Analysis to inform decisions evaluating bse
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Analysis to Inform Decisions: Evaluating BSE. Joshua Cohen and George Gray Harvard Center for Risk Analysis Harvard School of Public Health. Contributors. Harvard Center for Risk Analysis Joshua T. Cohen Keith Duggar George M. Gray Silvia Kreindel

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Analysis to Inform Decisions: Evaluating BSE

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Analysis to inform decisions evaluating bse

Analysis to Inform Decisions:Evaluating BSE

Joshua Cohen

and

George Gray

Harvard Center for Risk Analysis

Harvard School of Public Health


Contributors

Contributors

  • Harvard Center for Risk Analysis

    • Joshua T. Cohen

    • Keith Duggar

    • George M. Gray

    • Silvia Kreindel

  • Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University

    • Hatim Gubara

    • Tsegaye HabteMariam

    • David Oryang

    • Berhanu Tameru


What usda asked us to do

What USDA Asked Us to Do

  • Identify and characterize possible sources for BSE (or a TSE disease with similar clinical and pathologic signs as BSE - will refer to as BSE for brevity) infectivity in U.S. cattle

  • Identify and characterize pathways for cattle-derived BSE infectivity in the U.S. cattle herd or human food supply

  • Evaluate implications over time of possible introduction of BSE into US system


Why we chose a simulation approach

Why We Chose a Simulation Approach

  • No historical data - build understanding up from biology, agriculture, etc.

  • Time matters - e.g., incubation period of BSE

  • Allow quantitative comparison of importance of different pathways of spread and different risk management

  • Can help focus collection of information


Learning from uk experience

Learning from UK Experience

We assume the prevailing hypothesis of UK BSE spread is correct:


Model overview

  • Infectivity Sources

Cattle Population

Number Infected

Number Clinical

Death and Disposal

Feed Administered to Cattle

Slaughter

Disposal

Human Food

Death / Rendering

Rendering and

Feed Production

Other Uses and Elimination from System

Other Protein Sources

Model Overview


Cattle dynamics

Cattle Dynamics


Key assumptions susceptibility

Key Assumptions - Susceptibility


Infectivity level in bovine vs time since infection

Infectivity Level in Bovine vs. Time Since Infection


Distribution of infectivity

Distribution of Infectivity

Relative Infectivity of Specific Tissues Specified from an Infected Bovine(Based on [SSC, 1999a])a


Slaughter process

Out

Out

Out

Antemortem Inspection

Sick Animal Characteristics

Stunning

Exsanguination

Disposition of Brain

Tissues for Possible Human Consumption

AMR/ Spinal Cord/DRG

Postmortem Inspection

Splitting

Tissues to rendering

Processing

Out

Out

Slaughter Process


Rendering and feed production

6

12

3

Prohibited

MBM production

Prohibited

feed production

7

2

1

13

4

9

10

5

Tissues to rendering

Feeding of cattle on farm

14

Non-prohibited MBM production

Non-Prohibited feed production

8

3

11

6

12

Blood

12

Rendering and Feed Production


Analyses

Analyses

  • Base Case

    • Assume BSE not currently present in U.S.

    • Introduce 10 BSE infected animals (also simulated importation of 1 to 500 BSE infected cows)

    • Follow for 20 years

  • Example Risk management Options

    • Ban on rendering cattle that die on farm

    • UK-style “Specified Risk Material” ban

    • Test with introduction of 10 infected animals and follow for 20 years

  • Others

    • Potential for pre-1989 imports from England to introduce BSE to U.S.

    • Switzerland

    • Spontaneous

    • Scrapie as source


Model is probabilistic

Initialize Model

Run 1000

Run Simulation

Run 3

Record Results

Run 2

Run 1

Model is Probabilistic

Number of Infected

Cattle over 20 Years


Results base case

Results: Base Case

  • Few new cases of BSE

    • mean = 3 and 95th percentile = 11

    • Primarily through feed ban leaks

    • 40% of animals predicted to die on farm introduce 96% of infectivity to system

  • BSE gone within 20 years of introduction


Base case results continued

Base Case Results(continued)

  • Little infectivity for potential human exposure (mean 35 cattle oral ID50s, 95th 170)

    • Brain26%

    • Beef on bone11%

    • AMR meat56%

    • Spinal cord5%

  • Conservative assumptions (e.g., no change if case detected)


Base case summary

Base Case – Summary


Base case summary1

Base Case - Summary


Base case summary2

Base Case - Summary

Number of Cattle Infected:

Probability of Prevalence Value Exceeding Zero


Base case summary3

Base Case - Summary

Number of Cattle Infected: Range of Prevalence Values


Base case summary4

Base Case – Summary

Number of Cattle Clinical: Probability of Prevalence Exceeding Zero


Base case changes over time

Base Case – Changes Over Time

Number of Cattle Clinical:

Range of Prevalence Values


Model predictions for more substantial imports of infected cattle

Model Predictions for More Substantial Imports of Infected Cattle

250

Additional Infected Cattle

200

150

100

50

0

0

100

200

300

400

500

600

Number of BSE-Infected Cattle Imported


Model predictions for more substantial imports of infected cattle1

2500

2000

1500

1000

500

0

0

100

200

300

400

500

600

Model Predictions for More Substantial Imports of Infected Cattle

Number of ID50s Available for Potential Human Consumption

Number of BSE-Infected Cattle Imported


Key sources of uncertainty influencing the predicted number of infected cattle

Key Sources of Uncertainty Influencing the Predicted Number of Infected Cattle


Analysis to inform decisions evaluating bse

Key Sources of Uncertainty Influencing Predicted Human Exposure(ID50s Available for Human Consumption)


Key management points

Key Management Points

  • Spread in cattle herd

    • Mostly due to leaks in FDA feed ban and some maternal transmission

    • Animals that die on farm with provide greatest infectivity to animal feed system

  • Potential human exposure

    • Handling of brain and spinal cord in processing very important

    • Primary routes of exposure are cattle brain, spinal cord, beef on bone and AMR meat


Imports from england before 1989

Imports from England Before 1989

  • Evaluated potential for 173 (of 334) English imports not known to have been destroyed to introduce infectivity to U.S. cattle and implications

  • Used information on birth year, export year, animal type and sex, last sighting and more to estimate likelihood and potential magnitude of introductions of BSE infectivity to U.S. cattle feed

  • Used model to look at new BSE cases if introduction of different sizes did occur


Analysis to inform decisions evaluating bse

Cumulative Distribution for the U.S. Cattle Exposure to Cattle Oral ID50s from Animals Imported from the UK During the 1980s


Analysis to inform decisions evaluating bse

Cumulative Distribution for the Number of BSE-Clinical Cattle in the Year 2000 for Different Levels of Infectivity Introduced via Import of UK Cattle During the 1980s


Strengths of analytic approach

Strengths of Analytic Approach

  • Identify key assumptions and data

  • Understand relative importance of different paths

  • Compare relative effectiveness of different risk management measures

  • Facilitates value of information (VOI) analysis to identify critical research areas


Weaknesses of analytic approach

Weaknesses of Analytic Approach

  • Overconfidence in results?

  • Dependent on underlying structure and assumptions

  • Difficulty in calibration/validation

  • What is the alternative?


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