Haemolytic Uraemic Syndrome (Hus) In Children

The given answer is "YES" because it states that a small group of atypical hemolytic uremic syndrome (aHUS) cases can occur in the post bone marrow transplantation period. This can be caused by immunosuppressive drugs like cyclosporine, as well as exposure to herbicides or pesticides, and severe scorpion envenomation. Therefore, the answer affirms that these factors can indeed cause aHUS in this specific period.

Approximately 5%-10% of all HUS cases have an "atypical" or recurrent course. This means that a small percentage of individuals with HUS experience a different or recurring pattern of symptoms compared to the typical presentation of the disease.

The given statement suggests that causes for aHUS include complement disorders, disorders interfering with the degradation of von Willebrand factor (VWF), the cobalamin metabolism, pregnancy – (HELLP syndrome), drugs such as many chemotherapeutic agents, autoimmune, and other disorders. Therefore, the answer "YES" indicates that the statement is correct and all of these factors can contribute to the development of aHUS.

The given statement is true. HUS, or Hemolytic Uremic Syndrome, can indeed be caused by various bacterial and viral infections, including Shigellosis, Streptococcus pneumoniae, Clostridium difficile, Salmonella, Yersinia, Campylobacter species, varicella, echovirus, coxsackie A and B, and human immunodeficiency virus (HIV). These infections can lead to damage to the blood vessels and red blood cells, resulting in the characteristic symptoms of HUS, such as anemia, kidney damage, and low platelet count.

Non-O157 E. coli refers to strains of E. coli bacteria that do not belong to the O157 serogroup. These strains can also cause Shiga toxin-producing E. coli (STEC) infections, similar to the O157 serogroup. Studies have shown that non-O157 E. coli may account for a significant proportion of all STEC infections, ranging from 20% to 50%. Therefore, the statement "Non-O157 E. coli may account for up to 20%-50% of all STEC infections" is correct.

The best way to prevent HUS is to prevent primary infection with Shiga-toxin-producing bacteria by appropriate personal and public hygiene procedures or through an uptake of appropriately designed vaccines. In addition to the commonly suspected ground (minced) beef, unpasteurized dairy products and contaminated, water person-to-person spread can transmit this pathogen to other people. Secondary prevention through prompt isolation of index cases of ETEC-associated diarrhea is recommended.
Research efforts are currently being directed at the development of vaccines in the prevention of VTEC/STEC infection.

Atypical- or non-Shiga toxin-associated HUS can occur sporadically or run in families. Up to 50% of cases involve abnormalities in complement regulatory genes such as CFH, MCP, and IF. Other cases can be caused by mutations in ADAMTS 13 or defects in vitamin B12 metabolism. Approximately 5% of patients with atypical HUS have mutations in factor B or serum thrombomodulin. Patients with the CFH mutation have the worst prognosis, with 60% of them developing end-stage renal disease or dying within one year.

HUS has a case fatality rate of between 2% and 7% and a rate of long-term sequelae, such as renal impairment, neurological injury, or hypertension, in 12% to 30% of the cases. Early mortality remains high in pneumococcal-associated HUS (8-fold that of VTEC-induced HUS) as a result of those cases associated with meningitis.

The typical laboratory findings include a moderate leucocytosis, microangiopathic hemolytic anaemia and elevated reticulocyte count with the presence of schistocytes (fragmented, deformed, irregular, or helmet-shaped red cells) and evidence of thrombocytopenia in the peripheral blood smear. The prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen are within the reference ranges, thus differentiating HUS/TTP from disseminated intravascular coagulation (DIC).
Blood urea nitrogen (BUN) and creatinine are markedly elevated. However, these do not reflect the severity of the renal disease. Urine may contain mild to moderate levels of protein, hemoglobin, haemosiderin, leucocytes and red blood cells.

Approximately 5%-15% of children with STEC infection will develop HUS.
STEC causes a wide spectrum of diseases ranging from asymptomatic carriage through to hemorrhagic colitis and HUS. Faeco-oral transmission is the main route of acquiring new infections, requiring a much smaller bacterial inoculum (

The outcome of kidney transplantation in patients with genetic HUS is generally poor, with disease recurring in 60% of patients, over 90% of whom develop graft failure.
The presence of factor H (CFH) and factor I (IF) mutations have been associated with a high incidence of graft failure (over 80%), often due to early graft thrombosis (50%) or HUS recurrence within 2 years of transplantation. In contrast, graft outcome is more favorable in all patients who carry MCP mutations.

There are no universally agreed identifiable risk factors for predicting the development of HUS in susceptible individuals. A few studies have shown that fever, leukocytosis, and elevated C-Reactive protein levels may predict progression from STEC infection to HUS

The vast majority of children with STEC-HUS undergo acute kidney injury with 40-50% requiring renal replacement therapy, while a further 2.5% to 10% will either die or develop chronic kidney disease

No specific clinical prognostic factors have been identified for patients with HUS. A marked deactivation of polymorphonuclear (PMN) cells have been detected in severe cases, and the functional state of PMN in HUS patients have been suggested to be of a possible prognostic value (70). D+ HUS patients presenting with oligo-anuria, dehydration, WBC >20 x 10(9)/L and haematocrit >23% are at substantial risk for dying from HUS

Although most patients with typical HUS recover renal functions, recent analysis has shown that typical HUS is not a benign disease in the long term.

The mainstay of care for patients with HUS is to provide adequate supportive management including appropriate fluid and electrolyte management, and anti-hypertensive therapy if necessary. Parenteral volume expansion as soon as a patient is suspected to be infected with ETEC 0157:H7 may counteract the effect of thrombotic process before development of HUS and attenuate renal injury (3, 40). Patients with anemia need to be transfused to raise haemoglobin up to 70 g/L (not to normal). Platelet transfusions may also be required for active bleeding or surgery, as well as dialysis for anuria greater than 24-48 hrs. Use of antibiotics, anti-motility agents, narcotics and non-steroidal anti-inflammatory drugs should be avoided during the acute phase.

The characteristic pathologic findings in HUS are renal endothelial swelling, thrombi in the arterioles and capillaries, and subendothelial fibrin deposits.

Despite over 40 years of clinical research on HUS, no effective treatment has been developed for STEC-induced HUS.
Clinical practice in relation to the use of antibiotics in the management of STEC-related HUS remains controversial. Antimicrobials may have a potentially harmful role and may increase the risk of HUS in children with E. coli O157:H7 infection with high mortality and/or longer duration of diarrhea, possibly by inducing intestinal production of Stx during the diarrheal phase of the illness. Certain antibiotics, especially DNA-damaging antibacterial agents at sub-lethal concentrations, have been found to increase the release of Shiga-like toxins, and no clinical studies have indicated that antibiotics are effective in reducing the duration of E. coli O157:H7 infection or the duration of diarrhea or bloody diarrhea specifically. Stx genes are carried on bacteriophages, which may be induced into the lytic phase with significantly increased production of Shiga toxins by bacterial DNA damage.

Several studies have shown that patients with D- HUS caused by pathogens other than STEC (including S pneumoniae and HIV) require dialysis therapy more often and are hospitalized or have persistent thrombocytopenia more than twice as long during the acute episode compared with those with D+ HUS. They are also more likely to require platelet transfusions (83% vs 47%) and need more packed red blood cell transfusions (7.8 vs 2.0). Though S pneumoniae-related HUS is associated with a less favorable short-term course than other types of non-enteropathic HUS, the long-term prognosis for recovery of renal function appears to be good in these patients.