Multimodal biomarker discovery for active Onchocerca volvulus infection

Area of Science:

• Neglected tropical diseases
• Infectious disease diagnostics
• Biomarker discovery

Background:

• Onchocerciasis (river blindness) affects 17 million globally, primarily in Africa.
• Current diagnostics lack non-invasive methods for infection detection and program monitoring.
• Novel drug development requires efficacy biomarkers and surrogate endpoints.

Purpose of the Study:

• To identify non-invasive biomarkers for onchocerciasis detection using mass spectrometry.
• To evaluate potential biomarkers for monitoring treatment and elimination efforts.
• To discover new tools for clinical trials and epidemiological studies.

Main Methods:

• Multimodal untargeted mass spectrometry (metabolomics and lipidomics) on urine and plasma samples.
• Analysis of samples from onchocerciasis cases, lymphatic filariasis cases, and controls.
• Targeted validation of identified metabolite biomarkers.

Main Results:

• Plasma inosine and hypoxanthine identified as biomarkers for filarial infection.
• Urine cis-cinnamoylglycine (CCG) initially identified but later invalidated as an O. volvulus biomarker.
• Inosine and hypoxanthine confirmed as reliable plasma biomarkers for filarial infection.

Conclusions:

• Plasma inosine and hypoxanthine are validated non-invasive biomarkers for filarial infection.
• These biomarkers can support clinical trials and monitoring of onchocerciasis elimination programs.
• Further investigation using targeted LC-MS can unlock their full potential.