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J Infect Dis. 2019 Jun 14. pii: jiz307. doi: 10.1093/infdis/jiz307. [Epub ahead of print]

Integrating multiple biomarkers to increase sensitivity for the detection of Onchocerca volvulus infection.

Author information

1
Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
2
Diagnostic Global Program, PATH, Seattle, WA, USA.
3
Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA.
4
Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.

Abstract

Serological assessments for human onchocerciasis are based on IgG4 reactivity against the OV-16 antigen, with sensitivity around 60-80%. We previously identified 7 novel proteins that could enhance onchocerciasis sero-diagnosis. Further screening by luciferase immunoprecipitation assays identified OVOC10469 and OVOC3261 as the most promising candidates. IgG4-based ELISA using recombinant proteins, yielded sensitivities of 53% for rOVOC10469 and 78% for rOVOC3261, while specificity for each was >99%. Moreover, the newly-identified biomarkers detected some (but not all) of the mf-positive samples not detected by OV-16. The new antigens in combination with OV-16, increased the sensitivity for patent infections to 94%, demonstrating the benefits of adding a complementary antigen to OV-16-based serology. The kinetics of appearance of these IgG4 responses based on experimentally infected non-human primates indicated that they were patency driven. Of note, the IgG4 responses to both OVOC10469 and OVOC3261 (as well as to OV-16) drop significantly (p<0.05) following successful treatment for onchocerciasis. A prototype of a lateral flow rapid assay was developed and tested, showing an overall 94% sensitivity. These data showed that the combined use of rOVOC3261 with OV-16 improved case detection, a current and urgent need for the efforts to achieve the worldwide elimination of transmission of O. volvulus.

KEYWORDS:

OV-16; OVOC3261; biomarkers; diagnostics; onchocerciasis

PMID:
31201416
DOI:
10.1093/infdis/jiz307

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