Evolution of the Mad Cow Disease in the United States Denish Moorthy, Eugene Shubnikov, Ron LaPorte

1. Evolution of the Mad Cow Disease in the United States Denish Moorthy, Eugene Shubnikov, Ron LaPorte The Supercourse Network of the Global Health University www.pitt.edu/~super1/

2. Outline of Presentation • The Mad Cow Disease – What is It? • What Causes it? • How is it Diagnosed? • How Does it Spread? • Should Humans Be Worried? • What is Creutzfeld-Jakob Disease (CJD)? • What Happens in CJD? • Is there a Cure? • Epidemiology • Implication for World Trade • The UK Story • We are faced with a potential problem

3. Mad Cow Disease: What is it? • The Mad Cow Disease in Cows, Scrapie in Sheep, the Creutzfeldt-Jakob Disease in human beings belong to a class of disease called Transmissible Spongiform Encephalopathy(TSEs) • Initially thought to be due to “slow viruses”, due to the long incubation period between time of infection and appearance of disease, these are now known to be caused by agents called prions.

4. Transmissible Spongiform Encephalopathy (TSE) What Are They? • Transmissible Spongiform Encephalopathy (TSEs) are rare forms of progressive neurodegenerative disorders that affect both humans & animals • They are caused by similar agents (prions) • They are called so because they produce spongiform changes in the brain • Also, the agent causing the disease is found at the highest titre in the brain

5. Mad Cow Disease • Scientific Name: Bovine Spongiform Encepalopathy • It is found on any type of cloven hoofed animals such as: pigs, sheep, and cattle • Sheep: Scrapie Spongiform Encepalopathy. • There is a human form called Creutzfeldt-Jakobs Disease

6. Bovine Spongiform Encephalopathy (BSE) is so named because of the spongy appearance of the brain tissue of infected cattle (and also in the human beings) when sections are examined under a microscope

7. The incubation period (the time from when an animal becomes infected until it first shows disease signs) varies from 2 to 8 years. Following the onset of clinical signs, the animals condition deteriorates until it either dies or is destroyed. This process usually takes from 2 weeks to 6 months. Most cases in Great Britain (where it was first detected) have occurred in dairy cows between 3 to 6 years of age. How Does it Progress?

8. There are three phases of BSE in cattle: • The first phase: • Low infectivity rate, and the cow does not pose a large threat to humans at this level • The second phase: • Symptoms are not evident, but the infectivity level is very high • The prion agent is abundant in both the spinal chord and the brain – the cow is a risk to public health • The third phase: • Clinical symptoms, & then death follows shortly

9. What Causes Mad Cow Disease?

10. Initially thought to have been caused by a “slow” viruses, these were classified as “slow Viral Diseases • Now there is evidence to point out Prions as the causative factor

11. Shortened form of Proteinaceous infectious particles • Prions are single molecules containing about 250 amino acids • They are abnormal variants of proteins which normally occur in cells • Prions have the ability • to convert the normal • forms that they come • into contact with into • abnormal forms Prions

12. PrP is a normal cellular protein referred to as PrPc • Diseased brain contains aberrant PrP which is referred to as PrPSc • PrPSc has the ability to convert PrPc to itself • A chain reaction follows, resulting in a cluster of tangled, nonfunctional proteins called plaques, which are aggregates of PrPSc in the brain • The body defences remove these PrPSc aggregates leaving behind holes • This causes degeneration of the brain cells leading to mental changes and ultimately, death Prion Hypothesis

14. Variant CJD in humans: section of cerebral cortex stained to show aggregates of PrPSc within plaques and more finely distributed throughout the grey matter (PrP stains brown)

15. Prion Characteristics • No antibiotics can cure disease caused by prions • They are not typical of a prokaryotic organism or a eukaryotic organism • All that is present in this pathogen is the protein PrPSc, the mutation of PrPC • PrPSc is resistant to any form of digestion • Prions are non immunogens and do not induce an immune response • Prions are not easy to decompose biologically • They are resistant to high temperatures & disinfectants

16. How is it Diagnosed in Cattle?

17. Cattle affected by BSE experience progressive degeneration of the nervous system. Affected animals may display changes in temperament, such as nervousness or aggression, abnormal posture, inco-ordination and difficulty in rising, decreased milk production, or loss of body weight despite continued appetite Clinical Signs - 1

18. Clinical Signs - 2 • The clinical signs are: • Apprehension • Hyperaesthesia • Frequent licking with progressive paresis, & ataxia • No blindness or circling is seen (At the London Zoo it was first noticed by the public when a Puma became ataxic).

19. Diagnosis • Currently, there is no test to detect the disease in a live animal or in humans • Veterinary pathologists confirm BSE by postmortem microscopic examination of brain tissue or by the detection of the abnormal form of the prion protein

20. Histological Findings on Post Mortem • Histological findings include • Vacuolation of the neurones and neuronal ground substance in cerebella/cortex • Perivascular fibrils of amyloid in which PrPsc can be demonstrated by immunostaining and congo red bifringence • Astrocyte infiltration.

21. How Does it Spread?

22. The Source of Prion • Prion in cattle is mainly are from the carcasses of scrapie-infected sheep. • After these infected sheep having died , their brains and other sheep byproducts infected with scrapie is used to feed cattle with the meat and bone mill (MBM)

23. How does it spread from animal to animal? • Feeding cattle animal bi-products such as meat-n-bone mill that has an infected prion causes the infection in the cattle • The prions are concentrated in the brain, and spinal cord of these animals • There is no evidence that it is concentrated in the muscle mass of cattle, and they are considered safe as long as they are not in contact with the brain and spinal cord during the slaughter process

24. How did BSE Transfer to Humans • Sheep with Scrapie used in Meat and Bone Meal (MBM) – known as “Offal” • MBM fed to cattle • Infected Beef eaten by humans • Not affected by cooking

25. Should Humans be Worried?

26. Mad Cow Disease in Humans • When cattle brains and other cattle byproducts infected with BSE are ingested by humans, there is a risk of developing the Creutzfeldt-Jakob Disease

27. What is Creutzfeldt-Jakob Disease (CJD)?

28. Origins of CJD • Bovine Spongiform Encephalopathy (BSE) was first described in the UK in 1985 as a prion-based disease that affected cattle. • In 1996 it was first detected in a human being • It was suspected at that time (which turned out to be correct) that humans were contracting the disease from eating cows that had been infected with BSE • In humans, it is has been named the Creutzfeldt-Jakob Disease (CJD)

29. Types of CJD • CJD is classified into 2 forms: Classic CJD & Variant CJD • Classic CJD can be transmitted to other species, however other animals cannot carry it. • Sub classified into: Sporadic CJD and Iatrogenic CJD • Sporadic CJD - >85% of Classic CJD cases • Most common between 50 – 75 years • Characterized by rapidly increasing dementia • Iatrogenic CJD - < 5% Classic CJD cases • Transmission of prion via medications & surgical equipment

30. What is vCJD • Variant Creutzfeldtt-Jakob Disease (vCJD), is caused by the consumption of BSE infected meat products • The first 10 cases of variant CJD were observed in 1996, ten years after the outbreak of BSE in the UK • Variant CJD seems to affect mostly young patients

32. Clinical Symptoms CJD causes fatal degradation of brain tissue & the nervous system The symptoms include loss of expressiveness, muscular tremble, spasm, impaired muscle coordination, loss of memory & dementia vCJD patients also display unusual psychiatric problems There is no cure for CJD The condition of the patient deteriorates, finally resulting in death

33. Is there a Cure?

34. At Present, there is no Cure for the Mad Cow Disease (Bovine Spongiform Encephalitis) and for the Creutzfeldt-Jakob Disease Prevention is the only available option

35. Prevention • Don’t feed cattle animal bi-products • Watch to make sure you are feeding your animals safe feeds • Always vaccinate cattle properly

36. Prevention • USDA requires all imported meat to be inspected • US will not import cattle from Britian • Animals suspected of the disease are quarantined

37. Epidemiology

38. Mad Cow Disease in the world • Mad cow disease was first identified in Britian in 1985 • The outbreak infected more than 100,000 cows across Europe in the mid-1990s • The recent resurgence of the disease comes despite widespread beef import restrictions and other measures intended to protect the food supply

40. Mad Cow Disease in Europe • Cases of BSE have now been identified in 10 of the 15 European Union (EU) countries, as well as Switzerland and Liechtenstein • Although the incidence is low, the discovery of the disease across the continent has had a dramatic effect on beef consumption • Beef consumption has has fallen by 27% across the EU

41. vCJD in Europe • The number of people who have died from variant Creutzfeldt Jacobs Disease (vCJD), is also growing • By the end of 2000, nearly 90 people had either died or were dying from the disease in the UK • Deaths from vCJD have also been reported in France & Italy

42. vCJD in Europe • France • 160 cases of BSE were diagnosed in 2000 • Beef sales dropped by > 25% • Germany • Confirmed 20 cases of BSE in 2001 • Beef sales dropped by 50 percent • United Kingdom • Single largest source of BSE • 1,277 cases confirmed in 2000

43. Implications for World Trade

44. Consumer Perception of BSE • Beef Consumption • UK and EU decreased by 30% • US – Steady Overall • World – slight increase • Fast Food Chains • Demand BSE Free

45. Implications for World Trade • Increased Demand for Grass Fed and Grain Fed Beef due to low possibility of BSE • Reduced trade in products made from Beef by-products • Make up • Diet Supplements • Health Products

46. The United Kingdom (UK) Story

47. BSE First Discovered in the UK • BSE was discovered in ataxic cows by the Central Veterinary Laboratory in November 1986 by observing vacuolation of brains by histopathology • BSE considered to be caused by a single strain of scrapie

48. Confirmed cases of BSE plotted by month and year of clinical onset Feed ban introduced First histopathological confirmation 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

49. BSE in the UK • A further 750,000 cases of subclinical BSE may have occurred and been culled before the peak age for clincal disease of 5.5yr • Brains and spinal cords from 440,000 of these could have contributed to the human food chain before the offal regulations of 1989 • The disease should be almost extinct in the year 2001 when no animals fed on Meal and Bone Mill (or MBM) are left

50. Effects on the U.S. • Caused great worries for many beef consumers • Caused cattle ranchers to take many precautionary steps • “This disease has not been known to be in the US…” • “…And chances are, it never will because the US has so many safety standards”