The colitis caused by Escherichia coli (E. coli) O157:H7 is characterized by severe abdominal cramps, diarrhea that typically turns bloody within 24 hours, and sometimes fever. The incubation period—that is, the time from exposure to the onset of symptoms—in outbreaks is usually reported as 3 to 4 days but may be as short as 1 day or as long as 10 days. Infection can occur in people of all ages but is most common in children.
Unlike other E. coli pathogens, which remain on intestinal surfaces, Shiga toxin-producing bacteria, like O157:H7, are invasive. After ingestion, E. coli bacteria rapidly multiply in the large intestine and then bind tightly to cells in the intestinal lining. This snug attachment facilitates absorption of the toxins into the small capillaries within the bowel wall. Once in the systemic circulation, Shiga toxin becomes attached to weak receptors on white blood cells, thus allowing the toxin to “ride piggyback” to the kidneys where it is transferred to numerous avid (strong) Gb3 receptors that grasp and hold on to the toxin.
Inflammation caused by the toxins is believed to be the cause of hemorrhagic colitis, the first symptom of E. coli infection, which is characterized by the sudden onset of abdominal pain and severe cramps. Such symptoms are typically followed within 24 hours by diarrhea, sometimes fever. As the infection progresses, diarrhea becomes watery and then may become grossly bloody; that is, bloody to the naked eye. E. coli symptoms also may include vomiting and fever, although fever is an uncommon symptom.
The duration of an uncomplicated illness can range from one to twelve days. In reported outbreaks, the rate of death is 0-2%, with rates running as high as 16-35% in outbreaks involving the elderly, like those that have occurred at nursing homes.
On rare occasions, E. coli infection can cause bowel necrosis (tissue death) and perforation without progressing to hemolytic uremic syndrome (HUS)—a complication of E. coli infection that is now recognized as the most common cause of acute kidney failure in infants and young children. In about 10 percent of E. coli cases, the Shiga toxin attachment to Gb3 receptors results in HUS.
HUS accounts for the majority of the acute deaths and chronic injuries caused by the bacteria. HUS occurs in 2-7% of victims, primarily children, with onset five to ten days after diarrhea begins. “E. coli serotype O157:H7 infection has been recognized as the most common cause of HUS in the United States, with 6% of patients developing HUS within 2 to 14 days of onset of diarrhea.” And it is the most common cause of renal failure in children.
Approximately half of the children who suffer HUS require dialysis, and at least 5% of those who survive have long term renal impairment. The same number suffers severe brain damage. While somewhat rare, serious injury to the pancreas, resulting in death or the development of diabetes, also occurs. There is no cure or effective treatment for HUS. And, tragically, children with HUS too often die, with a mortality rate of five to ten percent.
Once Shiga toxins attach to receptors on the inside surface of blood vessel cells (endothelial cells), a chemical cascade begins that results in the formation of tiny thrombi (blood clots) within these vessels. Some organs seem more susceptible, perhaps due to the presence of increased numbers of receptors, and include the kidney, pancreas, and brain. Consequently, organ injury is primarily a function of receptor location and density.
Once they move into the interior of the cell (cytoplasm), Shiga toxins shut down protein machinery, causing cellular injury or death. This cellular injury activates blood platelets too, and the resulting “coagulation cascade” causes the formation of clots in the very small vessels of the kidney, leading to acute kidney failure.
The red blood cells are either directly destroyed by Shiga toxin (hemolytic destruction) or are damaged as cells attempt to pass through partially obstructed micro-vessels. Blood platelets become trapped in the tiny blood clots, or they are damaged and destroyed by the spleen.
By definition, when fully expressed, HUS presents with the triad of hemolytic anemia (destruction of red blood cells), thrombocytopenia (low platelet count), and renal failure (loss of kidney function). Although recognized in the medical community since at least the mid-1950s, HUS first captured the public’s widespread attention in 1993 following a large E. coli outbreak in Washington State that was linked to the consumption of contaminated hamburgers served at a fast-food chain. Over 500 cases of E. coli were reported; 151 were hospitalized (31%), 45 persons (mostly children) developed HUS (9%), and three died.
Of those who survive HUS, at least five percent will suffer end stage renal disease (ESRD) with the resultant need for dialysis or transplantation. But “because renal failure can progress slowly over decades, the eventual incidence of ESRD cannot yet be determined.” Other long-term problems include the risk for hypertension, proteinuria (abnormal amounts of protein in the urine that can portend a decline in renal function), and reduced kidney filtration rate. Since the longest available follow-up studies of HUS victims are 25 years, an accurate lifetime prognosis is not available and remains controversial.