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BSE Surveillance in the USA

BSE Surveillance in the USA. Guy H. Loneragan, BVSc, PhD Epidemiologist – Feedlot Research Group West Texas A&M University Canyon, Texas, USA Risk Management of Bovine Spongiform Encephalopathy U.S. MEAT EXPORT FEDERATION Mexico City, Mexico, 22 June 2005. Outline of Presentation.

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BSE Surveillance in the USA

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  1. BSE Surveillance in the USA Guy H. Loneragan, BVSc, PhD Epidemiologist – Feedlot Research Group West Texas A&M University Canyon, Texas, USA Risk Management of Bovine Spongiform Encephalopathy U.S. MEAT EXPORT FEDERATION Mexico City, Mexico, 22 June 2005 West Texas A&M University

  2. Outline of Presentation • Background BSE material • Epidemiological overview • What animals to target? • Enhanced Surveillance Program • Target Animals • Diagnostic Methods • Results • Interpretation of results • Future of Surveillance in the USA West Texas A&M University

  3. Background BSE Material • BSE is a much-studied and well-characterized disease. • Substantial understanding exists about: • The causative agent and its detection; • Pathogenesis and transmission; and • Epidemiology and effective control strategies. • Primary, if not only mode of BSE transmission is consumption of contaminated feeds. • No demonstrable horizontal transmission. • Unlike Scrapie and CWD. West Texas A&M University

  4. Background BSE Material • Classical BSE results from a point-source/common-source exposure to in-feed infectivity. • Theoretically, epidemiology of disease is fairly straightforward. • Much of the descriptive epidemiological information is obtained from BSE surveillance programs. • Data often used in predictive modeling. • Surveillance is a cornerstone component of national/regional BSE risk management. West Texas A&M University

  5. Background BSE Material • Appropriately designed surveillance is used for: • Detection of disease. • Demonstration of historical exposure. • Estimation of prevalence. • What is the burden of BSE in a country/region? • Evaluation of effectiveness of control measures. • When was the animal born. • What is the estimated incubation period? • Provide data for national/regional risk assessment. • Surveillance is reliant on appropriate use of tests and an understanding of their limitations. West Texas A&M University

  6. Surveillance • Testing does not protect human or animal health • SRM removal and feed bans do this if infectivity is present. • Testing is for surveillance purposes. • Some countries used tests to restore consumer confidence • Not science-based application of testing. • Extensive evidence suggests testing all animals is inefficient at finding cases. • Not supported by epidemiological data. • Expensive. • Impractical in a test-and-hold situation. • Poor surveillance yield. West Texas A&M University

  7. Surveillance Image: USDA:APHIS • Targeted selection of animals for BSE surveillance is largely dependent on limitations of diagnostic test. • Current tests: • Tissue samples collected postmortem. • No validated antemortem test. • Rely on detecting accumulated protein-resistant prion protein (PrPsc, PrPres) in brain tissue. • In classical BSE, > PrPsc accumulation in obex region of brainstem. • Current tests can only detect PrPsc in: • Animals a few months prior to clinical signs (i.e., pre-clinical). • Clinical cases. Image: Weybridge TSE Reference Laboratory West Texas A&M University

  8. Surveillance • If BSE present, 3 groups of animals in population: 1. Non-infected (majority); 2. Infected but not detectable (i.e., prior to the pre-clinical/clinical stage of disease); • Tests won’t identify these animals. • If live long enough, these animals move into: 3. Pre-clinical/clinical group. • Detectable using current tests. West Texas A&M University

  9. Surveillance • Infection and progression of BSE 5 to 8 years old ~1 year old Birth Period of greatest Susceptibility Long incubation period Pre-clinical Clinical Time West Texas A&M University

  10. Surveillance • Detectable PrPsc, i.e., BSE positive in surveillance Detectable with current tests 5 to 8 years old ~1 year old Birth Period of greatest Susceptibility Long incubation period Pre-clinical Clinical Time West Texas A&M University

  11. Animals to Target • An appropriate surveillance program should target animals from the adult population; • Only 1.4/1000 cases in peak of UK epidemic <36 months old. • No animal <30 months of age detected since 2001 in EU. • Data from EU indicates BSE cases 20 to 30 times more likely in animals with: • CNS clinical signs. • 4Ds (adult diseased, distressed, downers, dead on farm). • This represents the High-Risk population that should be targeted in surveillance. • i.e., to detect BSE, most likely to find it in high-risk cattle. West Texas A&M University

  12. USA Surveillance Program • Began in May, 1990. • Originally targeted animals with CNS lesions. • Expanded to include all high-risk adults. • OIE recommends testing 433 samples with an adult population of 40 million. * ** * BSE detected ** To May 31, 2004 USDA:APHIS. http://www.aphis.usda.gov/lpa/issues/bse/surveillance/figure2f.html West Texas A&M University

  13. USA Surveillance Program • Goal of surveillance was detection. • The surveillance program was not designed to estimate prevalence of BSE. • Sampling was not random. Rather, it targeted the high-risk population. • All tests used a diagnostic method called immunohistochemistry. • Takes several days to perform tests. • Detected a case of BSE in December, 2003. West Texas A&M University

  14. Expanded USA BSE Surveillance • USDA designed Expanded Surveillance Program. • One-time intensive effort to: • Detect BSE if at a very low level. • Provide information about prevalence. • (http://www.aphis.usda.gov/lpa/issues/bse_testing/plan.html) • Sample as many as possible from high-risk: • Cattle exhibiting signs of a CNS disorder; • Nonambulatory cattle (downer); • Cattle with other signs assoc. with BSE (diseased/distressed). • Dead cattle. • Samples to be collected over a 12- to 18-month period beginning 01JUN04. West Texas A&M University

  15. Expanded USA BSE Surveillance • There are ~45 million adult cattle in USA. • Desire to detect BSE (detectable) if occurs at 1/10 million in adult population. • i.e., ~5 cases during expanded surveillance program. • Assumption is that these cattle will be in high-risk group. • 20 to 50 times more likely according to EU/Japan. • High-risk population is ~ 1% of adult population. • Similar to estimates in other countries. • ~450,000 animals. West Texas A&M University

  16. Expanded USA BSE Surveillance Plan: • Not to sample from the 45 million adults. • Very inefficient use of resources. • Targeted sampling from the 450,000 high-risk population. • Most efficient method to find cases if they exist. West Texas A&M University

  17. ~1% of adult Population. 450,000 animals Target at least 268,500 animals Adult population 45 million cattle High-risk population Surveillance testing • Need to sample ~268,500 cattle from high-risk population (450K) to detect at least 1 of the 5 cases if present. • With 99% confidence (Cannon and Roe. Livestock Disease Surveys, 1982) • APHIS planned to test this number or more in 12-18 months. Sample BSE cases if present BSE cases assumed to be in high-risk population Very inefficient to test healthy adult cattle West Texas A&M University

  18. Expanded USA BSE Surveillance • 7 regional laboratories accredited and testing. • Plus NVSL in Ames, Iowa. • Ultimately, 8 laboratories have performed the tests. • At least 268,500 or more over a 12- to 18-month period of time beginning June 1, 2004. • Regional targets established in terms of number of samples needed. • Approximately representative of adult cattle populations within regions. West Texas A&M University

  19. Northeast 35,173 North central 44,876 Northwest 36,309 Southwest 51,394 South central 66,977 Southeast 33,764 Regional Approximate TargetsBased on goal of 268,500 samples Source of data: http://www.aphis.usda.gov/lpa/issues/bse_testing/test_results.html West Texas A&M University

  20. Expanded USA BSE Surveillance • Aggressive approach to collect samples • Voluntary program; samples collected from: • Rendering plants. • Packing plants. • On-farm. • Public health/Veterinary Diagnostic laboratories. • 3D/4D plants (e.g., pet food manufacturers). • Historically, USDA used immunohistochemistry on all samples. • Not practical for test-and-hold policy. • Uses a rapid (automated) screening process. West Texas A&M University

  21. Tests Used in USA • All tests used in US detects accumulation PrPsc. • Tests: • Screening test (rapid, automated): • ELISA. • Designed to identify suspicious (inconclusive) samples for further confirmatory tests. • False positives possible/probable from time to time. • Screening casts a wide net to detect any possible case. • Confirmatory tests: • Immunohistochemistry. • Western blot (proprietary and OIE SAF Immunoblot). West Texas A&M University

  22. ELISA. BioRad Fresh/frozen Sample Proteinase K Material transferred to plates pre-coated with primary antibody Homogenized PrP destroyed PrPsc remains 2nd antibody PrPsc Positive 1st antibody Secondary antibody added. Has enzyme Chemical added Wells washed West Texas A&M University

  23. ELISA. BioRad Fresh/frozen Sample Proteinase K Material transferred to plates pre-coated with primary antibody Homogenized PrP destroyed PrPsc remains 2nd antibody PrPsc Positive 1st antibody Secondary antibody added. Has enzyme Chemical added Wells washed Negative West Texas A&M University

  24. 1 2 3 Western Blot Fresh/frozen Sample Proteinase K Material transferred to a gel plate and an electrical charge is applied to plate to move charged proteins Homogenized PrP destroyed PrPsc remains Purification e.g., centrifuge - - - - - After applying electric field, gel is ‘blotted’ onto a membrane. Antibodies applied. + + + + 1 2 3 Washed Reaction read Image: Dr. Bruno Oesch, Prionics AG, Switzerland West Texas A&M University

  25. Immunohistochemistry • Formalin-fixed tissue sample. • Taken from obex region of brainstem. • Thin sections (3m) cut & mounted on microscope slides. • Autoclaved overnight. • Anti-prion antibody applied (primary antibody). • Apply secondary antibody. • Coupled with enzyme to effect color change when substrate added. http://www.oie.int/eng/normes/mmanual/A_00064.htm West Texas A&M University

  26. IHC BSE IHC Normal http://niah.naro.affrc.go.jp/.../ BSE/BSE-Chiba-En.html http://www.neurocenter-bern.ch/bse_e.shtml West Texas A&M University

  27. Results West Texas A&M University

  28. Number of Samples Collected Program development Seasonal peak in marketing of cull animals + * * * Inconclusive – confirmed negative. + Inconclusive – pending. West Texas A&M University

  29. Number of Samples Collected 388,309 cattle tested 1 result is pending + * * * Inconclusive – confirmed negative. + Inconclusive – pending. West Texas A&M University

  30. Number of Samples Collected 388,309 cattle tested 1 result is pending Minimum number of samples for a 12- to 18-month period + * * * Inconclusive – confirmed negative. + Inconclusive – pending. West Texas A&M University

  31. Northeast 35,173 North central 44,876 Northwest 36,309 Southwest 51,394 South central 66,977 Southeast 33,764 Regional Approximate TargetsExceeded targets in many regionsProjected to exceed targets in ALL regions Source of data: http://www.aphis.usda.gov/lpa/issues/bse_testing/test_results.html West Texas A&M University

  32. Inconclusive Results • 3 inconclusive results: • Week 4 (25JUN04) • Weak reactor on first run using ELISA screening test. • Negative on IHC and Western blot. • Week 5 (29JUN04) • Weak reactor on first run using ELISA screening test. • Negative on IHC and Western blot. [Changed protocol to repeat ELISA if positive on first run. Manufacturer’s instructions, 04AUG05] • Week 25 (18NOV04) • First and duplicate strong reactor. • ELISA-positive at NVSL. • IHC negative (NVSL, 25NOV04). • Western blot reactor (10JUN05). West Texas A&M University

  33. 18NOV04 Inconclusive Result • Because of conflicting results, sample sent to international TSE reference lab in Weybridge, UK (16JUN05). • Tests to be run: • Weybridge: • IHC, OIE WB, NaTTa WB, Prionics WB. • USDA: • IHC, BioRad ELISA, IDEXX ELISA, OIE WB, DNA sequencing of prnp gene. • Results soon… West Texas A&M University

  34. 18NOV04 Inconclusive Result • Collected from: • Beef breed of animal. • Not a dairy breed. • Born before the August, 1997, FDA Feed Ban. • No indication it was imported into US. • Native-born to US. • Carcass was incinerated. • No part of the animal entered: • Human food supply. • Animal (e.g., pet) feed supply. West Texas A&M University

  35. Results • In excess of 388,309 high-risk animals tested. • Of high-risk animals tested elsewhere: • Japan detected 1.8 BSE cases per 10,000 tests. • Number excludes dead on-farm animals. • EU detected 6.0 BSE cases per 10,000 tests (2003). • Pending current analyses, US has detected either: • 0.0 BSE cases per 10,000 tests. • 0.026 BSE cases per 10,000 tests. West Texas A&M University

  36. Results • All 4 Canadian cases and current US suspect were born prior to or at the time of feed ban implementation. • Epidemiological investigation (Canada) indicated exposure to feed produced prior to ban. • Recent estimates of compliance are excellent. • If US suspect confirmed as classical BSE, then presumption is similar. • That is, exposed to infected feed prior to ban. West Texas A&M University

  37. Implications • BSE burden in US (& Canada) is extraordinarily low. • No evidence that infective agent has been propagated since the feed ban. • i.e., long incubation period (low dose), no younger cases. • If BSE present in US, it is becoming even rarer. • Testament to controls established in US (and Canada). • Feed ban implemented ~6 years prior to detection. • Pro-active approach unlike many other countries that have experienced BSE. West Texas A&M University

  38. Implications • ‘Interlocking, overlapping, and sequential’ control barriers are working. • Redundancy built into mitigation strategies. • Mitigations include: • Live animal import restrictions (UK: 1989; EU: 1997). • Feed Ban (August, 1997). • Active surveillance (since May, 1990). • Expanded program includes ‘test and hold’. • SRM removal. • Slaughter and harvesting practices. • Stunning, MSB, nonambulatory animals banned. • North American (Mexico, US, Canada) BSE harmonization framework. • Equivalent risk mitigation in each country. • Developed April, 2005. West Texas A&M University

  39. Future of Surveillance • Expanded surveillance will continue at least until regional targets are met. • All targets will be exceeded by 18 months. • Some will be exceeded by > 100%! • Future will depend on: • Outcome of ongoing intensive assays of samples from suspect cow. • If more BSE cases are identified. • May be possible to target limited regions for continued intensive surveillance. • While reducing intensity in others??? West Texas A&M University

  40. Special thanks to Questions? Acknowledgements: Dr. Terry F. McElwain, WSU WADDL Dr. Bruno Oesch, Prionics AG, Switzerland Dr. Brian J. McCluskey, USDA:APHIS:VS Dr. Bruce A. Wagner, USDA:APHIS:VS Dr. William D. Hueston, Univ. of Minnesota Dr. Srinand Sreevatsan, Univ. of Minnesota West Texas A&M University

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