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Abstract
BackgroundDevelopment of robust, sensitive, and reproducible diagnostic tests for understanding the epidemiology of neglected tropical diseases is an integral aspect of the success of worldwide control and elimination programs. In the treatment of onchocerciasis, clinical diagnostics that can function in an elimination scenario are non-existent and desperately needed. Due to its sensitivity and quantitative reproducibility, liquid chromatography-mass spectrometry (LC-MS) based metabolomics is a powerful approach to this problem.Methodology/Principal FindingsAnalysis of an African sample set comprised of 73 serum and plasma samples revealed a set of 14 biomarkers that showed excellent discrimination between Onchocerca volvulus–positive and negative individuals by multivariate statistical analysis. Application of this biomarker set to an additional sample set from onchocerciasis endemic areas where long-term ivermectin treatment has been successful revealed that the biomarker set may also distinguish individuals with worms of compromised viability from those with active infection. Machine learning extended the utility of the biomarker set from a complex multivariate analysis to a binary format applicable for adaptation to a field-based diagnostic, validating the use of complex data mining tools applied to infectious disease biomarker discovery and diagnostic development.Conclusions/SignificanceAn LC-MS metabolomics-based diagnostic has the potential to monitor the progression of onchocerciasis in both endemic and non-endemic geographic areas, as well as provide an essential tool to multinational programs in the ongoing fight against this neglected tropical disease. Ultimately this technology can be expanded for the diagnosis of other filarial and/or neglected tropical diseases.
Highlights
Onchocerciasis, commonly referred to as ‘‘river blindness’’ is classified by the World Health Organization (WHO) as a neglected tropical disease, afflicting approximately 37 million people in Africa, Central and South America and Yemen, with 89 million more at risk [1]
Clinical diagnostics are desperately needed in order to achieve the goals of controlling and eliminating onchocerciasis and neglected tropical diseases in general
A metabolomics approach is introduced for the discovery of small molecule biomarkers that can be used to diagnose O. volvulus infection
Summary
Onchocerciasis, commonly referred to as ‘‘river blindness’’ is classified by the World Health Organization (WHO) as a neglected tropical disease, afflicting approximately 37 million people in Africa, Central and South America and Yemen, with 89 million more at risk [1]. The causative agent, the filarial nematode Onchocerca volvulus, is transmitted in its larval stage between human hosts through the bite of a Simulium (sp.) black fly. Once these parasites have matured into the adult form, they can live for approximately 14 years in subcutaneous nodules within a human host [3]. The combination of the lack of effect of annual ivermectin treatment on adult worm survival and the fecundity of adult females, along with significant fly and human migration patterns has helped to perpetuate the disease. Development of robust, sensitive, and reproducible diagnostic tests for understanding the epidemiology of neglected tropical diseases is an integral aspect of the success of worldwide control and elimination programs. Due to its sensitivity and quantitative reproducibility, liquid chromatography-mass spectrometry (LCMS) based metabolomics is a powerful approach to this problem
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