The hemolytic uremic syndrome (HUS) is a disease caused by eating food contaminated with the bacteria Escherichia coliproducer of Shiga toxin (STEC), which can be found in meat but also in fruits, vegetables, unpasteurized milk and even in water.
In Argentina there are around 5,000 infections per year due to STEC and about 500 boys develop the syndrome, 10 percent. It mainly affects children under 10 years of age. According to the World Health Organization, Argentina has the highest incidence in the world of the syndrome in children under 5 years of age.
The symptoms are mainly diarrhea with or without blood associated with severe abdominal pain, paleness and little desire to urinate. Diagnosis is made by a laboratory test that can detect the presence of the toxin within a few hours.
Until today there is still no treatment available in the world. affected people usually require dialysis for long periods, and years later, they may need a kidney transplant. In Argentina it is the cause of 20% of pediatric kidney transplants. The mortality rate is about 3 percent.
In this context, Argentina advances the world’s first treatment against HUS. Researchers from Inmunova and the Institute of Experimental Medicine (dependent on the National Academy of Medicine and Conicet) developed a biological medicine that would slow the progression of the disease.
It is a concentrate of antibodies with neutralizing capacity against the toxin that produces the disease. These antibodies recognize and block the toxin to prevent it from entering cells, which would prevent damage in affected children.
After preclinical trials, a Phase I clinical trial was carried out together with the Clinical Pharmacology team of the Hospital Italiano de Buenos Aires to evaluate the safety of the treatment in healthy adult volunteers. According to information from the laboratory, the results they were encouraging.
“The clinical development program, audited and approved by the ANMATappeared simultaneously before the US (FDA) and European (EMA) regulatory authorities incorporating the suggestions of the three entities into the final design of the study”, sources from Inmunova explained.
The next stage of the clinical study that will measure the efficacy and safety of the drug will begin shortly in 15 hospitals and clinics in the country, including the main national pediatric hospitals. At this stage, treatment will be given to approximately 80 boys from one to 12 years old who have a diagnosis of HUS.
Once the drug’s safety and efficacy have been proven at this stage, the study will be expanded to test its efficacy in a larger number of boys and girls, a requirement for final approval.
A microscope image of Escherichia coli bacteria. Photo: EFE
Paula Coccia, head of the Pediatric Nephrology service at Hospital Italiano, estimated that the study will start next summer. “The idea is that all patients who enter hospitals and clinics with confirmed HUS and are admitted with this diagnosis you can offer them this serum intravenously to neutralize the toxin,” he explained.
He added that “so far there have been efficacy studies in animals and in laboratory cells. Now you have to test it in reality. Until we try it in children with this pathology, we won’t know if this medication can help them avoid having to do dialysis, something that today it affects half of pediatric patients going through the disease. Or if they do dialysis for less time or that they have fewer subsequent chronic sequelae in the kidney or in the central nervous system. It is a disease that can be very serious. That’s why it’s so important to be able to find something to treat it.”
The treatment will be voluntary and the parents who agree must sign a consent so that their children can participate in the clinical trial. “All those who accept it will receive the medication. There will not be a group that will be given a placebo. The protocol is set up in such a way that the comparison will be made with children who had this disease in previous years in each center”, says the expert.
Why does Argentina have the highest incidence of HUS in the world? “There are studies done at the Malbrán Institute that say we have the most virulent strains that exist circulating especially at the level of cattle, which is a reservoir of the bacterium, which lives in the intestine of cows and does not cause any disease, although there are also some carriers who are human beings”, details Coccia.
And he adds: “When we eat something that is contaminated with this bacterium, either when the animal is slaughtered and it is not washed well and we do not cook it completely well, the bacterium does not die and we can get it. It’s fundamental incorporate hygiene and care habits: wash your hands with soap and water before and after using the bathroom or changing diapers, before handling food and after touching raw food; cook meat thoroughly, especially minced meat; avoid cross-contamination (contact of raw meat with other foods); wash fruits and vegetables well; consume drinking water and pasteurized milk.
Other countries such as the United States, Canada, Great Britain, and Japan have had outbreaks of HUS. In 2011, Germany suffered an outbreak that affected almost 4,000 people, caused by contaminated vegetables used in salads; 855 of those affected developed HUS with serious sequelae and 53 died. One of the most recent was at the beginning of 2019 in the United States, with 62 people infected with STEC.
PS