# Introducing a framework for within-host dynamics and mutations modelling of H5N1 influenza infection in humans

## TL;DR

This paper introduces a new model to study how H5N1 influenza behaves and mutates inside the human body, estimating the risk of it becoming transmissible between humans.

## Contribution

The novel contribution is a mechanistic within-host model that explicitly considers differences between upper and lower respiratory tracts for H5N1 influenza.

## Key findings

- The model estimates viral lifespans and replication rates in human H5N1 cases.
- The probability of generating a droplet transmissible strain through three mutations is approximately 10^-3.
- The three-mutation pathway is identified as a significant concern in human H5N1 cases.

## Abstract

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
10−3
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.