Shiga Toxin
Community acquired diarrhea outbreaks are most often caused by enteric pathogens such as Salmonella, Shigella, Campylobacter and Shiga toxin-producing E. coli (STEC). Although most strains of E. coli are harmless, E. coli O157: H7 has integrated the gene that produces Shiga toxin, possibly by means of a virus which transferred the gene from Shigella to E. coli. Most STEC infections are caused by E. coli O157:H7, which was first recognized as a pathogen in 1982. E. coli are serotyped on basis of their somatic (O) and flagellar (H) antigens. E coli O157:H7 is so named because it possesses the 157th somatic antigen ever identified and the 7th flagellar antigen.
Although E. coli O157: H7 is the major cause of large Shiga toxin related outbreaks in the U.S., non-O157: H7 outbreaks have been documented. Colitis due to many other serotypes has been reported in other parts of the world since 1984. Non-0157 E. coli are generally associated with less severe disease than 0157:H7. Non-O157 serogroups include O26, O45, O103, O111, O121 and O145. At least two reports of human disease caused by Shiga toxin producing Citrobacter freundii and Enterbacter cloacae have been reported.
STEC infections and HUS occur in patients of all ages, but the incidence of STEC infection and HUS is highest in children aged <5 years. STEC infections can occur throughout the year, but are most common during summer months. Each year in the U.S., STEC cause approximately 100,000 illnesses per year, 3000 hospitalizations, and 90 deaths. They are the leading cause of hemolytic uremic syndrome (HUS), the most common cause of acute renal failure in children. Endothelial cells in the intestine, kidney and brain are the major targets of the toxin.
STEC transmission occurs through consumption of a wide variety of contaminated water and foods, including undercooked ground beef, unpasteurized juice, raw milk, and raw produce such as lettuce, spinach and alfalfa sprouts. Most of these outbreaks are due to fecal contamination from ruminants, such as cattle. Transmission can also occur by person to person contact in settings with close contact and substandard hygiene, such as child care and institutionalized care settings. Both STEC and Shigella can cause infections after ingestion of only 10 to 100 organisms.
The onset of illness usually occurs between 3 and 7 days after exposure. STEC infection causes abdominal pain and acute, often bloody, diarrhea secondary to hemorrhagic colitis. Approximately 8% of persons with STEC infection develop hemolytic uremic syndrome (HUS), which is a life-threatening condition characterized by thrombocytopenia, hemolytic anemia and renal failure. The signs and symptoms of HUS are very similar to TTP. When TTP is diagnosed after a diarrheal illness, the condition is usually caused by infection with 0157 STEC and classified as HUS.
Currently there are no clear guidelines for who should be tested for Shiga toxin producing E. coli infection. Saint Luke’s Regional Laboratories tests all stools submitted for culture for Salmonella, Shigella, Campylobacter and STEC. Prompt and accurate diagnosis is important because appropriate treatment with parenteral volume expansion early in the course of the illness can decrease renal damage and improve outcome. Antibiotics may exacerbate disease by increasing toxin production and release. The laboratory detects STEC with bacterial culture on sorbitol-containing MaConkey selective media and toxin detection by enzyme immunoassay (EIA). Most 0157 E. coli are sorbitol nonfermenters and produce colorless colonies. Non-0157 strains are detected by Shiga toxin EIA. Positive cultures and toxin tests are sent to the state public health laboratory for confirmation and serotyping. STEC are difficult to detect in stool after the first week of illness, so samples should be submitted as early as possible after onset of infection.
Toxins produced by STEC were named based on their similarity to Shiga toxins produced by Shigella dystenteriae type 1. STEC that cause hemorrhagic colitis produce 1 of 2 types of Shiga toxin (Stx), STx1 and STx2. These toxins are encoded by separate genes, stx1 and stx2, one or both of which may be carried by E. coli organisms, independent of each other. STEC strains that produce only Stx2 toxin are more often associated with HUS than strains that only produce STx1 or that produce both toxins. EIA detects both types of toxin STx1 and STx2, produced by both E. coli 0157:H7 and non-O157 strains. EIA requires overnight broth cultures of fecal specimens for maximum sensitivity. Whether a STEC illness progresses to HUS depends on strain virulence and host factors.
