Evaluation of the clinical performance of two new onchocerciasis rapid diagnostic tests in districts targeted for elimination in Ghana

Abstract

Current diagnostic methods for onchocerciasis lack sufficient utility, sensitivity or specificity. Two new lateral flow assays developed by Bioaster and Global Access Diagnostics (BA/GADx) and Drugs and Diagnostics for Tropical Diseases (DDTD) multi-antigen test Biplex Version C (DDTDc) were evaluated in Ghanaian communities that have received mass drug administration for many years or are considered non-endemic to assess their potential for point-of-care use. Both tests detect IgG4 antibodies against the Onchocerca volvulus -specific antigen Ov16, while the DDTD test further detects antibodies to the O. volvulus -specific antigen OvOC3261. The study enrolled 1,700 participants (≥ 5 years) across seven communities. The tests were evaluated on whole blood in the field and on dried blood spots (DBS) in the laboratory. The results were compared with the O-150 qPCR on skin snips and the existing SD Ov16 RDT test on DBS. O-150 Skin snip qPCR identified only 26 positives, limiting the assessments. However, the sensitivities of the DDTDc and BA/GADx RDTs evaluated in the field and in laboratory compared to the O-150 qPCR ranged from 76.9% (95% CI: 56.4–91.0) to 69.2% (95% CI: 48.2–85.7) and 71.3% (95% CI: 52.2–88.4) to 69.2% (95% CI: 48.2–85.7), respectively. The specificities of the DDTDc and BA/GADx RDTs evaluated in the field and laboratory compared to the O-150 qPCR ranged from 68.3% (95% CI: 65.1–71.3) to 69.5% (95% CI: 66.4–72.6) and 72.5% (95% CI: 69.4–75.4) to 68.2% (95% CI: 65.0–71.3), respectively. The sensitivity and specificity of the SD Ov16 RDT based on O-150 qPCR were 65.4% (95% CI: 44.3–82.8) and 72.9% (95% CI: 69.8–75.8%), respectively. The concordance between the new tests and the SD Ov16 RDT was above 92%. There was substantial agreement between the DDTDc test in the field and the SD Ov16 RDT (Kappa = 0.63; SE: 0.03; 95% CI: 0.57–0.69), and between the DDTDc test in the laboratory and the SD Ov16 RDT (Kappa = 0.76; SE: 0.02; 95% CI: 0.71–0.80). Similarly, there was substantial agreement between the BA/GADx test in the field and the SD Ov16 RDT (Kappa = 0.79; SE: 0.02; 95% CI: 0.76–0.83), and between the BA/GADx test in the laboratory and the SD Ov16 RDT (Kappa = 0.76; SE: 0.02; 95% CI: 0.72–0.80). Both tests demonstrated field usability and adequate sensitivity, meeting the WHO TPP requirements for onchocerciasis mapping decisions but not for MDA stopping decisions. These advancements represent progress toward diagnostic tools available for elimination programs but underscore the need for continued diagnostic innovation to address the challenges of evaluating new diagnostic tests in disease elimination settings with a low number of true positives to assess the diagnostic performance of the tests.