Tissue distribution of bovine spongiform encephalopathy agent in primates after intravenous or oral infection

Background The disease-associated form of prion protein (PrPres) has been noted in lymphoreticular tissues in patients with variant Creutzfeldt-Jakob disease (vCJD). Thus, the disease could be transmitted iatrogenically by surgery or use of blood products. We aimed to assess transmissibility of the bovine spongiform encephalopathy (BSE) agent to primates by the intravenous route and study its tissue distribution compared with infection by the oral route. Methods Cynomolgus macaques were infected either intravenously or orally with brain homogenates from firstpassage animals with BSE. They were clinically monitored for occurrence of neurological signs and killed humanely at the terminal stage of the disease. Brain, lymphoreticular tissues, digestive tract, and peripheral nerves were obtained and analysed by sandwich ELISA and immunohistochemistry for quantitative and qualitative assessment of their PrPres content. Findings Incubation periods after intravenous transmission of BSE were much shorter than after oral infection. We noted that PrPres was present in lymphoreticular tissues such as spleen and tonsils and in the entire gut from the duodenum to the rectum. In the gut, PrPres was present in Peyerʹs patches and in the enteric nervous system and nerve fibres of intestinal mucosa. Furthermore, PrPres was found in locomotor peripheral nerves and the autonomic nervous system. Amount of PrPres ranged from 0•02% to more than 10% of that recorded in brain. Distribution of PrPres was similar in animals infected by the intravenous or oral route. Interpretation Our findings suggest that the possible risk of vCJD linked to endoscopic procedures might be currently underestimated. Human iatrogenic vCJD cases infected intravenously raise the same public-health concerns as primary cases and need the same precautionary measures with respect to blood and tissue donations and surgical procedures.