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 performed by the veterinarian. The subsequent multivariate model (multivariate Clog-log 1) (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 1 were significantly associated with the flock status (Table 3).

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 feeds containing meat and bone meal (MBM), was shown to have a major role in BSE infection of cattle (11). The agent of BSE is not inactivated 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 feeds 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 feeds 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 by MBM in feeds 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 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 by contact with infectious material such as central nervous system or paravertebral ganglia. In France, these fats were prohibited for use in farm animal feeds 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 feeds 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, 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 feeds. It might be scrapie, but it could be also BSE, since cattle were infected by feeds 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 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 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% a 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% a 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 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 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 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.