Lingering Doubts about Creutzfeldt-Jakob disease: Mode of transmission Running Title: Creutzfeldt-Jakob disease

Based on clinical and pathological observation Creutzfeldt-Jakob disease (CJD) been classified into three groups: (1) Familial: (2) Iatrogenic: (3) Sporadic: Shortly after the appearance of bovine spongiform encephalopathy (BSE), CJD a disease normally seen in older patients was identified in young patients with non-classical presentation. It now appears that patients all age groups have died of BSE infection. The distinguishing features between classical CJD and "new variant" (vCJD) include: a) Initial presentation with dementia; b) Confluent spongiform changes are very unusual in the cerebellum; c) PrP plaques are rarely observed. For vCJD: a) Initially, difficulty with balancing and ataxia; b) Confluent spongiform changes are seen in the cerebellum; c) A large number of PrP plaques are seen. The recipient of blood, human pituitary-derived growth hormone (hGH), and those infected with the BSE revealed extensive vacuolation of the cerebellum with numerous PrP positive plaques. However, in the brains of the blood recipient and hGH, PrP plaques were much smaller in size and have a similar distribution but is different from those infected with the BSE strain of the agent. These similarities and differences in size and distribution of PrP plaques demonstrate, the route of infection. Many of the brains of CJD cases infected through tissue grafts, electrodes and operations, have not been examined for PrP because immunostaining technique was not available in the past. To confirm human-to-human transmission it is important that these patients' brains should be re-examined for size and distribution of PrP plaques. The pattern and distribution of PrP plaques should be used as a guide to determine the strain and the route of infection. Increasing number of CJD cases in the young population has further increased the risk from human to human transmission through tissue grafts, operations and blood and blood products. It is obvious that symptom-free phase in humans and animals cannot be regarded as infection-free. There is an urgent need to screen all animals going into human food chain. And also human blood and organ donors for CJD. There is an urgent need to clean all the surgical and dental instruments from all patients before they are reused by a pre-soak method. There are two clinically distinct strains of scrapie in sheep: Type I, "itchy" and Type II, the ataxic "trembly" type. The clinical signs of Type II scrapie in sheep, ataxia is similar to those seen in BSE, vCJD and kuru. Evidence suggests that Type II is the cause of BSE, vCJD and Kuru. There is clear evidence of BSE maternal transmission. When cattle or mink are injected with the Type I strain, only a few will become ill exhibiting different clinical symptoms to those seen in BSE. When cattle, cat or mink are fed with Type I infected sheep brains, so far none developed clinical disease. By contrast feeding or injection with the BSE strain, 100% of calves, cats and mink develop the clinical disease. For eradication of BSE and to reduce the risk of infection to humans, the development of a vaccine against BSE is suggested. Such possibility should be fully explored.