{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:07:06Z","timestamp":1790856426019,"version":"4.1.0"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D22ZO-409"],"award-info":[{"award-number":["D22ZO-409"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009964","name":"American Association of Zoo Veterinarians","doi-asserted-by":"publisher","award":["2022-5"],"award-info":[{"award-number":["2022-5"]}],"id":[{"id":"10.13039\/100009964","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM085232"],"award-info":[{"award-number":["R01GM085232"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Fatal infections with the rare COUG strain of the zoonotic parasite <jats:italic>Toxoplasma gondii<\/jats:italic> were recently detected for the first time in four southern sea otters (<jats:italic>Enhydra lutris nereis<\/jats:italic>) exhibiting severe protozoal steatitis. The objectives of this study were to describe new COUG strain infections in sea otters, investigate the potential contributory role of a recently discovered parasite-infecting narnavirus (<jats:italic>Apocryptovirus odysseus<\/jats:italic>) in these infections, assess the potential contribution of vitamin E deficiency in the development of systemic steatitis, and explore the utility of serotyping for strain-specific diagnosis of <jats:italic>T. gondii<\/jats:italic> infections in sea otters. Since initial reporting, six additional sea otters died due to fatal COUG strain <jats:italic>T. gondii<\/jats:italic> infections. Five animals exhibited lesion patterns resembling the prior case definition including severe, widespread steatitis. The final case died due to severe <jats:italic>T. gondii<\/jats:italic>-associated meningoencephalitis with no grossly or microscopically apparent steatitis. In contrast with a recent report utilizing a cougar-derived parasite isolate, <jats:italic>A. odysseus<\/jats:italic> RNA was not detected in sea otter-derived COUG strain isolates, suggesting that this narnavirus is not associated with fatal COUG strain infections in sea otters. Serotyping using dense granule (GRA) peptides to distinguish between <jats:italic>T. gondii<\/jats:italic> strains infecting sea otters suggests that Type X, Type II, and COUG strains exhibit different peptide-reactivity profiles that may allow them to be distinguished serologically. COUG strain <jats:italic>T. gondii<\/jats:italic> infections are an emerging threat to southern sea otter population health, and this strain has the potential to infect other animal and human hosts that share their environment and food sources with sea otters. Additional studies are needed to clarify the environmental sources, epidemiology, pathophysiology, and premortem serodiagnosis of COUG strain <jats:italic>T. gondii<\/jats:italic> infections in southern sea otters and other susceptible hosts.<\/jats:p>","DOI":"10.1371\/journal.pone.0332223","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T17:36:07Z","timestamp":1757525767000},"page":"e0332223","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fatal Toxoplasma gondii COUG strain infections in southern sea otters (Enhydra lutris nereis): New insight on contributing factors and parasite serotyping"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7890-4833","authenticated-orcid":true,"given":"Devinn M.","family":"Sinnott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2647-3194","authenticated-orcid":true,"given":"David","family":"Arranz-Sol\u00eds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen P. J.","family":"Saeij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Batac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-2459","authenticated-orcid":true,"given":"Katherine","family":"Greenwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"pone.0332223.ref001","doi-asserted-by":"crossref","DOI":"10.3389\/fmars.2020.00582","article-title":"Predators, Disease, and Environmental Change in the Nearshore Ecosystem: Mortality in Southern Sea Otters (Enhydra lutris nereis) From 1998\u20132012","volume":"7","author":"MA Miller","year":"2020","journal-title":"Front Mar Sci"},{"key":"pone.0332223.ref002","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jcpa.2007.05.001","article-title":"Protozoal meningoencephalitis in sea otters (Enhydra lutris): a histopathological and immunohistochemical study of naturally occurring cases","volume":"137","author":"NJ Thomas","year":"2007","journal-title":"J Comp Pathol"},{"issue":"1","key":"pone.0332223.ref003","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1550-7408.1972.tb03431.x","article-title":"Cyst-induced toxoplasmosis in cats","volume":"19","author":"JP Dubey","year":"1972","journal-title":"J Protozool"},{"issue":"5686","key":"pone.0332223.ref004","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/bmj.4.5686.806-b","article-title":"Life cycle of Toxoplasma gondii","volume":"4","author":"WM Hutchison","year":"1969","journal-title":"Br Med J"},{"key":"pone.0332223.ref005","first-page":"425","article-title":"Protozoan Parasites of Marine Mammals","volume-title":"CRC Handbook of Marine Mammal Medicine","author":"M Miller","year":"2018","edition":"3"},{"issue":"1909","key":"pone.0332223.ref006","first-page":"20191334","article-title":"Type X strains of Toxoplasma gondii are virulent for southern sea otters (Enhydra lutris nereis) and present in felids from nearby watersheds","volume":"286","author":"K Shapiro","year":"2019","journal-title":"Proc Biol Sci"},{"issue":"3","key":"pone.0332223.ref007","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000404","article-title":"Selection at a single locus leads to widespread expansion of Toxoplasma gondii lineages that are virulent in mice","volume":"5","author":"A Khan","year":"2009","journal-title":"PLoS Genet"},{"issue":"12","key":"pone.0332223.ref008","article-title":"Transcriptional analysis of murine macrophages infected with different Toxoplasma strains identifies novel regulation of host signaling pathways","volume":"9","author":"MB Melo","year":"2013","journal-title":"PLoS Pathog"},{"key":"pone.0332223.ref009","doi-asserted-by":"crossref","DOI":"10.3389\/fmars.2023.1116899","article-title":"Newly detected, virulent Toxoplasma gondii COUG strain causing fatal steatitis and toxoplasmosis in southern sea otters (Enhydra lutris nereis)","volume":"10","author":"MA Miller","year":"2023","journal-title":"Front Mar Sci"},{"issue":"1","key":"pone.0332223.ref010","doi-asserted-by":"crossref","DOI":"10.1093\/ve\/veae040","article-title":"A parasite odyssey: An RNA virus concealed in Toxoplasma gondii","volume":"10","author":"P Gupta","year":"2024","journal-title":"Virus Evol"},{"key":"pone.0332223.ref011","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/B978-0-12-805306-5.00011-0","article-title":"Mustelids","author":"BH Williams","year":"2018","journal-title":"Pathol Wildlife Zoo Animals. Elsevier"},{"key":"pone.0332223.ref012","doi-asserted-by":"crossref","first-page":"408","DOI":"10.3389\/fcimb.2019.00408","article-title":"Serotyping of Toxoplasma gondii infection using peptide membrane arrays","volume":"9","author":"D Arranz-Sol\u00eds","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0332223.ref013","doi-asserted-by":"crossref","first-page":"621738","DOI":"10.3389\/fcimb.2021.621738","article-title":"Toxoplasma GRA Peptide-Specific Serologic Fingerprints Discriminate Among Major Strains Causing Toxoplasmosis","volume":"11","author":"D Arranz-Sol\u00eds","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0332223.ref014","doi-asserted-by":"crossref","first-page":"1384393","DOI":"10.3389\/fcimb.2024.1384393","article-title":"A combination of GRA3, GRA6 and GRA7 peptides offer a useful tool for serotyping type II and III Toxoplasma gondii infections in sheep and pigs","volume":"14","author":"D Arranz-Sol\u00eds","year":"2024","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0332223.ref015","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.vetpar.2009.08.013","article-title":"Prevalence and risk factors associated with Sarcocystis neurona infections in opossums (Didelphis virginiana) from central California","volume":"166","author":"D Rejmanek","year":"2009","journal-title":"Vet Parasitol"},{"issue":"1","key":"pone.0332223.ref016","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1128\/JCM.39.1.398-400.2001","article-title":"Rapid identification of virulent type I strains of the protozoan pathogen Toxoplasma gondii by PCR-restriction fragment length polymorphism analysis at the B1 gene","volume":"39","author":"ME Grigg","year":"2001","journal-title":"J Clin Microbiol"},{"issue":"15","key":"pone.0332223.ref017","doi-asserted-by":"crossref","first-page":"5844","DOI":"10.1073\/pnas.1203190109","article-title":"Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages","volume":"109","author":"C Su","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pone.0332223.ref018","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1086\/374647","article-title":"Serotyping of Toxoplasma gondii infections in humans using synthetic peptides","volume":"187","author":"J-T Kong","year":"2003","journal-title":"J Infect Dis"},{"issue":"3","key":"pone.0332223.ref019","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1645\/0022-3395(2002)088[0594:EOAIFA]2.0.CO;2","article-title":"Evaluation of an indirect fluorescent antibody test (ifat) for demonstration of antibodies to Toxoplasma gondii in the sea otter (Enhydra lutris)","volume":"88","author":"MA Miller","year":"2002","journal-title":"J Parasitol"},{"issue":"2","key":"pone.0332223.ref020","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1017\/S0950268899002113","article-title":"Potential contamination of drinking water with Toxoplasma gondii oocysts","volume":"122","author":"JJ Aramini","year":"1999","journal-title":"Epidemiol Infect"},{"issue":"1","key":"pone.0332223.ref021","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1645\/GE-1349.1","article-title":"Isolation and genetic characterization of Toxoplasma gondii from raccoons (Procyon lotor), cats (Felis domesticus), striped skunk (Mephitis mephitis), black bear (Ursus americanus), and cougar (Puma concolor) from Canada","volume":"94","author":"JP Dubey","year":"2008","journal-title":"J Parasitol"},{"key":"pone.0332223.ref022","doi-asserted-by":"crossref","first-page":"10147","DOI":"10.1038\/ncomms10147","article-title":"Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes","volume":"7","author":"H Lorenzi","year":"2016","journal-title":"Nat Commun"},{"issue":"6","key":"pone.0332223.ref023","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.meegid.2011.05.003","article-title":"Human impact on genetic diversity of Toxoplasma gondii: example of the anthropized environment from French Guiana","volume":"11","author":"A Mercier","year":"2011","journal-title":"Infect Genet Evol"},{"key":"pone.0332223.ref024","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.vetpar.2013.06.005","article-title":"A new atypical genotype mouse virulent strain of Toxoplasma gondii isolated from the heart of a wild caught puma (Felis concolor) from Durango, Mexico","volume":"197","author":"JP Dubey","year":"2013","journal-title":"Veterinary Parasitol"},{"issue":"7","key":"pone.0332223.ref025","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1073\/pnas.0806449106","article-title":"Prey choice and habitat use drive sea otter pathogen exposure in a resource-limited coastal system","volume":"106","author":"CK Johnson","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pone.0332223.ref026","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.ijpara.2008.02.005","article-title":"Type X Toxoplasma gondii in a wild mussel and terrestrial carnivores from coastal California: new linkages between terrestrial mammals, runoff and toxoplasmosis of sea otters","volume":"38","author":"MA Miller","year":"2008","journal-title":"Int J Parasitol"},{"key":"pone.0332223.ref027","author":"MT Tinker","year":"2017","journal-title":"Southern sea otter range expansion and habitat use in the Santa Barbara Channel, California. Open-File Report. US Geological Survey"},{"issue":"12","key":"pone.0332223.ref028","article-title":"High prevalence and diversity of Toxoplasma gondii DNA in feral cat feces from coastal California","volume":"17","author":"S Zhu","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"5","key":"pone.0332223.ref029","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0002852","article-title":"Using molecular epidemiology to track Toxoplasma gondii from terrestrial carnivores to marine hosts: implications for public health and conservation","volume":"8","author":"E VanWormer","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"6","key":"pone.0332223.ref030","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006362","article-title":"Host lipid droplets: an important source of lipids salvaged by the intracellular parasite Toxoplasma gondii","volume":"13","author":"SJ Nolan","year":"2017","journal-title":"PLoS Pathog"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0332223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T17:36:11Z","timestamp":1757525771000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0332223"}},"subtitle":[],"editor":[{"given":"Shawky M","family":"Aboelhadid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0332223","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]}}}