Noninvasive Urine Biomarker Lateral Flow Immunoassay for Monitoring Active Onchocerciasis

Abstract

The parasitic disease onchocerciasis is the second leading cause of preventable blindness, afflicting more than 18 million people worldwide. Despite an available treatment, ivermectin, and control efforts by the World Health Organization, onchocerciasis remains a burden in many regions. With an estimated 120 million people living in areas at risk of infection, efforts are now shifting from prevention to surveillance and elimination. The lack of a robust, point-of-care diagnostic for an active Onchocerca infection has been a limiting factor in these efforts. Previously, we reported the discovery of the biomarker N-acetyl-tyramine-O-glucuronide (NATOG) in human urine samples and its ability to track treatment progression between medicated patients relative to placebo; we also established its capability to monitor disease burden in a jird model. NATOG is a human-produced metabolite of tyramine, which itself is produced as a nematode neurotransmitter. The ability of NATOG to distinguish between active and past infection overcomes the limitations of antibody biomarkers and PCR methodologies. Lateral flow immunoassay (LFIA) diagnostics offer the versatility and simplicity to be employed in the field and are inexpensive enough to be utilized in large-scale screening efforts. Herein, we report the development and assessment of a NATOG-based urine LFIA for onchocerciasis, which accurately identified 85% of analyzed patient samples (N = 27).

Urinary N-acetyltyramine-O,β-glucuronide in Persons with Onchocerciasis-Associated Epilepsy

“…Indeed, the urinary NATOG concentrations and skin mf densities in the study by Lagatie et al were similar to those observed in our study participants after ivermectin treatment (Table 6). Recently, a lateral flow immunoassay (LFIA) test was developed to detect urinary NATOG [19]. In a small study, this test accurately diagnosed 23 (85%) of the 27 African samples tested, with a cut-off concentration set at 25 µM [19].…”

“…Recently, a lateral flow immunoassay (LFIA) test was developed to detect urinary NATOG [19]. In a small study, this test accurately diagnosed 23 (85%) of the 27 African samples tested, with a cut-off concentration set at 25 µM [19]. However, the authors of the above-mentioned study did not provide detailed information about mf densities.…”

Onchocerciasis (river blindness): larva‐induced eczema (onchodermatitis) from an important oculocutaneous tropical disease spilling over into North America and Europe

“…There are several options available for the diagnosis of onchocerciasis, principally the diethylcarbamazine (DEC) patch test, skin snip histopathology, DNA detection by polymerase chain reaction (PCR), and antibody assays . As emphasis shifts from prevention to surveillance and elimination in endemic areas and for detection of occasional patients in Europe and North America, a reliable, inexpensive noninvasive method to diagnosis active infections despite a history of prior ivermectin use is pivotal.…”

“…Molecular tools such as real‐time PCR have high diagnostic sensitivity and specificity, as well as high cost. A promising noninvasive urine biomarker immunoassay for diagnosing active onchocerciasis, representing the least invasive technology, has been developed . The use of rapid‐format antibody card test has also demonstrated promise as an alternative to skin snips for use in diagnostic confirmation of onchocerciasis.…”

Sensitive mass spectrometric analysis of carbonyl metabolites in human urine and fecal samples using chemoselective modification

“…13,14 Urine samples are the end-point of human metabolism and especially interesting as it is an ideal source for the discovery of non-invasive biomarkers that can be readily translated into diagnostic tools. [15][16][17][18][19][20][21] The detection of ketone and aldehyde molecules by liquid chromatography mass spectrometry (LC-MS) remains a challenge due to their poor ionization properties. 22 The development of chemical biology tools in this newly developed research field is limited in comparison with other well-established 'omics' fields.…”