{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:45:29Z","timestamp":1788245129496,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["671055"],"award-info":[{"award-number":["671055"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>We investigated urinary N-acetyltyramine-O,\u03b2-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 &lt; 0.001). The median urinary NATOG concentration was higher in PWE (3.67 \u00b5M) compared to men without epilepsy (1.74 \u00b5M), p = 0.017; and was higher in persons with severe (7.62 \u00b5M) compared to mild epilepsy (2.16 \u00b5M); p = 0.008. Non-epileptic participants with and without O. volvulus infection had similar NATOG levels (2.23 \u00b5M and 0.71 \u00b5M, 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\u20130.797). Using the previously proposed cut-off value of 13 \u00b5M 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.<\/jats:p>","DOI":"10.3390\/pathogens9030191","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T09:26:41Z","timestamp":1583486801000},"page":"191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Urinary N-acetyltyramine-O,\u03b2-glucuronide in Persons with Onchocerciasis-Associated Epilepsy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-4032","authenticated-orcid":false,"given":"An","family":"Hotterbeekx","sequence":"first","affiliation":[{"name":"Global Health Institute, University of Antwerp, B-2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Dusabimana","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, B-2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Mandro","sequence":"additional","affiliation":[{"name":"Provincial Health Division Ituri, Ministry of Health, 185 DRC 57 Ituri, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germain M","family":"Abhafule","sequence":"additional","affiliation":[{"name":"Provincial Health Division Ituri, Ministry of Health, 185 DRC 57 Ituri, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonya\u2019Rossy","family":"Deogratias","sequence":"additional","affiliation":[{"name":"Provincial Health Division Ituri, Ministry of Health, 185 DRC 57 Ituri, Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-1239","authenticated-orcid":false,"given":"Joseph N.","family":"Siewe Fodjo","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, B-2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7353-9304","authenticated-orcid":false,"given":"Steven","family":"Abrams","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, B-2610 Wilrijk, Belgium"},{"name":"Interuniversity Institute for Biostatistics and statistical Bioinformatics, Data Science Institute, UHasselt, B-3590 Diepenbeek, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1919-1340","authenticated-orcid":false,"given":"Robert","family":"Colebunders","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Antwerp, B-2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.pt.2017.11.009","article-title":"Onchocerciasis-Associated Epilepsy, an Additional Reason for Strengthening Onchocerciasis Elimination Programs","volume":"34","author":"Colebunders","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chesnais, C.B., Nana-Djeunga, H.C., Njamnshi, A.K., Lenou-Nanga, C.G., Boulle, C., Bissek, A.Z., Kamgno, J., Colebunders, R., and Boussinesq, M. (2018). The temporal relationship between onchocerciasis and epilepsy: A population-based cohort study. Lancet Infect. Dis.","DOI":"10.1016\/S1473-3099(18)30425-0"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ijid.2016.01.016","article-title":"Nodding syndrome\u2014We can now prevent it","volume":"44","author":"Colebunders","year":"2016","journal-title":"Int. J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s40249-016-0160-7","article-title":"Progress towards onchocerciasis elimination in the participating countries of the African Programme for Onchocerciasis Control: Epidemiological evaluation results","volume":"5","author":"Tekle","year":"2016","journal-title":"Infect. Dis. Poverty"},{"key":"ref_5","unstructured":"WHO (1995). Onchocerciasis and Its Control, World Health Organisation."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1046\/j.1365-3156.2003.01192.x","article-title":"Research for control: The onchocerciasis experience","volume":"9","author":"Remme","year":"2004","journal-title":"Trop. Med. Int. Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1086\/317629","article-title":"A rapid-format antibody card test for diagnosis of onchocerciasis","volume":"182","author":"Weil","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1086\/505081","article-title":"Field applicability of a rapid-format anti-Ov-16 antibody test for the assessment of onchocerciasis control measures in regions of endemicity","volume":"194","author":"Lipner","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1073\/pnas.1221969110","article-title":"Onchocerca volvulus-neurotransmitter tyramine is a biomarker for river blindness","volume":"110","author":"Globisch","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1016\/j.bmcl.2017.05.082","article-title":"Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG)","volume":"27","author":"Globisch","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bennuru, S., Cotton, J.A., Ribeiro, J.M., Grote, A., Harsha, B., Holroyd, N., Mhashilkar, A., Molina, D.M., Randall, A.Z., and Shandling, A.D. (2016). Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont. mBio, 7.","DOI":"10.1128\/mBio.02028-16"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/s13071-016-1582-6","article-title":"Evaluation of the diagnostic potential of urinary N-Acetyltyramine-O,beta-glucuronide (NATOG) as diagnostic biomarker for Onchocerca volvulus infection","volume":"9","author":"Lagatie","year":"2016","journal-title":"Parasit. Vectors"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40249-018-0452-1","article-title":"High prevalence of epilepsy in onchocerciasis endemic health areas in Democratic Republic of the Congo","volume":"7","author":"Lenaerts","year":"2018","journal-title":"Infect. Dis. Poverty"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mandro, M., Siewe Fodjo, J.N., Mukendi, D., Dusabimana, A., Menon, S., Haesendonckx, S., Lokonda, R., Nakato, S., Nyisi, F., and Abhafule, G. (2020). Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0007966"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2196\/resprot.7186","article-title":"Ivermectin Treatment in Patients With Onchocerciasis-Associated Epilepsy: Protocol of a Randomized Clinical Trial","volume":"6","author":"Colebunders","year":"2017","journal-title":"JMIR Res. Protoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1080\/01621459.1968.10480934","article-title":"Estimates of the Regression Coefficient Based on Kendall's Tau","volume":"63","author":"Sen","year":"1968","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_17","unstructured":"Lewis, C.B., and Adams, N. (2019). Phenobarbital. StatPearls, StatPearls Publishing."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1017\/S0031182005008218","article-title":"Glutamate-gated chloride channels and the mode of action of the avermectin\/milbemycin anthelmintics","volume":"131","author":"Wolstenholme","year":"2005","journal-title":"Parasitology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1021\/acsinfecdis.8b00163","article-title":"Noninvasive Urine Biomarker Lateral Flow Immunoassay for Monitoring Active Onchocerciasis","volume":"4","author":"Shirey","year":"2018","journal-title":"ACS Infect. Dis."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/3\/191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:04:32Z","timestamp":1760173472000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/3\/191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,5]]},"references-count":19,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["pathogens9030191"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9030191","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,5]]}}}