In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 15, No. 11 ( 2021-11-29), p. e0009999-
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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0009999
DOI:
10.1371/journal.pntd.0009999.g001
DOI:
10.1371/journal.pntd.0009999.g002
DOI:
10.1371/journal.pntd.0009999.g003
DOI:
10.1371/journal.pntd.0009999.g004
DOI:
10.1371/journal.pntd.0009999.t001
DOI:
10.1371/journal.pntd.0009999.t002
DOI:
10.1371/journal.pntd.0009999.t003
DOI:
10.1371/journal.pntd.0009999.s001
DOI:
10.1371/journal.pntd.0009999.s002
DOI:
10.1371/journal.pntd.0009999.s003
DOI:
10.1371/journal.pntd.0009999.s004
DOI:
10.1371/journal.pntd.0009999.s005
DOI:
10.1371/journal.pntd.0009999.s006
DOI:
10.1371/journal.pntd.0009999.s007
DOI:
10.1371/journal.pntd.0009999.s008
DOI:
10.1371/journal.pntd.0009999.s009
DOI:
10.1371/journal.pntd.0009999.s010
DOI:
10.1371/journal.pntd.0009999.s011
DOI:
10.1371/journal.pntd.0009999.s012
DOI:
10.1371/journal.pntd.0009999.s013
DOI:
10.1371/journal.pntd.0009999.s014
DOI:
10.1371/journal.pntd.0009999.s015
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2429704-5
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