distribution and burden of dengue. Nature 496(7446):504–507. Scholar
  7. Birungi G, Chen SM, Loy BP, Ng ML, Li SFY (2010) Metabolomics approach for investigation of effects of dengue virus infection using the EA hy926 cell line. J Proteome Res 9(12):6523–6534. Scholar
  8. Bisanz C, Bastien O, Grando D, Jouhet J, Maréchal E, Cesbron-Delauw MF (2006) Toxoplasma gondii acyl-lipid metabolism: de novo synthesis from apicoplast-generated fatty acids versus scavenging of host cell precursors. Biochem J 394:197–205. Scholar
  9. Brand HK, Hermans PW, de Groot R (2010) Host biomarkers and paediatric infectious diseases: from molecular profiles to clinical application. In: Finn A, Curtis N, Pollard AJ (eds) Hot topics in infection and immunity in children VI, 1st edn. Springer-Verlag, New York, pp 19–31CrossRefGoogle Scholar
  10. Buckle GC, Walker CL, Black RE (2012) Typhoid fever and paratyphoid fever: systematic review to estimate global morbidity and mortality for 2010. J Glob Health 2(1):010401. Scholar
  11. Burnham CA, Carroll KC (2013) Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories. Clin Microbiol Rev 26(3):604–630. Scholar
  12. Cassol E, Misra V, Dutta A, Morgello S, Gabuzda D (2014) Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment. AIDS 28(11):1579–1591. Scholar
  13. Ceccotti G, Meoni G, Tenori L, Gragnani L, Fognani E, Gianni E, Luchinat C, Zignego AL (2016) A serum metabolomic analysis of HCV-infected patients successfully treated with IFN-free DAA regimens. Hepatology 64:378A–378AGoogle Scholar
  14. Cheng J, Joyce A, Sterling RK, Sanyal AJ (2012) Metabolomic profiling identifies fibrosis-associated differences in hepatitis C virus infection. Gastroenterology 142(5):S968CrossRefGoogle Scholar
  15. Cribbs SK, Park Y, Guidot DM, Martin GS, Brown LA, Lennox J, Jones DP (2014) Metabolomics of bronchoalveolar lavage differentiate healthy HIV-1-infected subjects from controls. AIDS Res Hum Retroviruses 30(6):579–585. Scholar
  16. Cui L, Lee YH, Thein TL, Fang J, Pang J, Ooi EE, Leo YS, Ong CN, Tannenbaum SR (2016) Serum metabolomics reveals serotonin as a predictor of severe dengue in the early phase of dengue fever. Plos Negl Trop Dis.
  17. Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, Selva-Nayagam S, Anstey NM, Huffam SE, Snelling PL, Marks PJ, Stephens DP, Lum GD, Jacups SP, Krause VL (2000) Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature. Clin Infect Dis 31(4):981–986. Scholar
  18. da Luz JA, Hans E, Zeng A-P (2014) Automated fast filtration and on-filter quenching improve the intracellular metabolite analysis of microorganisms. Eng Life Sci 14(2):135–142. Scholar
  19. Dann S, Aitken S, Ross C, Tessier MEM, Loeffelholz M, Koussoulas K, Bornstein JC, Feng H, Versalovic J, Pothoulakis C, Garey KW, Savidge T (2015) Zolpidem confers disease susceptibility to Clostridium difficile infection. Gastroenterology 148(4):S727–S728CrossRefGoogle Scholar
  20. Das MK, Bishwal SC, Das A, Dabral D, Badireddy VK, Pandit B, Varghese GM, Nanda RK (2015) Deregulated tyrosine-phenylalanine metabolism in pulmonary tuberculosis patients. J Proteome Res 14(4):1947–1956. Scholar
  21. de Francisco TM, Zaramella IF, Gasparetto JC, Cerqueira LB, Piantavini MS, Pontarolo R, Campos FR (2015) Rapid detection of aspergillosis in immunocompromised patients using DIMS and chemometric analysis. Anal Methods 7(15):6346–6351. Scholar
  22. Denery JR, Nunes AAK, Hixon MS, Dickerson TJ, Janda KD (2010) Metabolomics-based discovery of diagnostic biomarkers for onchocerciasis. PloS Negl Trop Dis.
  23. Dessì A, Liori B, Caboni P, Corsello G, Giuffrè M, Noto A, Serraino F, Stronati M, Zaffanello M, Fanos V (2014) Monitoring neonatal fungal infection with metabolomics. J Matern Fetal Neonatal Med 27:34–38. Scholar
  24. Dettmer K, Aronov PA, Hammock BD (2007) Mass spectrometry-based metabolomics. Mass Spectrom Rev 26(1):51–78. Scholar
  25. du Preez I, Loots DT (2013) New sputum metabolite markers implicating adaptations of the host to Mycobacterium tuberculosis, and vice versa. Tuberculosis (Edinb) 93(3):330–337. Scholar
  26. du Preez I, Sithebe NP (2013) The use of metabolomics as a tool to investigate hepatitis C. Metabolomics 9(2):497–505. Scholar
  27. Dunn WB, Wilson ID, Nicholls AW, Broadhurst D (2012) The importance of experimental design and QC samples in large-scale and MS-driven untargeted metabolomic studies of humans. Bioanalysis 4(18):2249–2264. Scholar
  28. El-Bacha T, Struchiner CJ, Cordeiro MT, Almeida FCL, Marques ET Jr, Da Poian AT (2016) 1H nuclear magnetic resonance metabolomics of plasma unveils liver dysfunction in dengue patients. J Virol 90(16):7429–7443. Scholar
  29. Embade N, Marino Z, Diercks T, Cano A, Lens S, Cabrera D, Navasa M, Falcón-Pérez JM, Caballería J, Castro A, Bosch J, Mato JM, Millet O (2016) Metabolic characterization of advanced liver fibrosis in HCV patients as studied by serum 1H-NMR spectroscopy. PLoS One 11(5).
  30. Enoch DA, Yang H, Aliyu SH, Micallef C (2017) The changing epidemiology of invasive fungal infections. Methods Mol Biol 1508:17–65. Scholar
  31. Eoh H, Rhee KY (2013) Multifunctional essentiality of succinate metabolism in adaptation to hypoxia in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 110(16):6554–6559. Scholar
  32. Faden H, Heimerl M, Varma C, Goodman G, Winkelstein P (2002) Urinary excretion of pneumococcal cell wall polysaccharide in children. Pediatr Infect Dis J 21(8):791–793. Scholar
  33. Fatima Z, Hameed S, Saibabu V, Sharma S, Hans S (2017) Tuberculosis: propagation beyond lungs. In: Bhargava S (ed) Diagnosis & management of tuberculosis, 1st edn. Open Access eBooks, Wilmington, pp 1–21Google Scholar
  34. Feng S, Du Y-Q, Zhang L, Zhang L, Feng R-R, Liu S-Y (2015) Analysis of serum metabolic profile by ultra-performance liquid chromatography-mass spectrometry for biomarkers discovery: application in a pilot study to discriminate patients with tuberculosis. Chin Med J (Engl) 128(2):159–168. Scholar
  35. Fiehn O (2002) Metabolomics – the link between genotypes and phenotypes. Plant Mol Biol 48(1–2):155–171. Scholar
  36. Fontaine KA, Sanchez EL, Camarda R, Lagunoff M (2015) Dengue virus induces and requires glycolysis for optimal replication. J Virol 89(4):2358–2366. Scholar
  37. Frediani JK, Jones D, Tukvadze N, Sanikidze E, Kipiani M, Uppal K, Kurani S, Hebbar G, Colas R, Dalli J, Serhan C, Tangpricha V, Blumberg H, Ziegler T (2014a) Plasma high-resolution metabolomic profiling reveals upregulation of specific resolvins in patients with pulmonary tuberculosis. FASEB J 28(1)Google Scholar
  38. Frediani JK, Jones DP, Tukvadze N, Uppal K, Sanikidze E, Kipiani M, Tran VT, Hebbar G, Walker DI, Kempker RR, Kurani SS, Colas RA, Dalli J, Tangpricha V, Serhan CN, Blumberg HM, Ziegler TR (2014b) Plasma metabolomics in human pulmonary tuberculosis disease: a pilot study. PLoS ONE 9.
  39. Frediani JK, Chong E, Jones D, Yu T, Zhang L, Tukvadze N, Sanikidze E, Kipiani M, Hebbar G, Tran V, Kempker R, Tangpricha V, Blumberg H, Ziegler T (2015) Comparative plasma high-resolution metabolomic profiling in patients with drug-susceptible and multi-drug resistant pulmonary tuberculosis. FASEB J 29Google Scholar
  40. Ghannoum MA, Mukherjee PK, Jurevic RJ, Retuerto M, Brown RE, Sikaroodi M, Webster-Cyriaque J, Gillevet PM (2013) Metabolomics reveals differential levels of oral metabolites in HIV-infected patients: toward novel diagnostic targets. OMICS 17(1):5–15. Scholar
  41. Gironès N, Carbajosa S, Guerrero NA, Poveda C, Chillón-Marinas C, Fresno M (2014) Global metabolomic profiling of acute myocarditis caused by Trypanosoma cruzi infection. PloS Negl Trop Dis.
  42. Globisch D, Moreno AY, Hixon MS, Nunes AAK, Denery JR, Specht S, Hoerauf A, Janda KD (2013) Onchocerca volvulus-neurotransmitter tyramine is a biomarker for river blindness. Proc Natl Acad Sci U S A 110(11):4218–4223. Scholar
  43. Godzien J, Ciborowski M, Angulo S, Barbas C (2013) From numbers to a biological sense: how the strategy chosen for metabolomics data treatment may affect final results. A practical example based on urine fingerprints obtained by LC-MS. Electrophoresis 34(19):2812–2826. Scholar
  44. Godzien J, Alonso-Herranz V, Barbas C, Armitage EG (2015) Controlling the quality of metabolomics data: new strategies to get the best out of the QC sample. Metabolomics 11(3):518–528. Scholar
  45. Gowda GA, Shanaiah N, Raftery D (2012) Isotope enhanced approaches in metabolomics. Adv Exp Med Biol 992:147–164. Scholar
  46. Günther G (2014) Multidrug-resistant and extensively drug-resistant tuberculosis: a review of current concepts and future challenges. Clin Med (Lond) 14(3):279–285CrossRefGoogle Scholar
  47. Gupta A, Dwivedi M, Mahdi AA, Gowda GA, Khetrapal CL, Bhandari M (2009) 1H-nuclear magnetic resonance spectroscopy for identifying and quantifying common uropathogens: a metabolic approach to the urinary tract infection. BJU Int 104(2):236–244. Scholar
  48. Gupta A, Dwivedi M, Mahdi AA, Khetrapal CL, Bhandari M (2012) Broad identification of bacterial type in urinary tract infection using 1H NMR spectroscopy. J Proteome Res 11(3):1844–1854. Scholar
  49. Hänscheid T (2003) Current strategies to avoid misdiagnosis of malaria. Clin Microbiol Infect 9(6):497–504. Scholar
  50. Hewer R, Vorster J, Steffens FE, Meyer D (2006) Applying biofluid 1H NMR-based metabonomic techniques to distinguish between HIV-1 positive/AIDS patients on antiretroviral treatment and HIV-1 negative individuals. J Pharm Biomed Anal 41(4):1442–1446. Scholar
  51. Himmelreich U, Accurso R, Malik R, Dolenko B, Somorjai PR, Gupta RK, Gomes L, Mountford CE (2005) Identification of Staphylococcus aureus brain abscesses: rat and human studies with 1H MR spectroscopy. Radiology 236(1):261–270. Scholar
  52. Jain KK (2010) Role of Biomarkers in Health Care. In: Jain KK (ed) The Handbook of Biomarkers, 1st edn. Humana Press, New York, pp 134–149 Google Scholar
  53. John DV, Lin Y-S, Perng GC (2015) Biomarkers of severe dengue disease – a review. J Biomed Sci 22:83. Scholar
  54. Kao D, Ismond KP, Tso V, Millan B, Hotte N, Fedorak RN (2016) Urine-based metabolomic analysis of patients with Clostridium difficile infection: a pilot study. Metabolomics 12(8).
  55. Kennedy PG (2004) Human African trypanosomiasis of the CNS: current issues and challenges. J Clin Invest 113(4):496–504. Scholar
  56. Koo S, Thomas HR, Daniels SD, Lynch RC, Fortier SM, Shea MM, Rearden P, Comolli JC, Baden LR, Marty FM (2014) A breath fungal secondary metabolite signature to diagnose invasive aspergillosis. Clin Infect Dis 59(12):1733–1740. Scholar
  57. Laiakis EC, Hyduke DR, Fornace AJ Jr (2012) Comparison of mouse urinary metabolic profiles after exposure to the inflammatory stressors gamma radiation and lipopolysaccharide. Radiat Res 177(2):187–199. Scholar
  58. Lakshmanan V, Rhee KY, Daily JP (2011) Metabolomics and malaria biology. Mol Biochem Parasitol 175(2):104–111. Scholar
  59. Lakshmanan V, Rhee KY, Wang W, Yu Y, Khafizov K, Fiser A, Wu P, Ndir O, Mboup S, Ndiaye D, Daily JP (2012) Metabolomic analysis of patient plasma yields evidence of plant-like alpha-linolenic acid metabolism in Plasmodium falciparum. J Infect Dis 206(2):238–248. Scholar
  60. Lau SK, Lee KC, Lo GC, Ding VS, Chow WN, Ke TY, Curreem SO, To KK, Ho DT, Sridhar S, Wong SC, Chan JF, Hung IF, Sze KH, Lam CW, Yuen KY, Woo PC (2016) Metabolomic profiling of plasma from melioidosis patients using UHPLC-QTOF MS reveals novel biomarkers for diagnosis. Int J Mol Sci 17(3).
  61. Lenz EM, Bright J, Wilson ID, Morgan SR, Nash AF (2003) A 1H NMR-based metabonomic study of urine and plasma samples obtained from healthy human subjects. J Pharm Biomed Anal 33(5):1103–1115. Scholar
  62. Lenz EM, Bright J, Wilson ID, Hughes A, Morrisson J, Lindberg H, Lockton A (2004) Metabonomics, dietary influences and cultural differences: a 1H NMR-based study of urine samples obtained from healthy British and Swedish subjects. J Pharm Biomed Anal 36(4):841–849. Scholar
  63. Li Z, Du B, Li J, Zhang J, Zheng X, Jia H, Xing A, Sun Q, Liu F, Zhang Z (2017) Cerebrospinal fluid metabolomic profiling in tuberculous and viral meningitis: screening potential markers for differential diagnosis. Clin Chim Acta 466:38–45. Scholar
  64. Liew KL, Jee JM, Yap I, Yong PVC (2016) In vitro analysis of metabolites secreted during infection of lung epithelial cells by Cryptococcus neoformans. PLoS ONE.
  65. Limmathurotsakul D, Jamsen K, Arayawichanont A, Simpson JA, White LJ, Lee SJ, Wuthiekanun V, Chantratita N, Cheng A, Day NPJ, Verzilli C, Peacock SJ (2010) Defining the true sensitivity of culture for the diagnosis of melioidosis using Bayesian latent class models. PLoS One 5(8).
  66. Luier L, Loots DT (2016) Tuberculosis metabolomics reveals adaptations of man and microbe in order to outcompete and survive. Metabolomics 12(3).
  67. Lv H, Hung CS, Chaturvedi KS, Hooton TM, Henderson JP (2011) Development of an integrated metabolomic profiling approach for infectious diseases research. Analyst 136(22):4752–4763. Scholar
  68. Mahapatra S, Hess AM, Johnson JL, Eisenach KD, DeGroote MA, Gitta P, Joloba ML, Kaplan G, Walzl G, Boom WH, Belisle JT (2014) A metabolic biosignature of early response to anti-tuberculosis treatment. BMC Infect Dis 14:53. Scholar
  69. Marston BJ, Plouffe JF, File TM, Hackman BA, Salstrom SJ, Lipman HB, Kolczak MS, Breiman RF (1997) Incidence of community-acquired pneumonia requiring hospitalization – results of a population-based active surveillance study in Ohio. Arch Intern Med 157(15):1709–1718CrossRefPubMedGoogle Scholar
  70. Martin GS (2012) Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes. Expert Rev Anti Infect Ther 10(6):701–706. Scholar
  71. Martina BE, Koraka P, Osterhaus AD (2009) Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22(4):564–581. Scholar
  72. Mason S, van Furth AMT, Solomons R, Wevers RA, van Reenen M, Reinecke CJ (2016) A putative urinary biosignature for diagnosis and follow-up of tuberculous meningitis in children: outcome of a metabolomics study disclosing host-pathogen responses. Metabolomics 12(7):110. Scholar
  73. Mayeux R (2004) Biomarkers: potential uses and limitations. NeuroRx 1(2):182–188. Scholar
  74. Mirnaghi FS, Caudy AA (2014) Challenges of analyzing different classes of metabolites by a single analytical method. Bioanalysis 6(24):3393–3416. Scholar
  75. MMWR Recommendations and reports (1996) Defining the public health impact of drug-resistant Streptococcus pneumoniae: report of a working group. Accessed 16 May 2017
  76. Mushtaq MY, Choi YH, Verpoorte R, Wilson EG (2014) Extraction for metabolomics: access to the metabolome. Phytochem Anal 25(4):291–306. Scholar
  77. Näsström E, Thieu NT, Dongol S, Karkey A, Voong Vinh P, Ha Thanh T, Johansson A, Amit A, Thwaites G, Dolecek C, Basnyat B, Baker S, Antti H (2014) Salmonella typhi and Salmonella paratyphi A elaborate distinct systemic metabolite signatures during enteric fever. eLife.
  78. Ng JS, Ryan U, Trengove RD, Maker GL (2012) Development of an untargeted metabolomics method for the analysis of human faecal samples using Cryptosporidium-infected samples. Mol Biochem Parasitol 185(2):145–150. Scholar
  79. Oliver SG, Winson MK, Kell DB, Baganz F (1998) Systematic functional analysis of the yeast genome. Trends Biotechnol 16(9):373–378. Scholar
  80. Olszewski KL, Llinás M (2011) Central carbon metabolism of Plasmodium parasites. Mol Biochem Parasitol 175(2):95–103. Scholar
  81. Pappa V, Seydel K, Gupta S, Feintuch CM, Potchen MJ, Kampondeni S, Goldman-Yassen A, Veenstra M, Lopez L, Kim RS, Berman JW, Taylor T, Daily JP (2015) Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria. Malar J 14:513. Scholar
  82. Parry CM, Wijedoru L, Arjyal A, Baker S (2011) The utility of diagnostic tests for enteric fever in endemic locations. Expert Rev Anti Infect Ther 9(6):711–725. Scholar
  83. Pawlotsky JM (2004) Pathophysiology of hepatitis C virus infection and related liver disease. Trends Microbiol 12(2):96–102. Scholar
  84. Pearle MS (2004) Does the midstream urine culture and sensitivity test reliably predict infected urine near a ureteral obstruction? Nat Clin Pract Urol 1(1):16–17. Scholar
  85. Ptolemy AS, Rifai N (2010) What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema. Scand J Clin Lab Invest Suppl 242:6–14. Scholar
  86. Ramakrishnan S, Docampo MD, MacRae JI, Pujol FM, Brooks CF, van Dooren GG, Hiltunen JK, Kastaniotis AJ, McConville MJ, Striepen B (2012) Apicoplast and endoplasmic reticulum cooperate in fatty acid biosynthesis in apicomplexan parasite Toxoplasma gondii. J Biol Chem 287(7):4957–4971. Scholar
  87. Ramautar R, Nevedomskaya E, Mayboroda OA, Deelder AM, Wilson ID, Gika HG, Theodoridis GA, Somsen GW, de Jong GJ (2011) Metabolic profiling of human urine by CE-MS using a positively charged capillary coating and comparison with UPLC-MS. Mol Biosyst 7(1):194–199. Scholar
  88. Rojo D (2014) Metabolómica e integración multiómica en organismos unicelulares. Hacia la comprensión de sistemas biológicos. Dissertation, CEU San Pablo UniversityGoogle Scholar
  89. Rojo D, Gosalbes MJ, Ferrari R, Pérez-Cobas AE, Hernández E, Oltra R, Buesa J, Latorre A, Barbas C, Ferrer M, Moya A (2015) Clostridium difficile heterogeneously impacts intestinal community architecture but drives stable metabolome responses. ISME J 9(10):2206–2220. Scholar
  90. Ronald A (2003) The etiology of urinary tract infection: traditional and emerging pathogens. Dis Mon 49(2):71–82. Scholar
  91. Rowan DD (2011) Volatile metabolites. Metabolites 1(1):41–63. Scholar
  92. Saito T, Sugimoto M, Igarashi K, Saito K, Shao L, Katsumi T, Tomita K, Sato C, Okumoto K, Nishise Y, Watanabe H, Tomita M, Ueno Y, Soga T (2013) Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin: a metabolomics analysis. Metabolism 62(11):1577–1586. Scholar
  93. Salek RM, Maguire ML, Bentley E, Rubtsov DV, Hough T, Cheeseman M, Nunez D, Sweatman BC, Haselden JN, Cox RD, Connor SC, Griffin JL (2007) A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human. Physiol Genomics 29(2):99–108. Scholar
  94. Sanchez EL, Lagunoff M (2015) Viral activation of cellular metabolism. Virology 479–480:609–618. Scholar
  95. Sengupta A, Ghosh S, Basant A, Malusare S, Johri P, Pathak S, Sharma S, Sonawat HM (2011) Global host metabolic response to Plasmodium vivax infection: a 1H NMR based urinary metabonomic study. Malar J 10:384. Scholar
  96. Sengupta A, Ghosh S, Pathak S, Gogtay N, Thatte U, Doshi M, Sharma S, Sonawat HM (2015) Metabolomic analysis of urine samples of vivax malaria in-patients for biomarker identification. Metabolomics 11(5):1351–1362. Scholar
  97. Sengupta A, Ghosh S, Das BK, Panda A, Tripathy R, Pied S, Ravindran B, Pathak S, Sharma S, Sonawat HM (2016) Host metabolic responses to Plasmodium falciparum infections evaluated by 1H NMR metabolomics. Mol Biosyst 12(11):3324–3332. Scholar
  98. Shahfiza N, Osman H, Hock TT, Shaari K, Abdel-Hamid AH (2015) Metabolomics for characterization of gender differences in patients infected with dengue virus. Asian Pac J Trop Med 8(6):452–457. Scholar
  99. Singh S, Srivastava S, Roy R, Gaurav K, Kumar S, Sonkar AA, Goel MM, Garg R (2014) Metabolic profiling of cervical tubercular lymphadenitis tissues by proton HR-MAS NMR spectroscopy. Metabolomics 10(5):975–985. Scholar
  100. Slupsky CM, Rankin KN, Fu H, Chang D, Rowe BH, Charles PG, McGeer A, Low D, Long R, Kunimoto D, Sawyer MB, Fedorak RN, Adamko DJ, Saude EJ, Shah SL, Marrie TJ (2009) Pneumococcal pneumonia: potential for diagnosis through a urinary metabolic profile. J Proteome Res 8(12):5550–5558. Scholar
  101. Soga T, Sugimoto M, Honma M, Mori M, Igarashi K, Kashikura K, Ikeda S, Hirayama A, Yamamoto T, Yoshida H, Otsuka M, Tsuji S, Yatomi Y, Sakuragawa T, Watanabe H, Nihei K, Saito T, Kawata S, Suzuki H, Tomita M, Suematsu M (2011) Serum metabolomics reveals gamma-glutamyl dipeptides as biomarkers for discrimination among different forms of liver disease. J Hepatol 55(4):896–905. Scholar
  102. Sonawat HM, Sharma S (2012) Host responses in malaria disease evaluated through nuclear magnetic resonance-based metabonomics. Clin Lab Med 32(2):129–142. Scholar
  103. Su L, Huang Y, Zhu Y, Xia L, Wang R, Xiao K, Wang H, Yan P, Wen B, Cao L, Meng N, Luan H, Liu C, Li X, Xie L (2014) Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach. BMJ Open Respir Res.
  104. Subramani E, Dutta M, Jothiramajayam M, Joshi M, Srivastava S, Mukherjee A, Chakravarty B, Chaudhury K (2016) Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis. Metabolomics 12(6):99. Scholar
  105. Surowiec I, Orikiiriza J, Karlsson E, Nelson M, Bonde M, Kyamanwa P, Karenzi B, Bergström S, Trygg J, Normark J (2015) Metabolic signature profiling as a diagnostic and prognostic tool in pediatric Plasmodium falciparum malaria. Open Forum Infect Dis 2(2):ofv062. Scholar
  106. Sweatman BC, Farrant RD, Lindon JC (1993) NMR of biofluids: detection of 2H-acetate and 2H-formate in urine as an indicator of microbiological contamination. J Pharm Biomed Anal 11(2):169–172. Scholar
  107. Syed IH, Balakrishnan P, Solomon SS, Murugavel KG, Kumarasamy N, Vidya S, Martin SP, Thyagarajan SP, Mayer KH, Solomon S (2005) HIV-1 western blot assay: what determines an indeterminate status? Indian J Med Sci 59(10):443–450CrossRefPubMedGoogle Scholar
  108. Teixeira AR, Hecht MM, Guimaro MC, Sousa AO, Nitz N (2011) Pathogenesis of Chagas’ disease: parasite persistence and autoimmunity. Clin Microbiol Rev 24(3):592–630. Scholar
  109. Vincent IM, Daly R, Courtioux B, Cattanach AM, Bieler S, Ndung’u JM, Bisser S, Barrett MP (2016) Metabolomics identifies multiple candidate biomarkers to diagnose and stage human African trypanosomiasis. PloS Negl Trop Dis.
  110. Voge NV, Perera R, Mahapatra S, Gresh L, Balmaseda A, Loroño-Pino MA, Hopf-Jannasch AS, Belisle JT, Harris E, Blair CD, Beaty BJ (2016) Metabolomics-based discovery of small molecule biomarkers in serum associated with dengue virus infections and disease outcomes. PLoS Negl Trop Dis.
  111. Voskuil J (2015) How difficult is the validation of clinical biomarkers? F1000Res 4:101. Scholar
  112. Weiner J 3rd, Parida SK, Maertzdorf J, Black GF, Repsilber D, Telaar A, Mohney RP, Arndt-Sullivan C, Ganoza CA, Faé KC, Walzl G, Kaufmann SH (2012) Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients. PLoS ONE 7(7).
  113. WHO (2017a) The top 10 causes of death. Accessed 29 May 2017
  114. WHO (2017b) Global hepatitis report 2017. World Health Organization, GenevaGoogle Scholar
  115. WHO (2017c) Trypanosomiasis, human African (sleeping sickness). Accessed 28 May 2017
  116. WHO (2017d) World health statistics 2017: monitoring health for the SDGs, sustainable development goals. World Health Organization, GenevaGoogle Scholar
  117. Winder CL, Dunn WB, Schuler S, Broadhurst D, Jarvis R, Stephens GM, Goodacre R (2008) Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites. Anal Chem 80(8):2939–2948. Scholar
  118. Xia J, Broadhurst DI, Wilson M, Wishart DS (2013) Translational biomarker discovery in clinical metabolomics: an introductory tutorial. Metabolomics 9(2):280–299. Scholar
  119. Zaki SA, Karande S (2011) Multidrug-resistant typhoid fever: a review. J Infect Dev Ctries 5(5):324–337CrossRefPubMedGoogle Scholar
  120. Zhang QW, Takahashi M, Noguchi Y, Sugimoto T, Kimura T, Okumura A, Ishikawa T, Kakumu S (2006) Plasma amino acid profiles applied for diagnosis of advanced liver fibrosis in patients with chronic hepatitis C infection. Hepatol Res 34(3):170–177. Scholar
  121. Zhang W, Hankemeier T, Ramautar R (2017) Next-generation capillary electrophoresis-mass spectrometry approaches in metabolomics. Curr Opin Biotechnol 43:1–7. Scholar
  122. Zhong L, Zhou J, Chen X, Yin Y (2016) Serum metabolomic study for the detection of candidate biomarkers of tuberculosis. Int J of Clin Exp Pathol 9(3):3256–3266Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Miguel Fernández-García
    • 1
  • David Rojo
    • 1
  • Fernanda Rey-Stolle
    • 1
  • Antonia García
    • 1
  • Coral Barbas
    • 1
  1. 1.Center for Metabolomics and Bioanalysis (CEMBIO)CEU San Pablo UniversityBoadilla del MonteSpain

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