New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development

Enteric bacterial infections, causing diarrhea, dysentery, and enteric fevers, are important health problems throughout the world. These bacterial infections represent a notable burden, in particular, for children living in less-developed regions of the world; they also pose a risk for travelers from industrialized countries who visit less-developed areas. Among the most important enteric bacterial pathogens recognized are the following: (i) enterotoxigenic Escherichia coli (ETEC) as a cause of diarrhea in travelers and in infants in less-developed countries; (ii) Vibrio cholerae O1, responsible for endemic and epidemic cholera; (iii) Campylobacter jejuni, an important cause of diarrhea in young children throughout the world, as well as an agent of diarrhea in travelers; (iv) Shigella species as a cause of both watery diarrhea and dysentery (loose stools with blood and mucus), particularly in less-developed areas; (v) Salmonella typhi, the etiological agent of typhoid fever, the most common enteric fever (a generalized infection of the reticuloendothelial system and intestinal lymphoid tissue accompanied by sustained fever and bacteremia); and (vi) nontyphoidal Salmonella sp., an important cause of acute gastroenteritis in individuals in both developing and industrialized countries. For many years attempts have been made to prepare immunizing agents against some of these infections, with variable results. In many instances the vaccines prepared represented empirical approaches with no recognizable scientific basis for following that approach (e.g., phenolized heat-killed V. cholerae used as a parenteral vaccine). More recently, however, there have occurred great advances in our knowledge of the pathogenesis of infections due to these bacterial enteropathogens. This new information has been applied toward vaccine development, resulting in fresh evaluations of older vaccines as well as innovative new approaches. In this review, we attempt to synthesize the new knowledge of pathogenesis of bacterial enteric infections and relate this information to vaccine development. We restrict ourselves to human infections and to those in which significant strides have been made.