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

Abstract

BackgroundCurrently 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.MethodsThe 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.ResultsThe 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.ConclusionThe urinary biomarkers of malaria identified have potential for the development of non-invasive and rapid diagnostic test of P. falciparum infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1875-z) contains supplementary material, which is available to authorized users.

Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite

“…The increase in pipecolate was associated with the schizont stage (32-40 h) of the iRBC (Additional file 5), in broad agreement with a recent study [18]. Furthermore, pipecolate, which accumulates in the plasma [17] and urine [31,32] of patients with severe malaria, has been suggested as a candidate clinical biomarker of malaria. Pipecolate is strongly associated with parasite-infected cultures and may be necessary for IDC progression; it is also associated with increased inflammation [33], oxidative stress [34,35], and epilepsy [36].…”

Insights into malaria pathogenesis gained from host metabolomics

“…In the process, Plasmodium produces various by-products including pipecolic acid, a catabolite of lysine ( Fig 1E). Pipecolic acid is detected in in vitro P. falciparum cultures, murine malaria models, and humans with P. falciparum, but not in uninfected RBC cultures or in humans without malaria infection [43][44][45]. Other metabolites potentially generated by the parasite include VOCs pinene and limonene, which may derive from Plasmodium's isoprenoid biosynthetic pathways and are detected in P. falciparum cultures and breath of humans with falciparum malaria [46].…”

Perturbations of Metabolomic Profiling of Spleen From Rats Infected With Clonorchis sinensis Determined by LC-MS/MS Method

“…These metabolites might be a direct signal of C. sinensis activity or the consequence of the host response to the parasite. Generally, these dynamic metabolites not only could suggest the interaction between the host and C. sinensis , but also might perturb the biochemical profiles of them ( Abdelrazig et al, 2017 ).…”