{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:27:06Z","timestamp":1787005626716,"version":"build-2736575974"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,3,12]]},"abstract":"<jats:p>\n                    Onchocerciasis, also known as \u201criver blindness\u201d, is a neglected tropical disease infecting millions of people mainly in Africa and the Middle East but also in South America and Central America. Disease infectivity initiates from the filarial parasitic nematode\n                    <jats:italic>Onchocerca volvulus<\/jats:italic>\n                    , which is transmitted by the blackfly vector\n                    <jats:italic>Simulium<\/jats:italic>\n                    sp. carrying infectious third-stage larvae. Ivermectin has controlled transmission of microfilariae, with an African Program elimination target date of 2025. However, there is currently no point-of-care diagnostic that can distinguish the burden of infection\u2014including active and\/or past infection\u2014and enable the elimination program to be effectively monitored. Here, we describe how liquid chromatography-MS\u2013based urine metabolome analysis can be exploited for the identification of a unique biomarker,\n                    <jats:italic>N<\/jats:italic>\n                    -acetyltyramine-\n                    <jats:italic>O<\/jats:italic>\n                    ,\u03b2-glucuronide (NATOG), a neurotransmitter-derived secretion metabolite from\n                    <jats:italic>O. volvulus<\/jats:italic>\n                    . The regulation of this tyramine neurotransmitter was found to be linked to patient disease infection, including the controversial antibiotic doxycycline treatment that has been shown to both sterilize and kill adult female worms. Further clues to its regulation have been elucidated through biosynthetic pathway determination within the nematode and its human host. Our results demonstrate that NATOG tracks\n                    <jats:italic>O. volvulus<\/jats:italic>\n                    metabolism in both worms and humans, and thus can be considered a host-specific biomarker for onchocerciasis progression. Liquid chromatography-MS\u2013based urine metabolome analysis discovery of NATOG not only has broad implications for a noninvasive host-specific onchocerciasis diagnostic but provides a basis for the metabolome mining of other neglected tropical diseases for the discovery of distinct biomarkers and monitoring of disease progression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1221969110","type":"journal-article","created":{"date-parts":[[2013,2,26]],"date-time":"2013-02-26T00:41:51Z","timestamp":1361839311000},"page":"4218-4223","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":71,"title":["<i>Onchocerca volvulus<\/i>\n                    -neurotransmitter tyramine is a biomarker for river blindness"],"prefix":"10.1073","volume":"110","author":[{"given":"Daniel","family":"Globisch","sequence":"first","affiliation":[{"name":"Departments of Chemistry, Immunology, and Microbial Science, and Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira Y.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Immunology, and Microbial Science, and Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Hixon","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Immunology, and Microbial Science, and Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA 92037;"},{"name":"Takeda California, Inc., San Diego, CA 92121; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee A. K.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Immunology, and Microbial Science, and Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith R.","family":"Denery","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Immunology, and Microbial Science, and Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Specht","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Immunology, and Parasitology, University Hospital Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Hoerauf","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Immunology, and Parasitology, University Hospital Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim D.","family":"Janda","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Immunology, and Microbial Science, and Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,2,25]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2011.10.003"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09456-4"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-53"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068732"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S8372"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2004.01384.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001712"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000438"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/mas.20108"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb900271r"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000834"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac300698c"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(72)90073-5"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200902740"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02095-X"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-007-0062-1"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-008-1217-8"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(99)00184-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-706X(96)00613-4"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2010.01.014"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ento.50.071803.130404"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01065.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2001.017"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000077957"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004360050128"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200003339171"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1972.tb08973.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8794"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(67)90289-6"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.336.6078.144"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1039\/B106958F"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1221969110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:32:51Z","timestamp":1649802771000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1221969110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,25]]},"references-count":31,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2013,3,12]]}},"alternative-id":["10.1073\/pnas.1221969110"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1221969110","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,25]]},"assertion":[{"value":"2013-02-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}