Trends in Parasitology
Research FocusProteomic fingerprinting for the diagnosis of human African trypanosomiasis
Section snippets
Diagnostic challenges posed by human African trypanosomiasis
Human African trypanosomiasis (HAT) is caused by two subspecies of Trypanosoma brucei – Tb rhodesiense and Tb gambiense – responsible for the East and West African forms of the disease, respectively. Approximately 500 000 people are infected with HAT at any one time, equating to ∼1 598 000 disability-adjusted life years (DALYs) and ∼50 000 deaths per year 1, 2. Both geographical forms of the disease progress from an initial haemolymphatic phase to a meningoencephalitic stage that is fatal if
The concept of a proteomic fingerprint
The fundamental premise underlying the study by Papadopolous et al. [5] is that disease states might be associated with distinctive configurations of circulating proteins: so-called ‘proteomic fingerprints’. More than 1000 distinct gene products can be discerned in human plasma [6], although only a handful of detection assays are currently in routine clinical use. The biological complexity of most disease states means that single biomarkers, with a few notable exceptions such as Troponin I or
A proteomic fingerprint for HAT
The study by Papadopolous et al. [5] shows that a highly discriminatory serum proteomic fingerprint exists for the West African form of HAT. By training three sophisticated data-mining algorithms – a neural network, a genetic algorithm and a decision-tree classifier (Box 2) – to distinguish between sera mass-spectra generated by SELDI-TOF MS from patients with HAT and those from a range of controls, Papadopoulos et al. extracted a proteomic pattern that identified HAT in an independent set of
From cutting-edge to field-applicable technology
In its present form, the cost and complexity of the technique preclude its use as a routine diagnostic test for HAT in an African setting. Moreover, even if cost were not an issue, the sensitivity of the technology to artefacts associated with suboptimal sample collection and storage in a resource-poor clinical setting would limit its reliability in the field. Generation of reproducible SELDI-TOF spectra requires prompt separation of serum and storage at −20°C or below, and repeated freeze–thaw
Perspective
The work by Papadopoulos et al. [5] shows that proteomic fingerprinting might have great potential as a powerful discovery tool in the design of improved diagnostic and staging tests for HAT. However, major technical and conceptual challenges still need to be met before this technology can have a direct impact on the management of HAT in sub-Saharan Africa.
Acknowledgements
Our work was supported by a WHO (TDR) grant (A20536) and a Wellcome Trust Advanced Training Fellowship to D.A. (GR063634MA). We thank colleagues at ANGOTRIP in Uige (Angola) and Marios Papadopoulos.
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