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

An Hotterbeekx,Michel Mandro,Robert Colebunders,Steven Abrams,Alfred Dusabimana,Germain M Abhafule,Joseph N Siewe Fodjo,Wonya’Rossy Deogratias

doi:10.3390/pathogens9030191

An Hotterbeekx, Michel Mandro + Show 6 more

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https://doi.org/10.3390/pathogens9030191

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Journal: Pathogens	Publication Date: Mar 5, 2020
Citations: 9	License type: CC BY 4.0

Affiliation: University of Antwerp, Hasselt University

Abstract

We investigated urinary N-acetyltyramine-O,β-glucuronide (NATOG) levels as a biomarker for active Onchocerca volvulus infection in an onchocerciasis-endemic area in the Democratic Republic of Congo with a high epilepsy prevalence. Urinary NATOG was measured in non-epileptic men with and without O. volvulus infection, and in O. volvulus-infected persons with epilepsy (PWE). Urinary NATOG concentration was positively associated with microfilarial density (p < 0.001). The median urinary NATOG concentration was higher in PWE (3.67 µM) compared to men without epilepsy (1.74 µM), p = 0.017; and was higher in persons with severe (7.62 µM) compared to mild epilepsy (2.16 µM); p = 0.008. Non-epileptic participants with and without O. volvulus infection had similar NATOG levels (2.23 µM and 0.71 µM, p = 0.426). In a receiver operating characteristic curve analysis to investigate the diagnostic value of urinary NATOG, the area under the curve was 0.721 (95% CI: 0.633–0.797). Using the previously proposed cut-off value of 13 µM to distinguish between an active O. volvulus infection and an uninfected state, the sensitivity was 15.9% and the specificity 95.9%. In conclusion, an O. volvulus infection is associated with an increased urinary NATOG concentration, which correlates with the individual parasitic load. However, the NATOG concentration has a low discriminating power to differentiate between infected and uninfected individuals.

Highlights

The filarial nematode Onchocerca volvulus is transmitted by blackflies (Simuliidae) and causes skin disease, eye disease, and epilepsy (onchocerciasis-associated epilepsy (OAE)) [1]
Twenty O. volvulus-infected and 19 uninfected ivermectin-naive men without epilepsy participated in the study
This is the first study investigating the association between urinary NATOG concentration and

Summary

Introduction

The filarial nematode Onchocerca volvulus is transmitted by blackflies (Simuliidae) and causes skin disease (itching and rash), eye disease (progressive loss of vision), and epilepsy (onchocerciasis-associated epilepsy (OAE)) [1]. A recent study showed that children with a high microfilarial (mf, larval stage) density (>200 mf/skin snip) were 28 times more likely to develop epilepsy as compared to children without mf [2]. Elimination programs are ongoing in onchocerciasis-endemic regions through the mass distribution of ivermectin (community-directed treatment with ivermectin (CDTI)) [4,5]. Onchocerciasis is diagnosed through the detection of microfilariae in skin snips. Obtaining skin snips requires an invasive, slightly painful procedure and is not accepted everywhere, especially in low-endemic regions. Exposure to O. volvulus can be estimated by means of a rapid diagnostic test (RDT) detecting IgG4 antibodies against the OV16 antigen of O. volvulus [7]. A disadvantage of the aforementioned test is that it does not differentiate between active infection and past exposure and that it does not provide information about infection load

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