The germ theory revisited: A noncentric view on infection outcome.

The germ theory states that pathogenic microorganisms are responsible for causing infectious diseases. The theory is inherently microbe-centric and does not account for variability in disease severity among individuals and asymptomatic carriership-two phenomena indicating an important role for host variability in infection outcome. The basic tenet of the germ theory was recently challenged, and a radically host-centric paradigm referred to as the "full-blown host theory" was proposed. According to this view, the pathogen is reduced to a passive environmental trigger, and the development of disease is instead due to pre-existing immunodeficiencies of the host. Here, we consider the factors that determine disease severity using established knowledge concerning evolutionary biology, microbial pathogenesis, and host-pathogen interactions. We note that the available data support a noncentric view that recognizes key roles for both the causative microbe and the host in dictating infection outcome.