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Infectious diseases remain one of the leading causes of death in both developed and developing countries. Infections cause significant morbidity and mortality, especially in individuals who are most vulnerable to illness: the very young, the elderly, the immunocompromised, and the disenfranchised.
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The pathogenesis of infectious diseases reflects 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 specific 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 these settings.
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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 through infected saliva into the host bloodstream, causing disease.
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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 group settings such as homeless shelters, prisons, 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 human immunodeficiency virus [HIV]) are at particularly high risk for developing active 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 ...