{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:30:03Z","timestamp":1792819803012,"version":"4.5.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014423","name":"Environmental Restoration and Conservation Agency","doi-asserted-by":"publisher","award":["JPMEERF20254004"],"award-info":[{"award-number":["JPMEERF20254004"]}],"id":[{"id":"10.13039\/100014423","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP223fa627005"],"award-info":[{"award-number":["JP223fa627005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24wm000125008"],"award-info":[{"award-number":["JP24wm000125008"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["1801"],"award-info":[{"award-number":["1801"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJSP2119"],"award-info":[{"award-number":["JPMJSP2119"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    High pathogenicity avian influenza virus (HPAIV) infections have been frequently reported in wild birds since 2020. Because HPAIV infection has occasionally caused outbreaks in captive rare birds, treatment using antiviral drugs has been considered from the perspective of conservation medicine. In this study, the therapeutic efficacy of baloxavir marboxil (BXM) was evaluated using a duck model to support the establishment of post-infection strategies for captive avian species. Sixteen four-week-old ducks were divided into four groups and intranasally inoculated with the HPAIV strain, A\/crow\/Hokkaido\/0103B065\/2022 (H5N1). BXM was administered orally once daily at doses of 12.5, 2.5, 0.5, or 0\u2009mg\/kg to each of the four groups from 2 to 6 days post-infection. Blood samples were collected at 2, 8, and 24 hours after the initial BXM administration to measure the plasma concentrations of its active form, baloxavir acid (BXA). All ducks were monitored until 14 days post-infection, and oral and cloacal swabs were collected for virus recovery. All eight ducks administered either 12.5 or 2.5\u2009mg\/kg of BXM survived, demonstrating a significant reduction in virus recovery compared with the 0\u2009mg\/kg group. To further characterize the relationship between BXA exposure and virus shedding, an additional experiment was conducted in which ducks received a single oral administration of BXM at doses of 7.3, 4.3, or 0.5\u2009mg\/kg at 2 days post-infection. Pharmacokinetic\/pharmacodynamic analysis of BXA across all dose groups showed that reductions in virus shedding from oral swabs were positively correlated with BXA exposure, and AUC\n                    <jats:sub>0\u201324hr<\/jats:sub>\n                    exhibited the strongest association. These findings demonstrate that BXM administration within 48 hours post-HPAIV infection in ducks effectively reduces mortality and virus shedding. Comparison of pharmacokinetic parameters may facilitate the estimation of optimal BXM dosing options for captive avian species.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0347205","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:45:03Z","timestamp":1776275103000},"page":"e0347205","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of therapeutic efficacy of baloxavir marboxil against high pathogenicity avian influenza virus infection in duck model"],"prefix":"10.1371","volume":"21","author":[{"given":"Yo","family":"Shimazu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norikazu","family":"Isoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Hiono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yik Lim","family":"Hew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0072-1042","authenticated-orcid":true,"given":"Daiki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misato","family":"Shibazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao Linh","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuru","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo Daniel","family":"Obara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Miki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Osaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2549-0945","authenticated-orcid":true,"given":"Takao","family":"Shishido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Ikenaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-1688","authenticated-orcid":true,"given":"Yoshihiro","family":"Sakoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"issue":"1","key":"pone.0347205.ref001","doi-asserted-by":"crossref","first-page":"19","DOI":"10.20506\/rst.28.1.1856","article-title":"History of highly pathogenic avian influenza","volume":"28","author":"DJ Alexander","year":"2009","journal-title":"Rev Sci Tech"},{"key":"pone.0347205.ref002","article-title":"Clade 2.3.4.4b highly pathogenic avian influenza H5N1 viruses: knowns, unknowns, and challenges","author":"Z Xie","year":"2025","journal-title":"J Virol"},{"key":"pone.0347205.ref003","doi-asserted-by":"crossref","first-page":"5322378","DOI":"10.1155\/2024\/5322378","article-title":"Novel epidemiologic features of high pathogenicity avian influenza virus A H5N1 2.3.3.4b panzootic: a review","volume":"2024","author":"C Sacrist\u00e1n","year":"2024","journal-title":"Transbound Emerg Dis"},{"issue":"1","key":"pone.0347205.ref004","doi-asserted-by":"crossref","first-page":"7433","DOI":"10.1038\/s41467-024-51490-8","article-title":"Detection and spread of high pathogenicity avian influenza virus H5N1 in the Antarctic region","volume":"15","author":"AC Banyard","year":"2024","journal-title":"Nat Commun"},{"issue":"2","key":"pone.0347205.ref005","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/tbed.13386","article-title":"Outbreaks of highly pathogenic avian influenza in zoo birds caused by HA clade 2.3.4.4 H5N6 subtype viruses in Japan in winter 2016","volume":"67","author":"T Usui","year":"2020","journal-title":"Transbound Emerg Dis"},{"issue":"6","key":"pone.0347205.ref006","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1080\/03079457.2025.2513338","article-title":"High pathogenicity avian influenza H5N1 clade 2.3.4.4b natural infection in captive Humboldt penguins (Spheniscus humboldti)","volume":"54","author":"A-LD Schlachter","year":"2025","journal-title":"Avian Pathol"},{"issue":"22","key":"pone.0347205.ref007","doi-asserted-by":"crossref","first-page":"4345","DOI":"10.1016\/j.vaccine.2007.03.043","article-title":"Serological response to vaccination against avian influenza in zoo-birds using an inactivated H5N9 vaccine","volume":"25","author":"MF Bertelsen","year":"2007","journal-title":"Vaccine"},{"issue":"10","key":"pone.0347205.ref008","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1136\/vr.157.10.299","article-title":"Field study on the use of inactivated H5N2 vaccine in avian species","volume":"157","author":"S Oh","year":"2005","journal-title":"Vet Rec"},{"issue":"50","key":"pone.0347205.ref009","doi-asserted-by":"crossref","first-page":"5743","DOI":"10.1016\/j.vaccine.2005.09.013","article-title":"Highly pathogenic avian influenza (H7N7): vaccination of zoo birds and transmission to non-poultry species","volume":"23","author":"JDW Philippa","year":"2005","journal-title":"Vaccine"},{"issue":"5","key":"pone.0347205.ref010","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1128\/CVI.00013-11","article-title":"Comprehensive serological analysis of two successive heterologous vaccines against H5N1 avian influenza virus in exotic birds in zoos","volume":"18","author":"J Vergara-Alert","year":"2011","journal-title":"Clin Vaccine Immunol"},{"issue":"6","key":"pone.0347205.ref011","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.3201\/eid3106.241558","article-title":"Safety and immunogenicity of poultry vaccine for protecting critically endangered avian species against highly pathogenic avian influenza virus, United States","volume":"31","author":"TE Katzner","year":"2025","journal-title":"Emerg Infect Dis"},{"issue":"4","key":"pone.0347205.ref012","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1111\/tbed.13515","article-title":"Control of avian influenza in China: strategies and lessons","volume":"67","author":"S Liu","year":"2020","journal-title":"Transbound Emerg Dis"},{"issue":"6428","key":"pone.0347205.ref013","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/363418a0","article-title":"Rational design of potent sialidase-based inhibitors of influenza virus replication","volume":"363","author":"M von Itzstein","year":"1993","journal-title":"Nature"},{"key":"pone.0347205.ref014","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.ics.2004.01.020","article-title":"Oseltamivir reduces transmission, morbidity, and mortality of highly pathogenic avian influenza in chickens","volume":"1263","author":"A Meijer","year":"2004","journal-title":"Int Congr Ser"},{"issue":"12","key":"pone.0347205.ref015","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.3390\/v12121407","article-title":"Evaluation of baloxavir marboxil and peramivir for the treatment of high pathogenicity avian influenza in chickens","volume":"12","author":"A Twabela","year":"2020","journal-title":"Viruses"},{"issue":"7240","key":"pone.0347205.ref016","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nature07745","article-title":"The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit","volume":"458","author":"A Dias","year":"2009","journal-title":"Nature"},{"issue":"10","key":"pone.0347205.ref017","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.3390\/v12101139","article-title":"In vitro combinations of baloxavir acid and other inhibitors against seasonal influenza A viruses","volume":"12","author":"L Checkmahomed","year":"2020","journal-title":"Viruses"},{"key":"pone.0347205.ref018","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/03079450802499118","article-title":"The onset of virus shedding and clinical signs in chickens infected with high-pathogenicity and low-pathogenicity avian influenza viruses","volume":"51","author":"AR Spickler","year":"2008","journal-title":"Avian Pathol"},{"key":"pone.0347205.ref019","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.vetmic.2015.11.009","article-title":"Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission","volume":"182","author":"T Hiono","year":"2016","journal-title":"Vet Microbiol"},{"key":"pone.0347205.ref020","doi-asserted-by":"crossref","first-page":"2399970","DOI":"10.1080\/22221751.2024.2399970","article-title":"Experimental infection of chickens, Pekin ducks, Eurasian wigeons and barnacle geese with two recent highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses","volume":"13","author":"L Bordes","year":"2024","journal-title":"Emerg Microbes Infect"},{"key":"pone.0347205.ref021","doi-asserted-by":"crossref","first-page":"1007350","DOI":"10.3389\/fmicb.2022.1007350","article-title":"Experimental and natural infections of white-tailed sea eagles (Haliaeetus albicilla) with high pathogenicity avian influenza virus of H5 subtype","volume":"13","author":"Y Fujimoto","year":"2022","journal-title":"Front Microbiol"},{"issue":"2","key":"pone.0347205.ref022","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1080\/03079457.2021.2022599","article-title":"Susceptibility of herons (family: Ardeidae) to clade 2.3.2.1 H5N1 subtype high pathogenicity avian influenza virus","volume":"51","author":"K Soda","year":"2022","journal-title":"Avian Pathol"},{"issue":"10","key":"pone.0347205.ref023","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.3390\/v14102168","article-title":"Detection of new H5N1 high pathogenicity avian influenza viruses in winter 2021-2022 in the Far East, which are genetically close to those in Europe","volume":"14","author":"N Isoda","year":"2022","journal-title":"Viruses"},{"issue":"4","key":"pone.0347205.ref024","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3201\/eid2304.161957","article-title":"Characterization of highly pathogenic avian influenza virus A(H5N6), Japan, November 2016","volume":"23","author":"M Okamatsu","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"pone.0347205.ref025","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1099\/vir.0.037572-0","article-title":"Reintroduction of H5N1 highly pathogenic avian influenza virus by migratory water birds, causing poultry outbreaks in the 2010-2011 winter season in Japan","volume":"93","author":"Y Sakoda","year":"2012","journal-title":"J Gen Virol"},{"key":"pone.0347205.ref026","unstructured":"World Organisation for Animal Health. Avian influenza (Including infection with high pathogenicity avian influenza virus). 2024."},{"key":"pone.0347205.ref027","first-page":"493","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"LJ Reed","year":"1938","journal-title":"Am J Hyg"},{"key":"pone.0347205.ref028","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12985-015-0250-3","article-title":"Detection of highly pathogenic zoonotic influenza virus H5N6 by reverse-transcriptase quantitative polymerase chain reaction","volume":"12","author":"HG Heine","year":"2015","journal-title":"Virol J"},{"issue":"3","key":"pone.0347205.ref029","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1080\/03079457.2023.2196258","article-title":"The pathogenesis of a 2022 North American highly pathogenic clade 2.3.4.4b H5N1 avian influenza virus in mallards (Anas platyrhynchos)","volume":"52","author":"E Spackman","year":"2023","journal-title":"Avian Pathol"},{"issue":"7","key":"pone.0347205.ref030","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1007\/s00705-004-0473-x","article-title":"Pathogenicity of H5 influenza viruses for ducks","volume":"150","author":"N Kishida","year":"2005","journal-title":"Arch Virol"},{"issue":"12","key":"pone.0347205.ref031","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.1523\/JNEUROSCI.1740-17.2018","article-title":"Long-Term Neuroinflammation Induced by Influenza A Virus Infection and the Impact on Hippocampal Neuron Morphology and Function","volume":"38","author":"S Hosseini","year":"2018","journal-title":"J Neurosci"},{"issue":"1","key":"pone.0347205.ref032","doi-asserted-by":"crossref","first-page":"5356","DOI":"10.1038\/s41467-025-60791-5","article-title":"Efficacy of baloxavir marboxil against bovine H5N1 virus in mice","volume":"16","author":"M Kiso","year":"2025","journal-title":"Nat Commun"},{"issue":"2","key":"pone.0347205.ref033","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00705-023-05958-5","article-title":"The impact of PA\/I38 substitutions and PA polymorphisms on the susceptibility of zoonotic influenza A viruses to baloxavir","volume":"169","author":"K Taniguchi","year":"2024","journal-title":"Arch Virol"},{"issue":"1","key":"pone.0347205.ref034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0083417","article-title":"Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding","volume":"9","author":"H Wibawa","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pone.0347205.ref035","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/jac\/dkaa393","article-title":"Pharmacokinetic and pharmacodynamic analysis of baloxavir marboxil, a novel cap-dependent endonuclease inhibitor, in a murine model of influenza virus infection","volume":"76","author":"Y Ando","year":"2021","journal-title":"J Antimicrob Chemother"},{"issue":"3","key":"pone.0347205.ref036","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0345055","article-title":"Assessment of a baloxavir marboxil treatment protocol for high pathogenicity avian influenza in Okinawa rails, an endangered species endemic to Japan","volume":"21","author":"M Miki","year":"2026","journal-title":"PLoS ONE"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:45:11Z","timestamp":1776275111000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347205"}},"subtitle":[],"editor":[{"given":"Mohamed Samy","family":"Abousenna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":36,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0347205","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}