Sheep feed and scrapie, France.Scrapie scrapie: see prion. is a small ruminant ruminant, any of a group of hooved mammals that chew their cud, i.e., that regurgitate and chew again food that has already been swallowed. Ruminants have an even number of toes on each foot and a stomach with either three or four chambers. , transmissible spongiform encephalopathy Transmissible spongiform encephalopathies (TSEs, also known as prion diseases) are a group of progressive conditions that affect the brain and nervous system of humans and animals and are transmitted by prions. (TSE See Tokyo Stock Exchange. TSE 1. See Tokyo Stock Exchange (TSE). 2. See Toronto Stock Exchange (TSE). ). Although in the past scrapie has not been considered a zoonosis Zoonosis Definition Zoonosis, also called zoonotic disease refers to diseases that can be passed from animals, whether wild or domesticated, to humans. , the emergence of bovine spongiform encephalopathy bovine spongiform encephalopathy: see prion. , transmissible transmissible /trans·mis·si·ble/ (trans-mis´i-b'l) capable of being transmitted. trans·mis·si·ble adj. Capable of being conveyed from one person to another. to humans and experimentally to sheep, indicates that risk exists for small ruminant TSEs in humans. To identify the risk factors for introducing scrapie into sheep flocks, a case-control study case-control study, n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. was conducted in France from 1999 to 2000. Ninety-four case and 350 control flocks were matched by location and main breed. Three main hypotheses were tested: direct contact between flocks, indirect environmental contact, and foodborne risk. Statistical analysis was performed by using adjusted generalized linear models Not to be confused with general linear model. In statistics, the generalized linear model (GLM) is a useful generalization of ordinary least squares regression. It relates the random distribution of the measured variable of the experiment (the with the complementary log-log link function, considering flock size as an offset. A notable effect of using proprietary concentrates and milk replacers was observed. The risk was heterogeneous among feed factories. Contacts between flocks were not shown to be a risk factor. ********** Scrapie is a transmissible spongiform encephalopathy (TSE) affecting sheep and goats (1), as is Creutzfeldt-Jakob disease Creutzfeldt-Jakob disease: see prion. Creutzfeldt-Jakob disease or CJD Rare fatal disease of the central nervous system. It destroys brain tissue, making it spongy and causing progressive loss of mental functioning and motor control. (CJD CJD abbr. Creutzfeldt-Jakob disease CJD Creutzfeldt-Jakob disease, see there ) in humans or bovine spongiform encephalopathy (BSE See Bombay Stock Exchange. BSE See Boston Stock Exchange (BSE). ) in cattle. Moreover, scrapie is contagious in natural conditions (2). Though genetic determinism Genetic determinism is the belief that genes determine physical and behavioral phenotypes. The term may be applied to the mapping of a single gene to a single phenotype or to the belief that most or all phenotypes are determined mostly or exclusively by genes. is a major feature of scrapie, the infectious agent infectious agent Pathogen, see there is nonetheless needed for the disease to develop (3,4). Known to exist for centuries, scrapie was thought to be a possible origin of BSE, although this hypothesis has not yet been verified. Sheep and goats can be experimentally infected with BSE, resulting in a disease that is impossible to distinguish from natural scrapie (5). Since BSE is implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. in the emergence of variant CJD (6,7), the existence of BSE in small ruminants poses a further risk for human health. Scrapie has become a public health challenge, and its propagation must be stopped; therefore, the risk factors for the introduction of scrapie in sheep must be understood. In sheep infected with scrapie, the infectious agent is widely distributed Adj. 1. widely distributed - growing or occurring in many parts of the world; "a cosmopolitan herb"; "cosmopolitan in distribution" cosmopolitan bionomics, environmental science, ecology - the branch of biology concerned with the relations between organisms in the organism. In particular, the gut-associated lymphoid tissues gut-associated lymphoid tissue GALT. See there. and the placenta placenta (pləsĕn`tə) or afterbirth, organ that develops in the uterus during pregnancy. It is a unique characteristic of the higher (or placental) mammals. In humans it is a thick mass, about 7 in. are considered highly important in spreading the disease (8) and can contaminate con·tam·i·nate v. 1. To make impure or unclean by contact or mixture. 2. To expose to or permeate with radioactivity. con·tam·i·nant n. the environment (9). Because feed is considered to be the main, if not the only, contamination source of BSE in cattle (10,11), it can also be presumed to be a potential risk factor for scrapie in sheep. A case-control study of infected and scrapie-free flocks was conducted to identify risk factors for scrapie in sheep flocks in France. Various risk factors hypotheses were tested from the most plausible to the weakest. Materials and Methods Study Design A case-control study of infected and scrapie-free flocks was designed (see online appendix for details; http:// www.cdc.gov/ncidod/EfD/vol11no08/04-1223_app.htm). A flock was defined as having at least 20 adult ewes. To consider the heterogeneity het·er·o·ge·ne·i·ty n. The quality or state of being heterogeneous. heterogeneity the state of being heterogeneous. of exposure to scrapie risk, cases and controls were matched according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. main sheep breed and location. A "case" was any flock having [greater than or equal to] 1 animal that had been shown as scrapie-positive by the French surveillance network from January 1996 to July 2000 (12). Four frequency-matched control flocks were randomly selected from the sheep flocks in which scrapie had never been reported. Flocks that did not meet this criterion were excluded. The suspected risk factors were grouped into 3 categories corresponding to the main working hypotheses of scrapie dissemination. The first category covered risks for transmission by direct contact between flocks and indirectly through the environment. The second category covered foodborne risks. The third category covered other environmental dissemination risks such as equipment sharing between farms or transmission through hay mites. Table 1 describes the 22 potential risk factors studied. Data Collection Information was collected by using a preestablished questionnaire to interview farmers and analyzing farm records. Questions related to potential risk factors covered the 4-year period preceding detection of the first clinical case of scrapie in case flocks and the 4-year period preceding the interview for controls. Additionally, information regarding potential confounding confounding when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies. confounding factor factors including flock size, production type (dairy, meat, or mixed), and intensification level of the flock production was recorded (Table 2). Interviews were conducted from May 1999 to July 2000 with 453 flock owners (98 cases and 355 controls). Nine flocks were excluded because they did not meet the inclusion criteria
Inclusion criteria are a set of conditions that must be met in order to participate in a clinical trial. . A total of 444 flocks (94 cases and 350 controls) were included in the study. Data were encoded and then stored in an Access database (Microsoft Access A database program for Windows, available separately or included in the Microsoft Office suite. Access is programmable using Visual Basic for Applications (VBA). Access can read Paradox, dBASE and Btrieve files, and using ODBC, Microsoft SQL Server, SYBASE SQL Server and Oracle data. 97 SR-2, Microsoft Corporation (company) Microsoft Corporation - The biggest supplier of operating systems and other software for IBM PC compatibles. Software products include MS-DOS, Microsoft Windows, Windows NT, Microsoft Access, LAN Manager, MS Client, SQL Server, Open Data Base Connectivity (ODBC), MS Mail, , Redmond, WA, USA). Study Sample The flocks were mainly located in 2 departments (Pyrenees Atlantiques, n = 267/444, Aveyron n = 51/444). The others were widely distributed throughout metropolitan France Metropolitan France (French: France métropolitaine or la Métropole, or colloquially l'Hexagone) is the part of France located in Europe, including Corsica. . Ten mixed breeds and 23 pure breeds were included in the study. The flocks were mainly specialized in 1 type of production (66% in dairy production, 32% in meat production) (Table 2). The flock size ranged from 21 to 1,787 ewes (mean 274, SD 198). Analysis Data analysis was conducted in 2 steps by using statistical models adjusted for the 2 matching factors through the corresponding cross-variable "strata" (main breed and location) treated as a stratification variable (13). First, to identify the confounding factors to be further analyzed (14), a log-linear model log-linear model a statistical model which models frequency counts in contingency tables by using an analysis of variance approach. considered 5 factors, including flock size (number of ewes), production type, intensification level of the flock production as potential confounding factors, flock status, and strata. The model introduced the main effect of these 5 factors with all second interaction terms. Flock size was the only potential confounding factor notably associated with the flock status (Table 2). Second, to assess associations between flock status and risk factors, a generalized linear model for binary outcome was set up with the complementary log-log link function (Clog-log model) (14) (see online Appendix, available at http://www.cdc.gov/ncidod/EID/vol11no08/041223_app.htm). This model considered the flock size by using the logarithm logarithm (lŏg`ərĭthəm) [Gr.,=relation number], number associated with a positive number, being the power to which a third number, called the base, must be raised in order to obtain the given positive number. of the flock size as an offset (15,16). All exposures were considered as binary, and the absence of exposition was the reference modality modality /mo·dal·i·ty/ (mo-dal´i-te) 1. a method of application of, or the employment of, any therapeutic agent, especially a physical agent. 2. for each risk factor. Factors notably associated with the flock status at 20% level through univariate analysis (Table 1) were selected for subsequent multivariate The use of multiple variables in a forecasting model. analyses. The univariate analysis consisted of the construction of a Clog-log model for each risk factor; strata were systematically introduced as covariate. Furthermore, 2 distinct multivariate models were applied to consider colinearity between feed type and feed factories in the foodborne risk study. The first model (multivariate Clog-log 1) analyzed feed types without regard to factories, whereas the second one (multivariate Clog-log 2) evaluated the risk according to the feed factories that produced milk replacers and proprietary concentrates. Regarding the proprietary feed factories, only the purchase of milk replacers and proprietary concentrates at factory 1 and the purchase of proprietary concentrates at factory 2 occurred frequently enough to be studied separately. Statistical software Splus (S-Plus 2000 Professional Release 2, Mathsoft, Inc., Seattle, WA, USA) was used to analyze the data. Results According to the univariate analysis, 8 potential risk factors were selected (Table 1). Six risk factors were related to foodborne risk; the other 2 were related to purchasing ewes, and cesarean sections cesarean section (sĭzâr`ēən), delivery of an infant by surgical removal from the uterus through an abdominal incision. The operation is of ancient origin: indeed, the name derives from the legend that Julius Caesar was born in this performed by the veterinarian veterinarian /vet·er·i·nar·i·an/ (vet?er-i-nar´e-an) a person trained and authorized to practice veterinary medicine and surgery; a doctor of veterinary medicine. vet·er·i·nar·i·an n. . The subsequent multivariate model (multivariate Clog-log l) (Table 3) showed a significant association between the flock status and using milk replacers. In addition, using the multivariate Clog-log 2 model milk replacers and proprietary concentrates from factory I were significantly associated with the flock status (Table 3). Discussion The main finding of the study was the role of feed as a risk factor for scrapie. This is consistent with what has been shown for BSE in cattle. The use of proprietary concentrates, and more precisely the use of feed containing meat and bone meal Meat and bone meal (MBM) is a product of the rendering industry. It is typically about 50% protein, 35% ash, 8-12% fat, and 4-7% moisture. It is primarily used in the formulation of animal feed to improve the amino acid profile of the feed. (MBM MBM meat and bone meal. ), was shown to have a major role in BSE infection of cattle (11). The agent of BSE is not inactivated inactivated rendered inactive; the activity is destroyed. inactivated viruses treated so that they are no longer able to produce evidence of growth or damaging effect on tissue. by MBM processing methods, which were put into place by the industry in the late 1970s (17). In France, MBM was authorized for small ruminants until July 1994. Moreover, the MBM ban proved to be <100% efficient; hundreds of BSE cases were observed in cattle in France born after the MBM ban of feed for cattle. The exposure period that was investigated in the current study was from 1991 to June 2000, depending on the case. It occurred before the French MBM ban in feed for all farmed animals in November 2000; furthermore, the period investigated was before the MBM ban for small ruminants in France for more than half of the cases. It is, therefore, plausible that sheep may have been contaminated contaminated, v 1. made radioactive by the addition of small quantities of radioactive material. 2. made contaminated by adding infective or radiographic materials. 3. an infective surface or object. by MBM in feed throughout the 1990s, despite control measures. The results showed that 1 feed company was at risk for proprietary concentrates when others were not. This finding is in agreement with the fact that risk might depend on the type of raw materials used in the factory, as well as the way they were processed and used. The risk attributable to milk replacers is the first evidence of such a TSE risk in animals. Milk replacers for all farmed species are made of skimmed skim v. skimmed, skim·ming, skims v.tr. 1. a. To remove floating matter from (a liquid). b. To remove (floating matter) from a liquid. c. cow milk enriched with vegetable or animal fats. Milk has not been shown to be at risk for scrapie transmission (18-20). Even if animal fat is not infectious, the animal fats that were incorporated in milk replacers may have been contaminated. Contamination could have occurred during collection at the slaughterhouse slaughterhouse: see abattoir; meatpacking. by contact with infectious material such as central nervous system or paravertebral ganglia ganglia /gan·glia/ (gang´gle-ah) plural of ganglion. . In France, these fats were prohibited for use in farm animal feed in November 2000. The same factory was identified as selling both the milk replacers and the proprietary concentrates at risk for scrapie. Most farmers buy both their feed concentrates and milk replacers from the same wholesaler (which, in turn, buys from the same factory). Even if the effect of the 2 factors remained in the multivariate analysis multivariate analysis, n a statistical approach used to evaluate multiple variables. multivariate analysis, n a set of techniques used when variation in several variables has to be studied simultaneously. , a confounding effect between these 2 factors cannot be excluded. The main concern raised by this study is the nature of the infectious agent that was transmitted to sheep by means of feed. It might be scrapie, but it could be also BSE, since cattle were infected by teed during the same period in France. In 2005, BSE in a goat was first reported in France (21); in the United Kingdom, a goat that was thought to have scrapie in 1990 is being reexamined because it is now suspected to have had BSE (http://www.defra.gov.uk/ news/2005/050208a.htm). In France, every index case animal from infected small ruminant flocks that has been reported since the surveillance began in 1990 has been biochemically tested to distinguish natural scrapie isolates from isolates sharing common biochemical features with experimental ovine ovine pertaining to, characteristic of, or derived from sheep. ovine atopic dermatitis symmetrical erythema, alopecia, lichenification, excoriation on woolless areas; sporadic cases, recur each summer. BSE (validated by the TSEs Community Reference Laboratory of Weybridge, UK [unpub. data]). Among >400 small ruminant field isolates tested in France, only 1 isolate from a goat was indistinguishable from BSE. These arguments suggest that the agent transmitted to sheep by food was scrapie rather than BSE. Moreover, BSE is thought to have been transmitted and amplified by recycling contaminated carcasses into MBM on a regional basis (22). It follows that if the sheep identified as having scrapie did in fact have BSE, this misconception mis·con·cep·tion n. A mistaken thought, idea, or notion; a misunderstanding: had many misconceptions about the new tax program. would have occurred in the same regions as BSE in cattle. That the areas of France most at risk for BSE in cattle (23) were different from those where scrapie occurred during the study does not suggest that the infectious agent for sheep was BSE. Unexpectedly, the other hypotheses concerning the contamination of flocks with scrapie were not confirmed by the present study. In Norway, a matched case-control study showed 3 risk factors, though at a 10% [alpha] level: purchasing females, sharing rams, and sharing pastures between flocks (24). However, in a recent Irish study, purchasing breeding sheep through markets was not a risk factor for scrapie at a 5% [alpha] level (25). In the Norwegian study, feed did not appear to be a risk factor, whereas in the Irish study, feeding proprietary concentrates to lambs appeared to be protective. In the present study, purchasing ewes may not have emerged as a risk factor merely because of the lack of power of the study. The link between cesarean sections and scrapie occurrence that was observed in the univariate analysis was likely due to a confounding effect with the real risk factors and so became nonsignificant non·sig·nif·i·cant adj. 1. Not significant. 2. Having, producing, or being a value obtained from a statistical test that lies within the limits for being of random occurrence. in the multivariate analyses. Beyond the limits of the study, our results clearly show that in France, and more precisely in southwest France where most of the studied farms were located, the major risk for the introduction of scrapie in a flock during the 1990s was feeding certain proprietary concentrates and, possibly, milk replacers to sheep. Exposing sheep to TSE risk by feeding has certainly decreased since that time because of the complementary control measures taken in 1996 (ban on specified risk materials Specified risk materials (SRMs) are the parts of ruminant animal most likely to be contaminated with TSE prions. These can include brains, eyes, spinal cord, and other organs. The exact definition varies by jurisdiction. and cadavers in the processing of MBM) and 2000 (complete ban of MBM and certain animal fats for all farmed animals). However, it is essential to monitor these risk factors over time in France and to extend this kind of study to other countries in which the disease occurs. The study results show strong evidence that TSEs can spread to sheep through feeding in field conditions, as is the case for cattle. Given the potential risk for humans, the possibility of BSE spreading to sheep must be taken seriously, even though the horizontal transmission horizontal transmission n. Transmission of infection by contact. horizontal transmission Epidemiology The transmission of an infection from one to another person of the same generation in the same population. of BSE in sheep would occur and stay at a low level (26), should such contamination occur (27). In any case, such findings support the need for a more comprehensive surveillance of TSEs in sheep, as well as the need to systematically examine all scrapie cases for their resemblance to BSE.
Table 1. Univariate analysis of potential risk factors
Risk factors Modalities No. controls (%)
Direct contacts between flocks
and indirect environmental
contacts
Purchase of ewes No 227 (65)
Yes 123 (35)
Purchase of rams No 146 (42)
Yes 204 (58)
Temporary direct contacts No 230 (66)
between flocks ([dagger]) Yes 120 (34)
Stay of animals in other No 319 (91)
flocks with direct Yes 31 (9)
contacts
Stay of animals from other No 332 (95)
flocks with direct Yes 18 (5)
contacts
Presence of small ruminants No 71 (20)
in the vicinity of the Yes 279 (80)
farm
Sharing paths No 149 (43)
Yes 201 (57)
Other indirect environmental No 311 (89)
contacts ([double dagger]) Yes 39 (11)
Feeding
Purchase of raw materials No 213 (61)
([section]) Yes 137 (39)
Purchase of milk replacers No 287 (82)
([paragraph]) Yes 63 (18)
Purchase of proprietary No 79 (23)
concentrates ([paragraph]) Yes 271 (77)
Purchase of milk replacers No 329 (94)
from factory 1 Yes 21 (6)
Purchase of milk replacers No 317 (91)
from other factories Yes 33 (9)
Purchase of proprietary No 271 (77)
concentrates from Yes 79 (23)
factory 1
Purchase of proprietary No 292 (83)
concentrates from Yes 58 (17)
factory 2
Purchase of proprietary No 228 (65)
concentrates from other Yes 122 (35)
factories
Other indirect contacts
Artificial insemination No 247 (71)
Yes 103 (29)
Cesarean section performed No 163 (47)
by veterinarian Yes 187 (53)
Ear-tagging No 236 (67)
Yes 114 (33)
Sharing of farming devices No 85 (24)
Yes 265 (76)
Presence of dogs on the farm No 325 (93)
Yes 25 (7)
Purchase of hay No 247 (71)
Yes 103 (29)
Risk factors Modalities No. cases (%)
Direct contacts between flocks
and indirect environmental
contacts
Purchase of ewes No 55 (59)
Yes 39 (41)
Purchase of rams No 33 (35)
Yes 61 (65)
Temporary direct contacts No 66 (70)
between flocks ([dagger]) Yes 28 (30)
Stay of animals in other No 87 (93)
flocks with direct Yes 7 (7)
contacts
Stay of animals from other No 91 (97)
flocks with direct Yes 3 (3)
contacts
Presence of small ruminants No 14 (15)
in the vicinity of the Yes 80 (85)
farm
Sharing paths No 39 (41)
Yes 55 (59)
Other indirect environmental No 85 (90)
contacts ([double dagger]) Yes 9 (10)
Feeding
Purchase of raw materials No 66 (70)
([section]) Yes 28 (30)
Purchase of milk replacers No 66 (70)
([paragraph]) Yes 28 (30)
Purchase of proprietary No 7 (7)
concentrates ([paragraph]) Yes 87 (93)
Purchase of milk replacers No 76 (81)
from factory 1 Yes 18 (19)
Purchase of milk replacers No 87 (93)
from other factories Yes 7 (7)
Purchase of proprietary No 48 (51)
concentrates from Yes 46 (49)
factory 1
Purchase of proprietary No 85 (90)
concentrates from Yes 9 (10)
factory 2
Purchase of proprietary No 54 (57)
concentrates from other Yes 40 (43)
factories
Other indirect contacts
Artificial insemination No 57 (61)
Yes 37 (39)
Cesarean section performed No 28 (30)
by veterinarian Yes 66 (70)
Ear-tagging No 55 (59)
Yes 39 (41)
Sharing of farming devices No 22 (23)
Yes 72 (77)
Presence of dogs on the farm No 84 (89)
Yes 10 (11)
Purchase of hay No 70 (74)
Yes 24 (26)
Univariate
Clog-log model
Risk factors Modalities OR * 80% CI
Direct contacts between flocks
and indirect environmental
contacts
Purchase of ewes No 1.0 --
Yes 1.3 1.0-1.8
Purchase of rams No 1.0 --
Yes 1.0 0.8-1.4
Temporary direct contacts No 1.0 --
between flocks ([dagger]) Yes 0.7 0.5-1.1
Stay of animals in other No 1.0 --
flocks with direct Yes 0.7 0.4-1.3
contacts
Stay of animals from other No 1.0 --
flocks with direct Yes 0.8 0.4-1.9
contacts
Presence of small ruminants No 1.0 --
in the vicinity of the Yes 1.1 0.7-1.7
farm
Sharing paths No 1.0 --
Yes 0.9 0.7-1.2
Other indirect environmental No 1.0 --
contacts ([double dagger]) Yes 0.7 0.4-1.2
Feeding
Purchase of raw materials No 1.0 --
([section]) Yes 0.6 0.4-0.8
Purchase of milk replacers No 1.0 --
([paragraph]) Yes 2.0 1.4-2.7
Purchase of proprietary No 1.0 --
concentrates ([paragraph]) Yes 2.2 1.2-3.8
Purchase of milk replacers No 1.0 --
from factory 1 Yes 3.1 2.1-4.6
Purchase of milk replacers No 1.0 --
from other factories Yes 0.9 0.5-1.6
Purchase of proprietary No 1.0 --
concentrates from Yes 2.6 1.9-3.5
factory 1
Purchase of proprietary No 1.0 --
concentrates from Yes 0.4 0.2-0.7
factory 2
Purchase of proprietary No 1.0 --
concentrates from other Yes 1.2 0.8-1.7
factories
Other indirect contacts
Artificial insemination No 1.0 --
Yes 1.0 0.7-1.5
Cesarean section performed No 1.0 --
by veterinarian Yes 1.9 1.3-2.7
Ear-tagging No 1.0 --
Yes 1.1 0.8-1.6
Sharing of farming devices No 1.0 --
Yes 0.7 0.5-1.0
Presence of dogs on the farm No 1.0 --
Yes 1.1 0.7-1.7
Purchase of hay No 1.0 --
Yes 0.7 0.5-1.0
* OR, odds ratio; CI, confidence interval.
([dagger]) Contacts by transhumance or common pastures
with contacts between animals.
([double dagger]) e.g., common pastures without direct
contacts between animals.
([section]) Purchase of hay excluded because considered
in other indirect contacts.
([paragraph]) Independently of the factories.
Table 2. Multivariate analysis of potential confounding factors
Factors Modalities * No. controls (%) No. cases (%)
Flock size <133 * 100 (29) 11 (12)
133-236 87 (25) 24 (25)
237-366 77 (22) 33 (35)
>366 86 (25) 26 (28)
Type of flock Dairy * 229 (65) 64 (68)
Meat 113 (32) 27 (29)
Mixed 8 (2) 3 (3)
Intensification None * 241 (69) 56 (60)
criteria Production 38 (11) 16 (17)
monitoring
Involvement in a 71 (20) 22 (23)
breeding scheme
Log-linear model
Factors Modalities * OR ([dagger]) 95% CI
Flock size <133 * 1.0 --
133-236 2.5 1.1-5.5
237-366 4.0 1.8-8.6
>366 3.0 1.3-7.0
Type of flock Dairy * 1.0 --
Meat 1.0 0.3-3.2
Mixed 1.2 0.3-5.5
Intensification None * 1.0 --
criteria Production 1.8 0.8-3.8
monitoring
Involvement in a 1.1 0.6-2.1
breeding scheme
* Reference modality.
([dagger]) OR, odds ratio; CI, confidence interval.
Table 3. Multivariate analysis of risk factors
Risk factors Modalities * No. cases (%)
Direct contacts between flocks
and indirect environmental
contacts
Purchase of ewes No 39 (41)
Yes
Feeding
Purchase of raw materials No 28 (30)
(hay excluded) Yes
Purchase of milk replacers No 28 (30)
Yes
Purchase of proprietary No 87 (93)
concentrates Yes
Purchase of milk replacers No 18 (19)
from factory 1 Yes
Purchase of proprietary No 46 (49)
concentrates from Yes
factory 1
Purchase of proprietary No 9 (10)
concentrates from Yes
factory 2
Other indirect contacts
Cesarean section performed No 66 (70)
by veterinarian Yes
Risk factors Modalities * No. controls (%)
Direct contacts between flocks
and indirect environmental
contacts
Purchase of ewes No 123 (35)
Yes
Feeding
Purchase of raw materials No 137 (39)
(hay excluded) Yes
Purchase of milk replacers No 63 (18)
Yes
Purchase of proprietary No 271 (77)
concentrates Yes
Purchase of milk replacers No 21 (6)
from factory 1 Yes
Purchase of proprietary No 79 (23)
concentrates from Yes
factory 1
Purchase of proprietary No 58 (17)
concentrates from Yes
factory 2
Other indirect contacts
Cesarean section performed No 187 (53)
by veterinarian Yes
Multivariate
Clog-log 1
Risk factors Modalities * OR ([dagger]) 95% CI
Direct contacts between flocks
and indirect environmental
contacts
Purchase of ewes No 1 --
Yes 1.3 0.9-2.0
Feeding
Purchase of raw materials No 1 --
(hay excluded) Yes 0.6 0.4-1.0
Purchase of milk replacers No 1 --
Yes 1.9 1.2-3.0
Purchase of proprietary No 1 --
concentrates Yes 1.5 0.7-3.4
Purchase of milk replacers No
from factory 1 Yes NI
Purchase of proprietary No
concentrates from Yes NI
factory 1
Purchase of proprietary No
concentrates from Yes NI
factory 2
Other indirect contacts
Cesarean section performed No 1 --
by veterinarian Yes 1.6 0.9-2.8
Multivariate
Clog-log 2
Risk factors Modalities * OR 95% CI
Direct contacts between flocks
and indirect environmental
contacts
Purchase of ewes No 1 --
Yes 1.3 0.8-2.0
Feeding
Purchase of raw materials No 1 --
(hay excluded) Yes 0.7 0.4-1.0
Purchase of milk replacers No
Yes NI
Purchase of proprietary No
concentrates Yes NI
Purchase of milk replacers No 1 --
from factory 1 Yes 1.9 1.0-3.5
Purchase of proprietary No 1 --
concentrates from Yes 2.0 1.2-3.3
factory 1
Purchase of proprietary No 1 --
concentrates from Yes 0.7 0.3-1.5
factory 2
Other indirect contacts
Cesarean section performed No 1 --
by veterinarian Yes 1.4 0.8-2.5
* Reference modality = No.
([dagger]) OR, odds ratio; CI, confidence interval, NI, not in model.
Acknowledgments We thank N. Dorr for implementing the database, J.-P. Chacornac for data input, the farmers for their collaboration, the veterinarians Veterinarians and veterinary surgeons (vets) are medical professionals who operate exclusively on animals. Well-known and notable veterinarians include:
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Hunter N, Cairns Cairns, city (1991 pop. 64,463), Queensland, NE Australia, on Trinity Bay. It is a principal sugar port of Australia; lumber and other agricultural products are also exported. The city's proximity to the Great Barrier Reef has made it a tourist center. D, Foster JD, Smith G, Goldmann W, Donnelly K. Is scrapie solely a genetic disease? Nature. 1997;386:137. (4.) Prusiner SB. Genetic and infectious prion diseases Prion disease Transmissible spongiform encephalopathies in both humans and animals. Scrapie is the most common form in animals, while in humans the most prevalent form is Creutzfeldt-Jakob disease. . Arch Neurol. 1993;50:1129-53. (5.) Foster JD, Hope J, Fraser H. Transmission of bovine spongiform encephalopathy to sheep and goats. Vet Rec. 1993:133:339-41. (6.) Hill A, Desbruslais M, Joiner S join·er n. 1. A carpenter, especially a cabinetmaker. 2. Informal A person given to joining groups, organizations, or causes. , Sidle si·dle v. si·dled, si·dling, si·dles v.intr. 1. To move sideways: sidled through the narrow doorway. 2. KCL KCL - Kyoto Common Lisp . Gowland I, Collinge J. The same prion prion (prī`ŏn), infectious agent thought to cause a group of diseases known as prion diseases or transmissible spongiform encephalopathies. strain causes vCJD and BSE. Nature. 1997;389: 448-50. (7.) Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology aetiology see etiology. of 'new variant' CJD. Nature. 1996;383:685-90. (8.) Ryder S Ry·der , Albert Pinkham 1847-1917. American painter known for his rhythmic allegorical works, landscapes, and marine scenes, such as Toilers of the Sea (c. 1884). , Dexter G, Bellworthy S, Tongue S. Demonstration of lateral transmission of scrapie between sheep kept under natural conditions using lymphoid tissue lymphoid tissue Cells, tissues, and organs composing the immune system, including the bone marrow, thymus, spleen, and lymph nodes. The most highly organized components are the thymus and lymph nodes, and the least organized are the cells that wander in the loose biopsy. Res Vet Sci. 2004:76:211-7. (9.) Sigurdarson S. Epidemiology of scrapie in Iceland and experience with control measures. In: Bradley R, Savey M, Marchant B, editors. Sub-acute spongiform encephalopathies spongiform encephalopathy n. Encephalopathy characterized by progressive diffuse vacuolation of the cerebral cortex. . Brussels: Kluwer Academic Publishers; for the Commission of the European Communities European Community: see European Union. European Community (EC) Organization formed in 1967 with the merger of the European Economic Community, European Coal and Steel Community, and European Atomic Energy Community. ; 1991. p. 233-42. (10.) Wilesmith JW, Ryan JBM JBM Jamaica Bauxite Mines JBM Joint Border Management , Atkinson MJ. Bovine spongiform encephalopathy: epidemiological studies An Epidemiological study is a statistical study on human populations, which attempts to link human health effects to a specified cause. on the origin. Vet Rec. 1991;128:199-203. (11.) Wilesmith JW, Ryan JBM, Hueston WD. Bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal bone´meal` n. 1. ground bones, used as a fertilizer or as a component in animal feed; - it is high in phosphate content. Noun 1. inclusion in proprietary concentrates. Res Vet Sci. 1992:52:325-31. (12.) Calavas D, Philippe S, Ducrot C, Schelcher F, Andreoletti O, Belli P, et al. Bilan et analyse de trente mois de fonctionnement du Reseau ré·seau or re·seau n. pl. réseaus or réseaux 1. A net or mesh foundation for lace. 2. Astronomy francais d'epidemiosurveillance de la tremblante la tremblante [Fr.] see scrapie. des petits ruminants. Epidemiologie et Sante Animale. 1999;35:43-50. (13.) Breslow NE, Day NE: Statistical methods in cancer research. Lyon, France: IARC Scientific Publication; 1980. (14.) McCullagh P, Nelder JA. Generalized linear models. 2nd ed. Boca Raton Boca Raton (bō`kə rətōn`), city (1990 pop. 61,492), Palm Beach co., SE Fla., on the Atlantic; inc. 1925. Boca Raton is a popular resort and retirement community that experienced significant industrial development in the 1970s and 80s. (FL): Chapman and Hall Chapman and Hall was a British publishing house, founded in the first half of the 19th century by Edward Chapman and William Hall. Upon Hall's death in 1847, Chapman's cousin Frederic Chapman became partner in the company, of which he became sole manager upon the retirement of ; 1989. (15.) Allard R. A family of mathematical models to describe the risk of infection by a sexually transmitted agent. Epidemiology. 1990;1:30-3. (16.) Shiboski S, Padian NS. Population- and individual-based approaches to the design and analysis of epidemiologic studies epidemiologic study A study that compares 2 groups of people who are alike except for one factor, such as exposure to a chemical or the presence of a health effect; the investigators try to determine if any factor is associated with the health effect of sexually transmitted disease sexually transmitted disease (STD) or venereal disease, term for infections acquired mainly through sexual contact. Five diseases were traditionally known as venereal diseases: gonorrhea, syphilis, and the less common granuloma inguinale, transmission. J Infect Dis. 1996;174(Suppl 2):S188-200. (17.) Taylor DM, Fernie K, McConnell I, Ferguson CE, Steele PJ. Solvent extraction Solvent extraction A technique, also called liquid extraction, for separating the components of a liquid solution. This technique depends upon the selective dissolving of one or more constituents of the solution into a suitable immiscible liquid solvent. as all adjunct to rendering: the effect on BSE and scrapie agents of hot solvents followed by dry heat and steam. Vet Rec. 1998;143:6-9. (18.) Hadlow WJ, Kennedy RC, Race RE, Eklund CM. Virologic and neurohistologic findings in dairy goats affected with natural scrapie. Vet Pathol. 1980:17:187-99. (19.) Hourrigan JL. Experimentally induced bovine spongiform encephalopathy in cattle in Mission, Tex, and the control of scrapie. J Am Vet Med Assoc. 1990:196:1678-9. (20.) Pattison IH, Millson GC. Experimental transmission of scrapie to goats and sheep by the oral route. J Comp Pathol. 1961;71:171-6. (21.) Eloit M, Adjou K, Coulpier M, Fontaine JJ, Hamel Ham´el v. t. 1. Same as Hamble. R, Lilin T, et al. BSE agent signatures in a goat. Vet Rec. 2005;156:523-4. (22.) Ducrot C, Abrial D, Calavas D, Carpenter T. A spatio-temporal analysis of BSE cases born before and after the reinforced feed ban in France. Vet Res. 2005: In press. (23.) Abrial D, Calavas D, Jarrige N, Ducrot C. Spatial heterogeneity Environments with a wide variety of habitats such as different topographies, soil types and climates are able to accommodate a greater amount of species. Spatial heterogeneity of the risk of BSE in France following the ban of meal and bone meal in cattle feed. Prev Vet Med. 2005;67:69-82. (24.) Hopp P, Ulvund MJ, Jarp J. A case-control study on scrapie in Norwegian sheep flocks. Prev Vet Med. 2001;51:183-98. (25.) Healy AM, Hannon D, Morgan KL, Weavers E, Collins JD, Doherty ML. A paired case-control study of risk factors for scrapie in Irish sheep flocks. Prev Vet Med. 2004;64:73-83. (26.) Foster JD, Goldmann W, McKenzie C, Smith A, Parnham DW, Hunter N. Maternal transmission studies of BSE in sheep. J Gen Virol. 2004;85:3159-63. (27.) Kao RR, Gravenor MB, Baylis M, Bostock C J, Chihota CM, Evans JC, et al. The potential size and duration of an epidemic of bovine spongiform encephalopathy in British sheep. Science. 2002:295: 332-5. Sandrine Philippe, * Christian Ducrot, ([dagger]) Pascal Roy, ([double dagger double dagger n. A reference mark ( ) used in printing and writing. Also called diesis.Noun 1. ])Laurent Remontet, ([double dagger]) Nathalie Jarrige, * and Didier Calavas * * Agence Francaise de Securite Sanitaire des Aliments ALIMENTS. In the Roman and French law this word signifies the food and other things necessary to the support of life, as clothing and the like. The same name is given to the money allowed for aliments. Dig. 50, 16, 43. 2. , Lyon, France; ([dagger]) Institut National de la Recherche Agronomique “INRA” redirects here. For other uses, see INRA (disambiguation). The Institut National de la Recherche Agronomique (INRA) is a French public research institute dedicated to scientific studies surrounding the problems of agriculture. , Theix, France; and ([double dagger]) Centre Hospitalo-Universitaire Lyon-Sud, Lyon, France This work was funded by the Comite Interministeriel sur les ESST ESST European Inter-University Association on Society, Science and Technology ESST European Society of Sleep Technologists ESST Environmental Simulation for Sensitivity Training et les Prions and by the French Ministry of Agriculture. Ms. Philippe is an epidemiologist whose research interests include the epidemiology of animal transmissible spongiform encephalopathies. Address for correspondence: Didier Calavas, Agence francaise de secu rite sanitaire des aliments, 31 av. Tony Gamier, F69364 Lyon Cedex 07, France; fax: 33-4-78-61-91-45; email: d.calavas@lyon.afssa.fr |
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) used in printing and writing. Also called diesis.
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