The concept of pertussis as a toxin-mediated disease

Abstract

Pertussis (whooping cough), a two-stage process of disease (respiratory colonization and toxin-mediated disease) is caused by B. pertussis. The bacterium is unique. It is a pathogenic parasite with habitat only in human beings. Growth in the pathogenic form, both in in vitro and in vivo, requires conditions that permit the expression of pertussis toxin (PT) (also known as histamine-sensitizing factor, lymphocyte-leukocyte-promoting factor, islet-activating factor and pertussigen). The expression of growth and PT appear to be genetically interrelated. For multiplication in vitro the medium must be free of substances, such as fatty acids, that inhibit the enzymatic action required for elaboration of PT. In vivo the bacteria are uniquely localized to the cilia of the respiratory epithelium where they multiply. In situ the bacteria inhibit natural defenses of the respiratory tract (cilial, phagocytic and other activities); they tend not to spread and do not invade the underlying tissue. The extent of the areas of colonization, directly related to the number of bacteria in the infecting inoculum, influences the amount of toxin elaborated and consequently the intensity of the clinical symptoms. Other factors that influence the clinical disease are the inordinate susceptibility of the infant and genetically controlled susceptibility. A specific role for PT in the initial establishment of the infection is not clear, but it seems definite that PT-specific immunity influences the clearance of colonization in about 4 to 5 weeks. The clinical symptoms become manifest when the bacteria are waning. This clearance is influenced by the synthesis of IgA antibodies and pertussis toxin antibodies that may act by inhibiting the "enzyme" required for growth or by another mechanism. The pathology of the disease is the result of altered cellular functions of toxin-sensitized cells, not by histologic damage. PT is composed of two functional components like other exotoxins that cause infectious disease (e.g. diphtheria, cholera). Certain sites on one component enable PT to bind to specific receptors on tissue cells and enter the cell. The toxin ADP ribosylates a regulatory protein of the cytoplasmic membrane and thereby alters the function of the cell. Affected (sensitized) cells are insulin-secretory islets of the pancreas, lymphocytes and leukocytes, heart cells and others that have not been clearly identified, e.g. those that effect paroxysms and neurologic disturbances. The altered function of the cell in vitro is irreversible, and the restoration of the function of a particular tissue in vivo appears to be dependent on the renewal of the cells.(ABSTRACT TRUNCATED AT 400 WORDS)