Chapter 7: Pathogenesis

PRINCIPLES OF PATHOGENESIS

A microorganism is a pathogen if it is capable of causing disease; however, some organisms are highly pathogenic (i.e., they often cause disease), whereas others cause disease rarely. Opportunistic pathogens are those that rarely, if ever, cause disease in immunocompetent people but can cause serious infection in patients with reduced host defenses (immunocompromised) and, as discussed in Chapter 6, are frequent members of the body’s normal flora.

Virulence is a quantitative measure of pathogenicity and is measured by the number of organisms required to cause disease. The 50% lethal dose (LD₅₀) is the number of organisms needed to kill half of the hosts that are exposed to the pathogen, while the 50% infectious dose (ID₅₀) is the number needed to cause infection in half of the exposed hosts. Organisms with a lower LD₅₀ (or ID₅₀) are said to be more virulent than those with a higher LD₅₀ (or ID₅₀) because fewer organisms are needed to cause death or disease.

The infectious dose of an organism required to cause disease varies greatly among the pathogenic bacteria. For example, Shigella and Salmonella both cause diarrhea by infecting the gastrointestinal tract, but the infectious dose of Shigella is less than 100 organisms, whereas the infectious dose of Salmonella is on the order of 100,000 organisms. The infectious dose of bacteria depends primarily on their virulence factors (e.g., whether their pili allow them to adhere well to mucous membranes, whether they produce exotoxins or endotoxins, whether they possess a capsule to protect them from phagocytosis, and whether they can survive various nonspecific host defenses such as acid in the stomach).

There are two uses of the word parasite. Within the context of this chapter, the term refers to the parasitic relationship of the bacteria to the host cells (i.e., the presence of the bacteria is detrimental to the host cells). Bacteria that are human pathogens can be thought of, therefore, as parasites. Some bacterial pathogens are obligate intracellular parasites (e.g., Chlamydia and Rickettsia), because they can grow only within host cells. Many bacteria are facultative parasites because they can grow within cells, outside cells, or on bacteriologic media. The other use of the term parasite refers to the protozoa and the helminths, which are discussed in Part VI of this book.

WHY DO PEOPLE GET INFECTIOUS DISEASES?

People get infectious diseases when microorganisms overpower our host defenses (i.e., when the balance between the organism and the host shifts in favor of the organism). The organism or its products are then present in sufficient amount to induce various symptoms, such as fever and inflammation, which we interpret as those of an infectious disease.

From the organism’s perspective, the two critical determinants in overpowering the host are the number of organisms to ...