{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T01:04:07Z","timestamp":1785027847692,"version":"3.55.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2025ZD01901300"],"award-info":[{"award-number":["2025ZD01901300"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304205"],"award-info":[{"award-number":["82304205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["824B2101"],"award-info":[{"award-number":["824B2101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Highly pathogenic avian influenza (HPAI) A(H5) viruses have caused sporadic human infections since 1997, with recent detections in the Americas and Asia. However, the evolutionary dynamics of different HPAI A(H5) viruses at the animal\u2013human interface, along with their associated disease severity, propensity for animal-to-human (zoonotic) spillover, and human-to-human transmission potential, remain unclear. Here, we combine available genetic and epidemiological data with mechanistic models to better understand the global spread of HPAI A(H5) viruses that spilled over to humans in 1997\u20132025. Analysis of 7445 subsampled hemagglutinin gene sequences revealed frequent regional succession of HPAI A(H5) virus clades that varied by geographic location. The 1104 reported human HPAI A(H5) cases exhibited subtype- and clade-specific heterogeneity in age, gender, and exposure sources (p\u00a0&amp;lt;\u00a00.001). After adjusting for under-reporting, we estimated case-fatality risk to be low for HPAI A(H5N1) clade 2.3.4.4b (0.7%, 95%CI: 0.02%\u20133.9%) and for A(H5N6) clades 2.3.4x (0%, 0%\u20131.1%) and 2.3.4.4b (1.6%, 0.7%\u20133.2%), compared with other A(H5) clades (range: 4.7%\u201315.0%). We also show that, while the transmissibility of HPAI A(H5) viruses between humans remains very low to date (mean Rt: 0.10\u20130.23), zoonotic transmission has increased with the emergence of bovine-origin clade 2.3.4.4b (incidence: 7.85 per million people per year), relative to other avian-origin A(H5) clades (range: 1.54\u20135.04 per million people per year). Although other factors such as exposure sources, routes of transmission, immune function, underlying medical conditions, and clinical management can influence outcomes of case-patients, these findings highlight the ongoing pandemic threat posed by HPAI A(H5) viruses and the need for ongoing comprehensive surveillance, genotypic and phenotypic characterization, and preparedness.<\/jats:p>","DOI":"10.1093\/nsr\/nwaf471","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T12:20:13Z","timestamp":1762777213000},"source":"Crossref","is-referenced-by-count":4,"title":["Human infections with avian influenza A(H5) viruses with potential pandemic risk: 1997\u20132025"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4056-3732","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabao","family":"Xing","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Beijing Chest Hospital, Capital Medical University , Beijing 100071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayu","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxuan","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4409-1667","authenticated-orcid":false,"given":"Jian","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences, Peking University , Beijing 100871 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J","family":"Cowling","sequence":"additional","affiliation":[{"name":"School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Hong Kong 999077 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9822-1586","authenticated-orcid":false,"given":"Peter","family":"Horby","sequence":"additional","affiliation":[{"name":"Pandemic Sciences Institute , Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Webby","sequence":"additional","affiliation":[{"name":"St Jude Children\u2019s Research Hospital , Memphis, TN 38105 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5338-8668","authenticated-orcid":false,"given":"Timothy M","family":"Uyeki","sequence":"additional","affiliation":[{"name":"Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, GA 30329 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6335-5648","authenticated-orcid":false,"given":"Hongjie","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education , Shanghai 200032 ,","place":["China"]},{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Fudan University , Shanghai 200032 ,","place":["China"]},{"name":"Huashan Hospital, Fudan University Department of Infectious Diseases, , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"2026042910463959600_bib1","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1093\/infdis\/jiae379","article-title":"An update on highly pathogenic avian influenza A(H5N1) virus, clade 2.3.4.4b","volume":"230","author":"Webby","year":"2024","journal-title":"J Infect Dis"},{"key":"2026042910463959600_bib2","first-page":"1204","article-title":"Isolation of avian influenza A(H5N1) viruses from humans\u2013Hong Kong, 1997\u20131998","volume":"46","author":"Centers for Disease Control and Prevention (CDC)","year":"1998","journal-title":"MMWR Morb Mortal Wkly 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