Virtually every time an E. coli O157:H7 outbreak occurs, the most severely injured people develop a condition called hemolytic uremic syndrome (HUS). The cluster being investigated by health officials in Belgium, Wisconsin is no exception. At least one of the cases, believed to be a child, developed HUS and spent multiple weeks hospitalized at Children’s Hospital of Wisconsin.
What is HUS?
Post-diarrheal Hemolytic Uremic Syndrome (D+HUS) is a severe, life-threatening complication that occurs in about 10% of those infected with E. coli O157:H7 or other Shiga toxin (Stx) producing E. coli. D+HUS was first described in 1955, but was not known to be secondary to E. coli infections until 1982. It is now recognized as the most common cause of acute kidney failure in infants and young children. Adolescents and adults are also susceptible, as are the elderly who often succumb to the disease.
How did these otherwise harmless E. coli become such killers?
It seems likely that DNA from a Shiga toxin producing bacterium known as Shigella dysenteriae type 1 was transferred by a bacteriophage (bacteria infected with a virus) to harmless E. coli bacteria, thereby providing them with the genes to produce one of the most potent toxins known to man. So potent, that the Department of Homeland Security lists it as a potential bioterrorist agent. Although E. coli O157:H7 are responsible for the majority of cases in America, there are many additional Stx producing E. coli that can cause D+ HUS.
From Diarrhea to Dialysis
The chain of events leading to HUS begins with ingestion of Stx producing E. coli (e.g., E. coli O157: H7) in contaminated food, beverages or through person to person transmission. These E. coli rapidly multiply in the intestines causing colitis (diarrhea), and tightly bind to cells that line the large intestine. This snug attachment facilitates absorption of the toxin into the circulation where it becomes attached to weak receptors on white blood cells (WBC) 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. Organ injury is primarily a function of Gb3 receptor location and density. Receptors are probably heterogeneously distributed in the major body organs, and this may explain why some patients develop injury in other organs (e.g., brain, pancreas).
Once Stx attaches to receptors, it moves into the cell’s cytoplasm where it shuts down the cells’ protein machinery resulting in cellular injury and/or death. This cellular injury activates blood platelets and the coagulation cascade which results in the formation of clots in the very small vessels of the kidney resulting in acute kidney injury and failure. The red blood cells are hemolyized (destroyed) by Stx and/or damaged as they attempt to pass through partially obstructed microvessels. Blood platelets (required for normal blood clotting), are trapped in the tiny blood clots or are damaged and destroyed by the spleen.