Abstract:
Pathogen interference is the ability of one pathogen to alter the course and clinical outcomes
of infection by another. With up to 3000 species of human pathogens the potential combinations
are vast. These combinations operate within further immune complexity induced by infection with
multiple persistent pathogens, and by the role which the human microbiome plays in maintaining
health, immune function, and resistance to infection. All the above are further complicated by
malnutrition in children and the elderly. Influenza vaccination offers a measure of protection for
elderly individuals subsequently infected with influenza. However, all vaccines induce both specific
and non-specific effects. The specific effects involve stimulation of humoral and cellular immunity,
while the nonspecific effects are far more nuanced including changes in gene expression patterns
and production of small RNAs which contribute to pathogen interference. Little is known about the
outcomes of vaccinated elderly not subsequently infected with influenza but infected with multiple
other non-influenza winter pathogens. In this review we propose that in certain years the specific
antigen mix in the seasonal influenza vaccine inadvertently increases the risk of infection from other
non-influenza pathogens. The possibility that vaccination could upset the pathogen balance, and that
the timing of vaccination relative to the pathogen balance was critical to success, was proposed in
2010 but was seemingly ignored. Persons vaccinated early in the winter are more likely to experience
higher pathogen interference. Implications to the estimation of vaccine effectiveness and influenza
deaths are discussed.
