Background:
Group A streptococcus (GAS) and Influenza A virus (IAV) are important respiratory pathogens, causing severe or potentially fatal disease in children. Evidence indicates that IAV exacerbates GAS infection and disease. The mechanisms underlying viral-bacterial synergy are unclear. We developed two models to investigate IAV-GAS coinfection in children.
Methods:
Our novel in vitro model of coinfection follows nasal brushings from children, and produces fully differentiated epithelial monolayers, cultured in an air-liquid-interface system. These cultures were infected and examined for evidence that IAV infection synergised GAS attachment, invasion and transmigration. In our infant mouse model of upper respiratory tract coinfection, five- or nine-day old BALB/c mice were intranasally infected with GAS and/or IAV. Upper respiratory tract tissue was collected for bacterial viable counts and viral quantification.
Results:
Following GAS monoinfection of in vitro cultures, we observed that 0.17% of GAS inoculum adhered, however internalisation was not detected. When IAV infection preceded GAS (i.e. secondary bacterial infection), we observed 1.8% adherence and internalisation at 0.3% of inoculum, a 10-fold and >2-fold increase over monoinfection respectively. In mice, following infection at five- or nine-days old, GAS was detected up to seven days post infection in 93% and 97% respectively. Likewise, IAV was detected in 94% of nine-day old mice, up to 5 days post infection. Coinfection with non-lethal IAV doses has commenced.
Conclusion:
Using these models, we can address the limited understanding of IAV/GAS coinfection by identifying and investigating key underlying mechanisms. Our findings may have important public health implications, including for bacterial and viral vaccination strategies in young children.