{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:17:48Z","timestamp":1793197068803,"version":"4.5.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006939","name":"Emory University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006939","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Non-invasive health monitoring is advantageous for wild and captive primate populations because it reduces the need for traditional invasive techniques (i.e., anesthetization) that can be stressful and potentially harmful for individuals. The biomarker neopterin is an emerging tool in primatology to measure immune activation and immunosenescence, however, most neopterin studies have focused on catarrhine species with little comparative work examining neopterin and health in platyrrhines. To address this gap, we validated a commercially available enzyme-linked immunosorbent assay (ELISA) to measure urinary neopterin in two types of capuchin monkeys, a wild population of white-faced capuchins (<jats:italic>Cebus imitator<\/jats:italic>) and a socially housed captive colony of tufted capuchins (<jats:italic>Sapajus apella<\/jats:italic>). We analytically validated methods for measuring urinary neopterin in two capuchin populations and demonstrated that two commonly-used methods to control for urine concentration\u2014creatinine and specific gravity (SG)\u2014produced highly concordant results. We also biologically validated these methods by examining variation in neopterin levels based on environment (captive and wild) and age, and changes in levels associated with immune-response. We found that neopterin increased after immune perturbation (rabies vaccine booster), varied by environmental condition, and mirrored expected trends in immune system ontogeny. Our results improve understanding of the innate immune system in platyrrhine species and suggest neopterin may be useful for non-invasive health monitoring in both captive and wild primates.<\/jats:p>","DOI":"10.3389\/fvets.2022.918036","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T09:48:28Z","timestamp":1657705708000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Validating Urinary Neopterin as a Biomarker of Immune Response in Captive and Wild Capuchin Monkeys"],"prefix":"10.3389","volume":"9","author":[{"given":"Jordan M.","family":"Lucore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F.","family":"Brosnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela E.","family":"Ben\u00edtez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.2307\/2387816","article-title":"Pathogens and the evolution of primate sociality","volume":"8","author":"Freeland","year":"1976","journal-title":"Biotropica."},{"key":"B2","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s10764-009-9333-6","article-title":"Field anesthesia and health assessment of free-ranging Cebus capucinus in Panama","volume":"30","author":"Crofoot","year":"2009","journal-title":"Int J Primatol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1002\/ajp.22581","article-title":"Physiological and parasitological implications of living in a city: the case of the white-footed tamarin (Saguinus leucopus)","volume":"78","author":"Soto-Calder\u00f3n","year":"2016","journal-title":"Am J Primatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/jmp.12036","article-title":"Hematologic and blood chemistry values of healthy Cebus flavius kept in northeast of Brazil","volume":"42","author":"Teixeira","year":"2013","journal-title":"J Med Primatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1002\/ajp.21986","article-title":"Primate disease ecology in comparative and theoretical perspective","volume":"74","author":"Nunn","year":"2012","journal-title":"Am J Primatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1002\/ajp.20825","article-title":"A longitudinal study of urinary dipstick parameters in wild chimpanzees (Pan troglodytes verus) in C\u00f4te d'Ivoire","volume":"72","author":"Leendertz","year":"2010","journal-title":"Am J Primatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"9017","DOI":"10.1073\/pnas.1206391109","article-title":"Social status predicts wound healing in wild baboons","volume":"109","author":"Archie","year":"2012","journal-title":"Proc Nat Acad Sci."},{"key":"B8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-816572-0.00001-2","article-title":"A functional overview of the immune system and immune components. in","volume-title":"Introductory Immunology","author":"Actor","year":"2019"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/emph\/eov033","article-title":"Trade-offs between acquired and innate immune defenses in humans","volume":"2016","author":"McDade","year":"2016","journal-title":"Evol Med Public Health."},{"key":"B10","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/j.1600-0625.1999.tb00367.x","article-title":"Neopterin: a review","volume":"8","author":"Hamerlinck","year":"1999","journal-title":"Exp Dermatol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"175","DOI":"10.2174\/1389200024605082","article-title":"Neopterin as a marker for immune system activation","volume":"3","author":"Murr","year":"2002","journal-title":"Curr Drug Metab."},{"key":"B12","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1515\/pteridines.1999.10.3.101","article-title":"The importance of neopterin as a laboratory diagnostic marker of immune activation","volume":"10","author":"Widner","year":"1999","journal-title":"Pteridines."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1189\/jlb.72.6.1148","article-title":"Monocyte-derived dendritic cells release neopterin","volume":"72","author":"Wirleitner","year":"2002","journal-title":"J Leukoc Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/0167-5699(88)91203-0","article-title":"Neopterin as a marker for activated cell-mediated immunity: application in HIV infection","volume":"9","author":"Fuchs","year":"1988","journal-title":"Immunol Today."},{"key":"B15","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1097\/00002030-198905000-00010","article-title":"Urinary neopterin concentrations in rhesus monkeys after infection with simian immunodeficiency virus (SIVmac 251)","volume":"3","author":"Fendrich","year":"1989","journal-title":"AIDS."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1515\/pteridines.2002.13.1.1","article-title":"Urinary neopterin indicates early infection and disease progression: Model studies with simian and human immunodeficiency viruses in macaques","volume":"13","author":"Stahl-Hennig","year":"2002","journal-title":"Pteridines."},{"key":"B17","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1002\/ajpa.22821","article-title":"Evaluating noninvasive markers of nonhuman primate immune activation and inflammation","volume":"158","author":"Higham","year":"2015","journal-title":"Am J Phys Anthropol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3389\/fphys.2017.00051","article-title":"Validation of a method for the assessment of urinary neopterin levels to monitor health status in non-human-primate species","volume":"8","author":"Behringer","year":"2017","journal-title":"Front Physiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-31563-7","article-title":"Urinary neopterin levels increase and predict survival during a respiratory outbreak in wild chimpanzees (Ta\u00ef National Park, C\u00f4te d'Ivoire)","volume":"8","author":"Wu","year":"2018","journal-title":"Sci Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40850-019-0041-1","article-title":"Elevated neopterin levels in wild, healthy chimpanzees indicate constant investment in unspecific immune system","volume":"4","author":"Behringer","year":"2019","journal-title":"BMC Zoology."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-88401-6","article-title":"Urinary neopterin of wild chimpanzees indicates that cell-mediated immune activity varies by age, sex, and female reproductive status","volume":"11","author":"Negrey","year":"2021","journal-title":"Sci Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1007\/s10393-018-1357-y","article-title":"The use of neopterin as a noninvasive marker in monitoring diseases in wild chimpanzees","volume":"15","author":"L\u00f6hrich","year":"2018","journal-title":"Ecohealth."},{"key":"B23","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3389\/fevo.2021.629094","article-title":"Cell-mediated immune ontogeny is affected by sex but not environmental context in a long-lived primate species","volume":"9","author":"Behringer","year":"2021","journal-title":"Front Ecol Evol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep41973","article-title":"Age, but not anthelmintic treatment, is associated with urinary neopterin levels in semi-free ranging Barbary macaques","volume":"7","author":"M\u00fcller","year":"2017","journal-title":"Sci Rep."},{"key":"B25","unstructured":"The IUCN Red List of Threatened Species2021"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40850-020-00051-9","article-title":"Detection of neopterin in the urine of captive and wild platyrrhines","volume":"5","author":"Sacco","year":"2020","journal-title":"BMC Zoology."},{"key":"B27","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1600-0684.2008.00333.x","article-title":"Pharmacokinetics and pharmacodynamics of interferon beta 1a in Cebus apella","volume":"38","author":"Lahoz","year":"2009","journal-title":"J Med Primatol."},{"key":"B28","first-page":"107","article-title":"The Cebines","volume-title":"Primates in Perspective.","author":"Jack","year":"2007"},{"key":"B29","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1002\/ajp.22269","article-title":"Capuchin monkey research priorities and urgent issues","volume":"76","author":"Lynch Alfaro","year":"2014","journal-title":"Am J Primatol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e1600946","DOI":"10.1126\/sciadv.1600946","article-title":"Impending extinction crisis of the world's primates: Why primates matter","volume":"3","author":"Estrada","year":"2017","journal-title":"Science advances."},{"key":"B31","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1002\/evan.20068","article-title":"Primates and the ecology of their infectious diseases: how will anthropogenic change affect host-parasite interactions?","volume":"14","author":"Chapman","year":"2005","journal-title":"Evolution Anthropol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1046\/j.1523-1739.2001.00336.x","article-title":"Putting theory into practice: wildlife health in conservation","volume":"15","author":"Deem","year":"2001","journal-title":"Conserv Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1126\/science.287.5452.443","article-title":"Emerging infectious diseases of wildlife\u2013threats to biodiversity and human health","volume":"287","author":"Daszak","year":"2000","journal-title":"Science."},{"key":"B34","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1201\/9780429019517-29","article-title":"Behavioral biology of capuchin monkeys","volume-title":"Behavioral Biology of Laboratory Animals","author":"Ben\u00edtez","year":"2021"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep16308","article-title":"Urinary neopterin, a non-invasive marker of mammalian cellular immune activation, is highly stable under field conditions","volume":"5","author":"Heistermann","year":"2015","journal-title":"Sci Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/ajp.20631","article-title":"Specific gravity as an alternative to creatinine for estimating urine concentration in captive and wild chimpanzee (Pan troglodytes) samples","volume":"71","author":"Anestis","year":"2009","journal-title":"Am J Primatol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1373\/clinchem.2004.032292","article-title":"Comparison of specific gravity and creatinine for normalizing urinary reproductive hormone concentrations","volume":"50","author":"Miller","year":"2004","journal-title":"Clin Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1093\/ajcn\/37.3.478","article-title":"Measurement of muscle mass in humans: validity of the 24-hour urinary creatinine method","volume":"37","author":"Heymsfield","year":"1983","journal-title":"Am J Clin Nutr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/ajpa.22157","article-title":"Variation in muscle mass in wild chimpanzees: Application of a modified urinary creatinine method","volume":"149","author":"Emery Thompson","year":"2012","journal-title":"Am J Phys Anthropol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/BF00378372","article-title":"Problems concerning the usefulness of adjustment of urinary cadmium for creatinine and specific gravity","volume":"55","author":"Berlin","year":"1985","journal-title":"Int Arch Occup Environ Health."},{"key":"B41","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1515\/pteridines.1990.2.3.147","article-title":"Distinct neopterin excretion patterns after vaccination","volume":"2","author":"Fuchs","year":"1990","journal-title":"Pteridines."},{"key":"B42","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1111\/j.0908-8857.2008.04408.x","article-title":"Captive and free-living red knots Calidris canutus exhibit differences in non-induced immunity that suggest different immune strategies in different environments","volume":"39","author":"Buehler","year":"2008","journal-title":"J Avian Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e0176202","DOI":"10.1371\/journal.pone.0176202","article-title":"The environment as a driver of immune and endocrine responses in dolphins (Tursiops truncatus)","volume":"12","author":"Fair","year":"2017","journal-title":"PLoS ONE."},{"key":"B44","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.ijppaw.2020.02.009","article-title":"Ecological, parasitological and individual determinants of plasma neopterin levels in a natural mandrill population","volume":"11","author":"Dibakou","year":"2020","journal-title":"Int J Parasitol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1111\/j.1474-9726.2012.00851.x","article-title":"Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function","volume":"11","author":"Hearps","year":"2012","journal-title":"Aging Cell."},{"key":"B46","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1515\/pteridines.2003.14.3.102","article-title":"Follow-up of urinary neopterin concentrations in two healthy children until adolescence","volume":"14","author":"Winkler","year":"2003","journal-title":"Pteridines."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e23096","DOI":"10.1002\/ajp.23096","article-title":"High density of white-faced capuchins (Cebus capucinus) and habitat quality in the Taboga Forest of Costa Rica","volume":"82","author":"Tinsley Johnson","year":"2020","journal-title":"Am J Primatol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e22877","DOI":"10.1002\/ajp.22877","article-title":"Urinary oxytocin in capuchin monkeys: Validation and the influence of social behavior","volume":"80","author":"Ben\u00edtez","year":"2018","journal-title":"Am J Primatol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1002\/ajpa.23239","article-title":"Using urinary parameters to estimate seasonal variation in the physical condition of female white-faced capuchin monkeys (Cebus capucinus imitator)","volume":"163","author":"Bergstrom","year":"2017","journal-title":"Am J Phys Anthropol."},{"key":"B50","article-title":"Steroid hormone validations in wild capuchins at an on-site laboratory","author":"Beehner","year":"","journal-title":"Gen Comp Endocrinol"},{"key":"B51","unstructured":"2021"},{"key":"B52","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3389\/fneur.2015.00179","article-title":"A practical guide to immunoassay method validation","volume":"6","author":"Andreasson","year":"2015","journal-title":"Front Neurol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/5643853","article-title":"Determination of urinary neopterin\/creatinine ratio to distinguish active tuberculosis from latent Mycobacterium tuberculosis infection","volume":"2016","author":"Eisenhut","year":"2016","journal-title":"J Biomark."},{"key":"B54","unstructured":"Guidelines for zoo and aquarium veterinary medical programs and veterinary hospitals17692\n            BackuesK\n            ClydeV\n            DenverM\n            FiorelloC\n            HilsenrothR\n            LamberskiN\n          22946394J Zoo Wildlife Med.422011"},{"key":"B55","first-page":"329","article-title":"The control of pests in the san diego zoo","volume":"29","author":"Mackie","year":"1967","journal-title":"J Environ Health."},{"key":"B56","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1753-4887.1993.tb03758.x","article-title":"The underprivileged, developing country child: environmental contamination and growth failure revisited","volume":"51","author":"Solomons","year":"1993","journal-title":"Nutr Rev."},{"key":"B57","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1111\/j.1365-2664.2005.01049.x","article-title":"Effects of logging on gastrointestinal parasite infections and infection risk in African primates","volume":"42","author":"Gillespie","year":"2005","journal-title":"J Appl Ecol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nri1571","article-title":"Stress-induced immune dysfunction: implications for health","volume":"5","author":"Glaser","year":"2005","journal-title":"Nat Rev Immunol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/ni1253","article-title":"Are innate immune signaling pathways in plants and animals conserved?","volume":"6","author":"Ausubel","year":"2005","journal-title":"Nat Immunol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/S0952-7915(98)80024-1","article-title":"An ancient system of host defense","volume":"10","author":"Medzhitov","year":"1998","journal-title":"Curr Opin Immunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/ajp.20650","article-title":"Reproductive aging in captive and wild common chimpanzees: factors influencing the rate of follicular depletion","volume":"71","author":"Atsalis","year":"2009","journal-title":"Am J Primatol."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.918036\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T09:48:38Z","timestamp":1657705718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.918036\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,13]]},"references-count":61,"alternative-id":["10.3389\/fvets.2022.918036"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2022.918036","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,13]]},"article-number":"918036"}}