EHEC How the HUS syndrome was defeated

How HUS was defeated with antibodies

15.11.2011

More than 3,500 people were, according to the Robert Koch Institute in the early summer of this year to the effects of EHEC germ in some cases seriously ill. In the majority of adults and predominantly women. Of these, 855 people suffered from severe kidney failure or acute brain damage. Especially at the University Hospital Hamburg-Eppendorf (UKE), there was a medical emergency for weeks. Conventional therapies with antibiotic drugs failed, so that the treating physicians had no choice but to test a novel drug with an antibody. In addition to the Hamburg University Hospital, seven other German hospitals participated in the testing of the remedy. As it turned out, the antibody labeled „eculizumab“ the decisive therapeutic breakthrough. A study from the year 2010 gave this the impetus.

A recent study involving 148 patients with EHEC showed that the antibody eculizumab is adequate for treating patients with the hemolytic uremic syndrome (HUS). Physicians and researchers from the University Hospital Hamburg-Eppendorf came to this conclusion. The study results were presented yesterday to a wider audience during a presentation. HUS syndrome caused serious health complications in about a quarter of EHEC patients. As a result, those affected suffered from acute kidney failure as well as significant brain function disorders.

Active ingredient brought the breakthrough in HUS treatment
The medical team around the kidney specialist Prof. Dr. med. Rolf Stahl and the neurologist Prof. dr. Christian Gerloff had evaluated the data of a total of 148 treated HUS patients during the study work. All patients were from Northern Germany and were treated with the antibodies eculizumab. The state of health of 95 percent of those treated had significantly improved over a period of eight weeks. In 61 percent of those treated with neurological disorders, a complete recovery set in. According to the data, the others still displayed slight symptoms, such as a slight disorientation, although overall there was an improvement in well-being, as Prof. Gerloff said during the presentation of the study.

21 subjects with epilepsy due to HUS no longer complained of epileptic seizures. The vast majority of patients (19) no longer need medication today. However, further final results are not available until the middle of next year. By mid-2012, another 120 patients will be following up and follow-up visits to the UKE hospital. The internist steel emphasized that treating with antibodies „It is not a miracle cure, but a medically rational therapy“.

HUS generated domino effect
The most exciting question, of course, was how the antibody therapy works. To do this, the researchers first had to find out how bacterial EHEC germs and, as a consequence, HUS were able to trigger such massive perturbations. To elucidate why the central nervous system, the blood picture and the kidneys are being attacked, Professor Stahl explained the chain reaction with the help of a domino game. The first stone in the „game“ is the so-called Shiga toxin. This toxin triggers a chain reaction that ends in severe kidney damage and brain function disorders. The drug used in the treatment eculizumab takes some in this series „Dominosteinchen“ out, so that further damage in the body fail. The organism then has the opportunity to regenerate. The symptoms improve and the patient is on the healing path. To a HUS patient can Dr. med. Gerloff still remember very well. The man was a marathon runner and was seriously ill with HUS. "He was in a coma - and today, after being treated with eculizumab, he's running another 20 kilometers - a sensational success."

Antibody was initially not the drug of choice
At the beginning of the EHEC epidemic, doctors used the antibody only occasionally in very severe patient cases. At the Klinikum Hamburg-Eppendorf, patients were given the medication for the first time on the 27th of May. At that time, the EHEC germ was just a week medial known and the first cases increased in Hamburg and Lower Saxony. Eculizumab was by no means that „Means of first choice“, but was only used when nothing else helped and the patients were already in acute mortal danger. The idea to use the novel therapeutic was provided by a medical report on treatment with eculizumab. In the web edition of the New England Journal of Medicine, scientists from Heidelberg, Paris and Montreal published the first treatment successes of three critically ill children with eculizumab. The small patients had infected with EHEC bacteria in 2010 and subsequently contracted HUS syndrome. The drug was able to save the three children and bring about a significant relief of the symptoms. The report was first published in the print medium, but was made in advance due to the looming EHEC epidemic in May 2011 online, so researchers could access the knowledge. Thus, all specialists in Germany's university clinics had access to it.

Afterwards, the doctors at the UKE Eculizumab first used for seriously ill patients. When the patients were on their way to recovery in a relatively short time, since June 2011 the drug has been used as a standard medication in almost all HUS patients throughout Germany. In addition to the eculizumab therapy, a blood plasma exchange (medical: plasmapheresis) was undertaken. "The data strongly suggests that this is related to the antibody," said neurologist Christian Gerloff. Without remaining doubts, however, this can not be proven. This would require further studies.

Study is a help for upcoming EHEC epidemics
The data analysis of the experts from Hamburg could help with possibly future HUS syndromes. Now the medical profession is better positioned, said the neurologist Dr. med. Christian Gerloff. As the standard agent, the antibody drug is not yet approved. This is decided by the European Medicines Agency (EMA). For this reason, must „Before any treatment, the application must be agreed first“, said the UKE doctors. When the admission process is completed, the doctors were unable to assess.

Allegations against sprouts-cultivation business
Serious allegations are made by scientists against the sprouts cultivation business. The farm had been closed by the health authorities, because this was the origin of the EHEC propagators. Hygiene professor Martin Exner told the news magazine „Focus“, An inspection of the farm revealed massive local hygiene deficiencies. For example, the toilets for the staff were located too close to the well used for sprout irrigation. The sprout producer has meanwhile filed suit against the blocking of its plant. A decision is still pending. (Sb)

Also read:
Positive outcome of the EHEC epidemic
Symptoms of EHEC infection
EHEC epidemic survived
Neurological disorders as EHEC symptoms

Picture: Gerd Altmann