Research Article: Evaluation of the Diagnostic Performance of Onchocerca volvulus Linear Epitopes in a Peptide Enzyme-Linked Immunosorbent Assay

Date Published: March 8, 2018

Publisher: The American Society of Tropical Medicine and Hygiene

Author(s): Ole Lagatie, Ann Verheyen, Erik Nijs, Bieke Van Dorst, Linda Batsa Debrah, Alex Debrah, Taniawati Supali, Erliyani Sartono, Lieven J. Stuyver.

http://doi.org/10.4269/ajtmh.17-0756

Abstract

Diagnostic tools for the detection of infection with Onchocerca volvulus are presently limited to microfilaria detection in skin biopsies and serological assessment using the Ov16 immunoglobulin G4 (IgG4) rapid test, both of which have limited sensitivity. We have investigated the diagnostic performance of a peptide enzyme-linked immunosorbent assay (ELISA) based on immunodominant linear epitopes previously discovered. Peptides that were used in these assays were designated O. volvulus motif peptides (OvMP): OvMP-1 (VSV-EPVTTQET-VSV), OvMP-2 (VSV-KDGEDK-VSV), OvMP-3 (VSV-QTSNLD-VSV), and the combination of the latter two, OvMP-23 (VSV-KDGEDK-VSV-QTSNLD-VSV). Sensitivity (O. volvulus infection), specificity (non-helminth infections), and cross-reactivity (helminth infections) were determined using several panels of clinical plasma isolates. OvMP-1 was found to be very sensitive (100%) and specific (98.7%), but showed substantial cross-reactivity with other helminths. Of the other peptides, OvMP-23 was the most promising peptide with a sensitivity of 92.7%, a specificity of 100%, and a cross-reactivity of 6%. It was also demonstrated that these peptides were immunoreactive to IgG but not IgG4, and there is no correlation with the Ov16 IgG4 status, making them promising candidates to complement this already available test. Combination of the Ov16 IgG4 rapid test and OvMP-23 peptide ELISA led to a sensitivity of 97.3% for the detection of O. volvulus infection, without compromising specificity and with minimal impact on cross-reactivity. The available results open the opportunity for a “clinical utility use case” discussion for improved O. volvulus epidemiological mapping.

Partial Text

One of the 20 communicable diseases listed on the World Health Organization (WHO) list of neglected tropical diseases is onchocerciasis (or river blindness), which is caused by infection with the filarial nematode Onchocerca volvulus.1–3 With at least 120 million people at risk to be infected, the majority of people suffering from this parasitic disease live in Africa.4,5 Recent updates on the Americas have reported that most of the last known areas of O. volvulus transmission have been freed of the parasite.6,7 However, challenges remain in the Amazonian focus straddling Venezuela and Brazil.8 In an effort to eliminate this disease, mass drug administration (MDA) programs with ivermectin have been ongoing for almost three decades.9,10 In 2016, the WHO released updated criteria for stopping MDA as a result of transmission interruption.11 The technical procedures and the corresponding cutoff values to confirm transmission interruption included the following: 1) screening pools of black flies by the polymerase chain reaction (PCR) for the DNA repeat sequence Ov150; minimal elimination value is < 1/2,000 Ov150-positive flies and 2) serological screening of school-aged children < 10 years of age for immunoglobulin G4 (IgG4) antibodies to the Ov16 antigen; elimination value is antibody prevalence < 0.1%. For the latter, a rapid-format test for the detection of IgG4 antibodies to the parasitic Ov16 antigen is available.12–17 We have developed peptide ELISAs based on three consensus immunodominant linear epitope motifs from O. volvulus. The assay based on OvMP-1 not only has excellent sensitivity for O. volvulus, but also cross-reacts substantially with other helminths. Further investigation using clinical samples from well-characterized helminth-infected and/or exposed individuals will be needed to have a clear picture on which helminths cross-react in this assay. The assay based on OvMP-23 has been shown to have a specificity of 100% with a sensitivity of 92% and minimal cross-reactivity with other helminths. When used in conjunction with the Ov16 IgG4 test, a total sensitivity of 97.3% was obtained. The available results open the opportunity for a “clinical utility use case” discussion for improved O. volvulus epidemiological mapping.   Source: http://doi.org/10.4269/ajtmh.17-0756

 

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