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E. coli is part of the normal intestinal flora of humans and other primates, and only a minority of strains are pathogenic for humans. Despite being the subject of intense research, the proportion of pathogenic to nonpathogenic strains is unknown. E. coli is the dominant species recovered from aerobic cultures of feces. While an important cause of gastroenteritis, especially in the developing world, its role in this setting is rarely diagnosed from clinical testing. E. coli is the etiologic agent in 70-90% of all cases of UTI, which may progress from simple urethritis to serious pyelonephritis, especially in young women and elderly adults. Urosepsis involving E. coli is not infrequently seen. Enterotoxigenic E. coli (ETEC) has a relatively large infectious dose (100 million to 10 billion bacteria) necessary to colonize the small intestine; infants may require fewer organisms for infection to be established. ETEC causes a secretory diarrhea ("traveller's diarrhea") that is encountered especially in developing countries. These organisms must be able to attach to target intestinal epithelial cells prior to toxin production. After attachment, the organism may produce one or two plasmid-encoded enterotoxins: heat-labile toxin and heat-stable toxin. The heat-labile toxin produces diarrhea by the same mode of action as does the Vibrio cholerae enterotoxin, causing active excretion of sodium and chloride ions from the intestinal mucosa and other cells into the lumen of the bowel, followed by osmotic excretion of water. Diarrhea is profuse and watery without blood or mucus. The heat-labile toxin shows great homology and antigenic similarity to cholera enterotoxin, while the heat-stable toxin is a small polypeptide that is specific for intestinal mucosal cells only. The disease is usually self-limiting. Enteropathogenic E. coli (EPEC) was first implicated in the 1940's as the cause of infant summer diarrhea, now known as infantile diarrhea. EPEC belong to serogroups epidemiologically implicated as pathogens but which fail to excrete typical E. coli enterotoxins. Source(s) and prevalence of EPEC remain controversial since foodborne outbreaks are sporadic. EPEC causes either a watery or bloody diarrhea. Watery diarrhea is associated with the attachment to, and physical alteration of, the integrity of the intestine. Bloody diarrhea is associated with attachment (plasmid-related adhesion) and an acute tissue-destructive process (enterocyte microvilli dissolution), perhaps caused by a toxin similar to Shigella dysenteriae verotoxin. In most of these strains the shiga-like toxin is cell-associated rather than excreted. Diarrhea can be severe, prolonged, and associated with high case fatality (up to 50% in third world countries). Since the late 1960's EPEC has largely disappeared in North America and Europe, but it remains a major agent of infant diarrhea elsewhere. EPEC infection is uncommon in breast-fed infants and outbreaks most often affect bottle-fed infants, suggesting that contaminated water is often used to rehydrate infant formulae in under-developed countries. EPEC is highly infectious for infants and the dose is presumably very low. Enteroinvasive E. coli (EIEC) strains are closely related to Shigella spp. This organism produces an illness known as bacillary dysentery. As with Shigella, the infectious dose of EIEC appears to be as few as ten organisms, which invade intestinal mucosal and submucosal epithelial cells. Here the organism multiplies, and within 12 to 72 hours following the ingestion of contaminated food a mild form of dysentery ensues with erythrocytes, PMN's, and mucus found in the stool. This dysentery is often mistaken for dysentery caused by Shigella. The hemolytic-uremic syndrome (HUS) commonly develops in pediatric cases (see EHEC below), but EIEC dysentery is generally self-limiting with no known complications. Enterohemorrhagic E. coli O157:H7 (EHEC) is a rare variety of E. coli that produces large quantities of one or more related, potent toxins that cause severe damage to the lining of the intestine. Infection is commonly related to ingestion of inadequately cooked beef, unpasteurized milk, and contamination from cow manure. First recognized in 1982, enterohemorrhagic colitis is characterized by severe cramping and watery diarrhea which becomes grossly bloody. Typically erythrocytes but not white cells are abundant in the stool. Occasionally vomiting occurs. Fever is either low-grade or absent. The illness is usually self-limited and lasts for an average of eight days. Up to 15% of hemorrhagic colitis victims may develop hemolytic-uremic syndrome (HUS: renal small blood vessel lining damage leads to formation of small clots, which in turn cause hemolysis as blood flows past; resulting kidney damage may lead to renal failure), characterized by renal failure and hemolytic anemia, which can lead to permanent loss of kidney function. HUS occurs particularly in very young patients. In the elderly, HUS, plus fever and neurologic symptoms, constitutes thrombotic thrombocytopenic purpura (TTP), having a mortality rate as high as 50%. EHEC elaborate potent cytotoxins (shiga-like toxins I and II, also known as verotoxins 1 and 2) which are closely related or identical to the toxin produced by Shigella dysenteriae. Besides the serotype E. coli O157:H7, other serogroups (O26:H11, O111:H8, and O104:H21) have been implicated in EHEC. Supportive therapy including dialysis and possible infusions of plasma, platelets, packed red cells, and possibly other components may be indicated, but the role of antibacterial treatment remains unresolved. The infectious dose may be similar to that of Shigella spp. (ten organisms).
Enteroaggregative E. coli (EAggEC) is an important cause of infant diarrhea in less-developed countries and it may cause persistant diarrhea. Virulence involves a novel heat-stable enterotoxin. Diffuse-Adherent E. coli (DAEC) may be more pathogenic in pre-school-aged children than in infants and toddlers, although the syndrome remains ill-defined. It is found in less-developed countries. In the clinical microbiology laboratory it is tempting to think that "an E. coli is an E. coli is an E. coli," but clearly this is not the case, for virulence factors are frequently associated with plasmid-encoded toxins, serogroups, etc. Besides the gastroenteritis-causing strains mentioned above, Uropathogenic E. coli (UPEC) strains are becoming increasingly well-characterized. While the same serotypes are often found in the stool as in the urine, it is apparent that UPEC possess virulence factors which enhance their ability to cause UTI, and UPEC strains recovered from UTI's are not necessarily the most prevalent fecal strains. A very limited number of O groups (including O1, O2, O4, O6, O7, O18 and O75) are associated with most UTI, as are a small number of K antigens (including K1, K2, K3, K5, K12 and K13). Furthermore, fimbriae known as p-pili (beacuse they specifically bind to the P-antigen, one of the blood grouping antigens) are an important virulence factor among UPEC strains. P-piliated E. coli strains show significantly increased binding to uroepithelial cells of persons with the P or P2 phenotype; however, other adhesins may also be involved. Many virulence factors appear to contribute to the ability of E. coli to cause UTI. A similar story is emerging in the case of Neonatal Meningitis E. coli (NMEC) infection. Up to 80% of cases of neonatal menigitis are due to E. coli, and about 80% of these isolates possess the K1 capsular antigen. This antigen, a polymer of N-acetylneuraminic acid (sialic acid), is identical to the group B acidic polysaccharide of Neisseria menigitidis. The K1 antigen masks underlying antigenic structures, preventing specific antibody responses and the activation of the alternate complement system, and is itself a poor immunogen. The NMEC serotypes isolated from neonatal meningitis cases can also be recovered from maternal stool specimens, suggesting this as a possible source of perinatal infection. | |
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Shigella spp. are enteric Gram-negative rods closely related to the genus Escherichia (intergeneric conjugation sometimes occurs). Humans are the only known reservoir of the organism. Shigellosis (bacillary dysentery) accounts for less than 10% of the reported outbreaks of foodborne illness in this country (300,000 cases of shigellosis occur annually in the U.S.). Remarkably, perhaps as few as ten cells constitute an infective dose of Shigella, depending on host age and condition (contrast with Salmonella spp., for which the infectious dose is 10,000 - 100,000,000 organisms). The transmission route is fecal-oral with contamination of salads, raw vegetables, dairy products, and poultry all documented. The disease occurs when virulent Shigella attaches to, and penetrates, intestinal mucosal epithelial cells. Intracellular multiplication follows, with subsequent spread to contiguous epithelial cells resulting in tissue destruction. Some strains produce enterotoxin and shiga toxin. A pseudomembrane comprised of PMN's, cellular debris, and bacteria held together by fibrin strands is found over the site of ulceration. Shigella spp. are less prone to be found in the bloodstream than are Salmonella spp. Within 12 to 50 hours of ingestion symptoms appear: abdominal pain, cramps, fever, vomiting, tenesmus, and diarrhea with blood, pus, or mucus in the stool. Later symptoms can include mucosal ulceration, rectal bleeding, and drastic dehydration. Convulsions can be an important complication in young children. In some strains fatality may be as high as 10-15%. Possible sequelae include Reiter's disease, reactive arthritis, and hemolytic-uremic syndrome. Although all Shigella spp. have been implicated in foodborne outbreaks, S. sonnei is by far the leading cause of shigellosis from food in the U.S. The other species are more closely associated with contaminated water, and S. flexneri is now thought to be in large part sexually transmitted. In the under-developed world, S. dysenteria, S. flexneri, and S. boydii are more prevalent than S. sonnei. Shigella dysenteria (Biogroup A) is the least common cause of shigellosis in the U.S., but it is also the most virulent species. The verotoxin produced by S. dysenteria type 1 (Shiga bacillus) yields both neurotoxic and enterotoxic effects. Complications include toxic megacolon and hemolytic-uremic syndrome. Mortality rates in hospitalized patients remain as high as 20%. Shigella flexneri (Biogroup B) produces small amounts of verotoxin. This species is thought in large part to be transmitted sexually. Certain strains can cause Reiter syndrome in genetically predisposed persons (HLA-B27 positive). Shigella boydii (Biogroup C) is a relatively infrequent cause of human disease. As mentioned previously, Shigella sonnei (Biogroup D) is the most common species recovered in the U.S. Symptoms with this species tend to be mild, and some patients may be asymptomatic. S. sonnei produces small amounts of verotoxin. | |
