Hamburg  - 1.8 million people  - Germany's second largest city  - founded in 88o C.E.  - Hamburg is Europe's second larges...
Rolf Stahl,  a 62-year-old kidney specialist, has been the head of the Third Medical Clinic and Polyclinic at the Universi...
The first stool sample arrived  to  Helge Karch, the director of the RKI's EHEC consulting laboratory at the Münster Unive...
I n  UKE  (02.06.2011) More than 100 patients with  HUS 27 children 5 pregnant women 20 are in ICU http://www.wochenblatt....
2 June 2011 10:00hrs The HPA can confirm one new case of HUS and three new cases of bloody diarrhoea in England.  All are ...
 
EHEC O104:H4 Shigatoxin 2 (vtx2a) : + (positive) ESBL: CTX-M-15 + (positive) Other ß-Lactamases: TEM-1 + (positive) Ampici...
Germany's national health agency said 1,534 people in the country had been infected by EHEC  with 17 deaths (plus 1 in Swe...
E.Coli  O157:H7  Outbreakes <ul><li>epidemic linked to hamburgers from Jack in the Box restaurants in the United States in...
Haemolytic Uraemic Syndrome Gasser Syndrome Hamburger disease (USA) Cucumber disease (DE)
Haemolytic uraemic syndrome (HUS) <ul><li>microangiopathic hemolytic an a emia, </li></ul><ul><li>thrombocytop a enia  </l...
Epidemiology of HUS <ul><li>approximately 2.1 cases per 100,000 persons per year </li></ul><ul><li>peak in children who ar...
D+HUS and E.coli <ul><li>D+ HUS  (diarrhoea positive)  is the classic form, accounting for 95% of cases of hemolytic uremi...
 
 
Causes in adults <ul><li>Idiopathic 40% </li></ul><ul><li>No apparent etiology or associated condition </li></ul><ul><li>D...
Additional/alternative diagnoses in patients presenting with  clinically suspected TTP-HUS <ul><li>Preeclampsia/eclampsia/...
Pathogenesis of HUS  <ul><li>S higa-like toxin  </li></ul><ul><li>ente rs  circulation via gastrointestinal mucosa,  </li>...
Symptoms <ul><li>Diarrhea hemorrhagic in 70% of cases, within 1-2 days of onset </li></ul><ul><li>Vomiting 30-60% </li></u...
Symptoms cont. <ul><li>Fever occurs in 30% of cases. </li></ul><ul><li>GI bleeding is often noted. </li></ul><ul><li>GI in...
Lab results <ul><li>hemoglobin level  typically less than 8 g/dL </li></ul><ul><li>Blood film – schistiocytes </li></ul><u...
 
Lab results <ul><li>Blood cultures are negative in  E coli –mediated disease since only the shiga-like toxin is circulatin...
Treatment <ul><li>Avoid antibiotics in diarrhoea -  antibiotic-induced injury to the bacterial   membrane favors the acute...
 
Treatment monitoring <ul><li>response to plasma exchange </li></ul><ul><li>neurologic symptoms resolve   immediately </li>...
Poor response <ul><li>If no platelet   count response or an exacerbation of disease activity during daily   plasma exchang...
What does not work <ul><li>aspirin, dipyridamole, </li></ul><ul><li>Vincristine,  other immunosuppressive agents </li></ul...
When to stop PE <ul><li>No clinical parameters predict the required duration for plasma   exchange </li></ul><ul><li>plate...
HUS - adults vs children <ul><li>In adults </li></ul><ul><li>females more affected </li></ul><ul><li>more  frequent severe...
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Haemolytic uraemic syndrome

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About HUS and German E.coli outbreak

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Haemolytic uraemic syndrome

  1. 1. Hamburg - 1.8 million people - Germany's second largest city - founded in 88o C.E. - Hamburg is Europe's second largest port. - Hamburg has 2300 bridges, more than both Amsterdam and Venice combined - St. Pauli district is largest adult entertainment district in Europe UKE Universitätsklinikum Hamburg-Eppendorf 80 clinics and institutes organized in 15 medical centers 1396 beds 1,300 doctors and scientists 3,000 nurses and therapists 2,100 technicians and administrative personnel 3,700 medical students
  2. 2. Rolf Stahl, a 62-year-old kidney specialist, has been the head of the Third Medical Clinic and Polyclinic at the University Medical Center Hamburg-Eppendorf (UKE) for almost 18 years. &quot;But none of us doctors has ever experienced anything quite like this,&quot; The story of the outbreak began in Stahl's clinic. When the first patient suspected of having contracted HUS was admitted there on a Wednesday evening two weeks ago (11.05) , none of the doctors had any idea what they were facing. &quot;We weren't even thinking of EHEC at first,&quot; says Stahl, &quot;because it normally only affects children.&quot; In adults, on the other hand, HUS can also be caused by genetic defects and autoimmune diseases, or as a side effect of cancer treatment. By the next day, however, there were suddenly seven or eight cases in the ward, and the laboratory reported that they were all infected with EHEC. Hamburg promptly notified the Robert Koch Institute. http://www.spiegel.de/international/germany/0,1518,765777-2,00.html
  3. 3. The first stool sample arrived to Helge Karch, the director of the RKI's EHEC consulting laboratory at the Münster University Hospital in western Germany on Monday (16.05) . The result was clear by Wednesday (18.05) evening: It was the extremely rare serotype O104:H4. After searching through a database for medical journals, Karch found only one article under the search term &quot;O104:H4&quot;: a case study from Korea. On the morning (20.05) after the RKI learned of the bizarre cases in Hamburg, four members made their way to the epicenter of the outbreak, Rolf Stahl's clinic in Hamburg. They brought along the epidemiologist's tool of choice: the questionnaire. The researchers sat patiently at the bedsides of 25 female patients. Hardly any of the patients had eaten raw meat or raw milk, the causes of almost all previous EHEC outbreaks, but almost all of them had eaten uncooked vegetables. By Wednesday morning, RKI was able to present the results: Tomatoes, lettuce or cucumbers were the most likely sources of the infection. The bacteria found on two of the four cucumber samples did not match up with the type of EHEC bacteria from the stool samples of patients, &quot;These initial results mean that our hope that we had discovered the source of the (outbreak) has unfortunately not been fulfilled,&quot;
  4. 4. I n UKE (02.06.2011) More than 100 patients with HUS 27 children 5 pregnant women 20 are in ICU http://www.wochenblatt.de/
  5. 5. 2 June 2011 10:00hrs The HPA can confirm one new case of HUS and three new cases of bloody diarrhoea in England. All are suspected to be related to this outbreak. Three of the four new cases, including the HUS case, are in UK residents with a recent travel history to Germany and one new case is in a German national on holiday in England. This brings the total number of cases in England to seven three HUS and four bloody diarrhoea. There are no reports of any secondary infections in England. http://www.hpa.org.uk/
  6. 7. EHEC O104:H4 Shigatoxin 2 (vtx2a) : + (positive) ESBL: CTX-M-15 + (positive) Other ß-Lactamases: TEM-1 + (positive) Ampicillin R Amoxicillin/Clavulanic acid R Piperacillin/Sulbactam R Piperacillin/Tazobactam R* Cefuroxim R Cefuroxim-Axetil R Cefoxitin R Cefotaxim R Cetfazidim R Cefpodoxim R Streptomycin R Nalidixinsäure R Trimethoprim/Sulfamethoxazol R Tetracyclin R Imipenem S Meropenem S Amikacin S Gentamicin S Kanamycin S Tobramycin S Ciprofloxacin S Norfloxacin S Nitrofurantoin S Chloramphenicol S Fosfomycin S
  7. 8. Germany's national health agency said 1,534 people in the country had been infected by EHEC with 17 deaths (plus 1 in Sweden). The Robert Koch Institute said 470 people in Germany were suffering from hemolytic uremic syndrome, or HUS, a number that independent experts called unprecedented in modern medical history. HUS normally occurs in 10 percent of EHEC infections, meaning the number seen in Germany could be expected in an outbreak three times the size being currently reported. Germany typically sees a maximum of 50 to 60 annual cases of HUS, which has up to a 5 percent fatality rate according to the World Health Organization. More than 60 percent of the EHEC cases in Germany have been women - 88 percent over the age of 20 - and nearly 90 percent of the HUS cases have been women over the age of 20 . 86 percent of those sickened in the current outbreak were adults Breaking news 2.06.2011
  8. 9. E.Coli O157:H7 Outbreakes <ul><li>epidemic linked to hamburgers from Jack in the Box restaurants in the United States in 1992 and 1993. A CDC report in 1994 put the total cases in the outbreak at 583 with 41 HUS cases, for an HUS rate of about 7%. </li></ul><ul><li>Another was linked to fresh spinach from California fields in 2006. Officials counted 205 total cases, with 31 HUS cases, for an HUS rate of about 15%. </li></ul><ul><li>in 1996 21 elderly people died and another 500 were made ill after eating contaminated meat supplied by a butcher's shop in Wishaw, Lanarkshire, UK </li></ul>
  9. 10. Haemolytic Uraemic Syndrome Gasser Syndrome Hamburger disease (USA) Cucumber disease (DE)
  10. 11. Haemolytic uraemic syndrome (HUS) <ul><li>microangiopathic hemolytic an a emia, </li></ul><ul><li>thrombocytop a enia </li></ul><ul><li>acute renal failure </li></ul><ul><li>In 1955 Gasser first described HUS as „ a self-limited illness associated with a prodrome of diarrhea that resulted in spontaneous recovery ” </li></ul>
  11. 12. Epidemiology of HUS <ul><li>approximately 2.1 cases per 100,000 persons per year </li></ul><ul><li>peak in children who are younger than 5 years (6.1 cases per 100,000 per year). </li></ul><ul><li>t he lowest rate adults aged 50-59 years (0.5 cases per 100,000 per year) </li></ul><ul><li>D+ HUS mortality less than 10% , adults poorer prognosis. </li></ul><ul><li>( D- HUS, overall mortality rate approaches 26% ) </li></ul>
  12. 13. D+HUS and E.coli <ul><li>D+ HUS (diarrhoea positive) is the classic form, accounting for 95% of cases of hemolytic uremic syndrome in children. </li></ul><ul><li>Escherichia coli, shiga-toxin producing (verocytotoxin), serotype O157:H 7 more than 80% of infections leading to hemolytic uremic syndrome </li></ul><ul><li>STEC=VTEC=EHEC (enterohaemorrhagic ) </li></ul>
  13. 16. Causes in adults <ul><li>Idiopathic 40% </li></ul><ul><li>No apparent etiology or associated condition </li></ul><ul><li>Drug-induced </li></ul><ul><li>Allergic: quinine, ticlopidine </li></ul><ul><li>Dose-related toxicity: mitomycin C, cyclosporine, pentostatin, gemcitabine </li></ul><ul><li>Pregnancy/postpartum </li></ul><ul><li>Bloody diarrhea </li></ul><ul><li>Infection, such as E coli 0157:H7 </li></ul><ul><li>Allogeneic bone marrow transplantation </li></ul><ul><li>HIV; hereditary factors </li></ul>
  14. 17. Additional/alternative diagnoses in patients presenting with clinically suspected TTP-HUS <ul><li>Preeclampsia/eclampsia/HELLP syndrome </li></ul><ul><li>Autoimmune disorders (systemic lupus erythematosus, scleroderma, antiphospholipid antibody syndrome) </li></ul><ul><li>Sepsis (Rocky Mountain spotted fever, cytomegaloviral sepsis, disseminated aspergillosis, b-streptococcal sepsis) </li></ul><ul><li>Disseminated malignancy (metastatic pancreatic or lung ca , acute lymphocytic leukemia) </li></ul><ul><li>Malignant hypertension </li></ul><ul><li>Heparin-induced thrombocytopenia/thrombosis </li></ul>
  15. 18. Pathogenesis of HUS <ul><li>S higa-like toxin </li></ul><ul><li>ente rs circulation via gastrointestinal mucosa, </li></ul><ul><li>preferentially localizes to the kidneys damadging endothelial cells (cortical necrosis) and initiates intravascular thrombogenesis . </li></ul><ul><li>this pot entiates renal microvascular thrombosis by promoting activation of the blood coagulation cascade. </li></ul><ul><li>Platelet aggregation results in a consumptive thrombocytopenia. </li></ul><ul><li>Microangiopathic hemolytic anemia results from mechanical damage to red blood cells circulating through partially occluded microcirculation. </li></ul>
  16. 19. Symptoms <ul><li>Diarrhea hemorrhagic in 70% of cases, within 1-2 days of onset </li></ul><ul><li>Vomiting 30-60% </li></ul><ul><li>Urine output reduced or absent </li></ul><ul><li>Neurologic symptoms in 33% ( irritability, seizures, altered mental status) </li></ul>
  17. 20. Symptoms cont. <ul><li>Fever occurs in 30% of cases. </li></ul><ul><li>GI bleeding is often noted. </li></ul><ul><li>GI involvement may lead to symptoms of an acute abdomen, with occasional peritonitis. </li></ul><ul><li>Cardiac involvement may lead to congestive heart failure (CHF) and arrhythmias. </li></ul><ul><li>Microinfarcts in the pancreas may cause pancreatitis or rarely, insulin-dependent diabetes mellitus. </li></ul><ul><li>Ocular involvement may lead to retinal or vitreous hemorrhages. </li></ul><ul><li>Hypertension and oliguria are typical findings consistent with renal compromise </li></ul>
  18. 21. Lab results <ul><li>hemoglobin level typically less than 8 g/dL </li></ul><ul><li>Blood film – schistiocytes </li></ul><ul><li>Thrombocytopenia platelet counts of less than 60,000 per mL. but no purpura nor active bleeding , INR and APTT, d-dimers, fibrinogen normal </li></ul><ul><li>LDH and indirect bilirubin levels reflects intravascular hemolysis. </li></ul><ul><li>urea and creatinine elevated </li></ul><ul><li>Coombs test results are negative, indicating that the anemia is not immunologically mediated </li></ul>
  19. 23. Lab results <ul><li>Blood cultures are negative in E coli –mediated disease since only the shiga-like toxin is circulating in the blood while the organisms remain in the GI lumen. </li></ul><ul><li>Stool cultures typically detect shiga toxin-producing E coli. </li></ul>
  20. 24. Treatment <ul><li>Avoid antibiotics in diarrhoea - antibiotic-induced injury to the bacterial membrane favors the acute release of large amounts of toxins , increases HUS 17-fold </li></ul><ul><li>Avoid antimotility agents in diarrhoea </li></ul><ul><li>Fluid balance, fluid resusciation, electrolytes, early RRT </li></ul><ul><li>Plasma exchange (plasmapheresis combined with fresh-frozen plasma replacement) is currently the treatment of choice. Plasma exchange is performed daily until remission is obtained. However, because 85% of children with hemolytic uremic syndrome recover after supportive therapy alone, plasma exchange is generall y reserved for the most severe cases. </li></ul><ul><li>Platelet transfusions can worsen the patient's status by inducing further organ damage. </li></ul>
  21. 26. Treatment monitoring <ul><li>response to plasma exchange </li></ul><ul><li>neurologic symptoms resolve immediately </li></ul><ul><li>thrombocytopenia several days </li></ul><ul><li>anemia may continue to worsen </li></ul><ul><li>r enal failure may worsen </li></ul><ul><li>platelet count is the most important parameter on which to base treatment decisions </li></ul>
  22. 27. Poor response <ul><li>If no platelet count response or an exacerbation of disease activity during daily plasma exchange, </li></ul><ul><li>- glucocorticoids are added </li></ul><ul><li>( prednisone 1 mg/kg per day p.o. or methylprednisolone 125 mg twice daily i.v. ) </li></ul><ul><li>- volume of plasma exchanged is increased to 2x daily sessions . </li></ul>
  23. 28. What does not work <ul><li>aspirin, dipyridamole, </li></ul><ul><li>Vincristine, other immunosuppressive agents </li></ul><ul><li>IVIg </li></ul><ul><li>Steroids? </li></ul>
  24. 29. When to stop PE <ul><li>No clinical parameters predict the required duration for plasma exchange </li></ul><ul><li>platelet count normal </li></ul><ul><li>nonfocal neurologic symptoms are resolved </li></ul><ul><li>h a ematocrit level is stable but will not yet be normal, </li></ul><ul><li>LDH value is normal or nearly normal </li></ul><ul><li>renal failure is beginning to ameliorate </li></ul>
  25. 30. HUS - adults vs children <ul><li>In adults </li></ul><ul><li>females more affected </li></ul><ul><li>more frequent severe neurological abnormalities, </li></ul><ul><li>more severe thrombocytopenia and anaemia </li></ul><ul><li>higher mortality </li></ul>

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