tetano
Editor, Senior Moderator
J R Soc Interface
. 2025 Jul;22(228):20240910.
doi: 10.1098/rsif.2024.0910. Epub 2025 Jul 2. Introducing a framework for within-host dynamics and mutations modelling of H5N1 influenza infection in humans
Daniel Higgins[SUP] #[/SUP][SUP] 1 2 [/SUP], Joshua Looker[SUP] #[/SUP][SUP] 1 2 [/SUP], Robert Sunnucks[SUP] #[/SUP][SUP] 1 2 [/SUP], Jonathan Carruthers[SUP] 3 [/SUP], Thomas Finnie[SUP] 3 [/SUP], Matt J Keeling[SUP] 2 4 [/SUP], Edward M Hill[SUP] 5 [/SUP]
Affiliations
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 [Formula: see text] 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-human versus avian-mammal-human routes), demonstrating the three-mutation pathway being a cause of concern in human cases.
Keywords: H5N1; branching process; influenza; viral mutations model; within-host model.
. 2025 Jul;22(228):20240910.
doi: 10.1098/rsif.2024.0910. Epub 2025 Jul 2. Introducing a framework for within-host dynamics and mutations modelling of H5N1 influenza infection in humans
Daniel Higgins[SUP] #[/SUP][SUP] 1 2 [/SUP], Joshua Looker[SUP] #[/SUP][SUP] 1 2 [/SUP], Robert Sunnucks[SUP] #[/SUP][SUP] 1 2 [/SUP], Jonathan Carruthers[SUP] 3 [/SUP], Thomas Finnie[SUP] 3 [/SUP], Matt J Keeling[SUP] 2 4 [/SUP], Edward M Hill[SUP] 5 [/SUP]
Affiliations
- PMID: 40592463
- DOI: 10.1098/rsif.2024.0910
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 [Formula: see text] 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-human versus avian-mammal-human routes), demonstrating the three-mutation pathway being a cause of concern in human cases.
Keywords: H5N1; branching process; influenza; viral mutations model; within-host model.