Investigations into the immunology, physiology and epidemiology of pertussis

Abstract

This volume contains an introduction to the topic of pertussis followed by twelve papers on pertussis arising from research conducted while I was a research fellow at St. George's Hospital Medical School from 1985 to 1988. Paper 1 provides a qualitative description of the serum antibody responses to several Bordetella pertussis antigens. It demonstrates that the serum antibody response to a specific B. pertussis antigen, following either natural infection or vaccination, is dependent both on the antigen and on the subject. Some B. pertussis antigens appear to consistently evoke strong serum antibody responses following either natural infection or vaccination, while other B. pertussis antigens appear to consistently fail to evoke any significant serum antibody response. Other B. pertussis antigens induce an antibody response in a variable proportion of subjects. Paper 2 describes the serum IgG, IgA and IgM responses to B. pertussis antigens in patients with pertussis. These antibody responses are compared with those in the family contacts of patients with pertussis and with those in infants immunised with a whole cell pertussis vaccine. It demonstrates that both pertussis and pertussis vaccination produce marked serum antibody responses to three B. pertussis antigens. In contrast, family contacts who are exposed to a patient with pertussis, but who themselves fail to develop disease, have a minor antibody response to the same antigens. Immunity to disease in these family contacts is associated with high titres of antibody to B. pertussis antigens at the time of exposure to infection. Paper 3 demonstrates the serum antibody responses to B. pertussis antigens in two subjects immunised with new acellular pertussis vaccines. The antibody responses are compared with those in subjects who had been immunised with a whole cell pertussis vaccine, and with those in subjects who had suffered natural infection. The new acellular pertussis vaccines are shown to induce antibody responses solely to two purified B. pertussis antigens, and not to other potential contaminating antigens. Paper 4 demonstrates that the IgA antibody response in nasal mucus in patients with pertussis is less pronounced than the serum antibody responses. It also demonstrates that titres of antibody in nasal mucus are not especially strongly correlated with immunity to pertussis in family contacts. Paper 5 compares the serum antibody responses to B. pertussis antigens in breast fed infants with pertussis with those in bottle fed infants with pertussis. It also compares the levels of IgA to B. pertussis antigens in breast milk from mothers of infants with pertussis with the levels in breast milk from mothers of healthy infants. This paper provides further evidence that B. pertussis infection does not produce an especially strong secretory immune response. Paper 6 provides evidence that B. pertussis infection does not produce a significant impairment of immunoglobulin synthesis. Paper 7 compares the responses of peripheral blood lymphocytes, from patients with pertussis and two control groups, to in vitro stimulation with B. pertussis antigens. This study is the first to show that B. pertussis infection induces cell mediated immune responses. Paper 8 describes the respiratory physiology of six infants with severe pertussis. It demonstrates that abrupt severe hypoxaemia may be due to prolonged apnoea or may occur despite continued breathing movements and respiratory airflow. It postulates that these findings are due to a ventilation perfusion mismatch secondary to alveolar atalectasis caused by a defect in lung surfactant synthesis, secretion or function. Paper 9 describes the effects of B. pertussis infection on the ciliary function and electron microscopic appearances of human nasal epithelial cells. These findings are extended by similiar investigations perfomed on human nasal epithelial cells exposed to B. pertussis toxins in vitro. Paper 10 attempts to explain the large-scale epidemiology of pertussis by a simple mathematical formula. This formula is then used to derive an estimate of the proportion of the population susceptible to pertussis. Finally the relationship between the incidence of pertussis and the level of vaccine uptake is illustrated using data from several countries during the last century. Paper 11 describes the small-scale epidemiology of pertussis and demonstrates that pertussis is usually transmitted by patients with clinical disease rather than by persons with either atypical disease or asymptomatic infection. Paper 12 briefly discusses the use of erythromycin and other antimicrobial agents in the treatment and prophylaxis of pertussis.