Abstract
Current diagnostic tools to determine infection with the helminth parasite Onchocerca volvulus have limited performance characteristics. In previous studies, a proteome-wide screen was conducted to identify linear epitopes in this parasite’s proteome, resulting in the discovery of 1110 antigenic peptide fragments. Here, we investigated three of these peptides using peptide ELISA’s and evaluated their sensitivity and specificity. Epitope mapping was performed, and peptides were constructed that contained only the minimal epitope, flanked by a linker. Investigation of the performance of these minimal epitope peptides demonstrated that all three of them have a specificity (as defined by lack of response in non-helminth-infected individuals) of 100%, low cross-reactivity (5.6%, 5.6%, and 9.3%, respectively), but low sensitivity (36.9%, 46.5%, and 41.2%, respectively). Some cross-reactivity was observed in samples from individuals infected with soil-transmitted helminths or Brugia malayi. Combining these three minimal epitopes in a single peptide, called OvNMP-48, resulted in a performance that exceeded the sum of the individual epitopes, with a sensitivity of 76.0%, a specificity of 97.4%, and a cross-reactivity of 11.1%. Cross-reactivity was observed in some STH and Brugia malayi-infected individuals. This work opens the opportunity to start exploring how these novel linear epitope markers might become part of the O. volvulus diagnostic toolbox.
Highlights
Of the 20 infectious diseases listed on the World Health Organization (WHO) list of Neglected Tropical Diseases, eight of them are caused by a helminth infection (Holmes 2014; Hotez et al 2008; WHO 2018)
For samples obtained from FR3, all were de-identified before they were provided to FR3, and usage of these samples for research purposes was approved by the Smith College Institutional Review Board (IRB)
Investigation of the performance of these minimal epitope peptides demonstrated that all three of them have a specificity of 100%, low cross-reactivity (< 10%), but rather low sensitivity (< 50%)
Summary
Of the 20 infectious diseases listed on the World Health Organization (WHO) list of Neglected Tropical Diseases, eight of them are caused by a helminth infection (Holmes 2014; Hotez et al 2008; WHO 2018). Onchocerciasis (or river blindness) is caused by infection with the filarial nematode Onchocerca volvulus. Current treatment programs are based on mass drug administration (MDA) of the microfilaricidal agent ivermectin (Mectizan, Merck) as no approved macrofilaricide drugs or vaccines are available. Contraindications in areas co-endemic for loiasis and an inability to break transmission in some foci ask for a change in strategy including vaccination in order to control or eliminate onchocerciasis (Hotez et al 2015; Makepeace et al 2015)
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