Neglected Tropical Diseases & Tuberculosis
Neglected tropical diseases (NTDs) are among the most debilitating illnesses affecting the world today. These diseases primarily inflict damage upon those countries that are poorest and thus, concern those populations that do not have the resources to maintain programs that monitor and/or eliminate these diseases. Indeed, there is strong evidence linking NTDs to various morbidities and mortality as well as the economic growth of afflicted countries.
Among the NTDs, onchocerciasis (“river blindness”), caused by the parasitic nematode Onchocerca volvulus, afflicts nearly 37 million people worldwide with symptoms of blindness and acute dermatitis, leading to a loss of %7e1 million disability adjusted life years annually. With many onchocerciasis control/elimination programs (e.g., APOC, OEPA) nearing two decades of continuous mass ivermectin treatment, novel approaches toward accurate, sensitive diagnostics are urgently needed given the complete lack of sensitive diagnostics for this disease.
We have developed a metabolomics-based workflow for the discovery of diagnostic biomarker sets for infectious disease. Using liquid chromatography electrospray ionization time of flight (LC/ESI-TOF) mass spectrometry analysis, a panel of sera collected from >300 O. volvulus infected individuals and uninfected controls was analyzed for onchocerciasis biomarkers. Thousands of chromatographic mass features were statistically compared to discover a set of 14 mass features that were significantly different between infected and uninfected individuals. This set of biomarkers was further validated as specific for onchocerciasis when compared with other related diseases (e.g., lympathic filariasis) or other tropical diseases (e.g., Chagas disease, Leishmaniasis). Using multivariate statistical analysis and machine learning algorithms, these biomarkers can be used to differentiate between infected and uninfected individuals and suggest that the diagnostic may even be sensitive enough to assess the viability of parasites. Indeed, the 14 candidate biomarkers showed excellent performance in an African sample set with up to 99–100% sensitivity and specificity when examined with single machine learning algorithms.
The achievement of the goals of elimination and eradication of onchocerciasis and of the neglected tropical diseases in general, ultimately depends upon the ability to measure and track the progress of disease elimination and recrudescence. Through the use of diagnostic technologies that provide near perfect sensitivity and specificity such as metabolite profiling, global goals of disease eradication may be possible.
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