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2005 UNITED STATES ANIMAL HEALTH REPORT BSE Surveillance Since 1990, the U.S. Department of Agriculture (USDA) has taken aggressive measures to prevent the introduction and potential spread of BSE. Following confirmation of BSE in an imported cow in December 2003, USDA designed and implemented an Enhanced BSE Surveillance Program to more accurately determine the level of disease present in the U.S. cattle population. The Enhanced BSE Surveillance Program tested as many cattle as possible in the targeted high-risk population beginning June 1, 2004. Collection at an enhanced level has continued beyond 18 months to ameliorate concerns of trading partners. Experience in the United Kingdom and Europe has shown that, if present, BSE is most likely to be detected in adult cattle exhibiting clinical signs consistent with the disease. In general, the highest risk categories are adult cattle showing clinical signs involving the central nervous system (CNS) and dead and nonambulatory cattle with clinical signs that could not be adequately evaluated. This population was estimated to total 445,886 adult cattle per year in the United States. This number was derived in part from National Animal Health Monitoring System (NAHMS) surveys of livestock producers and other estimates. This estimate includes adult cattle in the following categories: Condemned at slaughter for CNS signs; Moribund, dead, injured, or emaciated (FSIS data 2002); CNS abnormalities reported for FAD investigations (APHIS data 2003); Died onfarm of unknown causes; Lameness or injury that resulted in euthanasia; and Cattle that died with signs of incoordination or severe depression. The sampling strategy was designed to target animals in these categories. Between June 1, 2004, and March 17, 2006, BSE samples were collected from 5,776 unique locations across the United States. These locations included slaughter plants, renderers, farms, public health laboratories, veterinary diagnostic laboratories, and salvage slaughter (3D–4D)1 plants. To determine the extent to which the U.S. surveillance is consistent with OIE guidelines, we have evaluated and classified surveillance data over the past 7 years according to OIE standards (table 5). In May 2005, the OIE general Assembly approved a new chapter and appendix for BSE surveillance. This approach assigned point values to each sample, based on animal age and the subpopulation it was from, and the likelihood of detecting infected cattle of that age in that subpopulation. (Prior to May 2005, OIE had recommended a surveillance level based on the size of the adult cattle population—for the United States that number was 433 samples with clinical signs consistent with BSE per year.) Sample values were classified in the OIE system as belonging to four surveillance strata (streams): clinical suspect, casualty slaughter, fallen stock, and healthy slaughter. Samples were also stratified by age. Cattle were categorized in the clinical suspect stream if they were submitted under the submission types of highly suspicious for BSE, rabies suspects, CNS signs, or antemortem-condemned by FSIS with condemnation codes for CNS signs or rabies. In addition, many samples with a clinical history of signs likely to be associated with BSE were submitted in other categories. Many of these represented valuable samples, but the OIE definition of “clinical suspect” did not readily differentiate them from animals with other clinical signs compatible with BSE. Some of these cattle were subsequently categorized as clinical suspects by comparing the likelihood of finding the signs in histopathologically confirmed cases reported in the United Kingdom2 with the likelihood of finding the signs in uninfected animals from the enhancedsurveillance targeted population. For example, if a sign or combination of signs were found 30 percent of the time in BSE cases but only once in every 1,000 uninfected animals (0.1 percent), then it would be 0.30/0.001 = 300 times more likely to occur in the cases (likelihood ratio = 300 in this case). A likelihood ratio threshold of 807 was established as a cutoff value for determination of clinical suspects. This threshold was estimated using input data from the United Kingdom in the BSurvE3 model, which provided the average (expected) value for the ratio of probability of an infected animal showing clinical signs to an uninfected animal showing clinical signs. Thus, if a sample was submitted from an animal with combinations of clinical signs at least 807 times more likely to have been seen in BSE cases than in the U.S. high-risk population, it was classified as a clinical suspect. Cattle with likelihood ratios below the threshold were allocated into surveillance streams according to the animal’s submission type as follows: Submission types of “Nonambulatory” were classified in the “casualty slaughter” stream; Submission types of “Other clinical signs that may be associated with BSE” were classified in the “casualty slaughter” stream; Submission types of “FSIS antemortem condemned” were classified in the “casualty slaughter” stream as long as the condemnation reason was not “dead”; Submission types of “FSIS antemortem condemned” with a condemnation code of “dead” were classified in the “fallen stock” stream; Submission types of “dead” were classified in the “fallen stock” stream; Submission types of “apparently healthy” were classified in the “healthy slaughter” stream. BSE surveillance samples from 1999 through 2003 were collected before the OIE surveillance streams were established in 2005 and were not submitted with the same clinical history as that used for the enhanced surveillance in 2004–05. In order to apply the OIE point tables, data about these samples were requested from the National Veterinary Services Laboratories (NVSL) and were sorted by Centers for Epidemiology and Animal Health (CEAH) epidemiologists based on the history included with the sample. This information is excerpted from the report Summary of BSE Surveillance in the United States accessed and available on the Web as of May 2, 2006, at printable_version/SummaryEnhancedBSE-Surv4-26- 06.pdf>. Details on the Enhanced BSE Surveillance Program are posted at 2 Wilesmith, J. W.; Ryan, J. B.; Hueston, W. D. 1992. Bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates. Research in Veterinary Science 52(3): 325–331. 3 Available, as of April 20, 2006, at BSurvE tool is a Microsoft Excel™ spreadsheet application designed to estimate BSE prevalence based on targeted sampling strategies. 35 Chapter 2: National Animal Health Surveillance System (NAHSS) TABLE 5: OIE points from BSE surveillance in the U.S. accumulated for 7 years Year of testing1 Total samples2 Clinical suspects Fallen stock Casualty slaughter Healthy slaughter OIE points3 10/1/05 to 03/17/064 181,564 438 142,337 18,991 19,798 285,491 FY5 2005 413,647 1,527 361,557 50,557 6 899,642 FY 2004 90,085 1,066 62,054 25,096 1,869 592,369 FY 2003 20,778 577 3,106 16,613 482 267,480 FY 2002 20,380 569 2,818 16,045 948 251,740 FY 2001 5,340 665 1 4,515 159 299,177 FY 2000 2,753 664 0 2,064 25 266,891 4/1/99 to 9/30/996 666 265 15 351 35 111,014 Total surveillance (including enhanced surveillance) 7735,213 5,771 571,888 134,232 23,322 2,973,804 Total for enhanced surveillance only 6/1/04 to 3/17/06 667,767 2,602 559,546 84,534 21,085 1,583,127 1 Testing includes the most recent 7 years of data collected from Apr. 1, 1999, through March 17, 2006. 2 Number of samples and clinical suspects represents animals eligible for surveillance according to the Terrestrial Animal Health Code Article 3.8.4. 3 Note: Animals counted as eligible for OIE points included animals older than 1 year according to the OIE point allocation table. Removal of points from the “juvenile” category of the OIE points table would decrease the total by 2,843 points. Other documents showing U.S. data may vary due to inclusion or exclusion of young animals. 4 Includes 6 months of fiscal year 2006. 5 The U.S. Government’s fiscal year extends from October 1 through September 30 (e.g., FY 2005 began on 10/1/2004 and ended on 9/30/2005). 6 Includes 6 months of FY 1999. 7 Total includes two positive indigenous animals and one positive animal imported from Canada. 1 3D–4D facilities are slaughter facilities that salvage meat from dead, dying, disabled, or diseased animals, the meat from which would not likely pass inspection for human consumption (i.e., edible meat). Much of this meat goes into either pet food or rendering. 34 2005 United States Animal Health Report Scrapie Surveillance Evaluation In general, evaluating a surveillance program entails a systematic review to assess the degree to which the program fulfills its stated objectives and meets accepted surveillance standards. Program strengths and areas for improvement are identified, and the program’s ability to adapt to changing situations is evaluated. Evaluating the surveillance component of one VS program disease was identified as a key action item in the NAHSS strategic plan (see The surveillance component of the VS scrapie program was chosen for evaluation. Led by the NSU, an interdisciplinary working group was developed consisting of an economist, statistician, several veterinary epidemiologists, and an industry representative. The evaluation process focused on four main areas: surveillance structures (organization and communication), surveillance processes (data collection, data analysis and interpretation, and dissemination of results), qualitative attributes (i.e., simplicity, flexibility, acceptability), and resource distribution and utilization. Characteristics of the system were compared with the draft VS Surveillance Standards, as noted throughout the evaluation. The evaluation and data gathered focused primarily on the Regulatory Scrapie Slaughter Surveillance Program testing and other nonslaughter surveillance testing in sheep implemented since 2001. Although most of the evaluation results should be applicable to scrapie surveillance in goats, this component was not specifically evaluated. Phone interviews were conducted with State and/or VS field personnel involved in scrapie surveillance activities in nine different States representing both APHIS’ Eastern and Western Regions. Questions addressed the general objectives, importance, and efficiency of the program; the communication within the program; and the acceptability, compliance, and coverage of the program. Personnel interviewed were assured anonymity. The evaluation report has been completed and delivered to VS’ National Center for Animal Health Programs. snip... CHAPTER 3 Animal Disease Eradication Programs and Control and Certification Programs The following Veterinary Services (VS) programs are designed to eradicate, control, or prevent diseases that threaten the biological and commercial health of the U.S. livestock and poultry industries. Eradication Programs VS eradication programs include scrapie in sheep and goats, tuberculosis in cattle and cervids, pseudorabies and brucellosis in swine, and brucellosis in cattle and bison. Scrapie in Sheep and Goats Disease and Program History—Scrapie was first discovered in the United States in 1947 in a Michigan flock that, for several years, had imported sheep of British origin from Canada. Since 1952, VS has worked to control scrapie in the United States. As a result of increasing industry and public concern about transmissible spongiform encephalopathies (TSEs) and the discovery of new TSE diagnostic and control methods, VS initiated an accelerated scrapie eradication program in 2000. Current Program—The primary aspects of the scrapie eradication program are animal identification, surveillance, tracing of positive and exposed animals, testing of sheep and goats in exposed flocks, cleanup of infected flocks, and certification of flocks. Animal Identification—Identification of breeding sheep and culled breeding sheep is mandatory when ownership changes. The only sheep that do not have to be identified are those less than 18 months old and, in the case of ewes, those that also have not lambed or become pregnant and are in slaughter channels. As of September 30, 2005, 103,580 premises with sheep and/or goats were recorded in the scrapie national database. (In this database, a premises that contains both sheep and goats might be listed once for each species.) Of these premises, 73,807 have requested and received official eartags (tags approved for use by the Animal and Plant Health Inspection Service [APHIS] in the official scrapie eradication program). Regulatory Scrapie Slaughter Surveillance (RSSS)— The RSSS program, initiated on April 1, 2003, is the primary surveillance method for scrapie in the United States. RSSS identifies scrapie-infected flocks through targeted slaughter surveillance of sheep and goat populations that have been recognized as having higherthan- average scrapie prevalence. These are defined as mature black- or mottle-faced sheep and any mature sheep or goats showing clinical signs that could be associated with scrapie, such as poor body condition, wool loss, or gait abnormalities. Only sheep with some form of identification (e.g., such as United States Department of Agriculture [USDA]-approved eartags, electronic ID, backtags, and tattoos or lot identification) are sampled. This arrangement allows for tracing positive animals back to the farm of origin. During FY 2005, as part of the RSSS program, 30,247 sheep and goat samples, collected from 78 slaughter plants in 24 States, were tested for scrapie using immunohistochemistry on brain or lymphoid tissue, or both. Of the 106 animals diagnosed as positive for scrapie, 93 were black-faced, 11 were mottle-faced, 1 was whitefaced, and 1 was unknown. Under the scrapie program, positive test results are traced back to the animal’s flock of origin, and the flock is placed under movement restrictions until all high-risk animals (genetically susceptible females) are removed. High-risk animals that had been moved from these flocks before being placed under movement restrictions are traced and tested. Testing Summary—In response to epidemiologic suspicions of disease, field Veterinary Medical Officers conduct testing to determine if scrapie is present. Such cases are known as regulatory field cases. In addition to the 30,247 samples tested under the RSSS program in 2005, about 5,200 additional tests were conducted for scrapie—either by third-eyelid testing or necropsy—in response to epidemiologic suspicions of disease. Case and Infected Flock Summary—In FY 2005, 165 newly identified infected flocks were reported, and 598 scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) (table 6). A scrapie case is defined as an animal for which a diagnosis of scrapie has been made by the NVSL using a USDA-approved test (typically immunohistochemistry on the obex or a peripheral lymph node). During FY 2005, two scrapie cases were reported in goats. Figure 30 presents the geographic location of U.S. mature ewe populations (National Agricultural Statistics Service 2002 Census) relative to flocks found to be positive for scrapie through RSSS sampling or another regulatory or surveillance method (denoted by NVSL-positive flocks). 40 2005 United States Animal Health Report TABLE 6. Scrapie cases, FY 2003 through FY 2005 Number of cases Tests or examinations FY 2003 FY 2004 FY 2005 Necropsies 315 374 461 Regulatory third-eyelid 32 20 31 RSSS 123 86 106 Total 370 480 598 1 Includes part of FY 2003 (April 1–September 30, 2003). FIgURE 30: Distribution of mature ewe populations, by county, compared to positive flocks (FY 2003–early FY 2006). snip... Scrapie susceptibility in sheep in the United States has been associated with two codons that encode for amino acids in the PrP protein. These codons are at positions 136 and 171, the latter of which is thought to be the major determinant of scrapie susceptibility in the United States. For all the scrapie-positive sheep with known genotypes in FY 2005, 98.4 percent were QQ at codon 171. Of these, 82.6 percent were AA at codon 136, 5.4 percent were AV at codon 136, 0.4 percent were VV at codon 136, and 11.6 percent did not have results for codon 136. Of the remaining 1.6 percent that were not QQ at codon 171, 0.3 percent were AAQH and 1.3 percent were AVQR at codons 136 and 171. Scrapie Flock Certification Program (SFCP)—The SFCP is a cooperative effort among producers, State and Federal animal health agencies, and industry representatives. Through the SFCP, a flock becomes certified if, during a 5-year monitoring period, no sheep in the flock are diagnosed with scrapie and no clinical evidence of scrapie is found in the flock. The program categories are described in the following paragraphs. Complete Monitored Category—A flock in this category is approved to participate in the program. There are two status levels for flocks in this category: Enrolled flock: A flock entering the program is assigned enrolled status and is a “complete monitored enrolled flock.” Certified flock: An enrolled flock that has met program standards for 5 consecutive years advances to certified status, meaning that it is unlikely to contain any sheep infected with scrapie. Selective Monitored Category—This category, though open to any flock, was designed for producers of slaughter lambs to allow for scrapie surveillance in large production flocks. Only male animals over 1 year of age must have official identification. Producers agree on the basis of flock size to submit for scrapie diagnosis a portion of the mature animals that are culled or die. Additionally, an accredited veterinarian must inspect all cull ewes for clinical signs of scrapie before slaughter. Selective status is maintained indefinitely as long as the flock meets the category requirements. Trends in Plan Enrollment—Enrollment in the SFCP has increased since 2002. As of September 30, 2005, 1,961 flocks were participating, and of these 188 were certified flocks (table 7). One possible reason for the increased number of certifications in 2005 was participant awareness of standards changes, which now allow rams from lower status flocks to be added to certified flocks without lowering the certified flock’s status. l l Challenges—For the coming year, major challenges are to continue expanding surveillance efforts into underrepresented areas and to increase the traceability of sheep and goats presented for sampling. Traceability will be enhanced by increasing compliance activities and by improving methods for identifying and tracking sheep and goats through review and testing of available identification systems and integration with the National Animal Identification System. A second tier of challenges includes upgrading the scrapie national database, improving field data collection by refining sample collection and submission, and streamlining data entry and analysis. snip... Control and Certification Programs Chronic Wasting Disease (CWD) in Cervids Disease and Program History—First recognized in 1967 as a clinical “wasting” syndrome in mule deer at a wildlife research facility in northern Colorado, CWD was identified as a TSE in 1978. There is no known relationship between CWD, which occurs in cervids, and any other TSE of animals or humans. In the mid–1980s, CWD was detected in free-ranging deer and elk in contiguous areas of northeastern Colorado and southeastern Wyoming. In May 1999, CWD was found in free-ranging deer in the southwestern corner of Nebraska (adjacent to Colorado and Wyoming) and later in other areas in western and central Nebraska. Since 2002, CWD has also been detected in wild deer, elk, or both in south-central Wisconsin, southwestern South Dakota, the western slope of the Rocky Mountains in Colorado, southern New Mexico, northern Illinois, eastern and central Utah, central New York, the eastern arm of West Virginia, and northwestern Kansas. (Note: The Kansas positive deer was harvested in late 2005, but test results were not completed and confirmed until early 2006.) The first infected free-ranging moose was detected in Colorado in 2005. 49 Chapter 3: Animal Disease Eradication Programs and Control and Certification Programs The first CWD-positive farmed elk herd in the United States was detected in 1997 in South Dakota. Through December 31, 2005, 31 additional CWD-positive farmed elk herds and 8 CWD-positive farmed deer herds have been found, for a total of 40 infected farmed cervid herds. Current Program—APHIS–VS and State CWD surveillance in farmed animals began in late 1997 and has increased each year since. APHIS–VS pays laboratory costs for all surveillance testing of farmed cervids. Responses to onfarm CWD-positive cases include depopulation with indemnity or quarantine. Additionally, VS conducts traceforward and traceback epidemiologic investigations. A proposed rule for a CWD herd-certification program for farmed-cervid operations was published for comment in the Federal Register on December 24, 2003. Program goals are to control and eventually eradicate CWD from farmed cervid herds. The program would certify herds that demonstrate 5 years of CWD surveillance with no evidence of disease. The proposed program requirements include fencing, identification, inventory, and surveillance. The rule is intended to limit interstate movement of farmed cervids to herds enrolled in the herd-certification program. State programs meeting or exceeding Federal standards will be included in the Federal program. The final rule for this program will be published and the program implemented in 2006. APHIS–VS has also supported CWD surveillance in wildlife beginning in 1997. Since the national “Plan for Assisting States, Federal Agencies, and Tribes in Managing Chronic Wasting Disease in Wild and Captive Cervids” was adopted in June 2002, APHIS–VS has cooperated with the International Association of Fish and Wildlife Agencies to promote uniform, nationwide surveillance while allowing flexibility to meet individual State situations and needs. Since beginning to receive line-item funding for CWD in FY 2003, APHIS-VS has been providing assistance to State wildlife agencies and tribes through cooperative agreements to address the disease in free-ranging deer and elk. This funding has covered surveillance testing for some 90,000 hunter-killed and targeted animals in the 2002–03 and the 2003–04 hunting seasons. Similar numbers were projected for 2004–05 and 2005–06. All 50 States participated in the first 2 years of the program, and 47 States requested and received funding in FY 2005. Funding is distributed through a tiered system based on risk of disease developed in consultation with the International Association of Fish and Wildlife Agencies. In addition to individual tribal assistance, an agreement with the Native American Fish and Wildlife Society funds five regional CWD tribal biologists to assist tribes with CWD activities. Disease Status—In FY 2005, 15,628 farmed cervids were tested for CWD as compared to more than 15,000 animals in FY 2004 and more than 12,000 in FY 2003. From 1997 through 2005, CWD had been found in 32 farmed elk herds and 8 farmed deer herds in 9 States (table 11). Of the 40 positive herds identified as of December 31, 2005, 6 (4 in Colorado and 2 in Wisconsin) remained under State quarantine and 33 had been depopulated. The quarantine was lifted from one herd that underwent rigorous surveillance for more than 5 years with no further evidence of disease. Challenges—The key challenges in managing CWD result from the fact that cervids fall under multiple jurisdictions. In 2002, at the request of Congress, an interagency group was convened to develop a management plan to assist States, Federal agencies, and Native American tribes in managing CWD in captive and wild herds. Currently, this plan is implemented by State and Federal agencies, as budgets permit. A progress report on the implementation of the plan was completed and presented to Congress in May 2004. Additional challenges are related to the difficulties associated with testing wild cervids. High sample throughput and more rapid test technology were needed to meet the needs of wildlife agencies. By expanding its contract group of State and university laboratories, NVSL now has 26 laboratories approved to conduct CWD testing. In addition, the Center for Veterinary Biologics has approved four CWD antigen test kits based on enzymelinked immunosorbent assay (ELISA), allowing faster testing and greater throughput for surveillance testing of wild cervids. 50 2005 United States Animal Health Report snip...full text 120 pages ; of concern for the complaint of central nervous system (CNS) signs, such as changes in temperament, abnormal posture, and ataxia. In 2005, VS continued surveillance for BSE through its Enhanced BSE Surveillance Plan established in 2004, testing 419,268 brain submissions and conducting 12 FAD investigations for the complaint of CNS signs in bovines. .... snip...FROM HOW MANY DOWNERS ??? Cattle Death Loss by Cause, 2005 Since 1990, the percentage of cattle inventory lost to all causes has remained relatively constant at approximately 2 percent. The percentage of calf crop lost decreased from 7.25 percent in 1990 to just over 6 percent in 2005 (fig. 27). Cause of Loss—Predator and nonpredator cause-of-loss estimates for cattle and calves started in 1991 and were repeated for 1995, 2000, and 2005 as a cooperative effort between NASS and APHIS. The most recent estimates (2005) are presented here (fig. 28). Overall, 98.0 percent of cattle losses and 93.3 percent of calf losses were due to nonpredator causes. Important causes of loss for cattle were calving problems (11.1 percent), digestive problems (11.1 percent), and respiratory problems (24.8 percent). The most frequently reported causes of loss for calves were respiratory problems (31.8 percent), digestive problems (21.2 percent), and calving problems (17.7 percent) (fig. 29). SNIP...CATTLE UNKNOWN CAUSE OF DEATH AT 13.3 % AND CALVES AT 11.5 % NOW, for the rest of the story FROM ABOVE THAT ; CNS signs in bovines. ....WHAT A HOOT !!! MORE FACTS BELOW ; of Agriculture. For information on Non-ambulatory Cattle and Calves call Mike Miller at 720-3040, office hours 7:30 a.m. to 4:30 p.m. ET. Non-Ambulatory Cattle and Calves Non-ambulatory cattle and calves in the United States totaled 465,000 head during 2003 and 450,000 head during 2004. The number of non-ambulatory cattle 500 pounds or greater totaled 280,000 head in 2003 and 270,000 head in 2004. The number of calves under 500 pounds reported as non-ambulatory totaled 185,000 head in 2003 and 180,000 head in 2004. The number of operations that reported non-ambulatory cattle and calves was 103,000 in 2003 and 81,000 in 2004. In 2003, there were 66,800 beef cow operations reporting non-ambulatory cattle and calves compared to 49,700 in 2004. There were 22,800 dairy operations reporting nonambulatory cattle and calves in 2003 compared to 23,000 in 2004. This report is released as a cooperative effort between the National Agricultural Statistics Service and Animal and Plant Health Inspection Service - Veterinary Services. Data for this report were collected on the January 1, 2004 and 2005 Cattle Surveys. SNIP...FULL TEXT ; http://usda.mannlib.cornell.edu/usda/current/nacac/nacac-05-05-2005.pdf Audit Report Animal and Plant Health Inspection Service Bovine Spongiform Encephalopathy (BSE) Surveillance Program – Phase II and Food Safety and Inspection Service Controls Over BSE Sampling, Specified Risk Materials, and Advanced Meat Recovery Products - Phase III Report No. 50601-10-KC January 2006 Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain Our prior report identified a number of inherent problems in identifying and testing high-risk cattle. We reported that the challenges in identifying the universe of high-risk cattle, as well as the need to design procedures to obtain an appropriate representation of samples, was critical to the success of the BSE surveillance program. The surveillance program was designed to target nonambulatory cattle, cattle showing signs of CNS disease (including cattle testing negative for rabies), cattle showing signs not inconsistent with BSE, and dead cattle. Although APHIS designed procedures to ensure FSIS condemned cattle were sampled and made a concerted effort for outreach to obtain targeted samples, industry practices not considered in the design of the surveillance program reduced assurance that targeted animals were tested for BSE. In our prior report, we recommended that APHIS work with public health and State diagnostic laboratories to develop and test rabies-negative samples for BSE. This target group is important for determining the prevalence of BSE in the United States because rabies cases exhibit clinical signs not inconsistent with BSE; a negative rabies test means the cause of the clinical signs has not been diagnosed. APHIS agreed with our recommendation and initiated an outreach program with the American Association of Veterinary Laboratory Diagnosticians, as well as State laboratories. APHIS also agreed to do ongoing monitoring to ensure samples were obtained from this target population. Although APHIS increased the samples tested from this target group as compared to prior years, we found that conflicting APHIS instructions on the ages of cattle to test resulted in inconsistencies in what samples were submitted for BSE testing. Therefore, some laboratories did not refer their rabies negative samples to APHIS in order to maximize the number tested for this critical target population. In addition, APHIS did not monitor the number of submissions of rabies negative samples for BSE testing from specific laboratories. Rabies Negative Samples USDA/OIG-A/50601-10-KC Page 19 USDA/OIG-A/50601-10-KC Page 20 b. Public health laboratories – rabies negative cases. c. Slaughter facilities – CNS ante mortem condemned at slaughter, sampled by FSIS. d. On-the-farm – CNS cattle that do not meet the criteria for a foreign animal disease investigation. For FYs 2002, 2003, and 2004 (through February 2004), NVSL received 170, 133, and 45 rabies-negative samples, respectively. Between June 1, 2004, and May 29, 2005, the number of samples received for testing increased to 226 rabies suspect samples. The collection sites submitting these samples follow. Total 200 * 26 were tested but not counted by APHIS towards meeting the target goals because the obex was not submitted. We obtained a copy of a memorandum, dated July 13, 2004, that APHIS sent to diagnostic and public health laboratories providing them instructions on submitting samples for cattle showing signs of CNS diseases, but testing negative for rabies. The letter was sent to about 170 State veterinary diagnostic and public health laboratories and discussed the need to submit specimens to NVSL of all adult cattle (emphasis added) that showed signs of CNS diseases, but tested negative for rabies. This directive did not specify the age of the cattle. The Procedure Manual for BSE Surveillance, dated October 2004, specified samples of cattle of any age should be submitted. We contacted laboratories in six States to determine if it was standard procedure to submit all negative rabies samples to NVSL. We found that, because of the lack of specificity in the APHIS letter and inadequate followup by APHIS, there were inconsistencies in the age of cattle samples submitted for BSE testing. For those States contacted, the following samples were submitted versus tested as negative for rabies. Rabies Negative Tests Not Sent for BSE Testing Since June 1, 2004 33 85 12 7 5 4 146 94 52 a/ A Pennsylvania laboratory official said only rabies negative cattle over 20 months of age were submitted for BSE testing. The laboratory did not submit 18 samples for BSE testing because the animals were less than 20 months of age. b/ Kansas laboratory officials said early in the expanded surveillance program, there was confusion as to the cattle ages that should be submitted for BSE testing. They did not know if cattle should be submitted that were above 20 months or 30 months of age. Of the 16 animals not submitted for BSE testing, 14 were under 20 months of age from early in the expanded surveillance program. The other two animals were not tested due to internal laboratory issues. The Kansas and Nebraska area office officials contacted the laboratory and told the officials to submit rabies negative cattle of any age for BSE testing. The laboratory now submits all rabies negative cattle for BSE testing. c/ A Wisconsin laboratory official said only rabies negative cattle samples 30 months of age or older are submitted for BSE testing. Of the 11 animals not submitted for BSE testing, 8 were less than 30 months of age. Wisconsin laboratory officials were not certain why the other three samples were not submitted. d/ Laboratory officials from South Dakota said they did not receive notification from APHIS regarding the submission of rabies negative cases for BSE testing. The section supervisor and laboratory director were not aware of any letter sent to the laboratory. The section supervisor said most bovine rabies tests at the laboratory are performed on calves. We confirmed the laboratory’s address matched the address on APHIS’ letter distribution list. However, there was no evidence that the South Dakota area office contacted the laboratory. The laboratory was not listed on the documentation from the APHIS regional office detailing the area office contacts with laboratory personnel. We contacted the South Dakota area office and were advised that while some contact had been made with the laboratory, the contact may have involved Brucellosis rather than BSE. On May 4, 2005, the area office 33 Report from the Secretary’s Advisory Committee on Foreign Animal and Poultry Diseases, February 13, 2004. advised us they recently contacted the laboratory regarding the submission of rabies negative samples for BSE testing. e/ Arizona and Mississippi laboratory officials said they submitted all rabies negative samples for BSE testing regardless of the age of the animal. An NVSL official stated that APHIS is not concerned with rabies negatives samples from cattle less than 30 months of age. This position, however, is contrary to APHIS’ published target population. Our prior audit recognized the significant challenge for APHIS to obtain samples from some high-risk populations because of the inherent problems with obtaining voluntary compliance and transporting the carcasses for testing. USDA issued rules to prohibit nonambulatory animals (downers) from entering the food supply at inspected slaughterhouses. OIG recommended, and the International Review Subcommittee33 emphasized, that USDA should take additional steps to assure that facilitated pathways exist for dead and nonambulatory cattle to allow for the collection of samples and proper disposal of carcasses. Between June 1, 2004, and May 31, 2005, the APHIS database documents 27,617 samples were collected showing a reason for submission of nonambulatory and 325,225 samples were collected with reason of submission showing "dead." APHIS made extensive outreach efforts to notify producers and private veterinarians of the need to submit and have tested animals from these target groups. They also entered into financial arrangements with 123 renderers and other collection sites to reimburse them for costs associated with storing, transporting, and collecting samples. However, as shown in exhibit F, APHIS was not always successful in establishing agreements with non-slaughter collection sites in some States. APHIS stated that agreements do not necessarily reflect the entire universe of collection sites and that the presentation in exhibit F was incomplete because there were many collection sites without a payment involved or without a formal agreement. We note that over 90 percent of the samples collected were obtained from the 123 collection sites with agreements and; therefore, we believe agreements offer the best source to increase targeted samples in underrepresented areas. We found that APHIS did not consider industry practices in the design of its surveillance effort to provide reasonable assurance that cattle exhibiting possible clinical signs consistent with BSE were tested. Slaughter facilities do not always accept all cattle arriving for slaughter because of their business requirements. We found that, in one State visited, slaughter facilities pre-screened and rejected cattle (sick/down/dead/others not meeting business Downers and Cattle that Died on the Farm USDA/OIG-A/50601-10-KC Page 22 USDA/OIG-A/50601-10-KC Page 23 34 FSIS regulations do not specifically address the designation of an establishment’s "official" boundaries; however, FSIS Notices 29-04 (dated May 27, 2004) and 40-04 (dated July 29, 2004) make it clear that FSIS inspection staff are not responsible for sampling dead cattle that are not part of the "official" premises. 35 APHIS’ area office personnel stated that it was their understanding that some establishments in the State were not presenting cattle that died or were down on the transport vehicle to FSIS for ante mortem inspection. The dead and down cattle were left in the vehicle, if possible. In rare circumstances, dead cattle may be removed from the trailer by plant personnel to facilitate the unloading of other animals. 36 A May 20, 2004, Memorandum between the Administrators of APHIS and FSIS. standards) before presentation for slaughter in areas immediately adjacent or contiguous to the official slaughter establishment. These animals were not inspected and/or observed by either FSIS or APHIS officials located at the slaughter facilities. FSIS procedures state that they have no authority to inspect cattle not presented for slaughter. Further, APHIS officials stated they did not believe that they had the authority to go into these sorting and/or screening areas and require that the rejected animals be provided to APHIS for BSE sampling. Neither APHIS nor FSIS had any process to assure that animals left on transport vehicles and/or rejected for slaughter arrived at a collection site for BSE testing. FSIS allows slaughter facilities to designate the area of their establishment where federal inspection is performed; this is designated as the official slaughter establishment.34 We observed animals that were down or dead in pens outside the official premises that were to be picked up by renderers. Animals that were rejected by plant personnel were transported off the premises on the same vehicles that brought them to the plant.35 A policy statement36 regarding BSE sampling of condemned cattle at slaughter plants provided that effective June 1, 2004, FSIS would collect BSE samples for testing: 1) from all cattle regardless of age condemned by FSIS upon ante mortem inspection for CNS impairment, and 2) from all cattle, with the exception of veal calves, condemned by FSIS upon ante mortem inspection for any other reason. FSIS Notice 28-04, dated May 20, 2004, informed FSIS personnel that, "FSIS will be collecting brain samples from cattle at federally-inspected establishments for the purpose of BSE testing." The notice further states that, "Cattle off-loaded from the transport vehicle onto the premises of the federally-inspected establishment (emphasis added), whether dead or alive, will be sampled by the FSIS Public Health Veterinarian (PHV) for BSE after the cattle have been condemned during ante mortem inspection. In addition, cattle passing ante mortem inspection but later found dead prior to slaughter will be condemned and be sampled by the FSIS PHV." USDA/OIG-A/50601-10-KC Page 24 37 FSIS Notice 40-04, dated July 29, 2004. 38 FSIS Notice 29-04, dated May 27, 2004. APHIS has the responsibility for sampling dead cattle off-loaded onto plant-owned property that is adjoining to, but not considered part of, the "official premises.37 FSIS procedures38 provide that "Dead cattle that are off-loaded to facilitate the off-loading of live animals, but that will be re-loaded onto the transport vehicle, are not subject to sampling by FSIS. While performing our review in one State, we reviewed the circumstances at two slaughter facilities in the State that inspected and rejected unsuitable cattle before the animals entered the official receiving areas of the plants. This pre-screening activity was conducted in areas not designated by the facility as official premises of the establishment and not under the review or supervision of FSIS inspectors. The plant rejected all nonambulatory and dead/dying/sick animals delivered to the establishment. Plant personnel refused to offload any dead or downer animals to facilitate the offloading of ambulatory animals. Plant personnel said that the driver was responsible for ensuring nonambulatory animals were humanely euthanized and disposing of the carcasses of the dead animals. Plant personnel informed us that they did not want to jeopardize contracts with business partners by allowing unsuitable animals on their slaughter premises. In the second case, one family member owned a slaughter facility while another operated a livestock sale barn adjacent to the slaughter facility. The slaughter facility was under FSIS’ supervision while the sale barn was not. Cattle sometimes arrived at the sale barn that were sick/down/dead or would die or go down while at the sale barn. According to personnel at the sale barn, these animals were left for the renderer to collect. The healthy ambulatory animals that remained were marketed to many buyers including the adjacent slaughter facility. When the slaughter facility was ready to accept the ambulatory animals for processing, the cattle would be moved from the sale barn to the slaughter facility where they were subject to FSIS’ inspection. We requested the slaughter facilities to estimate the number of cattle rejected on a daily basis (there were no records to confirm the estimates). We visited a renderer in the area and found that the renderer had a contract with APHIS to collect samples for BSE testing. In this case, although we could not obtain assurance that all rejected cattle were sampled, the renderer processed a significant number of animals, as compared to the slaughter plants’ estimates of those rejected. Due to the close proximity (less than 5 miles) of the renderer to the slaughter facilities, and the premium it paid for dead cattle that were in good condition, there was a financial incentive for transport drivers to dispose of their dead animals at this renderer. USDA/OIG-A/50601-10-KC Page 25 In our discussions with APHIS officials in Wisconsin and Iowa, they confirmed that there were plants in their States that also used pre-screening practices. On May 27, 2005, we requested APHIS and FSIS to provide a list of all slaughter facilities that pre-screened cattle for slaughter in locations away from the area designated as the official slaughter facility. Along with this request, we asked for information to demonstrate that either APHIS or FSIS confirmed there was a high likelihood that high-risk animals were sampled at other collection sites. In response to our request, the APHIS BSE Program Manager stated that APHIS did not have information on slaughter plants that pre-screen or screen their animals for slaughter suitability off their official plant premises. To their knowledge, every company or producer that submits animals for slaughter pre-sorts or screens them for suitability at various locations away from the slaughter facility. For this reason, USDA focused its BSE sample collection efforts at other types of facilities such as renderers, pet food companies, landfills, and dead stock haulers. Further, in a letter to OIG on June 14, 2005, the administrators of APHIS and FSIS noted the following: "…we believe that no specific actions are necessary or appropriate to obtain reasonable assurance that animals not presented for slaughter are being tested for BSE. There are several reasons for our position. First, we do not believe that the practice is in fact causing us to not test a significant enough number of animals in our enhanced surveillance program to invalidate the overall results. Second, OIG has concluded that because of the geographical proximity and business relationships of the various entities involved in the case investigated, there is reasonable assurance that a majority of the rejected cattle had been sampled. Third, it is also important to remember that the goal of the enhanced surveillance program is to test a sufficient number of animals to allow us to draw conclusions about the level of BSE (if any) in the American herd…We believe that the number we may be not testing because of the "pre-sorting" practice does not rise to a significant level. The number of animals tested to date has far exceeded expectations, so it is reasonable to infer that there are few of the animals in question, or that we are testing them at some other point in the process…APHIS estimated…there were approximately 446,000 high risk cattle…[and APHIS has]…tested over 375,000 animals in less than 1 year. This indicated that we are missing few animals in the high-risk population, including those that might be pre-sorted before entering a slaughter facility’s property." We obtained 123 APHIS sampling agreements and contracts with firms and plotted their locations within the United States (see exhibit F). We also analyzed the samples tested to the BSE sampling goals allocated to each State under the prior surveillance program. This analysis showed that there are 39APHIS noted that sites with agreements do not necessarily reflect the entire universe of collection sites and at some sites APHIS collects samples with no payment involved and no agreement in place. OIG agrees that not all collection sites are reflected in our presentation of the 123 sites with reimbursable agreements. OIG believes obtaining sampling agreements is one of the primary methods available to increase sample numbers in areas with sampling gaps. sampling gaps in two large areas of the United States where APHIS did not have contracts with collection sites. These two areas are shown in the following chart (Montana, South Dakota, North Dakota and Wyoming – Group 1 and Louisiana, Oklahoma, Arkansas, and Tennessee – Group 2): Original Sampling Goal Based on (268,500 sampling goal) Samples collected as of May 31, 2005 182 2,792 174 61 2,407 353 3,050 452 12,452 APHIS notes that for the current surveillance program, it had established regional goals and APHIS was not trying to meet particular sampling levels in particular States. However, we believe that it would be advantageous for APHIS to monitor collection data and increase outreach when large geographical areas such as the above States do not provide samples in proportion to the numbers and types of cattle in the population. We also disagree with APHIS/FSIS’ contention that because they have tested over 375,000 of their 446,000 estimate of high risk cattle, few in the high-risk population are being missed, including those that might be pre-screened before entering a slaughter facility’s property. In our prior audit, we reported that APHIS underestimated the high-risk population; we found that this estimate should have been closer to 1 million animals (see Finding 1). We recognize that BSE samples are provided on a voluntary basis; however, APHIS should consider industry practice in any further maintenance surveillance effort. Animals unsuitable for slaughter exhibiting symptoms not inconsistent with BSE should be sampled and their clinical signs recorded. However, this cited industry practice results in rejected animals not being made available to either APHIS or FSIS veterinarians for their observation and identification of clinical signs exhibited ante mortem. Although these animals may be sampled later at other collection sites, the animals are provided post mortem without information as to relevant clinical signs exhibited ante mortem. For these reasons, we believe APHIS needs to USDA/OIG-A/50601-10-KC Page 27 observe these animals ante mortem when possible to assure the animals from the target population are ultimately sampled and the clinical signs evaluated. snip... http://www.usda.gov/oig/webdocs/50601-10-KC.pdf In November 2004, USDA announced that its rapid screening test produced an inconclusive BSE test result. A contract laboratory ran its rapid screening test on a brain sample collected for testing and produced three high positive reactive results. As required, the contract laboratory forwarded the inconclusive sample to APHIS’ National Veterinary Services Laboratories (NVSL) for confirmation. NVSL repeated the rapid screening test, which again produced three high positive reactive results. Following established protocol, NVSL ran its confirmatory test, an immunohistochemistry (IHC) test, which was interpreted as negative for BSE. Faced with conflicting results between the rapid screening and IHC tests, NVSL scientists recommended additional testing to resolve the discrepancy but APHIS headquarters officials concluded that no further testing was necessary since testing protocols were followed and the confirmatory test was negative. In our discussions with APHIS officials, they justified their decision to not do additional testing because the IHC test is internationally recognized as the "gold standard" of testing. Also, they believed that USDA/OIG-A/50601-10-KC/ Page iv conducting additional tests would undermine confidence in USDA’s testing protocols. OIG obtained evidence that indicated additional testing was prudent. We came to this conclusion because the rapid screening tests produced six high positive reactive results, the IHC tests conflicted, and various standard operating procedures were not followed. Also, our review of the relevant scientific literature, other countries’ protocols, and discussions with experts led us to conclude that additional confirmatory testing should be considered in the event of conflicting test results. To maintain objectivity and independence, we requested that USDA’s Agricultural Research Service (ARS) perform the Office International des Epizooties (OIE) Scrapie-Associated Fibrils (SAF) immunoblot test. The additional testing produced positive results. To confirm, the Secretary of Agriculture requested that an internationally recognized BSE laboratory in Weybridge, England (Weybridge) perform additional testing. Weybridge conducted various tests, including their own IHC tests and three Western blot tests. The tests confirmed that the cow was infected with BSE. The Secretary immediately directed USDA scientists to work with international experts to develop new protocols that include performing dual confirmatory tests in the event of an inconclusive BSE screening test. We attribute the failure to identify the BSE positive sample to rigid protocols, as well as the lack of adequate quality assurance controls over its testing program. Details of our concerns are discussed in Findings 3 and 4. snip... Section 2. Testing Protocols and Quality Assurance Controls In November 2004, USDA announced that its rapid screening test, Bio-Rad Enzyme Linked Immunosorbent Assay (ELISA), produced an inconclusive BSE test result as part of its enhanced BSE surveillance program. The ELISA rapid screening test performed at a BSE contract laboratory produced three high positive reactive results.40 As required,41 the contract laboratory forwarded the inconclusive sample to the APHIS National Veterinary Services Laboratories (NVSL) for confirmatory testing. NVSL repeated the ELISA testing and again produced three high positive reactive results.42 In accordance with its established protocol, NVSL ran its confirmatory test, an immunohistochemistry (IHC) test, which was interpreted as negative for BSE. In addition, NVSL performed a histological43 examination of the tissue and did not detect lesions44 consistent with BSE. Faced with conflicting results, NVSL scientists recommended additional testing to resolve the discrepancy but APHIS headquarters officials concluded no further testing was necessary because testing protocols were followed. In our discussions with APHIS officials, they justified their decision not to do additional testing because the IHC is internationally recognized as the “gold standard.” Also, they believed that conducting additional tests would undermine confidence in USDA’s established testing protocols. However, OIG obtained evidence that indicated additional testing was prudent to ensure that USDA’s testing protocols were effective in detecting BSE and that confidence in USDA’s testing procedures was maintained. OIG came to this conclusion because the rapid tests produced six high positive reactive results, confirmatory testing conflicted with the rapid test results, and various standard operating procedures were not followed. Also, our review of scientific literature, other country protocols, as well as discussions with internationally recognized experts led us to conclude that confirmatory testing should not be limited when conflicting test results are obtained. To maintain objectivity and independence in our assessment, we requested the USDA Agricultural Research Service (ARS) perform the Office International des Epizooties (OIE) Scrapie-Associated Fibrils (SAF) 40 ELISA test procedures require two additional (duplicate) tests if the initial test is reactive, before final interpretation. If either of the duplicate tests is reactive, the test is deemed inconclusive. 41 Protocol for BSE Contract Laboratories to Receive and Test Bovine Brain Samples and Report Results for BSE Surveillance Standard Operating Procedure (SOP), dated October 26, 2004. 42 The NVSL conducted an ELISA test on the original material tested at the contract laboratory and on two new cuts from the sample tissue. 43 A visual examination of brain tissue by a microscope. 44 A localized pathological change in a bodily organ or tissue. immunoblot.45 ARS performed the test at the National Animal Disease Center because NVSL did not have the necessary equipment46 (ultracentrifuge) to do the test. APHIS scientists observed and participated, as appropriate, in this effort. The additional tests conducted by ARS produced positive results. To confirm this finding, the Secretary requested the internationally recognized BSE reference laboratory in Weybridge, England, (Weybridge) to perform additional confirmatory testing. Weybridge conducted various tests, including their own IHC methods, as well as three Western blot methods. The tests confirmed that the suspect cow was infected with BSE. Also, Weybridge confirmed this case as an unequivocal positive case of BSE on the basis of IHC. As a result of this finding, the Secretary immediately directed USDA scientists to work with international experts to develop a new protocol that includes performing dual confirmatory tests in the event of another inconclusive BSE screening test. Finding 3 Rigid Protocols Reduced the Likelihood BSE Could be Detected APHIS relied on a single test method, as well as a histological examination of tissue for lesions consistent with BSE, to confirm the presence of BSE even though discrepant test results indicated further testing may be prudent. When IHC test results were interpreted as negative, APHIS concluded the sample tested negative for BSE. Subsequent independent tests initiated by OIG using a different testing method, as well as confirmatory testing by Weybridge, determined that the suspect sample was a positive case of BSE. APHIS Declares BSE Sample Negative Despite Conflicting Results When the tissue sample originally arrived at NVSL in November 2004 from the contract lab, NVSL scientists repeated the ELISA screening test and again produced three high positive reactive results. NVSL scientists cut out two sections of the brain sample for IHC testing. One section was used for an experimental procedure that was not part of the confirmatory testing protocol, and the other cut was for normal IHC testing using scrapie for a positive control.47 According to NVSL scientists, the experimental test results were inconclusive but the IHC test was interpreted as negative. The NVSL scientists were concerned with the inconsistencies and conducted 45 The OIE SAF immunoblot is an internationally recognized confirmatory test, often referred to as a Western blot test. There are different types of Western blots; the OIE SAF immunoblot includes enrichment steps taken with the sample prior to the standard Western blot steps. 46 APHIS has now ordered the necessary equipment for NVSL. USDA/OIG-A/50601-10-KC Page 32 47 A positive control is a sample that is known to contain a given disease or react in the test. The sample then can be used to make sure that the test for that disease works properly. In the case of BSE, tissue infected with either scrapie or BSE can serve as a positive control for an IHC test for BSE since both are different forms of the same disease (transmissible spongiform encephalopathy or TSE). another IHC test using BSE as a positive control.48 The test result was also interpreted as negative. Also, according to the NVSL scientists, the histological examination of the tissue did not detect lesions consistent with BSE. After the second negative IHC test, NVSL scientists supported doing additional testing. They prepared a plan for additional tests; if those tests had been conducted, BSE may have been detected in the sample. The additional tests recommended by NVSL scientists, but not approved by APHIS Headquarters officials, were the IHC using other antibodies (IHC testing using different antibodies ultimately produced positive results); IHC testing of additional regions of the brain (the cerebellum tested positive); regular and enriched (OIE-like) Western blots (the obex and cerebellum tested positive); and variable rapid tests (the obex and cerebellum tested positive with two different rapid tests). NVSL officials also recommended that the sample be sent to Weybridge for confirmatory testing (to conduct IHC and OIE Western blot tests). In June 2005, Weybridge conducted IHC testing with three different antibodies, including the antibody used in the United States (tested positive), the OIE Western blot (tested positive), a modified commercial kit Western blot (negative) and the NaPTA49 Western blot (tested positive). We obtained information as to the differing protocols used by other countries. We found that while APHIS determined that additional testing was unnecessary after the IHC test, other countries have used multiple tests to confirm positives. In Japan, for example, all reactive screening test samples are examined by both IHC and a Western blot (different from the OIE SAF immunoblot). In the United Kingdom (U.K.), IHC and Western blot (different from the OIE SAF immunoblot) tests are used for all animals that test positive with a screening test. When IHC and the Western blot fail to confirm a positive rapid test, the U.K. resorts to a third test, the OIE SAF immunoblot. With these procedures in place, both Japan and the U.K. have found BSE cases that were rapid test reactive, IHC negative, and finally confirmed positive with a Western blot. Evidence Indicated Additional Testing Would Be Prudent We also spoke with an internationally recognized BSE expert regarding the advisability of limiting confirmatory testing when conflicting results are obtained. This official expressed concern about limiting confirmatory tests to the IHC despite its status as one of the “gold standard” tests. He advised that the IHC is not one test; it is a test method that can vary significantly in sensitivity from laboratory to laboratory. New antibodies can improve or USDA/OIG-A/50601-10-KC Page 33 48 The NVSL uses scrapie as the positive control as part of its normal IHC testing procedures. Due to the conflicting results between the ELISA and IHC tests, the NVSL conducted another IHC test with BSE as the positive control. Subsequently, the NVSL modified the Confirming Inconclusive Results from BSE Testing Laboratories at the NVSL SOP to show that all IHC tested BSE inconclusive samples from contract laboratories will use BSE as the positive control. 49 Sodium phosphotungstic acid. USDA/OIG-A/50601-10-KC Page 34 reduce sensitivity, as can variations in many of the reagents50 used. He explained that his laboratory had experienced cases where an initial confirmatory IHC test was challenged by either a more extensive IHC test or “…applying a more sensitive immunoblot.” He emphasized the importance of having additional confirmatory testing to resolve discrepant results since there are many variables, and most of the variability appears to be due to test performance of the laboratory. OIG became concerned that APHIS relied on its confirmatory test methods when rapid screening tests produced high positive reactive results six times.51 Also, we found that APHIS did not pursue and/or investigate why the ELISA produced high reactive positives. An official from the manufacturer of the ELISA test kit told us that they requested, but did not receive, information on the inconclusive reported by USDA in November 2004. These officials requested this information in order to understand the reasons for the discrepant results. The Bio-Rad ELISA rapid screening test is internationally recognized as a highly reliable test and is the rapid screening test used for USDA’s surveillance effort. According to APHIS officials, they felt it would be inappropriate to collaborate on the one sample because Bio-Rad is a USDA-APHIS regulated biologics company and only one of several competing manufacturers. To maintain confidence in USDA’s test protocols, it would have been a prudent course of action for USDA to determine why such significant differing results were obtained. The fact that they did not pursue this matter caused concerns relating to testing quality assurance procedures. In this regard, we found lack of compliance with SOPs relating to laboratory proficiency and quality assurance (see Finding 4), and, in this case, the storage of sampled material and reporting of test results. We found that the NVSL did not prepare a report to document its confirmatory testing of the November 2004 sample. The SOP52 states that the BSE network laboratory initiating the inconclusive will receive a report of the case. NVSL officials could not explain why a final report had not been prepared. We also found that the inconclusive sample was frozen prior to IHC confirmatory testing. APHIS protocols state that samples are not to be frozen prior to laboratory submission. The OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals states that the tissues for histological or IHC examination are not to be frozen as this will provide artefactual53 lesions that may compromise the identification of vacuolation,54 and/or target site location. Although the sample was frozen, APHIS did not conduct a Western 50 A substance used in a chemical reaction to detect, measure, examine, or produce other substances. 51 The six high positive reactive results were from three tests of the submitted sample (multiple runs of the same test). 52 Confirming Inconclusive Results from Bovine Spongiform Encephalopathy Testing Laboratories at the NVSL SOP, dated August 13, 2004. 53 A structure or feature not normally present but visible as a result of an external agent or action, such as one seen in a microscopic specimen after fixation. 54 A small space or cavity in a tissue. USDA/OIG-A/50601-10-KC Page 35 blot test on the sample. An NVSL official said freezing the sample does not make it unsuitable for IHC. APHIS determined that the sample was suitable for IHC and therefore, in accordance with its SOP, did not conduct a Western blot test. APHIS also handled the December 2003 BSE positive differently than the November 2004 sample. For the December 2003 BSE positive sample, APHIS conducted several confirmatory tests in addition to the IHC testing and histological examination (unlike the November 2004 sample tests, both of these were interpreted as positive). ARS performed two Western blots (Prionics Check Western blot and an ARS developed Western blot). When we questioned why the samples were handled differently, APHIS officials stated that the Western blots were done because the IHC in December 2003 was positive. The additional testing was done to further characterize the case, because it was the first U.S. case; the additional testing was not done to decide whether the case was positive or negative. We discussed our concerns with limiting confirmatory testing, particularly given conflicting results, with the APHIS Administrator and staff in May 2005. He explained that international standards recognized more than one “gold standard” test. In setting up its testing protocols, USDA had chosen one as the confirming test, the IHC test, and stayed with it. APHIS protocols only allow a Western blot in cases where the sample has become unsuitable for IHC tests (e.g., in cases where the brainstem architecture is not evident). International standards, he continued, accept a tissue sample as negative for BSE if its IHC test is negative. Once the test is run in accordance with protocols, additional tests undermine the USDA testing protocol and the surveillance program. He concluded that since APHIS’ protocols accepted the IHC test as confirming the presence or absence of BSE, no further testing was necessary. According to protocol, the tissue sample was determined to have tested negative for BSE. On June 24, 2005, USDA announced that the additional testing by the BSE reference laboratory in England confirmed the presence of BSE in the tissue sample. To obviate the possibility that a future sample would be declared negative and then found positive, the Secretary of Agriculture announced a change to APHIS’ testing protocols that same day. He called for “dual confirmatory tests in the event of another ‘inconclusive’ [reactive] BSE screening test.” He also indicated that he would reinforce proper procedures so that samples will not be frozen, and to spot-check the laboratories to see that they complete reports as required. APHIS issued a SOP on the new confirmatory testing protocols on November 30, 2005. http://www.usda.gov/oig/webdocs/50601-10-KC.pdf 12/10/76 snip... A The Present Position with respect to Scrapie Scrapie is a natural disease of sheep and goats. It is a slow The field problem has been reviewed by a MAFF working group It is clear that scrapie in sheep is important commercially and Recently the question has again been brought up as to whether Whether true or not. the hypothesis that these agents might be snip... 76/10.12/4.6 http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf elaphus nelsoni) Odocoileus virginianus) wasting disease snip... infectivity in skeletal muscle of CWD-infected mule deer (Angers et al., 2006) has raised the level of concern on the issue of potential human health risks that might be encountered by consuming prion-containing meat. Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Rachel C. Angers,1* Shawn R. Browning,1*† Tanya S. Seward,2 Christina J. Sigurdson,4‡ Michael W. Miller,5 Edward A. Hoover,4 Glenn C. Telling1,2,3§ 1Department of Microbiology, Immunology and Molecular Genetics, 2Sanders Brown Center on Aging, 3Department of Neurology, University of Kentucky, Lexington, KY 40536, USA. 4Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA. 5Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526, USA. *These authors contributed equally to this work. †Present address: Department of Infectology, Scripps Research Institute, 5353 Parkside Drive, RF-2, Jupiter, Florida, 33458, USA. ‡Present address: Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland. §To whom correspondence should be addressed: E-mail: gtell2@uky.edu Prions are transmissible proteinaceous agents of mammals that cause fatal neurodegenerative diseases of the central nervous system (CNS). The presence of infectivity in skeletal muscle of experimentally infected mice raised the possibility that dietary exposure to prions might occur through meat consumption (1). Chronic wasting disease (CWD), an enigmatic and contagious prion disease of North American cervids, is of particular concern. The emergence of CWD in an increasingly wide geographic area and the interspecies transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt Jakob disease (vCJD) have raised concerns about zoonotic transmission of CWD. To test whether skeletal muscle of diseased cervids contained prion infectivity, Tg(CerPrP)1536 mice (2) expressing cervid prion protein (CerPrP), were inoculated intracerebrally with extracts prepared from the semitendinosus/semimembranosus muscle group of CWD-affected mule deer or from CWD-negative deer. The availability of CNS materials also afforded direct comparisons of prion infectivity in skeletal muscle and brain. All skeletal muscle extracts from CWD-affected deer induced progressive neurological dysfunction in Tg(CerPrP)1536 mice with mean incubation times ranging between 360 and ~490 d, whereas the incubation times of prions from the CNS ranged from ~230 to 280 d (Table 1). For each inoculation group, the diagnosis of prion disease was confirmed by the presence of PrPSc in the brains of multiple infected Tg(CerPrP)1536 mice (see supporting online material for examples). In contrast, skeletal muscle and brain material from CWD-negative deer failed to induce disease in Tg(CerPrP)1536 mice (Table 1) and PrPSc was not detected in the brains of sacrificed asymptomatic mice as late as 523 d after inoculation (supporting online material). Our results show that skeletal muscle as well as CNS tissue of deer with CWD contains infectious prions. Similar analyses of skeletal muscle BSE-affected cattle did not reveal high levels of prion infectivity (3). It will be important to assess the cellular location of PrPSc in muscle. Notably, while PrPSc has been detected in muscles of scrapie-affected sheep (4), previous studies failed to detect PrPSc by immunohistochemical analysis of skeletal muscle from deer with natural or experimental CWD (5, 6). Since the time of disease onset is inversely proportional to prion dose (7), the longer incubation times of prions from skeletal muscle extracts compared to matched brain samples indicated that prion titers were lower in muscle than in CNS where infectivity titers are known to reach high levels. Although possible effects of CWD strains or strain mixtures on these incubation times cannot be excluded, the variable 360 to ~490 d incubation times suggested a range of prion titers in skeletal muscles of CWD-affected deer. Muscle prion titers at the high end of the range produced the fastest incubation times that were ~30% longer than the incubation times of prions from the CNS of the same animal. Since all mice in each inoculation group developed disease, prion titers in muscle samples producing the longest incubation times were higher than the end point of the bioassay, defined as the infectious dose at which half the inoculated mice develop disease. Studies are in progress to accurately assess prion titers. While the risk of exposure to CWD infectivity following consumption of prions in muscle is mitigated by relatively inefficient prion transmission via the oral route (8), these / www.sciencexpress.org / 26 January 2006 / Page 1 / 10.1126/science.1122864 results show that semitendinosus/semimembranosus muscle, which is likely to be consumed by humans, is a significant source of prion infectivity. Humans consuming or handling meat from CWD-infected deer are therefore at risk to prion exposure. CWD Human health implications 14. Epidemiological data on possible CWD infection of humans are very limited. The possibility that clinical symptoms of CWD in humans differ from those of Creutzfeldt-Jakob Disease (CJD) cannot be excluded. There is no significant difference between the prevalence of CJD in CWD endemic areas and other areas of the world. However, because CJD surveillance in the USA is relatively recent, not all CJD cases may have been identified. Additionally, detection of a small increase in prevalence of such a rare disease is very difficult. Investigation of six cases of prion disease in young people ((> 54 years of age) diagnosed with sporadic CJD, no link with consumption of venison from CWD endemic areas was found. No causal link was found in an investigation of three men with neurological illnesses who were known to partake in “wild game feasts”. Only one of these subjects was found to have a prion disease and this was also indistinguishable from sporadic CJD. http://www.seac.gov.uk/statements/statement180105.pdf 10) HUMAN HEALTH CONCERNS 217. To date there are no known cases of human prion disease attributable to CWD transmitted to humans (Belay et al., 2004). While limited epidemiological investigations to date have not shown any links between CWD and humans with spongiform encephalopathies CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 45 of 66 this data must be considered along with a caveat: “because CWD is a relatively new TSE, it is unlikely that enough people have consumed enough CWD-affected cervids to result in a clinically or pathologically recognizable disease attributable to CWD, especially considering the very long incubation periods characteristic of TSE diseases.” (Race et al., 2002) Epidemiological investigations 218. Epidemiological investigations have failed to show any links between cases of prion disease in unusually young people or in hunters in the USA and CWD (CDC, 2003). Two major epidemiological investigations have been carried out, one on cases of CJD in unusually young individuals in the USA, the second on a group of men from Wisconsin who developed neurological diseases. 219. The first study (Belay et al., 2001) focused on three individuals, two 28 years of age and the third 30 years old, diagnosed with CJD in the USA between 1st January 1997 and 31st May 2000, and without any established risk factors for CJD (family history, receipt of human growth hormone, receipt of grafts of dura mater or cornea, or previous neurological surgery) and concluded that there was no strong evidence for a causal link with CWD. None of the individuals had travelled to Europe (therefore a link with BSE was unlikely). Two of the individuals were hunters who regularly consumed game meat while the third (case 1) had, as a young child, regularly consumed venison from animals hunted by family members and on two occasions from a family friend. Two of the individuals (cases 1 and 2) had undergone tonsillar surgery as children; the third had never received any surgical treatment. One individual (case 1) had eaten venison mainly hunted in Maine, occasionally hunted in New Jersey, and, on two occasions at about six years old, elk meat which had probably been harvested in Wyoming. The second person (case 2) had hunted cervids mainly in Utah, but had harvested an elk in southwestern Wyoming on one occasion (less than three years before onset of clinical signs) and had hunted in British Columbia on one occasion nine years before onset of illness. The third person (case 3) had hunted close to home and never in Colorado or Wyoming although the plant where he took his carcasses for processing did also process some elk from Colorado each year. The clinical signs, duration of illness and histopathological findings for the three individuals showed no obvious similarities to one another. One individual was methionine/methionine homozygous at codon 129 of the PRNP (case 1), one was homozygous for valine at this gene (case 2) and the third (case 3) was heterozygous methionine/valine. Immunohistochemistry revealed strong staining with a “synaptic” pattern in the first individual and weak staining with a “synaptic” pattern in the second case; in case 3, based on a brain biopsy sample obtained at an early point in the illness, staining was questionable and possibly showed a synaptic pattern. Cases 2 and 3 showed a “Type 1” immunoblot pattern, this test had not been carried out for case 1. It was noted that none of these three individuals had a definite history of consumption of venison from the geographical areas in which CWD was known to be endemic in Colorado and Wyoming, and no CWD had been identified in 299 deer and sampled from the area in which most of the venison consumed by patient 1 had originated, nor in 404 deer and 196 elk sampled from the area in which most of the venison consumed by patient 2 had originated, nor in 138 deer samples from the area in which most of the venison consumed by patient 1 had originated. Additionally, there was no homogeneity in phenotypic expression of the disease and all three possible options for coding at codon 129 of the PRNP gene were represented. Since a survey had indicated that approximately 40% of blood donors in the USA consumed venison from wild cervids, it was considered most likely that coincidence explained why three of the four young (30 years old or younger) individuals with sporadic CJD reported in the USA after March 1996 had consumed such meat (Belay et al., 2001). CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 46 of 66 220. The second major epidemiological investigation centred around three men from Wisconsin and Minnesota who had died from degenerative neurological illnesses and who had participated in “wild game feasts” in northern Wisconsin. Full investigation including examination of fixed brain tissue confirmed CJD in only one of the three individuals. Wild game eaten during the feasts was harvested mainly in Wisconsin but also in areas of Colorado, Wyoming and Montana; CWD was not known to be endemic in the areas where the game was hunted at the time that the game was harvested. Further investigations of other possible attendees of the feasts revealed 34 participants, all male, of whom a total of seven were deceased, including the three individuals in the initial investigation. Causes of death in the other four deceased individuals were not attributed to nor associated with any degenerative neurological disorder and no signs or symptoms associated with a degenerative neurological disorder were noted for any of the remaining living participants of the feasts. It was noted that only one case of CJD had occurred among known participants at the feasts, that this case was consistent with the commonest form of sporadic CJD, that this individual had only participated in one feast and that it was unlikely that he had consumed CWDinfected venison at the feasts “because venison and other game from outside Wisconsin that was served at these feasts did not originate from known CWD-endemic areas.” Limitations of the investigations were noted to include reliance on recall of events from up to 25 years previously and the fact that not all participants in the feasts could be contacted and interviewed. However, those who were interviewed agreed in their recall of events (CDC, 2003). 221. It is important to recognise that the limited epidemiological investigations that have been carried out are not able to rule out the possibility that CWD might play a role in causing illness in humans (CDC, 2003). 222. Three further cases of prion disease in young humans in the USA have been investigated for possible links to CWD (Belay et al., 2004). The first case was a 25-year-old man who died in 2001 after about 22 months of illness. Gerstmann-Sträussler-Scheinker syndrome (GSS) was diagnosed by analysis of the prion gene, with a P102L mutation together with valine at codon 129 in the mutant allele. It was noted that the disease had occurred at an unusually young age, even for GSS, and the possibility that exposure to CWDinfected venison contributed to early onset of the disease could not be ruled out; the patient’s grandfather had regularly hunted in southeastern Wyoming, around the known CWD-endemic area, and had given venison to the patient’s family. Two other cases of prion disease occurred in individuals of 26 and 28 years of age, from adjacent counties, and with onset of illness only months apart, therefore an environmental source of infection was investigated. However, these two individuals were finally diagnosed with different prion diseases: sporadic CJD in one case and GSS in the other, indicating that a common cause was unlikely. In the first case CJD was confirmed from autopsy samples (by histopathology, immunohistochemistry and immunoblotting); the individual had no history of hunting nor of regular consumption of venison, and although he may have eaten venison originating from the Upper Peninsula of Michigan while at college CWD has never been detected in deer from Michigan. Phenotypically this individual fit the “MM2 sporadic CJD” phenotype described by Parchi et al. (1999). In the other case post mortem immunohistochemistry revealed prion deposition which was consistent with GSS and a GSS P102L mutation was detected in a blood sample from one parent (appropriate samples were not available from the affected patient); this individual may possibly have eaten venison from Michigan on one occasion at about two years of age (Belay et al., 2004). 223. A further three cases of CJD in individuals of 54 to 66 years old who were deer and elk hunters (two individuals) or ate wild-harvested venison (one individual) have been CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 47 of 66 investigated. There was no evidence that any of these individuals had hunted in known CWDendemic areas; information available indicated hunting or eating venison from Washington State and Pennsylvania. Two individuals were V/V at codon 129 the third was M/M; they were considered to fit known subtypes of sporadic CJD (MM1, VV1 and VV2 subtypes as described by Parchi et al. (1999)). Further investigations were also made on the only two nonfamilial cases of CJD in individuals with a history of eating venison from the known CWD-endemic areas. One was reported to have eaten venison from two deer harvested in an area with endemic CWD, but both deer had been tested and not found to be CWD-positive; the patient’s illness was consistent with the CJD subtype MM1. The other individual grew up in a CWD-endemic area and ate locally-harvested venison; her disease fit the MM1 CJD phenotype and no atypical neurological features were noted (Belay et al., 2004). 224. Additional epidemiological notes are that the incidence and age distribution of CJD in Colorado and Wyoming, where CWD is thought to have been endemic for decades, are similar to those found in other areas of the USA. In Wyoming, seven cases of CJD have been reported between 1979 and 2000 with an average annual age-adjusted CJD death rate of 0.8 per million and no cases reported in humans less than 55 years old. In Colorado in the same period 67 cases of CJD have been reported, with an average annual age-adjusted CJD death rate of 1.2 per million (Belay et al., 2004). 225. In summary, there is no evidence of an increase in incidence of CJD in Colorado and Wyoming, nor have epidemiological investigations carried out so far found any evidence of a link between CWD and cases of CJD in persons in the USA (Belay et al., 2001; CDC, 2003; Belay et al., 2004). Laboratory studies 226. There is evidence from an in vitro cell-free system that there may be a considerable “species barrier” reducing the probability that CWD will affect humans. It was shown that PrPres associated with chronic wasting disease (PrPCWD) from elk, mule deer or white-tailed deer was able to readily induce substantial conversion of recombinant cervid PrPsen molecules form any of these three species to the protease-resistant state. In the same system, CWD-associated PrPres was shown to convert human PrPsen but at a much lower efficiency: more than 14-fold lower efficiency than inter-cervid conversion reactions and more than fivefold lower than conversion of human PrPsen by PrPres from the brains of humans with CJD (Raymond et al., 2000). While encouraging, interpretation of this study is complicated by the fact that conversion of human PrPC by PrPBSE and PrPSc from sheep were of similar efficacy, both being more than 10-fold less efficient compared with corresponding homologous conversions) and one of these appears to be orally transmissible to humans (BSE) while the other (scrapie) appears not to be (Raymond et al., 2000). In previous experiments PrPBSE had showed 10-fold greater conversion efficacy for bovine PrPsen than for human codon 129-M (methionine) PrPsen and 30-fold greater conversion efficacy than for human codon 129-V (valine) PrPsen, while ovine PrPSc showed five-fold greater conversion efficacy for ovine PrPsen than for human 129-M PrPsen and eight-fold greater conversion than for human 129- V PrPsen (Raymond et al., 1997). 227. Results of recent work in transgenic mice expressing human PrP (see paragraph 71), in which transmission of CWD from elk by intracerebral inoculation failed, was considered to “strongly suggest” a species barrier to transmission of elk CWD to humans (Kong et al., 2004). CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 48 of 66 Potential risk from consuming cervid products Velvet antler 228. Limited studies to date indicate risk from this product may be very low. No CWDspecific PrP accumulation was detected in a sample of velvet from an elk stag which developed clinical CWD about three months later; there were severe brain lesions and extensive CWD-specific PrP staining in both the brain and peripheral lymphoid tissue of the stag (Kahn et al., 2004). Consumption of venison and other parts of the animal 229. PrPCWD has not been detected in muscle tissue from infected cervids (Spraker et al., 2002c). However, it has been recommended by the World Health Organisation that no parts or products of any animal know to be CWD-positive should be consumed (WHO, 2000). Public health authorities in the USA and Canada have indicated agreement with this (Canadian Food Inspection Agency, 2003; Chronic Wasting Disease Alliance, 2004). It has been suggested that if a harvested cervid is being tested for CWD, the test results should be awaited before the meat is eaten (Wisconsin Department of Agriculture, Trade and Consumer Protection, 2002). Authorities in North America have widely advised that (a) tissues likely to contain the greatest amount of CWD agent in infected cervids, including the brain, spinal cord, lymph nodes, spleen, tonsils and eyes, should not be consumed from any harvested deer; (b) meat should be boned out and fat and connective tissue removed (which would also remove lymph nodes); and (c) hunters should avoid eating meat from deer or elk which look sick or which test positive for CWD (Buege, 2002; Chronic Wasting Disease Alliance, 2004; Williams et al., 2002; Wisconsin Department of Agriculture, Trade and Consumer Protection, 2002; Belay et al., 2004). Potential risk from handling and processing cervids 230. In order to minimise any potential risk from exposure to the agent of CWD, hunters, meat processors and taxidermists handling cervid carcasses are advised to wear latex or rubber gloves when handling or dressing cervids from CWD-endemic areas, to minimise handling of brain and spinal cord, and to thoroughly wash knives and other implements after use on deer or elk carcasses (Belay, 2004; Williams et al., 2002). It has been suggested that the risk of “build-up” of infectious CWD agent in a venison processing plant would be unlikely (Buege, 2002). Potential risk from disposal of carcasses and subsequent contamination of ground/water/air 231. In 2002, a risk analysis was produced on disposal of deer from Wisconsin in municipal solid landfills. It was noted that it is not known how much infected material a human (or animal) must consume or be exposed to in order to be infected with CWD. The report took into account the probable species barrier for transmission to humans (Raymond et al., 2000). It was noted that the CWD agent is hydrophobic and likely to adhere to organic materials within a landfill, taking several months to move through the landfill, and that any infectivity exiting the landfill would be captured in the landfill effluent. If effluent was transferred to a wastewater plant (rather than recirculated in the landfill) the agent would be expected to partition with the sludge fraction, which would be diluted greatly with other solids and mixed with nine inches (22.5 cm) of topsoil, providing “an extremely large dilution factor.” It was concluded that there was no significant risk to human health from disposing of deer infected with CWD in properly constructed landfill sites (Olander, 2002). SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM Bovine Spongiform Encephalopathy (BSE) is a prion Compelling evidence indicates that BSE can be Chronic Wasting Disease (CWD) is a prion disease of elk Interspecies Transmission of Chronic Wasting Disease Squirrel Monkeys (Saimiri sciureus) Richard F. Marsh,1? Anthony E. Kincaid,2 Richard A. Department of Animal Health and Biomedical Sciences, Physical Therapy2 and Department of Medical Nebraska 68178; and Department of Veterinary Molecular State University, Bozeman, Montana 597183 Received 3 May 2005/Accepted 10 August 2005 Chronic wasting disease (CWD) is an emerging prion to humans following exposure to CWD-infected tissues is primates to CWD, two squirrel monkeys were inoculated CWD-inoculated squirrel monkeys developed a progressive 31 and 34 months postinfection. Brain tissue from the isoform of the prion protein, PrP-res, and displayed transmission of CWD to primates. 0022-538X/05/$08.00!0 Copyright © 2005, American Society for Microbiology. Evidence of a molecular barrier limiting G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O?Rourke3, 1NIAID/NIH Rocky Mountain Laboratories, Hamilton, MT Abstract Chronic wasting disease (CWD) is a transmissible snip... Clearly, it is premature to draw firm conclusions about snip... every wonder why they are so big......mad cow protein ; http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html Subject: DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material Greetings FDA, i would kindly like to comment on; Docket 03D-0186 FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Several factors on this apparent voluntary proposal disturbs me greatly, 1. MY first point is the failure of the partial ruminant-to-ruminant feed 2. WHAT about sub-clinical TSE in deer and elk? with the recent 3. WE must ban not only CNS (SRMs specified risk materials), 4. THERE are and have been for some time many TSEs in the 5. UNTIL we ban all ruminant by-products from being fed back 6. IT is paramount that CJD be made reportable in every state 7. WE must learn from our past mistakes, not continue to make REFERENCES Department of Pathology, College of Veterinary Medicine and Biomedical Author for correspondence: Edward Hoover.Fax +1 970 491 0523. e-mail Mule deer fawns (Odocoileus hemionus) were inoculated orally with a snip... These results indicate that mule deer fawns develop detectable PrP res snip... http://vir.sgmjournals.org/cgi/content/full/80/10/2757 and Blood of Deer with Chronic Wasting Disease Robert J. Warren,5 Gary L. Mason,1 Sheila A. Hays,1 Jeanette Hayes-Klug,1 Davis M. Seelig,1 Margaret A. Wild,3 Lisa L. Wolfe,6 Terry R. Spraker,1,2 Michael W. Miller,6 Christina J. Sigurdson,1 Glenn C. Telling,7 Edward A. Hoover1* of cervids, is the potential presence of prions in body fluids. To address this issue directly, we exposed cohorts of CWD-nai¨ve deer to saliva, blood, or urine and feces from CWD-positive deer. We found infectious prions capable of transmitting CWD in saliva (by the oral route) and in blood (by transfusion). The results help to explain the facile transmission of CWD among cervids and prompt caution concerning contact with body fluids in prion infections. http://www.sciencemag.org/cgi/content/abstract/314/5796/133 http://www.sciencemag.org/ THE SEVEN SCIENTIST REPORT *** 03-025IFA http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=dignosing+and+reporting+creutzfeldt+jakob+disease&searchid=1048865596978_1528&stored_search=&FIRSTINDEX=0&journalcode=jama RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc? SOMETHING TO CHEW ON BMJ http://www.bmj.com/cgi/eletters/319/7220/1312/b#EL2 BMJ http://www.bmj.com/cgi/eletters/320/7226/8/b#EL1 USDA/FDA MAD COW PROTEIN IN COMMERCE 2006 Date: September 6, 2006 at 7:58 am PST PRODUCT Subject: MAD COW FEED RECALLS ENFORCEMENT REPORT FOR AUGUST 9, 2006 KY, LA, RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE - CLASS II PRODUCT ______________________________ PRODUCT ______________________________ ______________________________ PRODUCT ______________________________ PRODUCT ______________________________ PRODUCT ______________________________ PRODUCT END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006 ### ### ### ### PRODUCT END OF ENFORCEMENT REPORT FOR July 12, 2006 ### http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html New Orleans District Telephone: 615-781-5380 May 17, 2006 WARNING LETTER NO. 2006-NOL-06 FEDERAL EXPRESS Mr. William Shirley, Jr., Owner Dear Mr. Shirley: On February 12, 17, 21, and 22, 2006, a U.S. Food & Drug Administration Our investigation found you failed to provide measures, including sufficient You failed to use clean-out procedures or other means adequate to prevent You failed to maintain written procedures specifying the clean-out As a result . the poultry meal you manufacture may contain protein derived This letter is not intended as an all-inclusive list of violations at your You should notify this office in writing within 15 working days of receiving Your reply should be directed to Mark W. Rivero, Compliance Officer, U.S. Sincerely, /S Carol S. Sanchez Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, 100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg Primate (oral route)* 1/2 (50%) Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%) PrPres biochemical detection The comparison is made on the basis of calibration of the bovine inoculum inoculated into mice and cattle.8 *Data are number of animals bioassays is generally judged to be about plus or minus 1 log. ic Table 1: Comparison of transmission rates in primates and cattle infected http://www.thelancet.com/journal/journal.isa also have shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection. To cattle: 1 gram of infected brain material (by oral ingestion) Terry S. Singeltary Sr.
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