A novel and accurate diagnostic test for human African trypanosomiasis

Papadopoulos, Marios C.; Abel, Paulo M.; Agranoff, Dan; Stich, August; Tarelli, Edward; Bell, B. Anthony; Planche, Timothy; Loosemore, Alison; Saadoun, Samira; Wilkins, P.; Krishna, Sanjeev

doi:10.1016/s0140-6736(04)16046-7

Cited by 130 publications

(79 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Future studies should look at extending this work to other host-parasite models, e.g., hamsters infected with S. japonicum, and investigating human subjects infected with other trematodes (e.g., Fasciola hepatica), nematodes (e.g., hookworm infections), and intestinal protozoa (e.g., Entamoeba histolytica). An innovative proteonomics approach has just been developed as an accurate diagnostic test for human African trypanosomiasis, by means of mass spectrometry on serum coupled with the use of sophisticated data mining tools (50). We believe that metabonomics also represents an ''omics'' science that now requires comprehensive assessment and validation for its potential in individual and community diagnosis, particularly with regard to responses to treatment.…”

Section: Discussionmentioning

confidence: 99%

Metabonomic investigations in mice infected with Schistosoma mansoni : An approach for biomarker identification

Wang

Holmes

Nicholson

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

278

289

View full text Add to dashboard Cite

asis. Using a Schistosoma mansoni-mouse model, we present a characterization of a parasitic infection by metabolic profiling, employing 1 H NMR spectroscopy and multivariate pattern recognition techniques. We infected 10 mice with 80 S. mansoni cercariae each and collected urine samples 49 and 56 days postinfection. Urine samples were also obtained from 10 uninfected control mice at the same time. The metabolic signature of an S. mansoni infection consists of reduced levels of the tricarboxylic acid cycle intermediates, including citrate, succinate, and 2-oxoglutarate, and increased levels of pyruvate, suggesting stimulated glycolysis. A disturbance of amino acid metabolism was also associated with an S. mansoni infection, as indicated by depletion of taurine, 2-oxoisocaproate, and 2-oxoisovalerate and elevation of tryptophan in the urine. A range of microbial-related metabolites, i.e., trimethylamine, phenylacetylglycine, acetate, p-cresol glucuronide, butyrate, propionate, and hippurate, were also coupled with an S. mansoni infection, indicating disturbances in the gut microbiota. Our work highlights the potential of metabolic profiling to enhance our understanding of biological responses to parasitic infections. It also holds promise as a basis for novel diagnostic tests with high sensitivity and specificity and for improved disease surveillance and control.

show abstract

Section: Discussionmentioning

confidence: 99%

Metabonomic investigations in mice infected with Schistosoma mansoni : An approach for biomarker identification

Wang

Holmes

Nicholson

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

278

289

View full text Add to dashboard Cite

show abstract

“…With the advent of ''omics'' technologies, new approaches to the diagnosis of infectious diseases have been made possible. Both genomic and proteomic approaches have been applied to the diagnosis of HAT (11,12). However, as yet no satisfactory biomarkers, or combination thereof, have been identified.…”

mentioning

confidence: 99%

Global metabolic responses of mice to Trypanosoma brucei brucei infection

Wang

Utzinger²,

Saric

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

126

185

View full text Add to dashboard Cite

Human African trypanosomiasis (HAT) is transmitted by tsetse flies and, if untreated, is fatal. Treatment depends on infection stage, and early diagnosis is crucial for effective disease management. The systemic host biochemical changes induced by HAT that enable biomarker discovery or relate to therapeutic outcome are largely unknown. We have characterized the multivariate temporal responses of mice to Trypanosoma brucei brucei infection, using 1 H nuclear magnetic resonance (NMR) spectroscopic metabolic phenotyping of urine and plasma. Marked alterations in plasma metabolic profiles were detected already 1 day postinfection. Elevated plasma concentrations of lactate, branched chain amino acids, and acetylglycoprotein fragments were noted. T. brucei brucei-infected mice also had an imbalance of plasma alanine and valine, consistent with differential gluconeogenesis (parasite)-ketogenesis (host) pathway counterflux, involving stimulated host glycolysis, ketogenesis, and enhanced lipid oxidation in the host. Histopathologic evidence of T. brucei brucei-induced extramedullary hepatic hemopoiesis, renal interstitial nephritis, and a provoked inflammatory response was also noted. Metabolic disturbance of gut microbiotal activity was associated with infection, as indicated by changes in the urinary concentrations of the microbial co-metabolites, including hippurate. Concluding, parasite infection results in multiple systemic biochemical effects in the host and disturbance of the symbiotic gut microbial metabolic interactions. Investigation of these transgenomic metabolic alterations may underpin the development of new diagnostic criteria and metrics of therapeutic efficacy. diagnosis ͉ metabonomics ͉ NMR spectroscopy ͉ trypanosomiasis

show abstract

“…A variant of MALDI-TOF that has been more extensively used is surface-enhanced laser desorption/ionization (SELDI) TOF mass spectrometry, in which sample chips of differing surface chemistries selectively bind proteins, e.g., cations, in a sample before mass profiling (7 ). The potential of SELDI-TOF is illustrated by the many studies with biologically and clinically relevant results, including identification of ␣-defensins as the agents in CD8 T-cellderived anti-HIV1 activity (8 ); profiling of different ␤-amyloid forms in Alzheimer disease (9,10 ); and in combination with various computer algorithms, the generation of impressive predictive diagnostic tests in many studies encompassing a range of diseases, such as ovarian (11 ), prostate (12 ), and breast (13 ) cancers as well as trypanosomiasis (14 ) and alcoholism (15 ).…”

mentioning

confidence: 99%

Influences of Blood Sample Processing on Low–Molecular-Weight Proteome Identified by Surface-Enhanced Laser Desorption/Ionization Mass Spectrometry

et al. 2005

View full text Add to dashboard Cite

Background: Profiling approaches in proteomics, such as surface-enhanced laser desorption/ionization (SELDI) mass spectrometry, are used in disease marker discovery. The aim of this study was to investigate the potential influence of selected preanalytical factors on the results obtained. Methods: Plasma samples anticoagulated with EDTA, citrate, or heparin, and serum samples from healthy volunteers were profiled by SELDI on CM10, immobilized metal affinity capture (IMAC) array with copper, and H50 chip surfaces. Using linear mixed-effects models, we examined the influence of elapsed time between venipuncture and sample separation (immediate to 24 h) and the type of serum tube used (Greiner Vacuette activator, gel serum separator, or plain tubes). We analyzed purified platelets, as well as platelet-poor and platelet-rich plasma samples treated with calcium and/or thrombin to determine the platelet contribution, directly or via the clotting process, to the profiles generated. We then used cluster analysis to identify samples with similar peak profiles. Results: Different plasma types and sera could be distinguished on the basis of cluster analyses of their spectral profiles. Elapsed time between venipuncture and separation of plasma and serum from blood samples altered the profiles obtained, particularly for serum

show abstract

A novel and accurate diagnostic test for human African trypanosomiasis

Cited by 130 publications

References 17 publications

Metabonomic investigations in mice infected with Schistosoma mansoni : An approach for biomarker identification

Metabonomic investigations in mice infected with Schistosoma mansoni : An approach for biomarker identification

Global metabolic responses of mice to Trypanosoma brucei brucei infection

Influences of Blood Sample Processing on Low–Molecular-Weight Proteome Identified by Surface-Enhanced Laser Desorption/Ionization Mass Spectrometry

Contact Info

Product

Resources

About