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Updated: Jul 26, 2025
A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
Published on: September 21, 2019
Infection with different human influenza A subtypes affects the period of susceptibility to secondary bacterial
Edin J Mifsud1,2, Rubaiyea Farrukee2, Aeron C Hurt1
1WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia.
Abstract:
It is well-established that influenza virus infections predispose individuals to secondary bacterial infections (SBIs), which may result in a range of clinical outcomes from relatively mild (e.g. sinusitis and otitis media) to severe (e.g. pneumonia and septicaemia). The most common bacterial pathogen associated with SBI following influenza virus infections is Streptococcus pneumoniae(SPN). Of circulating human seasonal influenza viruses, influenza A viruses (IAV) of both the A(H1N1)pdm09 and A(H3N2) subtypes are associated with severe disease but have differing hospitalisation and complication rates. To study the interplay of these two IAV subtypes with SBI, we used a ferret model of influenza infection followed by secondary challenge with a clinical strain of SPN to determine the severity and the period of susceptibility for SBI. Ferrets challenged with SPN 5 days after infection with A(H3N2) or A(H1N1)pdm09 viruses developed severe disease that required euthanasia. When the time between viral infection and bacterial challenge was extended, A/H1N1pdm09-infected animals remained susceptible to SBI- for up to 10 days after the viral infection. For A(H3N2)- but not A(H1N1)pdm09-infected ferrets, susceptibility to SBI-associated disease could be extended out to 16 days postviral infection. While caution should be taken when extrapolating animal models to human infections, the differences between A(H3N2) and A(H1N1)pdm09 strains in duration of susceptibility to SBI observed in the ferret model, may provide some insight regarding the higher rates of SBI-associated disease associated with some strains of A(H3N2) viruses in humans.
Insights
Influenza A virus infection increases susceptibility to secondary bacterial infections, particularly Streptococcus pneumoniae. Ferret models show differing susceptibility periods for A(H3N2) and A(H1N1)pdm09 influenza strains, potentially explaining human disease rate variations.
Area of Science:
- Virology
- Bacteriology
- Immunology
Background:
- Influenza virus infections commonly lead to secondary bacterial infections (SBIs), ranging from mild to severe outcomes.
- Streptococcus pneumoniae (SPN) is the most frequent bacterial pathogen causing SBIs after influenza.
- Influenza A virus (IAV) subtypes A(H1N1)pdm09 and A(H3N2) are associated with severe disease, but exhibit different hospitalization and complication rates.
Purpose of the Study:
- To investigate the interplay between influenza A virus subtypes (A(H1N1)pdm09 and A(H3N2)) and secondary bacterial infections (SBIs).
- To determine the severity and duration of susceptibility to SPN challenge following IAV infection in a ferret model.
Main Methods:
- Ferrets were infected with either A(H1N1)pdm09 or A(H3N2) influenza A viruses.
- Following viral infection, ferrets were secondarily challenged with a clinical strain of Streptococcus pneumoniae at varying time points.
- Disease severity and duration of susceptibility to SBI were assessed.
Main Results:
- Ferrets challenged with SPN 5 days post-IAV infection developed severe disease requiring euthanasia, irrespective of the IAV subtype.
- A(H1N1)pdm09-infected ferrets remained susceptible to SBI for up to 10 days post-viral infection.
- A(H3N2)-infected ferrets showed extended susceptibility to SBI for up to 16 days post-viral infection, unlike A(H1N1)pdm09-infected ferrets.
Conclusions:
- The ferret model demonstrates distinct durations of susceptibility to SPN challenge following infection with A(H3N2) versus A(H1N1)pdm09 influenza A viruses.
- Observed differences in SBI susceptibility duration between IAV subtypes in ferrets may offer insights into higher SBI-associated disease rates linked to certain A(H3N2) strains in humans.
