Infectious diseases cause significant morbidity and mortality, especially
in individuals who are most vulnerable to illness: the very young,
the elderly, the immunocompromised, and the disenfranchised.
The pathogenesis of infectious diseases is dependent on the relationship
among the human host, the infectious agent, and the external environment. Figure 4–1 portrays a host-agent-environment
paradigm for the study of infectious diseases. The infectious agent
can be either exogenous (ie, not normally found on
or in the body) or endogenous (ie, one that may be
routinely cultured from a particular anatomic site but that does
not normally cause disease in the host). Infection results when
an exogenous agent is introduced into a host from the environment
or when an endogenous agent overcomes innate host immunity to cause
disease. Host susceptibility plays an important role in either of
The fundamental relationships involved in the host-agent-environment
interaction model. In the host, pathogenetic mechanisms extend from
the level of populations (eg, person-to-person transmission) to
the level of cellular and molecular processes (eg, genetic susceptibility).
The environment includes vectors (insects and other
carriers that transmit infectious agents) and zoonotic hosts or reservoirs (animals
that harbor infectious agents and often act to amplify the infectious
agent). For example, the white-footed mouse (Peromyscus
leucopus) serves as an animal reservoir for Borrelia
burgdorferi, the bacterium that causes Lyme disease. The Ixodes tick
serves as an insect vector. Infection in the mouse is asymptomatic,
and the bacteria can multiply to high levels in this animal. When
the tick larva feeds on an infected mouse, it becomes secondarily
infected with B burgdorferi, and this infection
persists when the tick molts into a nymph. Subsequently, when an
infected nymph feeds on a human, the bacterium is transmitted into
the host bloodstream, causing disease.
The study of infectious diseases requires understanding of pathogenesis
at the level of the population, the individual, the cell, and the
gene. For example, at the population level, the spread of tuberculosis
in the community is related to the social interactions of an infectious
human host. Outbreaks of tuberculosis have occurred in homeless
shelters, prisons, bars, and nursing homes when an index case comes
in close contact with susceptible persons. At the individual level,
tuberculosis results from inhalation of respiratory droplets containing
airborne tubercle bacilli. At the cellular level, these bacilli
activate T cells, which play a critical role in containing the infection.
Individuals with an impaired T-cell response (eg, those infected
with HIV) are at particularly high risk for primary tuberculosis
at the time of the initial infection or for reactivation of latent
tuberculosis as their immunity wanes. Finally, at the genetic level,
individuals with specific polymorphisms in a macrophage protein
gene may be at significantly higher risk for pulmonary tuberculosis.
Specific microorganisms have a tendency to cause certain ...