Insights into the interaction between influenza virus and pneumococcus

Abstract

Bacterial infections following influenza are an important cause of morbidity and mortality worldwide. Based on the historical importance of pneumonia as a cause of death during pandemic influenza, the increasingly likely possibility that highly pathogenic avian influenza viruses will trigger the next worldwide pandemic underscores the need to understand the multiple mechanisms underlying the interaction between influenza virus and bacterial pathogens such as Streptococcus pneumoniae. There is ample evidence to support the historical view that influenza virus alters the lungs in a way that predisposes to adherence, invasion, and induction of disease by pneumococcus. Access to receptors is a key factor and may be facilitated by the virus through epithelial damage, by exposure or up-regulation of receptors, or by provoking the epithelial regeneration response to cytotoxic damage. More recent data indicate that alteration of the immune response by diminishing the ability of the host to clear pneumococcus or by amplification of the inflammatory cascade is another key factor. Identification and exploration of the underlying mechanisms responsible for this synergism will provide targets for prevention and treatment using drugs and vaccines.

FIG. 1.

Excess mortality rates by year in selected cities in the United States. Excess mortality is defined as the number of deaths in excess of those that would be expected for a particular time of year in the absence of influenza; pictured is the rate of excess mortality attributable directly to pneumonia and influenza. Bars define the proportions attributable to different types and subtypes of influenza virus and are stacked together by year. Data are derived from those of Collins and Lehmann (25, 27, 28) (A), Housworth and Spoon (70) (B), and Reichert et al. and Simonsen et al. (128, 136) (C) and were calculated by different methods. Note the different scales. The first known epidemic of influenza B was in 1935, but the virus likely circulated before that time. H1N1 viruses circulated from 1917 to 1957 and then reentered humans in 1976 and have circulated since that time. It is postulated based on serology data that an H3N8 virus circulated prior to 1917.