Influenza interaction with cocirculating pathogens and its impact on surveillance, pathogenesis, and epidemic profile: A key role for mathematical modelling

Evidence is mounting that influenza virus interacts with other pathogens colonising or infecting the human respiratory tract. Taking into account interactions with other pathogens may
be critical to determining the real influenza burden and the full impact of public health policies targeting influenza. This is particularly true for mathematical modelling studies, which
have become critical in public health decision-making. Yet models usually focus on influenza
virus acquisition and infection alone, thereby making broad oversimplifications of pathogen
ecology. Herein, we report evidence of influenza virus interactions with bacteria and viruses
and systematically review the modelling studies that have incorporated interactions.
Despite the many studies examining possible associations between influenza and
Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Neisseria
meningitidis, respiratory syncytial virus (RSV), human rhinoviruses, human parainfluenza
viruses, etc., very few mathematical models have integrated other pathogens alongside
influenza. The notable exception is the pneumococcus–influenza interaction, for which several recent modelling studies demonstrate the power of dynamic modelling as an approach
to test biological hypotheses on interaction mechanisms and estimate the strength of those
interactions.
We explore how different interference mechanisms may lead to unexpected incidence
trends and possible misinterpretation, and we illustrate the impact of interactions on public
health surveillance using simple transmission models. We demonstrate that the development of multipathogen models is essential to assessing the true public health burden of influenza and that it is needed to help improve planning and evaluation of control measures.
Finally, we identify the public health, surveillance, modelling, and biological challenges and
propose avenues of research for the coming years.