Hemolytic uremic syndrome (HUS)

• Reporting criteria
• The disease and its epidemiology
• Case definition

• Laboratory testing
• Case investigation
• Disease control measures

• References
• Contact

What and how to report to the Colorado Department of Public Health and Environment (CDPHE) or local public health agency  

• Confirmed, probable and suspected HUS cases aged less than 18 years are reportable to Public Health within four (4) days of diagnosis. This includes suspected post-diarrheal and atypical HUS (aHUS) cases. Adult cases of HUS and TTP are not reportable to public health (however, adults with HUS/TTP would be reported to public health if they had a reportable illness preceding the HUS/TTP diagnosis).
• Cases should be reported using EpiTrax Reportal, fax or telephone to CDPHE or local health departments (telephone and fax numbers are listed at the end of this document).

Purpose of surveillance and reporting

• To identify cases for investigation and potential outbreaks
• To monitor trends in disease incidence

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Etiologic agent

Hemolytic uremic syndrome (HUS) is a serious clinical complication that can occur after infection with Shiga toxin-producing E. coli (STEC), especially E. coli O157 and non-O157 STEC that produces Shiga toxin 2. HUS is less common, but can occur, among people with STEC that only produces Shiga toxin 1. Other bacteria and viruses, such as Streptococcus pneumoniae and Shigella dysenteriae, can also cause HUS, but not as often as seen with STEC. The CDC estimates that about 80% of pediatric HUS cases had STEC infection.

Approximately 5-10% of HUS cases are classified as “atypical HUS” and are not caused by infectious agents. Atypical HUS (aHUS) can occur due to genetic causes, certain medications, pregnancy, organ transplantation, cancer, or unknown causes. Atypical HUS tends to lead to recurring bouts of HUS and subsequent hospitalizations.

Clinical description

Most cases of HUS are preceded by an infectious diarrheal illness, such as STEC, which damages and destroys red blood cells. The damaged red blood cells clog the filtering system in the kidneys, which may cause kidney failure. Symptoms of HUS include decreased urine output, blood and protein in the urine, swelling (can occur anywhere in the body but often noticed in the lower extremities), and hypertension. Blood tests show anemia, low platelet counts, elevated creatinine, and evidence of red blood cell destruction.

Children under the age of 5 years are at the greatest risk of developing post-diarrheal HUS. Post-diarrheal HUS is the most common cause of acute renal failure in children. Between 5-15% of children with STEC infection will develop HUS. Antibiotic and anti-diarrheal medication use during the diarrheal phase of illness among children has been shown to increase the risk of developing HUS. Adults can be affected, as well, and the condition in adults is often called thrombotic thrombocytopenic purpura (TTP). It’s estimated that up to 5% of people with HUS die. However, the observed case fatality rate for the United States’s FoodNet catchment area is lower (see Epidemiology section). The majority of patients with post-diarrheal HUS recover without major consequences. A small percentage have serious complications, such as chronic kidney disease that requires long term dialysis, seizures, heart problems, stroke, blood clotting issues, and/or high blood pressure. Timely and appropriate medical care is important for any case of HUS.

For clinical information about STEC, visit the STEC chapter in the CDPHE Communicable Disease Manual.

Reservoirs/Modes of transmission

HUS is a clinical syndrome and it is not transmissible from person to person. While HUS does not have a reservoir, the primary bacterial or viral pathogen which contributed to HUS may have various animal, environmental, and/or human reservoirs.

Incubation period

HUS develops on average seven days following the onset of diarrhea but can range from 2-14 days and rarely may develop up to 2-3 weeks later; onset of HUS after other types of infections is not well-described. See the STEC chapter of the CDPHE Communicable Disease Manual for additional information about STEC.

Infectious period

If HUS occurs after infection with STEC or some other bacteria or virus, the bacteria/virus may be transmissible to others for a variable amount of time, depending on the pathogen and current stage of infectivity. 

Epidemiology

In Colorado, only pediatric (< 18 years) HUS cases are reportable to public health. Similar to STEC, sporadic cases of HUS occur throughout the year with a peak during the summer months. During 2023, seven cases were reported in Colorado, with a five-year average of 10 cases per year (2019-2023). Among the 49 confirmed or probable cases reported during 2019-2023, 39 (80%) had laboratory evidence of STEC infection and five (10%) were outbreak-associated.

Between 2017 and 2021, there were 310 pediatric HUS cases reported within the FoodNet catchment area, which resulted in four deaths (1.3% CFR). The majority of cases were under the age of 5, and 87% of cases had laboratory evidence of an STEC infection. The most commonly reported serotype wes O157, accounting for 80.4% of cases.

For more data, see Colorado reportable disease data (Colorado data), CDC WONDER (national data), and CDC FoodNet Fast HUS Surveillance Tool (FoodNet catchment area data).

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Clinical description

HUS is characterized by the acute onset of microangiopathic hemolytic anemia (loss of red blood cells through destruction caused by factors in the small blood vessels), renal injury, and low platelet count. TTP is also characterized by these features but may have a more gradual onset, and can include central nervous system (CNS) involvement and fever. Most cases of HUS (but few cases of TTP) occur after an acute gastrointestinal illness (usually diarrheal).

Laboratory criteria for diagnosis

To meet the laboratory criteria for diagnosis, the following must both be present at some time during the illness:

1. Anemia (acute onset) with microangiopathic changes (i.e., schistocytes, burr cells, or helmet cells) on peripheral blood smear

      AND

2. Renal injury (acute onset) evidenced by either hematuria, proteinuria, or elevated creatinine level (i.e., greater than or equal to 1.0 mg/dL in a child aged less than 13 years; greater than or equal to 1.5 mg/dL in a person aged greater than or equal to 13 years; or greater than or equal to 50% increase over baseline)

Note: A low platelet count can usually, but not always, be detected early in the illness, but it may then become normal or even high. If a platelet count obtained within 7 days after onset of the acute gastrointestinal illness is not less than 150,000/mm³, other diagnoses should be considered.

Case classification

Confirmed

• An acute illness diagnosed as HUS or TTP that both meets the laboratory criteria AND began within 3 weeks after onset of an episode of acute or bloody diarrhea.

Probable

• An acute illness diagnosed as HUS or TTP that meets the laboratory criteria in a patient who does not have a clear history of acute or bloody diarrhea in preceding 3 weeks

OR

• An acute illness diagnosed as HUS or TTP, that a) has onset within 3 weeks after onset of an acute or bloody diarrhea AND meets the laboratory criteria except that microangiopathic changes are not confirmed

CSTE comments: Some investigators consider HUS and TTP to be part of a continuum of disease. Therefore, criteria for diagnosing TTP on the basis of CNS involvement and fever are not provided because cases diagnosed clinically as post-diarrheal TTP also should meet the criteria for HUS. These cases are reported as post-diarrheal HUS. Most diarrhea-associated HUS is caused by STEC, most commonly E. coli O157. If a patient meets the case definition for both STEC and HUS, the case should be reported for each of the conditions.

Colorado comments: When an HUS case is first entered into EpiTrax, it is typically entered without a case status until chart review can be completed by the investigating agency to determine if the case meets the probable or confirmed case definition. Cases that do not meet the probable or confirmed case definition but are diagnosed by a health care provider as having HUS are kept as suspect cases in EpiTrax. If a person has HUS that results from an infection with another reportable condition (such as STEC), the person will have two separate EpiTrax CMRs: one for HUS and one for the other reportable condition. 

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HUS is a clinical syndrome that is diagnosed by a medical provider; there is no testing to diagnose HUS. If there is a HUS case with diarrhea and they have not been tested for an infectious illness, CDPHE and CDC may be able to test. Always consult CDPHE before submitting any clinical specimens for testing or to determine if testing at CDC is an option.

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Local health departments have primary responsibility for HUS case investigations. The case investigation process for HUS cases depends on what information is known about the patient at the time of report (i.e., whether they had a preceding diarrheal illness and whether it was diagnosed as STEC or another condition). The following table describes the necessary case investigation steps for HUS cases, regardless of the case status (confirmed, probable, or suspect).

Independently, the Communicable Disease Branch will conduct a chart review for all HUS cases in the state. The chart review consists of pulling specific HUS lab-related data and hospitalization records that will be uploaded into CDC’s HUS Surveillance Database. This process does not impact the case investigation to be performed by the local health department.

Forms 

Follow the table above to determine the form needed for case investigation. If the HUS case has a recent reportable condition other than HUS already entered into EpiTrax, follow the guidelines of that specific pathogen (i.e., if they have STEC, complete the STEC investigation form in EpiTrax). If the case does not have a recent infectious disease diagnosis in EpiTrax but does have a preceding diarrheal illness, complete the STEC case investigation form, and upload it to the HUS CMR within the “Notes” tab. 

Identify and evaluate contacts

If the HUS case is determined to be a post-diarrheal case and there are symptomatic or asymptomatic contacts, follow the guidelines for symptomatic contacts outlined in the STEC Communicable Disease Manual chapter. Symptomatic contacts of a post-diarrheal HUS case should also be interviewed and provided disease control recommendations, in the event that the HUS case was infected with STEC.

Reported incidence is higher than usual/outbreak suspected

If the number of reported HUS cases in your jurisdiction is higher than usual, it may indicate an outbreak of a pathogen like STEC. Investigate reported HUS cases promptly to determine if the cases are post-diarrheal. Consult with a CDPHE Communicable Disease Epidemiologist. CDPHE staff can assist local public health agencies to investigate outbreaks and determine a course of action to prevent further cases, and can coordinate surveillance of cases that cross county lines.

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Hemolytic Uremic Syndrome (HUS)| CDC

Treatment

People with HUS may need dialysis and blood transfusions. Antibiotics and anti-diarrheal medications are generally not indicated for treatment of STEC because they may increase the risk of developing HUS. Antibiotics are generally not indicated for treatment of HUS unless the patient has infections in other parts of the body that require antibiotics. Careful follow-up of patients with bloody diarrhea is recommended to detect changes suggestive of HUS.

In general, individuals experiencing diarrhea are at risk of dehydration due to loss of fluids. If symptoms persist, worsen, or are severe, cases should seek prompt medical care.

Prophylaxis

No prophylactic treatment of close contacts is recommended.

Education

Encourage the case to:

• Avoid preparing food for other individuals until diarrhea has resolved.
• Always wash hands thoroughly with soap and water for at least 20 seconds before eating or preparing food, after using the toilet, after changing diapers, and after touching pets or other animals (especially farm animals and cattle).
• After changing diapers, wash your hands and the child’s hands. Clean and sanitize diaper changing stations/areas often.
  • In child care and other institutional settings, dispose of stool and soiled diapers/linens in a sanitary manner.
• Keep food that will be eaten raw, such as fruits and vegetables, from becoming contaminated by raw, animal-derived food products by cleaning or using different knives and cutting boards during preparation. Store raw, animal-derived foods away from other foods that will be eaten raw while in the refrigerator.
• Thoroughly cook all food products from animals and avoid consuming unpasteurized milk, or other unpasteurized products such as juices and unpasteurized apple cider.
• Cook all ground beef, hamburger, and needle-tenderized beef products thoroughly to an internal temperature of at least 160°F.
• If served an undercooked hamburger or other ground beef product in a restaurant, send it back for further cooking.

Managing special situations

Child care centers/preschools

When a known or suspected post-diarrheal HUS case occurs in a food handler or child care center, immediate involvement of public health authorities is critical. Follow the guidelines presented in the disease-specific chapter of the CDPHE Communicable Disease Manual if the patient had a diagnosed infection (such as STEC). If the patient did not have a diagnosed infection, implement control measures as if the patient was infected with STEC, which may require return to work/child care testing.

Schools/community residential programs*/patients in health care facilities** 

When a known or suspected post-diarrheal HUS case occurs in a school-aged child, a person residing in a community residential program that serves the developmentally disabled, or in a patient or staff of a health care facility, follow the guidelines presented in the disease-specific chapter of the CDPHE Communicable Disease Manual if the patient had a diagnosed infection (such as STEC). If the patient did not have a diagnosed infection, implement control measures as if the patient was infected with STEC.

*Including facilities serving the developmentally disabled

**Including hospitals, medical and dental clinics, skilled nursing, and long-term care facilities

Environmental measures

For post-diarrheal HUS cases, the environmental control measures are dependent on the infection that caused the HUS. Follow the guidelines presented in the disease-specific chapter of the CDPHE Communicable Disease Manual if the patient had a diagnosed infection (such as STEC).

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American Academy of Pediatrics. Red Book: 2024-2027 Report of the Committee on Infectious Diseases, 33rd Edition. Illinois, Academy of Pediatrics, 2024.  

Bhandari J, Rout P, Sedhai YR. Hemolytic Uremic Syndrome. [Updated 2023 Oct 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556038/

Centers for Disease Control and Prevention (CDC). FoodNet Fast: Hemolytic Uremic Syndrome Surveillance Tool. Atlanta, Georgia: U.S. Department of Health and Human Services. Available from URL: http://wwwn.cdc.gov/foodnetfast. Accessed 05/15/2025.

CDC Website (“Diseases and Conditions”) 

Hemolytic Uremic Syndrome, Post-diarrheal (HUS) 1996 Case Definition | CDC. (n.d.). https://ndc.services.cdc.gov/case-definitions/hemolytic-uremic-syndrome…

Heymann DL, ed. Control of Communicable Diseases Manual, 21st Edition. Washington, DC, American Public Health Association, 2022.

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CDPHE Communicable Disease Branch

• Phone: 303-692-2700 or 800-866-2759
• Fax: 303-782-0338
• After hours: 303-370-9395

CDPHE Lab Coordinators: 

• Email (preferred): cdphe_labcoordinators@state.co.us  
• Phone: 303-692-3480

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