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1.  Schistosomiasis in Cattle in Corsica, France 
Emerging Infectious Diseases  2014;20(12):2163-2164.
PMCID: PMC4257831  PMID: 25417654
schistosomiasis; humans; cattle; Corsica; France; trematodes; flukes; Schistosoma haematobium; S. bovis
2.  Spread and impact of the Schmallenberg virus epidemic in France in 2012–2013 
BMC Veterinary Research  2014;10(1):248.
The Schmallenberg virus (SBV) emerged in Europe in 2011 and caused a widespread epidemic in ruminants.
In France, SBV emergence was monitored through a national multi-stakeholder surveillance and investigation system. Based on the monitoring data collected from January 2012 to August 2013, we describe the spread of SBV in France during two seasons of dissemination (vector seasons 2011 and 2012) and we provide a large-scale assessment of the impact of this new disease in ruminants.
SBV impact in infected herds was primarily due to the birth of stillborns or deformed foetuses and neonates. Congenital SBV morbidity level was on average moderate, although higher in sheep than in other ruminant species. On average, 8% of lambs, 3% of calves and 2% of kids born in SBV-infected herds showed typical congenital SBV deformities. In addition, in infected herds, farmers reported retrospectively a lower prolificacy during the vector season, suggesting a potential impact of acute SBV infection during mating and early stages of gestation.
Due to the lack of available control and prevention measures, SBV spread quickly in the naive ruminant population. France continues to monitor for SBV, and updated information is made available online on a regular basis []. Outbreaks of congenital SBV are expected to occur sporadically from now on, but further epidemics may also occur if immunity at population level declines.
PMCID: PMC4210488  PMID: 25312811
Schmallenberg virus; France; Impact; Emerging disease; Sheep; Cattle
3.  Why do farmers and veterinarians not report all bovine abortions, as requested by the clinical brucellosis surveillance system in France? 
Since 2005, France has been officially free of brucellosis, an infectious disease that causes abortion in cattle and can be transmitted from cattle to humans. Recent animal and human cases have drawn attention to the need to prevent infection of humans and animals from any primary outbreaks. In order to detect any new outbreaks as soon as possible, a clinical surveillance system requires farmers and veterinarians to report each abortion and to test the aborting cow for brucellosis. However, under-reporting limits the sensitivity of this system. Our objective was to identify the barriers and motivations influencing field actors in their decision to report or not to report bovine abortions. We used a qualitative approach with semi-structured interviews of 12 cattle farmers and their eight veterinarians.
Our analysis showed that four main themes influence the decision-making process of farmers and veterinarians: 1) the perceived risk of brucellosis and other abortive diseases; 2) the definition of a suspected case of brucellosis and other abortive diseases adopted by field actors, which is less sensitive than the mandatory definition; 3) the cost-benefit analysis conducted by actors, taking into account regulatory and health aspects, economic and financial losses, technical and practical factors; 4) the level of cooperation within the socio-technical network. We discussed how early detection may be improved by revising the definition of abortion, extending the time frame for notification and generalising the differential diagnosis of the causes of abortion.
In contrast to quantitative approaches, qualitative studies can identify the factors (including unknown factors) influencing the decision-making process of field actors and reveal why they take those factors into consideration. Our qualitative study sheds light on the factors underlying the poor sensitivity of clinical brucellosis surveillance system for cattle in France, and suggests that early detection may be improved by considering actors’ perceptions. We believe our findings may provide further insight into ways of improving other clinical surveillance systems and thus reduce the risk of disease.
PMCID: PMC4036594  PMID: 24762103
4.  Assessment of the Impact of the 2003 and 2006 Heat Waves on Cattle Mortality in France 
PLoS ONE  2014;9(3):e93176.
While several studies have highlighted and quantified human mortality during the major heat waves that struck Western Europe in 2003 and 2006, the impact on farm animals has been overlooked. The aim of this study was to assess the effect of these two events on cattle mortality in France, one of the most severely impacted countries.
Poisson regressions were used to model the national baseline for cattle mortality between 2004 and 2005 and predict the weekly number of expected deaths in 2003 and 2006 for the whole cattle population and by subpopulation based on age and type of production. Observed and estimated values were compared to identify and quantify excess mortality. The same approach was used at a departmental scale (a French department being an administrative and territorial division) to assess the spatio-temporal evolution of the mortality pattern.
Overall, the models estimated relative excess mortality of 24% [95% confidence interval: 22–25%] for the two-week heat wave of 2003, and 12% [11–14%] for the three-week heat wave of 2006. In 2003, most cattle subpopulations were impacted during the heat wave and some in the following weeks too. In 2006, cattle subpopulations were impacted for a limited time only, with no excess mortality at the beginning or after the heat wave. No marked differences in cattle mortality were found among the different subpopulations by age and type of production. The implications of these results for risk prevention are discussed.
PMCID: PMC3965539  PMID: 24667835
5.  Did Vaccination Slow the Spread of Bluetongue in France? 
PLoS ONE  2014;9(1):e85444.
Vaccination is one of the most efficient ways to control the spread of infectious diseases. Simulations are now widely used to assess how vaccination can limit disease spread as well as mitigate morbidity or mortality in susceptible populations. However, field studies investigating how much vaccines decrease the velocity of epizootic wave-fronts during outbreaks are rare. This study aimed at investigating the effect of vaccination on the propagation of bluetongue, a vector-borne disease of ruminants. We used data from the 2008 bluetongue virus serotype 1 (BTV-1) epizootic of southwest France. As the virus was newly introduced in this area, natural immunity of livestock was absent. This allowed determination of the role of vaccination in changing the velocity of bluetongue spread while accounting for environmental factors that possibly influenced it. The average estimated velocity across the country despite restriction on animal movements was 5.4 km/day, which is very similar to the velocity of spread of the bluetongue virus serotype 8 epizootic in France also estimated in a context of restrictions on animal movements. Vaccination significantly reduced the propagation velocity of BTV-1. In comparison to municipalities with no vaccine coverage, the velocity of BTV-1 spread decreased by 1.7 km/day in municipalities with immunized animals. For the first time, the effect of vaccination has been quantified using data from a real epizootic whilst accounting for environmental factors known to modify the velocity of bluetongue spread. Our findings emphasize the importance of vaccination in limiting disease spread across natural landscape. Finally, environmental factors, specifically those related to vector abundance and activity, were found to be good predictors of the velocity of BTV-1 spread, indicating that these variables need to be adequately accounted for when evaluating the role of vaccination on bluetongue spread.
PMCID: PMC3897431  PMID: 24465562
6.  Assessing the Mandatory Bovine Abortion Notification System in France Using Unilist Capture-Recapture Approach 
PLoS ONE  2013;8(5):e63246.
The mandatory bovine abortion notification system in France aims to detect as soon as possible any resurgence of bovine brucellosis. However, under-reporting seems to be a major limitation of this system. We used a unilist capture-recapture approach to assess the sensitivity, i.e. the proportion of farmers who reported at least one abortion among those who detected such events, and representativeness of the system during 2006–2011. We implemented a zero-inflated Poisson model to estimate the proportion of farmers who detected at least one abortion, and among them, the proportion of farmers not reporting. We also applied a hurdle model to evaluate the effect of factors influencing the notification process. We found that the overall surveillance sensitivity was about 34%, and was higher in beef than dairy cattle farms. The observed increase in the proportion of notifying farmers from 2007 to 2009 resulted from an increase in the surveillance sensitivity in 2007/2008 and an increase in the proportion of farmers who detected at least one abortion in 2008/2009. These patterns suggest a raise in farmers’ awareness in 2007/2008 when the Bluetongue Virus (BTV) was detected in France, followed by an increase in the number of abortions in 2008/2009 as BTV spread across the country. Our study indicated a lack of sensitivity of the mandatory bovine abortion notification system, raising concerns about the ability to detect brucellosis outbreaks early. With the increasing need to survey the zoonotic Rift Valley Fever and Q fever diseases that may also cause bovine abortions, our approach is of primary interest for animal health stakeholders to develop information programs to increase abortion notifications. Our framework combining hurdle and ZIP models may also be applied to estimate the completeness of other clinical surveillance systems.
PMCID: PMC3653928  PMID: 23691004
7.  Defining syndromes using cattle meat inspection data for syndromic surveillance purposes: a statistical approach with the 2005–2010 data from ten French slaughterhouses 
The slaughterhouse is a central processing point for food animals and thus a source of both demographic data (age, breed, sex) and health-related data (reason for condemnation and condemned portions) that are not available through other sources. Using these data for syndromic surveillance is therefore tempting. However many possible reasons for condemnation and condemned portions exist, making the definition of relevant syndromes challenging.
The objective of this study was to determine a typology of cattle with at least one portion of the carcass condemned in order to define syndromes. Multiple factor analysis (MFA) in combination with clustering methods was performed using both health-related data and demographic data.
Analyses were performed on 381,186 cattle with at least one portion of the carcass condemned among the 1,937,917 cattle slaughtered in ten French abattoirs. Results of the MFA and clustering methods led to 12 clusters considered as stable according to year of slaughter and slaughterhouse. One cluster was specific to a disease of public health importance (cysticercosis). Two clusters were linked to the slaughtering process (fecal contamination of heart or lungs and deterioration lesions). Two clusters respectively characterized by chronic liver lesions and chronic peritonitis could be linked to diseases of economic importance to farmers. Three clusters could be linked respectively to reticulo-pericarditis, fatty liver syndrome and farmer’s lung syndrome, which are related to both diseases of economic importance to farmers and herd management issues. Three clusters respectively characterized by arthritis, myopathy and Dark Firm Dry (DFD) meat could notably be linked to animal welfare issues. Finally, one cluster, characterized by bronchopneumonia, could be linked to both animal health and herd management issues.
The statistical approach of combining multiple factor analysis with cluster analysis showed its relevance for the detection of syndromes using available large and complex slaughterhouse data. The advantages of this statistical approach are to i) define groups of reasons for condemnation based on meat inspection data, ii) help grouping reasons for condemnation among a list of various possible reasons for condemnation for which a consensus among experts could be difficult to reach, iii) assign each animal to a single syndrome which allows the detection of changes in trends of syndromes to detect unusual patterns in known diseases and emergence of new diseases.
PMCID: PMC3681570  PMID: 23628140
Syndromic surveillance; Animal health; Meat inspection; Slaughterhouses; Cattle
8.  Synergies Between Human and Animal Health Syndromic Surveillance: Triple-S Outputs 
The objective of this study, based on the Triple-S project outputs, was to present the existing synergies between human and animal health syndromic surveillance (SyS) systems in Europe and a proposal to enhance this kind of collaboration.
The Triple-S project (Syndromic Surveillance Systems in Europe,, co-financed by the European Commission and involving twenty four organizations from fourteen countries was launched in September 2010 with the following objectives 1) performing an inventory of existing or planned SyS systems in Europe both in animal and public health, 2) building a network of experts involved in SyS 3) producing guidelines to implement SyS systems, 4) developing synergies between human and animal health SyS systems. The project is based on a cooperation between human and animal health experts, as supported by the One Health initiative [1].
A network of European experts involved in SyS was identified through the Triple-S inventory of SyS systems. A meeting of human health experts was organized back to back with a similar meeting with animal health experts in Paris, September 12–14, 2011. A joint session human/animal health allowed experts to discuss the interest of synergies between both sides. The objectives were to 1) encourage experience and knowledge transfer, 2) discuss what and how information should be shared between both sides to improve respective performances.
The results of the inventory of veterinary SyS systems showed that 40% of identified systems already shared or had planned to share information with human health sector. For these systems the collaboration between human and animal health sectors consisted in meetings on a regular basis to discuss the surveillance results.
Discussions during the Triple-S meeting highlighted two reasons for enhancing synergies between both sides. First human health and animal health epidemiologists face common statistical and epidemiological issues when dealing with SyS, i.e. use of data collected for other purpose than surveillance; standardization of clinical observations; syndrome definition; anomaly detection; interpretation of unspecific signals; response to alerts. Both sides have thus interest in sharing their experiences and knowledge to improve their respective systems.
Second, systems on both sides have similar objectives and target health events potentially threatening both animal and human populations: zoonoses, extreme weather events, environmental / food contamination, bioterrorist attack... For those events, animal population can play the role of sentinel for human population. Regular information flow between human and animal SyS could thus enhance the timeliness and sensitivity of SyS systems for detecting unexpected health events. Moreover, sharing information could help animal and human health experts to interpret and confirm unspecific signals, and confirm the impact of common health threats.
All participants of the meeting agreed on the idea to routinely share outputs of the systems but were sceptical about sharing raw data to perform global analysis.
Each aspect of the Triple-S project includes both human and animal health and will thus contribute to build natural collaboration between both sides. Such a project has demonstrated that scientific community is more and more willing to collaborate beyond the boundaries of these two health fields.
Synergies between human and animal health seem as necessary for syndromic surveillance as it is for traditional surveillance, if not more. They seem especially important for the detection of emerging zoonotic threats but not only. Sharing surveillance outputs from both sides would be the first step of collaboration but deeper synergy, e.g. sharing data and analyse them globally, could also be considered. Triple-S guidelines for implementation of SyS systems in Europe will take into account and promote synergies between human and animal health.
PMCID: PMC3692807
syndromic surveillance; synergy; early warning
9.  Epidemiology, molecular virology and diagnostics of Schmallenberg virus, an emerging orthobunyavirus in Europe 
Veterinary Research  2013;44(1):31.
After the unexpected emergence of Bluetongue virus serotype 8 (BTV-8) in northern Europe in 2006, another arbovirus, Schmallenberg virus (SBV), emerged in Europe in 2011 causing a new economically important disease in ruminants. The virus, belonging to the Orthobunyavirus genus in the Bunyaviridae family, was first detected in Germany, in The Netherlands and in Belgium in 2011 and soon after in the United Kingdom, France, Italy, Luxembourg, Spain, Denmark and Switzerland. This review describes the current knowledge on the emergence, epidemiology, clinical signs, molecular virology and diagnosis of SBV infection.
PMCID: PMC3663787  PMID: 23675914
10.  Why Did Bluetongue Spread the Way It Did? Environmental Factors Influencing the Velocity of Bluetongue Virus Serotype 8 Epizootic Wave in France 
PLoS ONE  2012;7(8):e43360.
Understanding where and how fast an infectious disease will spread during an epidemic is critical for its control. However, the task is a challenging one as numerous factors may interact and drive the spread of a disease, specifically when vector-borne diseases are involved. We advocate the use of simultaneous autoregressive models to identify environmental features that significantly impact the velocity of disease spread. We illustrate this approach by exploring several environmental factors influencing the velocity of bluetongue (BT) spread in France during the 2007–2008 epizootic wave to determine which ones were the most important drivers. We used velocities of BT spread estimated in 4,495 municipalities and tested sixteen covariates defining five thematic groups of related variables: elevation, meteorological-related variables, landscape-related variables, host availability, and vaccination. We found that ecological factors associated with vector abundance and activity (elevation and meteorological-related variables), as well as with host availability, were important drivers of the spread of the disease. Specifically, the disease spread more slowly in areas with high elevation and when heavy rainfall associated with extreme temperature events occurred one or two months prior to the first clinical case. Moreover, the density of dairy cattle was correlated negatively with the velocity of BT spread. These findings add substantially to our understanding of BT spread in a temperate climate. Finally, the approach presented in this paper can be used with other infectious diseases, and provides a powerful tool to identify environmental features driving the velocity of disease spread.
PMCID: PMC3419712  PMID: 22916249
11.  Individual factors associated with L- and H-type Bovine Spongiform Encephalopathy in France 
Cattle with L-type (L-BSE) and H-type (H-BSE) atypical Bovine Spongiform encephalopathy (BSE) were identified in 2003 in Italy and France respectively before being identified in other countries worldwide. As of December 2011, around 60 atypical BSE cases have currently been reported in 13 countries, with over one third in France. While the epidemiology of classical BSE (C-BSE) has been widely described, atypical BSEs are still poorly documented, but appear to differ from C-BSE. We analysed the epidemiological characteristics of the 12 cases of L-BSE and 11 cases of H-BSE detected in France from January 2001 to late 2009 and looked for individual risk factors. As L-BSE cases did not appear to be homogeneously distributed throughout the country, two complementary methods were used: spatial analysis and regression modelling. L-BSE and H-BSE were studied separately as both the biochemical properties of their pathological prion protein and their features differ in animal models.
The median age at detection for L-BSE and H-BSE cases was 12.4 (range 8.4-18.7) and 12.5 (8.3-18.2) years respectively, with no significant difference between the two distributions. However, this median age differed significantly from that of classical BSE (7.0 (range 3.5-15.4) years). A significant geographical cluster was detected for L-BSE. Among animals over eight years of age, we showed that the risk of being detected as a L-BSE case increased with age at death. This was not the case for H-BSE.
To the best of our knowledge this is the first study to describe the epidemiology of the two types of atypical BSE. The geographical cluster detected for L-BSE could be partly due to the age structure of the background-tested bovine population. Our regression analyses, which adjusted for the effect of age and birth cohort showed an age effect for L-BSE and the descriptive analysis showed a particular age structure in the area where the cluster was detected. No birth cohort effect was evident. The relatively small number of cases of atypical BSE and the few individual data available for the tested population limited our analysis to the investigation of age and cohort effect only. We conclude that it is essential to maintain BSE surveillance to further elucidate our findings.
PMCID: PMC3514362  PMID: 22647660
Atypical bovine spongiform encephalopathy; L-BSE; H-BSE; Spatial analysis; Risk factors; France
12.  Estimating front-wave velocity of infectious diseases: a simple, efficient method applied to bluetongue 
Veterinary Research  2011;42(1):60.
Understanding the spatial dynamics of an infectious disease is critical when attempting to predict where and how fast the disease will spread. We illustrate an approach using a trend-surface analysis (TSA) model combined with a spatial error simultaneous autoregressive model (SARerr model) to estimate the speed of diffusion of bluetongue (BT), an infectious disease of ruminants caused by bluetongue virus (BTV) and transmitted by Culicoides. In a first step to gain further insight into the spatial transmission characteristics of BTV serotype 8, we used 2007-2008 clinical case reports in France and TSA modelling to identify the major directions and speed of disease diffusion. We accounted for spatial autocorrelation by combining TSA with a SARerr model, which led to a trend SARerr model. Overall, BT spread from north-eastern to south-western France. The average trend SARerr-estimated velocity across the country was 5.6 km/day. However, velocities differed between areas and time periods, varying between 2.1 and 9.3 km/day. For more than 83% of the contaminated municipalities, the trend SARerr-estimated velocity was less than 7 km/day. Our study was a first step in describing the diffusion process for BT in France. To our knowledge, it is the first to show that BT spread in France was primarily local and consistent with the active flight of Culicoides and local movements of farm animals. Models such as the trend SARerr models are powerful tools to provide information on direction and speed of disease diffusion when the only data available are date and location of cases.
PMCID: PMC3090993  PMID: 21507221
13.  Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002–2009 
Emerging Infectious Diseases  2011;17(1):55-63.
The agent that causes bovine spongiform encephalopathy (BSE) may be infecting small ruminants, which could have serious implications for human health. To distinguish BSE from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (PrPres), we used a specifically designed Western blot method to test isolates from 648 sheep and 53 goats. During 2002–2009, classical non-Nor98 transmissible spongiform encephalopathy had been confirmed among ≈1.7 million small ruminants in France. Five sheep and 2 goats that showed a PrPres pattern consistent with BSE, or with the CH1641 experimental scrapie source, were identified. Later, bioassays confirmed infection by the BSE agent in 1 of the 2 goats. Western blot testing of the 6 other isolates showed an additional C-terminally cleaved PrPres product, with an unglycosylated band at ≈14 kDa, similar to that found in the CH1641 experimental scrapie isolate and different from the BSE isolate.
PMCID: PMC3204636  PMID: 21192855
Prion; BSE; TSE; CH1641; scrapie; sheep; goat; molecular typing; France; research
14.  Unsupervised clustering of wildlife necropsy data for syndromic surveillance 
The importance of wildlife disease surveillance is increasing, because wild animals are playing a growing role as sources of emerging infectious disease events in humans. Syndromic surveillance methods have been developed as a complement to traditional health data analyses, to allow the early detection of unusual health events. Early detection of these events in wildlife could help to protect the health of domestic animals or humans. This paper aims to define syndromes that could be used for the syndromic surveillance of wildlife health data. Wildlife disease monitoring in France, from 1986 onward, has allowed numerous diagnostic data to be collected from wild animals found dead. The authors wanted to identify distinct pathological profiles from these historical data by a global analysis of the registered necropsy descriptions, and discuss how these profiles can be used to define syndromes. In view of the multiplicity and heterogeneity of the available information, the authors suggest constructing syndromic classes by a multivariate statistical analysis and classification procedure grouping cases that share similar pathological characteristics.
A three-step procedure was applied: first, a multiple correspondence analysis was performed on necropsy data to reduce them to their principal components. Then hierarchical ascendant clustering was used to partition the data. Finally the k-means algorithm was applied to strengthen the partitioning. Nine clusters were identified: three were species- and disease-specific, three were suggestive of specific pathological conditions but not species-specific, two covered a broader pathological condition and one was miscellaneous. The clusters reflected the most distinct and most frequent disease entities on which the surveillance network focused. They could be used to define distinct syndromes characterised by specific post-mortem findings.
The chosen statistical clustering method was found to be a useful tool to retrospectively group cases from our database into distinct and meaningful pathological entities. Syndrome definition from post-mortem findings is potentially useful for early outbreak detection because it uses the earliest available information on disease in wildlife. Furthermore, the proposed typology allows each case to be attributed to a syndrome, thus enabling the exhaustive surveillance of health events through time series analyses.
PMCID: PMC3018415  PMID: 21162732
15.  Mycoplasmoses of ruminants in France: recent data from the national surveillance network 
Ruminant mycoplasmoses are important diseases worldwide and several are listed by the World Organization for Animal Health to be of major economic significance. In France the distribution of mycoplasmal species isolated from clinical samples collected from diseased animals upon veterinary request, is monitored by a network known as VIGIMYC (for VIGIlance to MYCoplasmoses of ruminants). The veterinary diagnostic laboratories collaborating with VIGIMYC are responsible for isolating the mycoplasmas while identification of the isolates is centralized by the French Food Safety Agency (AFSSA) in Lyon. The VIGIMYC framework can also be used for specific surveys and one example, on the prevalence of M. bovis in bovine respiratory diseases, is presented here.
Between 2003 and 2008, 34 laboratories were involved in the network and 1904 mycoplasma isolates, originating from the main ruminant-breeding areas, were identified. For cattle, the high prevalence of M. bovis in bronchopneumonia, notably in young animals, was confirmed by VIGIMYC and an associated specific survey, whereas the non-emergence of species such as M. alkalescens and M. canis was also demonstrated. The etiological agent of bovine contagious pleuropneumonia was never isolated. The principal mycoplasmosis in goats was contagious agalactia with M. mycoides subsp. capri as main agent. Ovine mycoplasmoses, most of which were associated with pneumonia in lambs, were infrequently reported. One exception was ovine contagious agalactia (due to M. agalactiae) that has recently re-emerged in the Pyrénées where it had been endemic for years and was also reported in Corsica, which was previously considered free.
Although VIGIMYC is a passive network and somewhat biased as regards sample collection and processing, it has provided, in this study, an overview of the main mycoplasmoses of ruminants in France. The French epidemiological situation is compared to those existing elsewhere in the world.
PMCID: PMC2892444  PMID: 20525406
16.  Quantitative estimation of genetic risk for atypical scrapie in French sheep and potential consequences of the current breeding programme for resistance to scrapie on the risk of atypical scrapie 
Since 2002, active surveillance programmes have detected numerous atypical scrapie (AS) and classical scrapie cases (CS) in French sheep with almost all the PrP genotypes. The aim of this study was 1) to quantify the genetic risk of AS in French sheep and to compare it with the risk of CS, 2) to quantify the risk of AS associated with the increase of the ARR allele frequency as a result of the current genetic breeding programme against CS.
We obtained genotypes at codons 136, 141, 154 and 171 of the PRNP gene for representative samples of 248 AS and 245 CS cases. We used a random sample of 3,317 scrapie negative animals genotyped at codons 136, 154 and 171 and we made inferences on the position 141 by multiple imputations, using external data. To estimate the risk associated with PrP genotypes, we fitted multivariate logistic regression models and we estimated the prevalence of AS for the different genotypes. Then, we used the risk of AS estimated for the ALRR-ALRR genotype to analyse the risk of detecting an AS case in a flock homogenous for this genotype.
Genotypes most at risk for AS were those including an AFRQ or ALHQ allele while genotypes including a VLRQ allele were less commonly associated with AS. Compared to ALRQ-ALRQ, the ALRR-ALRR genotype was significantly at risk for AS and was very significantly protective for CS. The prevalence of AS among ALRR-ALRR animals was 0.6‰ and was not different from the prevalence in the general population.
In conclusion, further selection of ALRR-ALRR animals will not result in an overall increase of AS prevalence in the French sheep population although this genotype is clearly susceptible to AS. However the probability of detecting AS cases in flocks participating in genetic breeding programme against CS should be considered.
PMCID: PMC2880962  PMID: 20482755
17.  The prevalence of atypical scrapie in sheep from positive flocks is not higher than in the general sheep population in 11 European countries 
During the last decade, active surveillance for transmissible spongiform encephalopathies in small ruminants has been intensive in Europe. In many countries this has led to the detection of cases of atypical scrapie which, unlike classical scrapie, might not be contagious. EU legislation requires, that following detection of a scrapie case, control measures including further testing take place in affected flocks, including the culling of genotype susceptible to classical scrapie. This might result in the detection of additional cases. The aim of this study was to investigate the occurrence of additional cases in flocks affected by atypical scrapie using surveillance data collected in Europe in order to ascertain whether atypical scrapie, is contagious.
Questionnaires were used to collect, at national level, the results of active surveillance and testing associated with flock outbreaks in 12 European countries. The mean prevalence of atypical scrapie was 5.5 (5.0-6.0) cases per ten thousand in abattoir surveillance and 8.1 (7.3-9.0) cases per ten thousand in fallen stock. By using meta-analysis, on 11 out of the 12 countries, we found that the probability of detecting additional cases of atypical scrapie in positive flocks was similar to the probability observed in animals slaughtered for human consumption (odds ratio, OR = 1.07, CI95%: 0.70-1.63) or among fallen stock (OR = 0.78, CI95%: 0.51-1.2). In contrast, when comparing the two scrapie types, the probability of detecting additional cases in classical scrapie positive flocks was significantly higher than the probability of detecting additional cases in atypical scrapie positive flocks (OR = 32.4, CI95%: 20.7-50.7).
These results suggest that atypical scrapie is not contagious or has a very low transmissibility under natural conditions compared with classical scrapie. Furthermore this study stressed the importance of standardised data collection to make good use of the analyses undertaken by European countries in their efforts to control atypical and classical scrapie.
PMCID: PMC2832631  PMID: 20137097
18.  A Case–Control Study on the Origin of Atypical Scrapie in Sheep, France  
Emerging Infectious Diseases  2009;15(5):710-718.
Risk factors for this disease suggest a noninfectious origin influenced by genetic and metabolic factors.
A matched case–control study (95 cases and 220 controls) was designed to study risk factors for atypical scrapie in sheep in France. We analyzed contacts with animals from other flocks, lambing and feeding practices, and exposure to toxic substances. Data on the prnp genotype were collected for some case and control animals and included in a complementary analysis. Sheep dairy farms had a higher risk for scrapie (odds ratio [OR] 15.1, 95% confidence interval [CI] 3.3–69.7). Lower risk was associated with organic farms (OR 0.15, 95% CI 0.02–1.26), feeding corn silage (OR 0.16, 95% CI 0.05–0.53), and feeding vitamin and mineral supplements (OR 0.6, 95% CI 0.32–1.14). Genetic effects were quantitatively important but only marginally changed estimates of other variables. We did not find any risk factor associated with an infectious origin of scrapie. Atypical scrapie could be a spontaneous disease influenced by genetic and metabolic factors.
PMCID: PMC2687017  PMID: 19402956
Prions and related diseases; scrapie; transmissible spongiform encephalopathy; case–control study; sheep; epidemiology; France; research
19.  Comparison of strategies for substantiating freedom from scrapie in a sheep flock 
The public health threat represented by a potential circulation of bovine spongiform encephalopathy agent in sheep population has led European animal health authorities to launch large screening and genetic selection programmes. If demonstrated, such a circulation would have dramatic economic consequences for sheep breeding sector. In this context, it is important to evaluate the feasibility of qualification procedures that would allow sheep breeders demonstrating their flock is free from scrapie. Classical approaches, based on surveys designed to detect disease presence, do not account for scrapie specificities: the genetic variations of susceptibility and the absence of live diagnostic test routinely available. Adapting these approaches leads to a paradoxical situation in which a greater amount of testing is needed to substantiate disease freedom in genetically resistant flocks than in susceptible flocks, whereas probability of disease freedom is a priori higher in the former than in the latter. The goal of this study was to propose, evaluate and compare several qualification strategies for demonstrating a flock is free from scrapie.
A probabilistic framework was defined that accounts for scrapie specificities and allows solving the preceding paradox. Six qualification strategies were defined that combine genotyping data, diagnostic tests results and flock pedigree. These were compared in two types of simulated flocks: resistant and susceptible flocks. Two strategies allowed demonstrating disease freedom in several years, for the majority of simulated flocks: a strategy in which all the flock animals are genotyped, and a strategy in which only founders animals are genotyped, the flock pedigree being known. In both cases, diagnostic tests are performed on culled animals. The less costly strategy varied according to the genetic context (resistant or susceptible) and to the relative costs of a genotyping exam and of a diagnostic test.
This work demonstrates that combining data sources allows substantiating a flock is free from scrapie within a reasonable time frame. Qualification schemes could thus be a useful tool for voluntary or mandatory scrapie control programmes. However, there is no general strategy that would always minimize the costs and choice of the strategy should be adapted to local genetic conditions.
PMCID: PMC2697144  PMID: 19405956
20.  A descriptive study of the prevalence of atypical and classical scrapie in sheep in 20 European countries 
The development of active surveillance programmes for transmissible spongiform encephalopathies of small ruminants across Europe has led to the recent identification of a previously undetected form of ovine prion disease, 'atypical' scrapie. Knowledge of the epidemiology of this disease is still limited, as is whether it represents a risk for animal and/or public health.
The detection of atypical scrapie has been related to the use of only some of the EU agreed rapid tests. Information about the rapid tests used is not, as yet, available from public reports on the surveillance of transmissible spongiform encephalopathies in small ruminants. We collected detailed results of active surveillance from European countries to estimate and to compare the prevalence of atypical scrapie and classical scrapie in sheep for each country stratified by each surveillance stream; healthy slaughtered and found dead adult sheep.
From the 20 participating countries, it appeared that atypical scrapie was detected in Europe wherever the conditions necessary for its diagnosis were present. In most countries, atypical scrapie and classical scrapie occurred at low prevalence level. The classical scrapie prevalence estimates were more variable than those for atypical scrapie, which appeared remarkably homogeneous across countries, surveillance streams and calendar years of surveillance. Differences were observed in the age and genotype of atypical scrapie and classical scrapie cases that are consistent with previous published findings.
This work suggests that atypical scrapie is not rare compared to classical scrapie. The homogeneity of its prevalence, whatever the country, stream of surveillance or year of detection, contrasts with the epidemiological pattern of classical scrapie. This suggests that the aetiology of atypical scrapie differs from that of classical scrapie.
PMCID: PMC2442063  PMID: 18544152
21.  Atypical Bovine Spongiform Encephalopathies, France, 2001–2007 
Emerging Infectious Diseases  2008;14(2):298-300.
In France, through exhaustive active surveillance, ≈17.1 million adult cattle were tested for bovine spongiform encephalopathy from July 2001 through July 2007; ≈3.6 million were >8 years of age. Our retrospective Western blot study of all 645 confirmed cases found that 7 were H-type and 6 were L-type.
PMCID: PMC2600212  PMID: 18258124
BSE; H-type; L-type; BASE; prion; cattle; dispatch
22.  Sheep Feed and Scrapie, France 
Emerging Infectious Diseases  2005;11(8):1274-1279.
Proprietary concentrates and milk replacers were linked to risk for scrapie.
Scrapie is a small ruminant, transmissible spongiform encephalopathy (TSE). Although in the past scrapie has not been considered a zoonosis, the emergence of bovine spongiform encephalopathy, transmissible 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 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 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.
PMCID: PMC3320489  PMID: 16102318
Keywords: Scrapie; Sheep; Transmission; Epidemiology; Case-Control studies; Risk Factors; France; Transmissible Spongiform Encephalopathy
23.  Molecular Analysis of the Protease-Resistant Prion Protein in Scrapie and Bovine Spongiform Encephalopathy Transmitted to Ovine Transgenic and Wild-Type Mice 
Journal of Virology  2004;78(12):6243-6251.
The existence of different strains of infectious agents involved in scrapie, a transmissible spongiform encephalopathy (TSE) of sheep and goats, remains poorly explained. These strains can, however, be differentiated by characteristics of the disease in mice and also by the molecular features of the protease-resistant prion protein (PrPres) that accumulates into the infected tissues. For further analysis, we first transmitted the disease from brain samples of TSE-infected sheep to ovine transgenic [Tg(OvPrP4)] and to wild-type (C57BL/6) mice. We show that, as in sheep, molecular differences of PrPres detected by Western blotting can differentiate, in both ovine transgenic and wild-type mice, infection by the bovine spongiform encephalopathy (BSE) agent from most scrapie sources. Similarities of an experimental scrapie isolate (CH1641) with BSE were also likewise found following transmission in ovine transgenic mice. Secondly, we transmitted the disease to ovine transgenic mice by inoculation of brain samples of wild-type mice infected with different experimental scrapie strains (C506M3, 87V, 79A, and Chandler) or with BSE. Features of these strains in ovine transgenic mice were reminiscent of those previously described for wild-type mice, by both ratios and by molecular masses of the different PrPres glycoforms. Moreover, these studies revealed the diversity of scrapie strains and their differences with BSE according to labeling by a monoclonal antibody (P4). These data, in an experimental model expressing the prion protein of the host of natural scrapie, further suggest a genuine diversity of TSE infectious agents and emphasize its linkage to the molecular features of the abnormal prion protein.
PMCID: PMC416514  PMID: 15163717
24.  Similar Signature of the Prion Protein in Natural Sheep Scrapie and Bovine Spongiform Encephalopathy-Linked Diseases 
Journal of Clinical Microbiology  1999;37(11):3701-3704.
It has been suggested that specific molecular features could characterize the protease-resistant prion protein (PrP res) detected in animal species as well as in humans infected by the infectious agent strain that causes bovine spongiform encephalopathy (BSE). Studies of glycoform patterns in such diseases in French cattle and cheetahs, as well as in mice infected by isolates from both species, revealed this characteristic molecular signature. Similar studies of 42 French isolates of natural scrapie, from 21 different flocks in different regions of France, however, showed levels of the three glycoforms comparable to those found in BSE-linked diseases. Moreover, the apparent molecular size of the unglycosylated form was also indistinguishable among all different sheep isolates, as well as isolates from BSE in cattle. Overall results suggest that scrapie cases with features similar to those of BSE could be found more frequently in sheep than previously described.
PMCID: PMC85730  PMID: 10523578

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