Vaccines and Other Approaches to the Prevention of Intractable Infant Diarrhea by the Prevention of Intestinal Colonization*

In developing preventive measures and treatments for intractable infant diarrhea, one must first have an understanding of the etiology of these diseases. It is a reasonable hypothesis, although one not yet proven, that these illnesses are induced by the establishment of chronic colonization of the small intestine by enteric bacterial pathogens and that this colonization leads to a pattern of chronic and continuing mucosal injury. The organisms involved may be common but difficult to recognize as pathogens. Inadequate nutrition, either before initial infection and/or aggravated by the diarrheal state and continuing mucosal damage, may contribute to an inadequate local immune response and delayed clearing of the organisms. Alternatively, in some cases, chronic intestinal disease may be induced by an aberrant and self-destructive immune response to an encounter with an enteric pathogen. In either case, measures aimed at prevention of recognized enteric infection may be expected to reduce the incidence of chronic and/or intractable acute diarrheal disease. In an earlier chapter (E. C. Boedeker, Chapter 19, this volume), the known mechanisms whereby enteric bacterial pathogens, and, in particular, pathogenic E. coli strains, interact with the intestinal mucosa and achieve mucosal colonization were reviewed. This chapter reviews established and theoretically promising methods for preventing intestinal colonization by pathogenic E. coli. The following approaches will be reviewed: (a) passive immune protection with antibodies to E. coli surface components, (b) active immunization with isolated colonization factor antigens or attenuated live organisms expressing these antigens, (c) competitive colonization with nonpathogenic strains, (d) variations of receptor analog therapy, and (e) potential methods for in vivo suppression of virulence factors. Most successful examples of prevention and therapy come from the veterinary literature or from animal models. It should be emphasized that none of the methods is currently established for use in man. Prophylaxis