# Presentation: 709487

## Canadian and U.S. BSE Risk 

- Steven Anderson, Ph.D, MPP
- Office of Biostatistics & Epidemiology
- Center for Biologics Evaluation & Research
- U.S. Food & Drug Administration
- TSE Advisory Committee
- February 12, 2004

**Notes:**
Good Afternoon – My name is Steve Anderson and I am the Associate Director for Risk Assessment

in the Office of Biostatistics and Epidemiology at the Center for Biologics Evaluation and Research.

Today I am going to present work that we have recently done on evaluating BSE risk for Canada and the United States

## Policy questions for BSE in North America

- What is the BSE risk for the U.S. and Canada?
- Part I - Estimating BSE risk: Potential exposure pathways in U.S. and Canada
- What is the risk for the general U.S. population? What are the implications for the blood supply?
- Part II – Estimating BSE exposure and                         risks in the U.S.

**Notes:**
At the beginning of this work 2 questions were posed to us 

The first question  - What is the BSE risk for the U.S. and Canada?
I will address that question in  part I of this talk 
I will discuss the approach–
Basically we evaluated various pathways by which BSE might have been introduced into the U.S. and Canada

The second question  What is the risk for the general U.S. population?  And then extending that to our area of interest for the blood supply we wanted to know 
What are the implications for the blood supply
So we conducted a risk evaluation to estimate BSE exposure and risks in the U.S.

## North American beef production statistics

|  | U.S.A. | Canada |
| --- | --- | --- |
| Total Cattle  | 96.1 million | 13.3 million |
| Slaughtered | 35.7 million | 3.6 million |
| Commercial carcass weight (est) | 27 billion lbs | ~3.8 billion lbs |
| Total beef (bone-in) | 8.75 million 
metric tons | 908,000 
metric tons |
| % Beef exported | ~ 9.8 % | > 60% |

**Notes:**

Just some general background on North American beef production

Total cattle currently in the US here is 96 million and in Canada there are approximately 13 million cattle – of course these numbers are approximate and can vary slightly from year to year – but there is an approximately 7 fold difference between the US and Canadian cattle populations

Approximately 36 million cattle were slaughtered last year compared to 3.6 million in Canada

I won’t go through everything but you can see some of the basic information
About 10% of beef exported from the US and a much larger percentage of Canadian beef is exported by comparison

## Part I – Estimating BSE risk:                                    Potential exposure pathways in U.S. and Canada

- Imports from BSE countries of:
- A.  Live animals
- B.  Mammalian-derived feed ingredients
- Meat and bone meal, meals, etc.
- C.  U.S. and Canada – bilateral imports / exports
- Has implications for movement of potentially infected cattle and contaminated products
- Focus on imports from:
- U.K.  -  since 1980
- BSE countries - since 1986

**Notes:**
When looking at the potential pathways by which BSE might be introduced into the United States or 
Canada we look at 3 pathways 
Live animals
Mammalian-derived feed ingredients and
US/Canadian imports exports across borders.

The focus on imports from outside North America focused on UK cattle and cattle products since 1980 and imports in BSE countries since 1986.

## Potential Exposure Pathways – Live AnimalsA. Cattle Imports from United Kingdom

|  | U.S.A. | Canada |
| --- | --- | --- |
| Total Animals imported | 334 | 288 |
| Disposition known | 161 | 182 |
| Imports from UK farms with known BSE cases | 0 | 10 |
| Disposition unknown | 173 | 106 |
| BSE positives (1993)          cow from U.K. |  | 1 |

**Notes:**

Many of you have probably seen these statistics of cattle imports from the United Kingdom into
The United States and Canada
A total of 334 animals imported into the US from the UK and 288 from Canada
Disposition of more than 50% of these animals for the US and Canada is known – many did not enter the human food supply but could have entered the feed supply.

Of imports from UK farms with known BSE cases 10 of these animals were imported into Canada.

The disposition of the remaining animals is unknown – and they may or may not have entered the human food chain or feed chain.  
It is important to emphasize that we don’t know whether any of these animals were infected with BSE--- 
There is a small possibility that some of these animals were infected.  The herd prevalences of BSE at the height of the epidemic was around 0.1% 

We do know that one infected animal was identified in 1993 in Canada and was imported from the UK

In May 2003 BSE was diagnosed in a cow in Canada. And a Case was identified in the U.S. in September – in a cow imported from Canada.

It is important to say that many of these animals were imported into North America before 1990 when the BSE epidemic was underway.  They would have likely been processed before the feed ban and if any diseased animals entered the system the disease could have spread. 
It is difficult to say with confidence if such events occurred – whether BSE may have been introduced – and whether other animals may have been infected in North America.

## Potential Exposure Pathways – Live Animals A. Cattle Imports from BSE countries

|  | U.S.A. | Canada |
| --- | --- | --- |
| Total Animals imported 1980 - 2002 | 1,671 | 633 |
| Imports Ireland / Europe before 1986 (low risk) | 521 | 298 |
| Total Animals imported from U.K. since 1980 | 334 | 288 |
| Other BSE countries      since 1986 | 816 | 47 |

**Notes:**
Total imports of cattle from BSE countries – are 1671 imported into the US and 633 into Canada

This slide includes animals from the UK discussed before and 
several hundred low risk animals (POINT) imported from Ireland and Europe prior to 1986
And animals imported into the US and Canada are shown on the bottom line 
AGAIN THE STATUS OF THESE IMPORTS IS UNKNOWN – They likely did not have BSE but there is a small chance some may have

## Potential Exposure Pathways – Feed B. Feed ingredients  from BSE countries

**U.S.**** **
- feed meal imports from UK since 1980 – total 81 tons
- 12 tons in 1981
- 10 tons in 1984
-  2 tons in 1985
- 20 tons in 1989 (Disputed by U.S. authorities)
- 37 tons in 1997
- U.S.A. imported ~10,500 metric tons of inedible meat byproducts from 1980-2000 from BSE countries
**Canada**
- reported no MBM imports from UK since 1980.
- Canada imported ~8,523 metric tons of mammalian flours, meals, meat pellets from 1993-2000 from Denmark, Germany, Japan & France.

**Notes:**

Moving on to feed ingredients as a possible exposure pathway.

For the most part many of these feed ingredients are relatively low risk.

The US did receive small shipments of feed meal  ( an estimated total of 81 tons) from the UK and shipments of 10,500 metric tons from other BSE countries.  Again, the BSE risk associated with these products is difficult to estimate.

Canada reports no Meat and bone meal imports from the UK since 1980 and 8,500 tons of mammalian meals and product from European BSE countries.

Overall, these feed products could pose a risk of containing BSE agent – however that risk for many of these products is unknown but thought to be low.

## Cattle and beef trade in North America

- Considerable movement of animals, feed ingredients, and beef products
- Trade and production practices similar for each country
- Import/export could introduce or spread infected animals or contaminated products

**Notes:**
Discussing the third pathway –
It is a North American pathway – that is the exchange of live cattle and ruminants across the US/Canada border.

There is considerable movement of animals feed and beef across the borders
 production practices are similar in each country and many of the same producers have facilities in both countries.

This integration is important to consider – and can serve to spread the infected animals and contaminated products – that is -  if there is risk   - it could be spread /

## C.  Cattle trade in North America        U.S. Cattle imports and exports 1992 to 2002

**Notes:**
This slide shows US cattle imports which for 2002 were at approximately 170,000 head imported.  Also over the last few years imports from Canada have been increasing. (POINT)

Far fewer animals were shipped from the US to Canada. (POINT)

## C.  Beef trade in North America     U.S. Beef imports and exports 1992 to 2002

**Notes:**
As for beef imports into the US – this graphic indicates that beef imports have been increasing (POINT) 
At over 350,000 metric tons last year.  

Conversely the amounts going into Canada are lower  - around 60,000 metric tons annually- and have been pretty constant over the decade (POINT)

To briefly summarize there is significant exchange of animals and beef between the US and Canada 
That process could have an influence on BSE  risk for each country – potentially spreading or shifting the risk around – or between countries. 

## Conclusions Part I: Estimating BSE risk U.S. and Canada 

- Difficult to estimate absolute risk for U.S. and Canada
- Most potential for introduction of BSE agent would have occurred prior to 1990
- Potential amount of BSE agent introduced unknown
- Numerous chance events would be involved over last 10 to 15 years
- Rendering
- Fed to other cattle, dead on farm, etc.
- Imports of live animals and feed materials from BSE countries occurred since 1980 but was small
- Qualitative estimate of risk predicted to be low but difficult to estimate with certainty

**Notes:**

Given that any potential introduction of BSE agent may have occurred prior to 1990 it is difficult to estimate the absolute risk for each country.
It is difficult to quantify the probabilities of introduction or the quantities of BSE agent involved 
Also given the myriad of potential chance events involved it is difficult to say if the disease was introduced, how it might have spread or not spread, etc.

Given the number and percentages of live animals and feed ingredients imported from BSE countries was very small 
Qualitatively one could assume that the predicted risk would be small – but that would be an assumption with some uncertainty.

Given the recent identification of cases in Canada and the US.  It is certain the disease was introduced albeit it seems to be at a low level.  

## Part II – Estimating BSE exposure and risks for the US population

- Many potential routes for human exposure to beef and bovine products
- Primary source of potential BSE exposure
- Food
- High risk tissues – brain, spinal cord, eyes, dorsal root ganglia, small intestine
- Other sources
- Dietary supplements
- Medical products – devices, biologics, drugs

**Notes:**
Moving beyond the BSE risks to cattle 
We then proceeded to estimate the BSE risk for the US population
There are a few major pathways by which human exposure to the BSE agent could occur
We divided the pathways into food and other sources such as medical products.

We focused on estimating the food associated risks since those seem to be the primary source of potential 
BSE exposure 
Of interest are exposures to high risk tissues such as bovine brain, spinal cord, eyes, dorsal root ganglia and small intestine that might be present in food.

Other potential sources of exposure include dietary supplements which can contain high risk bovine materials and medical products such as devices, biologics, and drugs. We did not estimate the risks for these products in this current analysis.

## II.  BSE exposure pathways        	for US population via beef

- A.  Consumption of _large_ amounts high risk   	tissue (very low probability event)
- Bovine brain or spinal cord
- B.  Consumption of _small_ amounts high risk 	tissues 	in processed foods
- Advanced meat recovery beef product
- Ground beef products, beef sausages, hot dogs, processed meat sauces, etc.

**Notes:**
Exposure pathways for beef products could be divided into 2 categories.  
First – where there is consumption of large amounts of high risk tissue such as the brain or spinal cord (POINT)
Examples include bovine brain and spinal cord – in an  infected animal these two tissues contain ~90% of infectivity.
Brain and spinal cord are high risk tissues that might be eaten in large portions and could pose a risk of a large exposure if derived from an infected animal.  We would assign this as a low probability event with potential for high exposure.

Second – where small amounts of high risk tissue may get into processed beef products. (POINT)
Examples include Advanced meat recovery product – which is found in sausages, hot dogs and other processed beef products.
We would say that this is a higher probability of eating AMR since it is in so many processed beef products..... But the amounts of high risk tissue that might be present would be residual and present in tiny amounts.

##  II.  BSE exposure pathways        	for US population via beef

- U.S. risk
- Probability of exposure to infected cow in 2003
- 1 positive identified – 35 million slaughtered
-                      1 in 35 million   (3.5 x 10-7 )
- Worst case – Based on statistical analysis USDA surveillance (~20,000 tests)
- 			   ~1 in 1 million   (1 x 10-6)

**Notes:**
To estimate potential risk of BSE – we know that in 2003 that 1 animal was positively identified with BSE in the US
That gives us a minimal incidence of 1 in 35 million or 3.5 x 10-7.  
As a worst case we assumed based on estimates by USDA for their surveillance program that a maximum rate might be 1 in 1 million or 10-6.  
Again that 1 in 1 million is an assumption with significant uncertainty.

So this provides us with a potential minimum and maximum range for 
the risk of BSE exposure of (3.5 x 10-7 to 1 x 10-6) in 2003 in the U.S.

## A.  Consumption of large amounts 	high risk tissue: bovine brain

- Probability of exposure: brain rarely consumed by Americans (100,000 – 180,000 servings)
- Many servings from low risk cattle – calf brains, etc.
- Probability infected brain  in 2003     3.5 x 10-7   to  10-6
- Quantity of exposure:  assume brain late stage BSE-infected cow 5,000 to 6,500 cattle oral ID50
- Conclusions:**  **
**   **There is risk of exposure via this route     	         Risk to the U.S. general population is low

**Notes:**

Taking an example of consuming bovine brain – 
We do know that people do consume brain we estimated from consumption surveys that this might be approximately 100,000 to 180,000 servings on an annual basis.

If a person consumed an entire cattle brain of a late stage animal they might consume >5,000 cattle oral ID50s
This would put the person at significant risk of infection – especially if they were susceptible to the agent.

However, the probability of consuming a brain from an infected animal in the US is very remote – 1 in 35 million to 1 in 1 million.

Given that exposure would be on an individual level the risk to the US general population would be assumed to be low.

## B.  Consumption of small amounts      high risk tissue: advanced meat recovery

- Advanced Meat Recovery (AMR):
- Removes remaining meat from carcass, vertebral column and bone by machinery
- Spinal cord usually removed before process
- Dorsal root ganglia on vertebral column
-  > 70% of carcasses processed with AMR
- Process would mix and dilute residual BSE agent present

**Notes:**
The second type of potential exposure might occur through beef product produced through Advanced meat recovery processing.  This is a process that removes remaining meat from the carcass and vertebral column and bone by machinery.  Usually spinal cord is removed from the vertebral column but dorsal root ganglia can remain. 

It is estimated that greater than 70% of carcasses are processed in this manner.

AMR machines process 4,500 lbs or more of bone an hour  - from 15 or more animals simultaneously.  The issue here is that if carcass material from one infected animal goes into the machine the entire batch of product can potentially become contaminated.

An important factor to remember as I go through this example is that AMR will mix and dilute materials and BSE infectivity to a significant degree.  For our example we assume homogeneous mixing of materials and infectivity throughout a batch of AMR product.

## B.  Consumption of small amounts      high risk tissue: advanced meat recovery

- Machines can process 4,500 to 7,000 lbs bones per hour
- Represents material from 20 to >35 animals
- 5 – 10 lbs meat recovered per carcass
- Estimated as much as 250 million lbs AMR meat produced annually

**Notes:**
AMR machines can process 4,500 to 7500 lbs of bones an hour  - representing bones from many animals.
Anywhere from 5 to 10 lbs of meat is recovered per carcass.

Estimates suggest that as much as 250 million lbs of AMR meat is produced annually

## B.  Consumption of small amounts      high risk tissue: advanced meat recovery

- Probability of exposure: advanced meat recovery (AMR) product consumed frequently
- Dilution of BSE infectivity throughout a batch of AMR product
- Probability infected cow in 2003
- 3.5 x 10-7   to  10-6   annually
- Amount BSE infectivity present – estimated to be low because of dilution via AMR
- Estimate ~ < 2 x 10-2  (<4 x 10-3 to 2 x 10-2) cattle oral ID50 per average serving
- Greater than a hundred of servings from                            each batch of AMR product

**Notes:**
As I said before AMR has a diluting effect on materials in the system..

Again we had estimated a probability of an infected cow in 2003 as being 3.5 x 10-7 to 1 x 10-6.

I don’t have time to go through the calculations but our preliminary estimates suggest that the amount of BSE infectivity estimated to be present in a serving of AMR beef from a cow 
would be less than < 2 x 10-2 cattle oral ID50s

At this point it is important to emphasize that at levels of 2 x 10-2 cattle oral ID50s or less are very small and unlikely to cause infection in a human.

There are a hundred or more food servings that could come from a batch of AMR

And the calculations are shown for the risk per serving in the next slide.

## B.  Consumption of small amounts      high risk tissue: advanced meat recovery

**Assuming BSE infected animal(s) enter AMR and residual infectivity present in vertebral column:**
- Probability exposure via AMR is low
- 1 x10-7  to  2 x10-5 per serving beef AMR product per year
-  Probability of infection even lower
- Assuming a species barrier of 1,000
- Reduction by oral route of >90%
- Assume ~40% population sensitive - methionine homozygous at codon 129 of PrP
- Probability of infection would be estimated to be less than        < 3 x10-9  (2 x10-10  to  3 x10-9) annually in the U.S.

**Notes:**
We calculated the probability of exposure via AMR again assuming anywhere from 1 in 35 million infected cows and a worst case of 1 in 1 million animals may have entered the food supply.

The initial estimates of risk of exposure to  <10-2 cattle oral ID50s is 10-7 to 2 x 10-5 per serving of beef annually. (POINT)  because the estimate is derived using some assumptions in the calculations there is significant uncertainty in these estimates.

It is important to emphasize that level of agent predicted to be present would be very small.

Also, as we go on with the calculation we can’t assume that exposure will necessarily lead to infection
We assumed that the species barrier would lower the risk by 1000 fold.  There would also be reduction by the oral route in efficiency of infection that would lower risk by greater than 90%.
Furthermore only an estimated 40% of the population may be susceptible.  To date the vCJD cases have all seen homozygous for methionine at position 129 of the PrP protein – again that phenotype is only seen in about 40% of the population.
There are also other factors that may influence host susceptibility to BSE infectivity .

To move from estimates of exposure to estimates of infection  - 
The model estimates the probability of infection in the US would be less than 3 x 10-9
Again I need to emphasize that there is significant uncertainty in these estimates.

## B.  Consumption of small amounts      high risk tissue: advanced meat recovery

- Conclusions
- Our preliminary estimates suggest that there is a  low risk of human exposure to BSE agent via beef AMR product
- Probability of human infection even lower
- There is uncertainty in the estimates and some assumptions were made to estimate the risk
- Risk to general population and blood supply is low

**Notes:**
We have generated very preliminary estimates of risk here in this analysis
With all models and with BSE models especially – because assumptions about various parameters are made – the risk estimates have a significant degree of uncertainty associated with them.  

Additional development of the model and data are needed to refine and improve the risk estimates.

Our preliminary estimates suggests that there is a potential for very low levels  of human exposure to the BSE agent

However the probability of human infection would presumably be several orders of magnitude lower.

The analysis does offer some insight into the potential magnitude of risk in the United States for the general population.  

Based on these very preliminary and somewhat uncertain risk estimates it seems that the risk to the general population is low.

Similarly we can assume that the risk for blood donors, recipients and the blood supply are also low.

## Recent BSE risk-reduction measures for food supply & feed

- Should dramatically reduce small BSE risk for U.S.A.
- Recent USDA measures Dec 30, 2003 prohibit:
- Use of “downers” for human food
- High risk tissue in AMR
- Use of animals >30 months  in AMR
- January 2003 FDA feed ban prohibits:
- Ruminant blood protein in feed
- Plate waste, poultry litter
- Requires dedicated feed processing lines for non-prohibited and prohibited feeds

**Notes:**

The further risk reduction measures being put in place should further reduce the BSE risk in the future for cattle and the human population in the United States.

The recent USDA measures should further reduce the small risks for AMR processing and downers.

The FDA feed ban should further limit any exposure of cattle to the BSE agent and prevent its spread.

With that I will end with a last slide.

## Acknowledgements

- Dr. Sonja Sandberg (OBE)
- Rene Suarez-Soto (OBE)
- Dr. David Asher (OBRR)
- Dr. Rolf Taffs (OBRR)
- Dr. Pedro Piccardo (OBRR)
- Others at CBER

**Notes:**
Id like to thank the following for their help with the analysis

## Slide 23

**Notes:**
Overall 

Risks would seem to be low but there is a lot of uncertainty with this estimate

Doing a rough comparison to the UK situation

An estimated 180,000 animals were diagnosed with BSE – estimates suggest that up to 750,000 animals 
May have entered the human food supply
A decade or so after that there are approximately 140 cases of vCJD in the UK

The United States has 1 confirmed cow – maybe more entered the food supply
By rough comparison we have 3 or 4 orders of magnitude fewer BSE animals that may enter the human food supply
One could assume that the probability of infection in humans in the US might be similarly 3 or 4 orders of magnitude less and that theoretically we may not see a case of vCJD or if we did that number would be very low

## Factors considered in estimation

- Total cattle slaughtered annually
- 70% - 80% processed via AMMR
- # animals/batch
- 5-9lbs AMR per Animal
- Percentage lost to imports, waste, non-use
- Conversion lbs to servings
- Total est AMR meat servings /yr
- Servings AMR meat contaminated/Total AMR servings per yr
- And / or
- Dilution of ID50s from 1 cow in a batch of AMR

**Notes:**
These are the factors considered in the estimates