Surgical Management of a Salter-Harris Type I Distal Physeal Fracture of the Tibia in a Calf: A Case Report.

Fractures are common conditions in cattle, including tibial fractures. Physeal tibial fractures are more specific and less frequently met in field conditions. A calf with a Salter-Harris type I distal physeal fracture of the tibia was referred to the National Veterinary School of Toulouse (ENVT), France. Although the use of external fixators in the treatment of tibial fractures is common, distal physeal tibial fractures require a different and specific technique involving them. They were first used as a lever arm to reduce the fracture due to the severe displacement. A hock joint bypass was then performed. Six weeks after treatment, the calf recovered successfully from the use of the affected limb without any adverse sequelae. The present case provides management of a distal tibial fracture using external fixators. This innovative and accessible surgical technique may be used by veterinary practitioners in future similar cases of distal tibial fractures when pins in the distal end cannot be inserted.

Presence or severity of hypophosphatemia is not associated with survival outcome in postpartum downer dairy cows.

OBJECTIVE: To evaluate the association between serum phosphorus concentration and the outcome of postpartum downer cows. ANIMALS: Postpartum downer dairy cows presented over a 22-year period. PROCEDURES: In this cross-sectional study (1994 to 2016), medical records of all postpartum downer cows presented to a referral large animal hospital were reviewed. The association between serum inorganic phosphorus concentration and survival was assessed using a multivariable logistic regression. RESULTS: 907 postpartum downer dairy cows were included and classified as hypophosphatemic (mild: > 2.25 to < 3.25 mg/dL, moderate: > 1.50 to ≤ 2.25 mg/dL, and severe: ≤ 1.50 mg/dL), normophosphatemic (≥ 3.25 and ≤ 8.76 mg/dL) or hyperphosphatemic (> 8.76 mg/dL). Hypophosphatemia was observed in 19.4% of the cows (n = 176). Of those, 54.5% (n = 96) were also hypocalcemic. Overall, 58.4% cows (n = 530) survived after hospitalization. Hypophosphatemia was not significantly associated with the outcome of postpartum downer cows (mild: OR = 1.0, 95% CI: 0.6 to 1.8; moderate: OR = 0.5, 95% CI: 0.2 to 1.1; severe: OR = 1.0, 95% CI: 0.4 to 2.4). CLINICAL RELEVANCE: Low serum phosphorus concentration was frequently observed with hypocalcemia and was not associated with the outcome of postpartum downer cows.

Pruritic eosinophilic dermatitis in Jersey cows infested with Leptotrombidium spp (Acari: Trombiculidae).

Eosinophilic dermatitis was observed in skin samples from Jersey cows, sampled in mid-October in south-west France. The inflammatory response was considered to be the result of Trombiculidae bites. Clinical signs were assumed to be due partly to self-trauma and included patchy alopecia with crusted papules; lesions were observed on the jaws, dewlap, perineum and distal limbs. Identified parasites were larvae of Leptotrombidium spp. The lesions had completely self-resolved by December.

La dermatite éosinophilique a été observée dans des échantillons cutanés prélevés sur des vaches Jersey à la mi-octobre dans le sud-est de la France. La réponse inflammatoire a été considérée comme résultant de piqures de Trombiculidae. Les signes cliniques ont été considérés comme étant en partie dus à des auto-traumatismes et comprenaient une alopécie en patch avec papules croûteuses ; les lésions ont été observées sur les mâchoires, les fanons, le périnée et les extrémités distales des membres. Les parasites identifiés étaient des larves de Leptotrombidium spp. Les lésions se sont résolues en totalité spontanément en décembre.

Se observó dermatitis eosinofílica en muestras de piel de vacas Jersey, muestreadas a mediados de octubre en el suroeste de Francia. Se consideró que la respuesta inflamatoria era el resultado de las picaduras de Trombiculidae. Se asumió que los signos clínicos se debían en parte al autotraumatismo e incluían alopecia en parches con pápulas costrosas; se observaron lesiones en mandíbulas, papada, perineo y extremidades distales. Los parásitos identificados fueron larvas de Leptotrombidium spp. Las lesiones se habían resuelto completamente en diciembre.

Observou-se dermatite eosinofílica em amostras de pele de vacas Jersey, coletadas no meio de outubro no sudoeste da França. A resposta inflamatória foi considerada resultante de picadas de trombiculídeos. Os sinais clínicos foram considerados como sendo causados parcialmente por auto-traumatismo e incluíram alopécia focal com pápulas crostosas; as lesões foram observadas nas mandíbulas, barbela, períneo e região distal dos membros. Os parasitas identificados foram larvas de Leptotrombidium spp. O quadro apresentou resolução espontânea completa em dezembro.

First detection of Mycoplasma wenyonii in France: Identification, evaluation of the clinical impact and development of a new specific detection assay.

Mycoplasma wenyonii, a hemoplasma infecting cattle, was never detected in France. In 2014, evocative inclusions were observed in erythrocytes from cattle presenting milk drops, anemia, and edema in Brittany (France). A survey was then initiated to investigate the epidemiological situation and correlate mycoplasma detection with clinical signs. For this purpose, a new PCR assay targeting polC gene was designed. Comparative results with published PCR assays place this new one as more specific, allowing a one-step diagnosis without further sequencing. A total of 181 cows were included in this study and 4.97% (n = 9) were positive, resulting in the first molecular identification of M. wenyonii in France. All positive animals presented anemia, edema and milk drop. When selecting animals presenting evocative clinical signs, the prevalence of M. wenyonii in Brittany was estimated to 25.6%. Further studies are needed to evaluate the importance of the infection, the implication of arthropods and the existence of asymptomatic carriers.

Urinalysis and determination of the urine protein-to-creatinine ratio reference interval in healthy cows.

BACKGROUND: There are no reference intervals for urinalysis in cattle. HYPOTHESIS/OBJECTIVES: Characterize the urine of healthy cows, establish urine protein-to-creatinine ratio (UPC) reference intervals, and test possible differences among dairy and beef cattle, age groups, or stage of lactation. ANIMALS: Seventy-seven dairy and 74 beef 2.5 to 17 year-old cows of different breeds housed mainly in free stall. METHODS: In this prospective study, urine specimens were collected by catheterization. Complete urinalysis was performed within 1 hour including specific gravity, dipstick evaluation, visual urine pH evaluation with 0.3 pH unit graded strips, and microscopic evaluation of the sediment. Urinary protein and creatinine concentrations and protein electrophoresis were determined on frozen aliquots. RESULTS: Overall reference intervals were 1.020 to 1.045 for USG, 7.0 to 8.7 for pH, and 0.04 to 0.25 for UPC; because of differences in creatinine concentration, UPC was lower in beef (0.04-0.14) than in dairy (0.05-0.25) cows and in the latter in dry than lactating cows. With dipstick evaluation, most analytes were absent except for blood, ketone, and protein in 24.7, 16.0, and 64.7% of cases, respectively. Microscopic evaluation revealed less than 3 red blood cells, leukocytes, and epithelial cells in 84, 99.3, and 100% cows, respectively. No band was observed at electrophoresis, except in 1 case at MW ~66 000. CONCLUSIONS AND CLINICAL IMPORTANCE: Creatininuria is higher in beef than dairy cows and proteinuria is likely more efficiently characterized by protein concentration than by UPC.

Hematology reference intervals for adult cows in France using the Sysmex XT-2000iV analyzer.

In order to develop bovine hematology reference intervals (RIs) in accordance with new international recommendations, we analyzed 156 blood specimens of healthy adult dairy and beef cows from 32 farms with a Sysmex XT-2000iV analyzer, and by manual scoring of platelet clumps and white blood cell (WBC) differential. We established RIs by the nonparametric method, and examined effects of age, production type (beef vs. dairy), and stage of lactation. RIs could not be determined for platelet count and indices because clumps were observed in 80% of specimens. Optical and impedance red blood cell (RBC) counts were similar, although statistically different. RIs for analyzer and manual WBC differentials were not different except for lymphocyte concentration, the subpopulations of which were counted manually. Hematocrit was higher in beef than dairy cattle, and hemoglobin was lower in early lactation. Increases in RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and RBC distribution width were noted with increasing age, along with decreases in WBC count, neutrophils, and lymphocytes. Most RIs in our study, with the exception of neutrophils, were similar to those previously reported using a flow cytometry analyzer.

Classical scrapie transmission in ARR/ARR genotype sheep.

The ARR allele is considered to provide a very strong resistance against classical scrapie infection in sheep. In this study, we report the occurrence of clinical transmissible spongiform encephalopathy in ARR/ARR sheep, following their inoculation by the intracerebral route with a classical scrapie isolate. On first passage, the disease displayed an incomplete attack rate transmission, with incubation periods exceeding 6 years. On second passage, the obtained prion did not display better abilities to propagate than the original isolate. These transmission results contrasted with the 100 % attack rate and the short incubation periods observed in ARQ/ARQ sheep challenged with the same isolate. These data confirm that ARR/ARR sheep cannot be considered to be fully resistant to classical scrapie. However, they also support the contention that classical scrapie has a very limited capacity to transmit and adapt to ARR/ARR sheep.

Efficacy of sainfoin (Onobrychis viciifolia) pellets against multi resistant Haemonchus contortus and interaction with oral ivermectin: Implications for on-farm control.

The worldwide spread of resistance to anthelmintic (AH) drugs in gastrointestinal nematodes (GINs) imposes to explore alternative solutions. Amongst those, the possible use of tannin-containing nutraceuticals appears as a relevant option to replace (or decrease the frequency of) chemical-based treatments. Our objectives were to test the AH efficacy of sainfoin pellets against a multiresistant strain of Haemonchus contortus in experimentally infected lambs and to examine possible interaction between ivermectin (IVM) and condensed tannins (CT)-rich ressource. In vivo study was performed with twenty-four lambs were inoculated (Day 0) with multiresistant H. contortus infective larvae. On D21 Post-Infection, the lambs were assigned to two dietary treatments (sainfoin vs lucerne control pellets). On D39, half of the animals per group received 0.25ml/kg of an oral ivermectin treatment. On D47, animals were slaughtered to count worms. The consumption of sainfoin was associated with higher packed cell volume (PCV) values (P<0.05) and reduced faecal egg counts (FECs) (P<0.05). For the experimental feeding period, FECs were overall reduced by 50% in the sainfoin group. The diet did not have significant effect on the worm number but sainfoin significantly reduced female fertility. Decrease in plasma IVM concentrations was observed in the sainfoin-fed animals and was associated with a decrease of IVM efficiency when compared with the control group. Incubating tannin in vitro with ivermectin and rumen fluid showed a blocking of ivermectin by the tannins. This suggests that tannins lower the IVM intestinal absorption compromising thereby drug plasma bioavailability and efficacy. Tannin-containing nutraceuticals alter the biology of multiresistant nematodes, thus representing an option for their sustainable control. In vivo and in vitro interactions between nutraceuticals and chemicals impose caution when both tannin-rich diet and drug-based treatments are combined. Further studies are required to clarify the mechanisms that support such interactions.

PrP expression level and sensitivity to prion infection.

Mice overexpressing the prion protein (PrP) sequence from various host species are widely used for measuring infectious titers in prion disease. However, the impact that the transgene expression level might have on the susceptibility to infection raises some concerns about the final biological relevance of these models. Here we report that endpoint titration of a sheep scrapie isolate in sheep and in mice overexpressing the ovine PrP results in similar estimates of the infectious titer.

Genetic resistance to scrapie infection in experimentally challenged goats.

In goats, several field studies have identified coding mutations of the gene encoding the prion protein (I/M142, N/D146, S/D146, R/Q211, and Q/K222) that are associated with a lower risk of developing classical scrapie. However, the data related to the levels of resistance to transmissible spongiform encephalopathies (TSEs) of these different PRNP gene mutations are still considered insufficient for developing large-scale genetic selection against scrapie in this species. In this study, we inoculated wild-type (WT) PRNP (I142R154R211Q222) goats and homozygous and/or heterozygous I/M142, R/H154, R/Q211, and Q/K222 goats with a goat natural scrapie isolate by either the oral or the intracerebral (i.c.) route. Our results indicate that the I/M142 PRNP polymorphism does not provide substantial resistance to scrapie infection following intracerebral or oral inoculation. They also demonstrate that H154, Q211, and K222 PRNP allele carriers are all resistant to scrapie infection following oral exposure. However, in comparison to WT animals, the H154 and Q211 allele carriers displayed only moderate increases in the incubation period following i.c. challenge. After i.c. challenge, heterozygous K222 and a small proportion of homozygous K222 goats also developed the disease, but with incubation periods that were 4 to 5 times longer than those in WT animals. These results support the contention that the K222 goat prion protein variant provides a strong but not absolutely protective effect against classical scrapie.

The limits of test-based scrapie eradication programs in goats.

Small ruminant post-mortem testing programs were initially designed for monitoring the prevalence of prion disease. They are now considered as a potential alternative to genetic selection for eradicating/controlling classical scrapie at population level. If such policy should be implemented, its success would be crucially dependent on the efficiency of the surveillance system used to identify infected flocks. In this study, we first determined the performance of post-mortem classical scrapie detection in eight naturally affected goat herds (total n = 1961 animals) according to the age at culling. These results provided us with necessary parameters to estimate, through a Monte Carlo simulation model, the performance of scrapie detection in a commercial population. According to this model, whatever the number of tests performed, post mortem surveillance will have limited success in identifying infected herds. These data support the contention that scrapie eradication programs relying solely on post mortem testing in goats will probably fail. Considering the epidemiological and pathological similarities of scrapie in sheep and goats, the efficiency of scrapie surveillance in both species is likely to be similar.

PrP-associated resistance to scrapie in five highly infected goat herds.

The PrP gene polymorphisms at codons 142 (I/M), 154 (R/H), 211 (R/Q), 222 (Q/K) and 240 (S/P) and their association with susceptibility to classical scrapie infection were investigated in five French goat herds displaying a high disease prevalence (>10%). On the basis of PrP(Sc) detection in the central nervous system and in various lymphoid tissues, 301 of 1343 goats were found to be scrapie infected. The statistical analyses indicated that while P(240) mutation had no direct impact on scrapie infection risk, the H(154), Q(211) and K(222) mutations were associated with high resistance to scrapie. The M(142) mutated allele was associated with a limited protection level against the disease. These results further reinforce the view that, like in sheep, the control and eradication of classical scrapie through the selection of certain PrP alleles could be envisaged in commercial goat population.

Bluetongue virus serotype 1 in wild ruminants, France, 2008-10.

The persistence of Bluetongue virus serotype 1 (BTV-1) circulation was evaluated in red deer (Cervus elaphus), roe deer (Capreolus capreolus), mouflons (Ovis ammon), and Pyrenean chamois (Rupicapra pyrenaica pyrenaica) sampled during two hunting seasons between September 2008 and February 2010 in the East Pyrenean Mountains, France. The prevalence of BTV antibody in red deer was high and not significantly different between the two hunting seasons (50.9% and 49.6%, respectively). The prevalence of BTV-1 RNA in red deer was 50.3% in 2008. Conversely, only 10.8% of samples from red deer were BTV-1 RNA-positive in 2010, and most of them showed only weak positive results. In other investigated species, the prevalence of infection was low. High elevation was associated with reduced infection rates and could explain the low prevalence observed in mouflons and Pyrenean chamois. These results support the hypothesis that, apart from red deer, wild ungulates are unlikely to be involved in the maintenance or circulation of BTV in the investigated region. Mass vaccination in livestock might have reduced BTV-1 circulation in red deer, although annual variation due to acquired immunity or fluctuations in vector abundance should also be considered.

Impact of leucocyte depletion and prion reduction filters on TSE blood borne transmission.

The identification in the UK of 4 v-CJD infected patients thought to be due to the use of transfused Red Blood Cell units prepared from blood of donors incubating v-CJD raised major concerns in transfusion medicine. The demonstration of leucocyte associated infectivity using various animal models of TSE infection led to the implementation of systematic leuco-depletion (LD) of Red Blood cells concentrates (RBCs) in a number of countries. In the same models, plasma also demonstrated a significant level of infectivity which raised questions on the impact of LD on the v-CJD transmission risk. The recent development of filters combining LD and the capture of non-leucocyte associated prion infectivity meant a comparison of the benefits of LD alone versus LD/prion-reduction filters (LD/PR) on blood-borne TSE transmission could be made. Due to the similarity of blood/plasma volumes to human transfusion medicine an experimental TSE sheep model was used to characterize the abilities of whole blood, RBCs, plasma and buffy-coat to transmit the disease through the transfusion route. The impact of a standard RBCs LD filter and of two different RBCs LD/PR prototype filters on the disease transmission was then measured. Homologous recipients transfused with whole-blood, buffy-coat and RBCs developed the disease with 100% efficiency. Conversely, plasma, when intravenously administered resulted in an inconstant infection of the recipients and no disease transmission was observed in sheep that received cryo-precipitated fraction or supernatant obtained from infectious plasma. Despite their high efficacy, LD and LD/PR filtration of the Red Blood Cells concentrate did not provide absolute protection from infection. These results support the view that leuco-depletion strongly mitigates the v-CJD blood borne transmission risk and provide information about the relative benefits of prion reduction filters.

Highly efficient prion transmission by blood transfusion.

It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 10³ID50 as measured by intracerebral inoculation of tg338 mice (ID50 IC in tg338). This was consistent with a whole blood titer greater than 10³·6ID50 IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation.

Fetal protection against bovine viral diarrhoea type 1 virus infection after one administration of a live-attenuated vaccine.

A modified-live vaccine has been shown previously to prevent fetal infection with bovine viral diarrhoea virus (BVDV)-2 and, to some extent BVDV-1, when used in association with an inactivated vaccine in a two-step vaccination protocol. In this challenge study, the modified-live vaccine used alone was able to protect 13 heifers between 49 and 96 days of gestation at challenge from leucopenia and virus replication and, for a 4-month period, to prevent fetal infection. The efficacy of the BVDV-1f 22146/Han81 challenge was demonstrated by virus isolation from the fetuses of all nine non-vaccinated, control heifers. However, the small number of heifers tested meant that the vaccination failure rate could be as high as 10% in the field.

Prionemia and leukocyte-platelet-associated infectivity in sheep transmissible spongiform encephalopathy models.

The dynamics of the circulation and distribution of transmissible spongiform encephalopathy (TSE) agents in the blood of infected individuals remain largely unknown. This clearly limits the understanding of the role of blood in TSE pathogenesis and the development of a reliable TSE blood detection assay. Using two distinct sheep scrapie models and blood transfusion, this work demonstrates the occurrence of a very early and persistent prionemia. This ability to transmit disease by blood transfusion was correlated with the presence of infectivity in white blood cells (WBC) and peripheral blood mononucleated cells (PBMC) as detected by bioassay in mice overexpressing the ovine prion protein PrP (tg338 mice) and with the identification of abnormal PrP in WBC after using protein misfolding cyclic amplification (PMCA). Platelets and a large variety of leukocyte subpopulations also were shown to be infectious. The use of endpoint titration in tg338 mice indicated that the infectivity in WBC (per ml of blood) was 10(6.5)-fold lower than that in 1 g of posterior brainstem sample. In both WBC and brainstem, infectivity displayed similar resistance to PK digestion. The data strongly support the concept that WBC are an accurate target for reliable TSE detection by PMCA. The presence of infectivity in short-life-span blood cellular elements raises the question of the origin of prionemia.

Alloantibodies against MHC class I: a novel mechanism of neonatal pancytopenia linked to vaccination.

Fetal/neonatal alloimmune thrombocytopenia is a frequent disease in humans where alloantibodies against platelet Ags lead to platelet destruction and hemorrhage. Although a role in the disease for Abs against MHC has been suspected, this has not been formally demonstrated. Since 2007, a hemorrhagic syndrome due to thrombocytopenia and designated as bovine neonatal pancytopenia (BNP) has been recognized in calves in several European countries. An inactivated antiviral vaccine is strongly suspected to be involved in this syndrome because of its highly frequent use in the dams of affected calves. In this study, we show that BNP is an alloimmune disease, as we reproduced the signs by transferring serum Abs from vaccinated BNP dams into healthy neonatal calves. Ab specificity was strongly associated with the presence of allogeneic MHC class I Abs in the dams. MHC class I staining was also observed on Madin-Darby bovine kidney cells, a cell line related to the one used to produce the vaccine Ag. Our report emphatically demonstrates that alloimmunization against MHC class I is associated with a substantial risk of developing cytopenia-associated syndromes in neonates when a cell line of the same species is used to produce an inactivated vaccine injected into the mother.

Clinical, electroretinographic and histomorphometric evaluation of the retina in sheep with natural scrapie.

BACKGROUND: The retina is part of the diencephalon in a peripheral location and may be involved in prion diseases. Retinal function and structural changes were assessed in naturally scrapie-affected red face Manech ewes presenting the classical signs of the disease, and clinically healthy age-matched subjects for controls. Ophthalmic examination was done prior to electroretinography (ERG), which was carried out under conditions that allowed photopic and scotopic activities to be assessed. Histomorphometry of the inner and outer retinal layers was performed post-mortem, and retinas were also examined for evidence of abnormal prion protein (PrPSc) accumulation and glial fibrillary acidic protein (GFAP) upregulation as a marker of gliosis. Scrapie status was determined by examination of brain tissue RESULTS: Ocular reflexes and ophthalmoscopy did not reveal any difference between scrapie affected and control animals. Although the light-and dark-adapted ERG responses of both rod-and cone-mediated functions had a similar waveform in scrapie-affected and control sheep, a significant reduction in the amplitude of the ERG a-and b-waves was observed in affected animals compared to controls. These functional alterations were correlated with a substantial loss of cells in the outer nuclear layer (ONL), lengthening and disorganization in photoreceptor segments, and substantial reduction in cellularity and thickness of the inner nuclear layer (INL). The degenerative changes in the INL and ONL were most marked in the central and paracentral areas of the scrapie retinas, and were accompanied in all scrapie retinas by PrPSc deposition in the ganglion cell and synaptic layers. GFAP immunoreactivity was mainly increased in the ganglion cell and inner plexiform layers. CONCLUSIONS: No appreciable fundoscopic changes were observed in the scrapie-affected ewes although reproducible changes in retinal function as measured by ERG were observed in these animals. The alterations in the receptoral and post-receptoral pathways corresponded to the degenerative lesions observed in the ONL and INL of the scrapie retinas. The retinal degeneration was associated with prion protein infectivity which presumably spread via the optic nerve.

Atypical/Nor98 scrapie infectivity in sheep peripheral tissues.

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrP(Sc) negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.