Assessment of multiplex Onchocerca volvulus peptide ELISA in non-endemic tropical regions

Abstract

BackgroundCurrently, serodiagnosis of infection with the helminth parasite Onchocerca volvulus is limited to the Ov-16 IgG4 test, a test that has limited sensitivity and suboptimal specificity. In previous studies, we identified several linear epitopes that have the potential to supplement the diagnostic toolbox for onchocerciasis.MethodsIn this study three peptides, bearing in total six linear epitopes were transferred to a multiplex ELISA platform. This multiplex ELISA was used to assess the clinical utility of the peptide serology markers by analyzing sample sets from both O. volvulus endemic and non-endemic regions.ResultsThe multiplex platform was shown to be reproducible and data obtained on the multiplex platform were comparable to the singleplex ELISA data. The clinical utility assessment showed that in a population of school-aged children from western Kenya, a virtually O. volvulus-free area, significant cross-reactivity with an as-yet to be determined immunogen was detected.ConclusionsThe observations made in this study invalidate the usefulness of the peptide serology markers for onchocerciasis detection. We discuss what could be the origin of this unexpected serological response, but also highlight the need for better characterized biobanks for biomarker discovery activities.

Multimodal biomarker discovery for active Onchocerca volvulus infection

“…In our previous work on clinical utility testing of peptide biomarkers, we came to a similar observation when investigating this population of children in Kenya [39]. More than 50% of the children were indeed seroreactive to the peptide epitopes, without presenting any evidence for being infected, or being exposed, or residing in an endemic area.…”

“…No significant difference between the non-infected and different infection groups was observed (P χ 2 = 0.7042), suggesting that none of these intestinal parasites are linked to elevated CCG levels. The urine CCG data were also compared with the peptide serology data previously obtained from the same study population [ 39 ]. None of the 3 peptide markers correlated with urine CCG, with P-values from Chi square analysis ranging from 0.2362 to >0.999 ( Fig 4 ).…”

“…Also new serological markers have been proposed, such as the peptide makers OvMP-1 and OvMP-23, and OvNMP-48 [34][35][36][37][38]. The use of these peptide markers was subsequently found to be limited (specificity significantly less than the required �99.8%), due to unexplained cross-reactivity in a population of school-age children in a non-endemic area in southwest Kenya [39]. In the work presented here, we conducted a study using both plasma and urine samples from nodule positive individuals that had very low or negative mf counts due to treatment with ivermectin.…”

Identification of antigenic linear peptides in the soil-transmitted helminth and Schistosoma mansoni proteome

“…This has proven a successful approach for viral diseases like HIV and HCV [ 59 – 61 ]. However, our current data seem to indicate that it will not be as straightforward for helminth parasites [ 58 ]. It seems difficult to use antibody detection against linear epitopes as a good measure of helminth or parasite exposure.…”

“…A similar discussion on the need for well-characterized biobanks has also been made for O. volvulus. Several peptides were identified that were assumed to be linked to O. volvulus infection but were later found to be linked-at least partly-to other immunogens, possibly from parasitic origin [58].…”