{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T07:54:48Z","timestamp":1792569288895,"version":"4.5.0"},"reference-count":49,"publisher":"The Royal Society","issue":"228","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018336","name":"National Institute for Health Research Health Protection Research Unit","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["J. R. Soc. Interface."],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    Avian influenza A(H5N1) poses a public health risk due to its pandemic potential should the virus mutate to become human-to-human transmissible. To date, reported influenza A(H5N1) human cases have typically occurred in the lower respiratory tract with a high case fatality rate. There is prior evidence of some influenza A(H5N1) strains being a small number of amino acid mutations away from achieving droplet transmissibility, possibly allowing them to be spread between humans. We present a mechanistic within-host influenza A(H5N1) infection model, novel for its explicit consideration of the biological differences between the upper and lower respiratory tracts. We then estimate a distribution of viral lifespans and effective replication rates in human H5N1 influenza cases. By combining our within-host model with a viral mutation model, we determine the probability of an infected individual generating a droplet transmissible strain of influenza A(H5N1) through mutation. For three mutations, we found a peak probability of approximately\n                    <jats:inline-formula id=\"rsif.2024.0910_ui1\">\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" display=\"inline\" id=\"rsif.2024.0910_u1\" overflow=\"scroll\">\n                        <mml:msup>\n                          <mml:mn>10<\/mml:mn>\n                          <mml:mrow>\n                            <mml:mo lspace=\"0em\" rspace=\"0em\">\u2212<\/mml:mo>\n                            <mml:mn>3<\/mml:mn>\n                          <\/mml:mrow>\n                        <\/mml:msup>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    that a human case of H5N1 influenza produces at least one virion during the infectious period. Our findings provide insights into the risk of differing infectious pathways of influenza A(H5N1) (namely avian\u2013human versus avian\u2013mammal\u2013human routes), demonstrating the three-mutation pathway being a cause of concern in human cases.\n                  <\/jats:p>","DOI":"10.1098\/rsif.2024.0910","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T19:08:09Z","timestamp":1751396889000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Introducing a framework for within-host dynamics and mutations modelling of H5N1 influenza infection in humans"],"prefix":"10.1098","volume":"22","author":[{"given":"Daniel","family":"Higgins","sequence":"first","affiliation":[{"name":"EPSRC & MRC Centre for Doctoral Training in Mathematics for Real-World Systems, University of Warwick","place":["Coventry, UK"]},{"name":"The Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, University of Warwick","place":["Coventry, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7973-8072","authenticated-orcid":true,"given":"Joshua","family":"Looker","sequence":"additional","affiliation":[{"name":"EPSRC & MRC Centre for Doctoral Training in Mathematics for Real-World Systems, University of Warwick","place":["Coventry, UK"]},{"name":"The Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, University of Warwick","place":["Coventry, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sunnucks","sequence":"additional","affiliation":[{"name":"EPSRC & MRC Centre for Doctoral Training in Mathematics for Real-World Systems, University of Warwick","place":["Coventry, UK"]},{"name":"The Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, University of Warwick","place":["Coventry, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Carruthers","sequence":"additional","affiliation":[{"name":"Data, Analytics and Surveillance, UK Health Security Agency","place":["Porton Down, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Finnie","sequence":"additional","affiliation":[{"name":"Data, Analytics and Surveillance, UK Health Security Agency","place":["Porton Down, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-4765","authenticated-orcid":true,"given":"Matt J.","family":"Keeling","sequence":"additional","affiliation":[{"name":"The Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, University of Warwick","place":["Coventry, UK"]},{"name":"Mathematics Institute and School of Life Sciences, University of Warwick","place":["Coventry, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2992-2004","authenticated-orcid":true,"given":"Edward M.","family":"Hill","sequence":"additional","affiliation":[{"name":"Civic Health Innovation Labs and Institute of Population Health, University of Liverpool","place":["Liverpool, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"e_1_3_7_2_2","unstructured":"World Health Organisation . 2023 The panzootic spread of highly pathogenic avian influenza H5N1 sublineage 2.3.4.4b: a critical appraisal of one health preparedness and prevention. 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