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Multimodal biomarker discovery for active Onchocerca volvulus infection
- Source :
- PLoS Neglected Tropical Diseases, Vol 15, Iss 11, p e0009999 (2021), PLoS Neglected Tropical Diseases
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated.<br />Author summary Today’s diagnosis of infection with the filarial parasite Onchocerca volvulus mainly depends on the microscopic analysis of skin biopsies and serological testing. The work presented here describes the use of multiple mass spectrometry-based screening methods (metabolomics and lipidomics) to search for biomarkers indicative of infection with Onchocerca volvulus. This resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine as biomarker for O. volvulus. Further evaluation of these biomarkers in a geographically distinct non-endemic population however invalidated the use of urine cis-cinnamoylglycine. These findings are of utmost importance as it not only opens new avenues in the development of non-invasive diagnostic tools for filarial infections, but also emphasizes the need for evaluation and validation of newly discovered biomarkers in different populations from different geographies.
- Subjects :
- Male
Nematoda
Physiology
Metabolite
RC955-962
Glycobiology
Urine
Onchocerciasis
Biochemistry
Mass Spectrometry
Plasma
chemistry.chemical_compound
Medical Conditions
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Metabolites
Biomarker discovery
Lymphatic filariasis
education.field_of_study
biology
Eukaryota
Nucleosides
Lipids
Glycosylamines
Body Fluids
Infectious Diseases
Helminth Infections
Biomarker (medicine)
Female
Onchocerca
Anatomy
Public aspects of medicine
RA1-1270
Research Article
Neglected Tropical Diseases
Population
Macrofilaricide
Helminths
Parasitic Diseases
medicine
Animals
Metabolomics
Humans
education
business.industry
Organisms
Public Health, Environmental and Occupational Health
Biology and Life Sciences
Tropical Diseases
Lipid Metabolism
biology.organism_classification
medicine.disease
Invertebrates
Onchocerca volvulus
Inosine
Metabolism
chemistry
Immunology
business
Zoology
Biomarkers
Chromatography, Liquid
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 15
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....87798bbc7354ccb5f9801ef06ea619f5