Joseph P. Libonati

Serotype Distribution of Invasive Group B Streptococcal Isolates in Maryland: Implications for Vaccine Formulation

Invasive group B streptococcal (GBS) infection is a major health problem among infants and adults. The formulation of GBS vaccines depends on knowledge of the GBS serotype distribution. Serotype V GBS infection appears to have recently emerged, suggesting that the serotype distribution changes over time. GBS isolates from 210 pediatric patients, 23 pregnant women, and 314 nonpregnant adults with invasive infection in Maryland were studied. The predominant serotypes from infants with early-onset disease were as follows: serotype III, 38% of isolates; serotype Ia, 36%; serotype V, 13%; and serotype II, 11%. Although the majority (60%) of isolates among infants with late-onset infection were serotype III, serotype Ia (23%) was also common. The predominant serotype among isolates from nonpregnant adult patients was serotype V, accounting for 29% of the isolates. The serotype distribution differs between pediatric patients and adults and is changing over time. The inclusion of a relatively small number of serotypes in a GBS vaccine could provide protection against the vast majority of isolates.

Immunity of cholera in man: relative role of antibacterial versus antitoxic immunity.

Purified cholera toxoid is antigenic when given enterally and orally. Purified toxoid fails to provide protection against experimental challenge. Clinical cholera confers formidable protection against homologous or heterologous rechallenge. Failure to culture vibrios from intestinal fluid or stool of re-challenge volunteers suggests that the predominant immune mechanism is antibacterial rather than antitoxic.

EXPERIMENTAL MODELS IN THE INVESTIGATION OF THE VIRULENCE OF DYSENTERY BACILLI AND ESCHERICHIA COLI

The knowledge gained from experiments in laboratory models has been very useful in helping us to reach our present understanding of the pathogenesis of some diarrheal diseases of human beings. This is especially true of bacillary dysentery. Dysentery may be defined as a syndrome in which blood, inflammatory cells, and mucus are present in the watery stool. A cardinal feature of classical shigellosis is an ulcerative lesion of the colonic mucosa, for it is through this defect in the epithelial barrier that the red blood cells reach the intestinal lumen. Thus, in order to gain some insight into at least one aspect of the pathogenesis of classical bacillary dysentery, one must understand how the ulcerative lesion evolves. The previous concept of the evolution of the colonic ulcer envisioned consecutive waves of absorption and excretion of heat-stable toxin across the intestinal wall, resulting in hypoxia and death of the epithe1ium.l For a variety of reasons2 we rejected this hypothesis and sought an alternate explanation. We started by using a virulent Shigella flexneri 2a strain and an avirulent mutant derived from it. As far as could be ascertained, the two strains were identical, with the exception that the parent strain caused disease when fed to starved, opiated guinea pigs or to rhesus monkeys, while the mutant failed to do so. When animals infected with either of the strains were studied using the fluorescent antibody technique, a distinctly different pattern of distribution of the organisms in the intestine was observed. The avirulent mutant was seen only in the lumen of the bowel. On the other hand the virulent bacteria were present in the epithelial cells of the intestine, and also both free and within phagocytic cells in the lamina propria. Rarely were the organisms viewed in the submucosa or in the mesenteric lymph nodes.2 From the results of these experiments we concluded that an essential step in the pathogenesis of bacillary dysentery is the penetration of the intestinal epithelial cell by the pathogen. If the organism is unable to enter the epithelium for one reason or another, few, if any, signs of disease are observed. Similar observations have been made independently by Voino-Yasenetsky and Khavkin and confirmed in extensive studies by Ogawa and colleague^.^ Other procedures are available to test for the ability of dysentery bacilli to