Scientists of the Paul-Ehrlich-Institut succeed in investigating the cause of bleeding calf syndrome

Immunisations with the vaccine PregSure BVD cause formation of alloreactive antibodies in cattle. These antibodies are able to adhere to blood cells. If they are transmitted to the calf by the colostrum of a vaccinated cow, they can destroy blood cells and bone marrow cells. In affected farms this will lead to a disorder, which has become known as bleeding calf syndrome or 'blood sweating', in up to 15% of all new-born calves. A group of scientists under the supervision of Max Bastian of the Veterinary Medicine Division at the PEI have published their investigation on possible causes of this phenomenon in the Journal Vaccine. The publication is available online.

"For the first time, our results provide a plausible explanation how this new syndrome may be induced", said Professor Klaus Cichutek, President of the Paul-Ehrlich-Institut (PEI). "We will now be able to take action to prevent such reactions. This again demonstrates our success in combining regulatory work with own research at the PEI", he continued.

Bleeding calves show sudden uncontrollable bleeding from body orifices and lesions. The term 'blood sweating' derives from the fact that bleeding occurs from apparently intact skin areas. Meanwhile, the disease has been given the scientific name 'bovine neonatal pancytopenia' (BNP).

In March 2009, there were first indications that the frequent use of one particular vaccine against bovine viral diarrhoea, PregSure BVD, might be associated with the new syndrome. Since then more than 3,000 cases have been diagnosed in Germany alone (as of 28 February 2011); more than 4,500 cases have been reported in Europe. Since March 2010 the manufacturer has stopped marketing PregSure BVD in Germany on the recommendation of the PEI. On 16 July 2010, the Committee for Medicinal Products for Veterinary Use (CVMP) at the European Medicines Agency (EMA) followed the recommendations by the PEI to suspend the marketing authorisation of PregSure BVD. The suspension of the marketing authorisation came into force in October 2010 – the respective batches were recalled.

Previously, in early 2010, PEI scientists from the Divisions 'Veterinary Medicine' and 'Safety of Medicinal Products and Medical Devices', supported by the Cattle Health Service (Rindergesundheitsdienst) in the land (federal state) of North Rhine Westphalia had started investigating possible causes of BNP.

In the blood serum of vaccinated laboratory animals (guinea pigs) researchers identified antibodies that bound to bovine leukocytes (white blood cells of a cow). In non-immunized animals these leukocyte-binding antibodies were not detected. The same phenomenon was observed in cows immunized with PregSure BVD, but not in cattle that had received other vaccines. "The finding that these toxic antibodies of mothers of affected calves adhere to the cell line that is used for the manufacturing of PregSure BVD is a clear indicator for us that the vaccine is involved in the development of the disease", said Max Bastian. Based on these results, many peculiarities of BNP can be explained, in particular the transmission by colostrum. Now it is up to the manufacturer to modify the vaccine production so as to safely prevent the development of these antibodies. "The information that the occurrence of the disease is preventable, even if the animals are vaccinated with PregSure BVD is particularly important for the cattle owners", emphasised Dr Klaus Cussler, head of the 'Pharmacovigilance of Immunological Veterinary Products and Animal Welfare' Unit at the PEI. "Calves at risk must not receive their mothers’ colostrum. This will certainly prevent the disease", said Dr Cussler.