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  Oct 23, 2018

Hemolytic Uremic Syndrome Prevention

Hemolytic uremic syndrome (HUS) is the major cause of acute renal failure in children. It follows gastroenteritis caused by a Shiga toxin-producing E. coli strain, most frequently O157:H7, though other strains are also implicated in some outbreaks.

The infection is self-limited in most children, but in 10-15% of cases, the toxins are absorbed into the bloodstream and bind to receptors on endothelial cells in the brain, kidney and gastrointestinal tract. This binding activates the complement system and initiates a cascade of microthrombotic and inflammatory events leading to ischemic damage to multiple end-organs.

Understandably, the prevention of this chain of events is the key to lowering the incidence of HUS, however no specific antidote has yet been found. The measures listed below have been found useful in preventing HUS. The most important action to take is avoidance of any short-term intervention that may finally complicate the course of the disease or result in a worse prognosis.

Specific Management of STEC Infection

Experts advise the admission of all children with diarrhea and who test positive for enterohemorrhagic strains of E. coli to a separate unit. Family history of HUS should be asked for.

The presence of the following risk factors should be noted:

  • Relapsing D+HUS
  • Family history of HUS
  • Insidious onset of HUS

Epidemiological data should also be gathered.

Tests to be done include:

  • Stool sample testing for E. coli O157:H7 and other prevalent strains with culture and PCR
  • Serum antibody testing for O157 antigen
  • Culture of sterile body fluids if S. pneumoniae infection is suspected

In children with the above risk factors, overlapping of infectious and genetic etiology in HUS should be suspected and the following additional tests performed:

  • Assay of complement factors
  • Measurement of ADAMTS 13
  • Autoantibodies to CFH

It is important that relatives of these patients also be screened for complement abnormalities as they may develop the syndrome.

Close monitoring of the patient with STEC infections for any signs of HUS is mandatory, including the use of blood tests such as a full blood count and platelet count to detect thrombocytopenia and hemolytic anemia.

Supportive management is also important. Fluid balance maintenance is crucial in the pre-HUS stage, when there is diarrhea and nausea with or without vomiting, associated with intense colic. All of these are likely to precipitate dehydration. Volume depletion, leading to poor renal perfusion, is a factor which increases the risk of thrombosis in the context of the endothelial injury caused by STX. Best practice includes the administration of adequate fluids by appropriate routes to expand the intravascular volume, especially in the first 4 days. This has been shown to improve outcomes.

Avoidance of antibiotics and antimotility agents in the acute gastroenteritic phase of STEC infection is recommended. These may prolong the duration of exposure of the gastrointestinal cells to the toxins and increase their absorption into the bloodstream. They do not appear to affect the toxin-receptor binding.

Any case of gastroenteritis that presents with or develops bloody flux should be tested for STEC. This may be done by stool culture even if the diarrhea has stopped meanwhile. A faster and more reliable method involves testing for Shiga-like toxins (STX) 1 and 2 from stool samples, using ELISA-linked assay and PCR.

Public health measures

Since HUS in over 90% of children is due to the STEC serotype O157 H7, it is vital to investigate the source of this microbial infection. The O157 H7 strain is found in the intestinal tract of 1% of healthy cattle - it may contaminate the flesh during slaughter and meat processing. It is transmitted to children through undercooked beef, as well as by unhygienic hand-to-hand transfer by people involved in food preparation and serving.

Some foods which may spread STEC include:

  • Unpasteurized juices or milk
  • Undercooked venison, beef, or sausages made from beef
  • Non-chlorinated water
  • Lake water contaminated with feces
  • Certain raw vegetables such as leaf lettuce, alfalfa sprouts and radish sprouts
  • Farm animals (through hand contact)

Thus primary prevention of HUS requires public health recommendations and practices such as:

  • Attentiveness of patients and care providers to avoid transmitting infection during cooking of raw beef
  • Diaper changes only performed in a hygienic environment
  • Thorough cooking of all meat and milk, or products derived from these
  • Encouraging cattle vaccination to avoid contamination of feces and cattle hide with HUS-causing strains of STEC.