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Haemolytic uraemic syndrome (HUS)

Queensland Health Guidelines for Public Health Units

Revision History

 Version  Date  Changes
 1.0 May 2010  Full revision of guideline. 
2.0 July 2014 Full revision of guideline.

Infectious Agent

The most common infectious agent causing haemolytic uraemic syndrome (HUS) is Shiga toxin-producing Escherichia coli. Other infectious agents include Shigella and Streptococcus pneumoniae (1, 2). 'Atypical HUS' cases occur which are not related to an infectious agent (3).

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Notification Criteria

HUS is a notifiable condition regardless of cause.

Note: Where STEC/VTEC is isolated in the context of haemolytic uraemic syndrome (HUS), it should be notified as both STEC/VTEC and HUS.

Clinical evidence

1. Acute microangiopathic anaemia on peripheral blood smear (schistocytes, burr cells or helmet cells)

     AND AT LEAST ONE OF THE FOLLOWING:

2. Acute renal impairment (haematuria, proteinuria or elevated creatinine level)

    OR

3. Thrombocytopaenia, particularly during the first seven days of illness.

Objectives of surveillance

• To monitor the epidemiology of HUS.
• To identify cases and outbreaks, so as to enable prompt public health response.

Community Outbreak Criteria

This is defined in the context of the infectious agent – refer to the relevant guidelines.

Notification Procedure

Attending Medical Practitioners/Medical Superintendents (or Delegates)

Notify on clinical suspicion or confirmation by telephone or facsimile.

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Reporting to NOCS

Report only confirmed cases.

Confirmed case
A confirmed case requires clinical evidence.

Public Health Significance and Occurrence

HUS is characterised by microangiopathic haemolytic anaemia, thrombocytopenia, and acute renal failure. The disorder occurs most frequently in children under the age of 5 years who present with diarrhoea, which is often bloody (4). The classical form of diarrhoea associated HUS is caused by infectious agents, and it is a common cause of acute renal failure in children. Most cases with an infectious aetiology are caused by  Shiga toxin-producing Escherichia coli. Several other infectious agents can lead to HUS including Shigella dysenteriae and Streptococcus pneumoniae (1, 2). Infection by S. pneumoniae can be particularly severe and has a higher acute mortality and a higher long-term morbidity compared to HUS by Shiga toxin (5, 6). The majority of children with post-diarrhoeal or enteropathic HUS (eHUS) also develop some degree of renal insufficiency. Approximately 40 – 60% of children with eHUS will require dialysis therapy, and 3 – 5% die (7, 8).

Atypical HUS refers to HUS that is not caused by Shiga toxin producing bacteria or streptococci. Overactivation of the complement alternative pathway, either due to genetic factors or acquired autoantibodies against complement regulatory proteins, characterise the atypical form of HUS (9). This disorder represents 5 - 10% of HUS in children but the majority of HUS in adults (3). Atypical HUS has a poor prognosis, with 2 – 10% of patients dying and at least one third progressing to end stage renal disease at first presentation (7).

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Clinical Features

HUS is characterised by microangiopathic haemolytic anaemia, thrombocytopenia, and acute renal failure. The initial clinical features vary depending upon the cause. Most HUS is preceded with diarrhoea, often bloody (1). Diarrhoeal illness does not precede atypical HUS (7, 9).

In STEC related HUS, Shiga toxins are absorbed from the gut and damage vascular endothelial cells in target organs such as the gut and kidney. HUS usually develops within 7 days (up to 3 weeks) after the onset of diarrhoea (8). By the time HUS develops the STEC organism may no longer be detectable in the stool.

Reservoir

Depends on the infecting agent (in those cases identified as being caused by an infectious agent).

Mode of Transmission

Depends on the infecting agent (in those cases identified as being caused by an infectious agent). STEC and Shigella are transmitted via the faecal-oral route. Streptococcus pneumoniae is transmitted by droplet spread, direct oral contact, or indirectly through articles freshly soiled with respiratory discharges. Additional information can be found in relevant Queensland Health Guidelines for Public Health Units.

Incubation Period

The incubation periods for infectious diseases associated with HUS are described below:

STEC: Usually 2 to 10 days, though may be up to 14 days

Shigella: From 12 to 96 hours (up to 1 week for S. dysenteriae)

Invasive pneumococcal disease: Unknown, probably short (1 - 4 days)

In STEC-related HUS, HUS develops 7 days (up to 3 weeks) after the onset of diarrhoea.

Period of Communicability

The periods of communicability of infectious causes of HUS depend on the organism:

STEC:  Until the organism is no longer present in the faeces

Shigella:  Until the organism is no longer present in the faeces

Invasive pneumococcal disease: Until discharges of mouth and nose no longer contain virulent bacteria in significant numbers

Additional information can be found in relevant Queensland Health Guidelines for Public Health Units.

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Susceptibility and Resistance

Children less than 5 years of age are at greatest risk of developing HUS (4).

Management

Assume all cases of diarrhoea associated HUS to be STEC related until proven otherwise (see STEC guidelines).

Cases
 
Investigation
Investigate the case for the cause of HUS. All cases should have stool samples (or failing that, rectal swabs) collected and examined for evidence of STEC. Discuss with the consulting physician the suspected cause of HUS (including whether another potential cause has been identified or if patient is considered to have atypical HUS).

Treatment of STEC suspected HUS is supportive.

Antibiotics
The role of antibiotics in the management of STEC infections is controversial, due to concerns that antibiotics may trigger HUS. A prospective cohort study showed that antibiotic use during E coli O157 infections was associated with a higher rate of subsequent HUS in children (10).

In 2011, a large outbreak of E coli O104:H4 occurred in Germany and caused more than 3000 documented infections, including more than 800 confirmed cases of HUS. In this outbreak, antibiotic treatment of patients with established HUS was not harmful and was associated with a lower frequency of long-term STEC carriage (11, 12).

Where prolonged STEC carriage is causing a significant social or psychological burden, antibiotics may be considered in consultation with an infectious diseases physician and/ or paediatrician on a case by case basis.

Exclusion
Depends on the infectious agent - see relevant guidelines

Counselling
Depends on the infectious agent - see relevant guidelines.

Contacts

Management of contacts depends on the infectious agent - see relevant guidelines.

Community outbreaks/epidemics

Relevant only to STEC – refer to STEC guidelines.

Preventive Measures

Depends on the infectious agent - see relevant guidelines.

Feedback

Report to notifying agency.

In cases related to potentially foodborne bacteria (ie. STEC, Shigella) send a copy of the case report form to OzFoodNet.

Summary

For community outbreaks, prepare an outbreak summary report of the investigation for the Communicable Diseases Unit, Queensland Health.

References

  1. Walker CLF, Applegate JA, Black RE. Haemolytic-Uraemic Syndrome as a sequela of diarrhoeal disease. Journal of population health and nutrition 2012; 30(3): 257 – 261
  2. Copelvitch L, Kaplan BS. Streptococcus pneumoniae-associated hemolytic uremic syndrome: classification and the emergence of serotype 19A. Pediatrics 2009; 125: e174
  3. Loirat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet journal of rare diseases 2011; 6:60
  4. Page AV, Liles WC. Enterohemorrhagic Escherichia coli Infections and the hemolytic uremic syndrome. Medical Clinics of North America 2013; 97: 681 – 695
  5. Copelovitch L, Kaplan BS. Streptococcus pneumoniae-associated hemolytic uremic syndrome. Pediatric nephrology 2008; 23: 1951 – 1956
  6. Scheiring J, Andreoli SP, Zimmerhacki LB. Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Pediatric nephrology 2008; 23: 1749 – 1760
  7. Loirat C, Saland J, Bitzan M. Management of hemolytic uremic syndrome. Presse Med 2012, doi:10.1016/j.lpm.2011.11.013
  8. American Academy of Pediatrics. Escherichia coli Diarrhea. In: Pickering L.K. ed. Red Book: 2012 Report of the Committee on Infectious Diseaes, 29th edition. Elk Grove Village, Illinois: American Academy of Pediatrics, 2012: 324 – 328 
  9. Kavanagh D, Goodship TH, Richards A. Atypical hemolytic uremic syndrome. Seminars in nephrology 2013; 33(6): 508 – 530
  10. Wong CS, Mooney JC, Brandt JR, Staples AO, Jelacic S, Boster DR, et al. Risk factors for the hemolytic uremic syndrome in children infected with Escherichia coli O157LH7: A multivariable analysis. CID 2012; 55: 33 – 41
  11. Nitsche M, Sayk F, Hartel C, Roseland RT, Hauswaldt S, Steinhoff J, et al. Association between azithromycin therapy and duration of bacterial shedding among patients with shiga toxin-producing enteroaggregative Escherichia coli O104:H4. JAMA 2012; 307(10): 1046 – 1052
  12. Menne J, Nitsche M, Stingele R, Abu-Tair M, Beneke J, Bramstedt J, et al. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study. BMJ 2012; 345: e4565, doi:10.1136/bmj.e4565

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Last updated: 19 December 2014