Sequential infections with influenza and novel respiratory bacteria.

To the Editor—McCullers and colleagues [1] recently reported results of their studies of influenza and Streptococcus pneumoniae infection in ferrets. The findings documented that pneumococcal transmission was enhanced in ferrets previously infected with influenza: ferrets that were infected with pneumococci after—but not before—influenza infection developed lethal secondary pneumonias and other invasive complications [1]. These findings, if generalizable to humans, have important public health policy and practice implications. Most deaths during the 1918 influenza pandemic were caused by secondary bacterial pneumonias. The bacterial species most often implicated in fatal cases were S. pneumonia, S. pyogenes, and S. aureus; all are common colonizers of the nasopharynx of healthy humans [2, 3]. It has been presumed that the bacteria that caused most of the secondary pneumonias in 1918 were colonizers of their victims and that previously benign carriage strains were enabled to invade the lower respiratory tract of their hosts after influenza disrupted their physical and immunologic defenses. The findings of McCullers et al [1] suggest a different pathogenic sequence. Specifically, the life-threatening bacterial complications of influenza required sequential infections: first with an influenza virus that degraded the physical and immunologic defenses of the host’s lower respiratory tract, and then with a bacterial strain to which the host was susceptible (eg, the host lacked protective antibodies). Given this sequence, individuals infected with potentially invasive bacteria prior to infection with influenza would be at low risk of invasive disease (because intact physical barriers and immune responses would be protective). In addition, individuals would not be at risk of invasive complications from their own nasopharyngeal microflora because preexisting antibodies against them would be protective [4]. Only exposures to novel bacteria within several days after influenza infection would threaten to cause lethal pneumonias and other invasive complications. This pathogenic sequence is consistent with observations in military groups during the 1918 pandemic.