A mouse model of dual infection with influenza virus and Streptococcus pneumoniae

Abstract

Background: A lethal synergism exists between influenza virus and Streptococcus pneumoniae accounting for excess mortality during influenza epidemics. A small animal model of dual infection with these organisms would be useful for study of pathogenic mechanisms underlying this interaction. Methods: Groups of mice were infected with either mouse adapted influenza virus A/Puerto Rico/8/34 (H1N1), S. pneumoniae strain D39, both simultaneously, or pneumococcus following influenza virus. Weight loss, as a measure of morbidity, and mortality were followed. Blood cultures were collected 24 h after infection. Results: Mice infected simultaneously with both influenza virus and pneumococcus exhibited gradual weight loss and mortality commensurate with expectations for an additive process. In contrast, mice infected with pneumococcus 7 days following infection with influenza virus uniformly died in less than 24 h and were highly bacteremic. Discussion: A mouse model of sequential infection with influenza virus and S. pneumoniae has been developed. Mice infected with pneumococcus seven days after infection with influenza virus exhibit a synergistic lethality caused by overwhelming sepsis. This model will be useful for study of the mechanisms involved in pathogenic interactions between influenza virus and pneumococcus.