Rapid Identification of Individuals with Viable Adult Female Worms of Onchocerca Volvulus: A Means to the End (OvAF)

Identifying Ov-specific biomarkers and developing rapid point of care detection methods

Overview

Onchocerciasis, commonly known as river blindness, is caused by a parasitic nematode, Onchocerca volvulus (Ov). It is transmitted by Simulium (black fly) vectors. Infection leads to severe and disfiguring skin disease, lymphadenopathy, and visual impairment (including blindness). Onchocerciasis especially affects resource limited rural communities and leads to serious economic losses. There has been considerable success in the control of onchocerciasis through mass drug administration and vector control efforts. As efforts shift toward disease elimination in Africa and particularly toward the end-game, better tools are needed to test for the presence or absence of viable adult female worms of Onchocerca volvulus (OvAF), so as to be able to verify elimination. This project aimed to identify biomarkers that are indicators of viable OvAF infection and then make available rapid and field-friendly tests for use in the post treatment surveillance (PTS) phase when it is necessary to confirm whether transmission remains interrupted after interventions are stopped.

Goals

  • Use advanced, comparative bioinformatics coupled with proteomics, glycomics and metabolomics to identify biomarkers from viable OvAF.
  • Develop and evaluate prototype assays for detection of most promising biomarkers.
  • Validate any developed assays.

Partners

Public-Sector Partners

  • National Institute of Allergy and Infectious Diseases (NIAID)

Private-Sector Partners

  • Bill & Melinda Gates Foundation*
  • New York Blood Center

Academic Partners

  • Thomas Jefferson University
  • University of Buea, Buea Cameroon

*Provided financial or in-kind support for this program.

FNIH Contacts

Susan Wiener, Senior Project Manager; swiener@fnih.org

Results & Accomplishments

  • Identified OvAF-specific proteins, glycans and metabolites to create of a priority list of targets to use as the basis for assay development.
  • Generated reagents (antibodies, antigens) to develop and validate prototype antigen assays in small numbers of well-defined sera.
  • Developed antigen-detection immunoassays for the detection of the 2 most promising biomarkers, OvOC8995 and OvOC12838.
  • Showed that assays for these two biomarkers, when used in concert, provided sensitivities of ~89% with close to 100% specificity. Moreover, in a small set of longitudinally followed patients, the levels of OvOC8995 diminished or disappeared following cure.
  • Identified reasonable small animal systems to make adult Ov worms, and to ensure an adequate supply of L3 larvae with which to infect the mice.

Scientific Publications

  • Bennuru, S., S. Lustigman, D. Abraham, and T.B. Nutman. 2017. Metabolite profiling of infection-associated metabolic markers of onchocerciasis. Mol Biochem Parasitol 23:160-162.
  • Patton, J.B., S. Bennuru, M.L. Eberhard, J.A. Hess, A. Torigian, S. Lustigman, T.B. Nutman, and D. Abraham. 2018. Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum. PLoS Negl Trop Dis 12:e0006977.
  • Bennuru, S., G. Oduro-Boateng, C. Osigwe, P. Del Valle, A. Golden, G.M. Ogawa, V. Cama, S. Lustigman, and T.B. Nutman. 2020. Integrating Multiple Biomarkers to Increase Sensitivity for the Detection of Onchocerca volvulus Infection. J Infect Dis 221:1805-1815.