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1.  Simulation-Based Evaluation of the Performances of an Algorithm for Detecting Abnormal Disease-Related Features in Cattle Mortality Records 
PLoS ONE  2015;10(11):e0141273.
We performed a simulation study to evaluate the performances of an anomaly detection algorithm considered in the frame of an automated surveillance system of cattle mortality. The method consisted in a combination of temporal regression and spatial cluster detection which allows identifying, for a given week, clusters of spatial units showing an excess of deaths in comparison with their own historical fluctuations. First, we simulated 1,000 outbreaks of a disease causing extra deaths in the French cattle population (about 200,000 herds and 20 million cattle) according to a model mimicking the spreading patterns of an infectious disease and injected these disease-related extra deaths in an authentic mortality dataset, spanning from January 2005 to January 2010. Second, we applied our algorithm on each of the 1,000 semi-synthetic datasets to identify clusters of spatial units showing an excess of deaths considering their own historical fluctuations. Third, we verified if the clusters identified by the algorithm did contain simulated extra deaths in order to evaluate the ability of the algorithm to identify unusual mortality clusters caused by an outbreak. Among the 1,000 simulations, the median duration of simulated outbreaks was 8 weeks, with a median number of 5,627 simulated deaths and 441 infected herds. Within the 12-week trial period, 73% of the simulated outbreaks were detected, with a median timeliness of 1 week, and a mean of 1.4 weeks. The proportion of outbreak weeks flagged by an alarm was 61% (i.e. sensitivity) whereas one in three alarms was a true alarm (i.e. positive predictive value). The performances of the detection algorithm were evaluated for alternative combination of epidemiologic parameters. The results of our study confirmed that in certain conditions automated algorithms could help identifying abnormal cattle mortality increases possibly related to unidentified health events.
doi:10.1371/journal.pone.0141273
PMCID: PMC4633029  PMID: 26536596
2.  Prevalence of Carriage of Shiga Toxin-Producing Escherichia coli Serotypes O157:H7, O26:H11, O103:H2, O111:H8, and O145:H28 among Slaughtered Adult Cattle in France 
The main pathogenic enterohemorrhagic Escherichia coli (EHEC) strains are defined as Shiga toxin (Stx)-producing E. coli (STEC) belonging to one of the following serotypes: O157:H7, O26:H11, O103:H2, O111:H8, and O145:H28. Each of these five serotypes is known to be associated with a specific subtype of the intimin-encoding gene (eae). The objective of this study was to evaluate the prevalence of bovine carriers of these “top five” STEC in the four adult cattle categories slaughtered in France. Fecal samples were collected from 1,318 cattle, including 291 young dairy bulls, 296 young beef bulls, 337 dairy cows, and 394 beef cows. A total of 96 E. coli isolates, including 33 top five STEC and 63 atypical enteropathogenic E. coli (aEPEC) isolates, with the same genetic characteristics as the top five STEC strains except that they lacked an stx gene, were recovered from these samples. O157:H7 was the most frequently isolated STEC serotype. The prevalence of top five STEC (all serotypes included) was 4.5% in young dairy bulls, 2.4% in young beef bulls, 1.8% in dairy cows, and 1.0% in beef cows. It was significantly higher in young dairy bulls (P < 0.05) than in the other 3 categories. The basis for these differences between categories remains to be elucidated. Moreover, simultaneous carriage of STEC O26:H11 and STEC O103:H2 was detected in one young dairy bull. Lastly, the prevalence of bovine carriers of the top five STEC, evaluated through a weighted arithmetic mean of the prevalence by categories, was estimated to 1.8% in slaughtered adult cattle in France.
doi:10.1128/AEM.03315-14
PMCID: PMC4309698  PMID: 25527532
3.  Assessment of Adhesins as an Indicator of Pathovar-Associated Virulence Factors in Bovine Escherichia coli 
Applied and Environmental Microbiology  2014;80(23):7230-7234.
The CS31A, F17, and F5 adhesins are usually targeted by serology-based methods to detect pathogenic Escherichia coli associated with calf enteritis. However, the virulence traits of the selected isolates are still poorly described. Here, from a set of 349 diarrheagenic E. coli isolates from cattle, we demonstrated a 70.8% concordance rate (Cohen's kappa, 0.599) between serology- and PCR-based approaches for the detection of adhesins under field conditions. A 79% to 82.4% correspondence between the two methods was found for fimbrial adhesins, whereas major discrepancies (33%) were observed for CS31A-type antigens. Various F17A variants were found, such as F17Ac (20K) (50%), F17Aa (FY) (18.9%), F17Ab (8.1%), and F17Ad (111K) (5.4%), including a high proportion (17.6%) of new F17A internal combinations (F17Aab, F17Aac, and F17Abc) or untypeable variants. In addition, the highest proportion of pathovar-associated virulence factor (VF) genes was observed among E. coli isolates that produced F5/F41 adhesins. A specific link between the heat-stable toxins related to the enterotoxigenic E. coli (ETEC) pathovar and adhesins was identified. STa was significantly linked to F5/F41 and EAST1 to CS31A adhesins (P < 0.001), respectively, whereas NTEC was associated with F17 adhesin (P = 0.001). Clustering between phylogroups according to the adhesin types was also observed. Also, few Shiga toxin-producing E. coli (STEC) or enteropathogenic E. coli (EPEC) pathovars were identified. Finally, no statistically significant difference was observed in the occurrence of extended-spectrum beta lactamase (ESBL) production according to the adhesins expressed by the isolates (P = 0.09). Altogether, this study gives new insights into the relationship between adhesins, VF, and antimicrobial resistance in calf enteritis and supports the need for further standardization of methodologies for such approaches.
doi:10.1128/AEM.02365-14
PMCID: PMC4249168  PMID: 25217019
4.  Devising an Indicator to Detect Mid-Term Abortions in Dairy Cattle: A First Step Towards Syndromic Surveillance of Abortive Diseases 
PLoS ONE  2015;10(3):e0119012.
Bovine abortion surveillance is essential for human and animal health because it plays an important role in the early warning of several diseases. Due to the limited sensitivity of traditional surveillance systems, there is a growing interest for the development of syndromic surveillance. Our objective was to assess whether, routinely collected, artificial insemination (AI) data could be used, as part of a syndromic surveillance system, to devise an indicator of mid-term abortions in dairy cattle herds in France. A mid-term abortion incidence rate (MAIR) was computed as the ratio of the number of mid-term abortions to the number of female-weeks at risk. A mid-term abortion was defined as a return-to-service (i.e. a new AI) taking place 90 to 180 days after the previous AI. Weekly variations in the MAIR in heifers and parous cows were modeled with a time-dependent Poisson model at the département level (French administrative division) during the period of 2004 to 2010. The usefulness of monitoring this indicator to detect a disease-related increase in mid-term abortions was evaluated using data from the 2007–2008 episode of bluetongue serotype 8 (BT8) in France. An increase in the MAIR was identified in heifers and parous cows in 47% (n = 24) and 71% (n = 39) of the départements. On average, the weekly MAIR among heifers increased by 3.8% (min-max: 0.02–57.9%) when the mean number of BT8 cases that occurred in the previous 8 to 13 weeks increased by one. The weekly MAIR among parous cows increased by 1.4% (0.01–8.5%) when the mean number of BT8 cases occurring in the previous 6 to 12 weeks increased by one. These results underline the potential of the MAIR to identify an increase in mid-term abortions and suggest that it is a good candidate for the implementation of a syndromic surveillance system for bovine abortions.
doi:10.1371/journal.pone.0119012
PMCID: PMC4352010  PMID: 25746469
7.  Intimin Gene (eae) Subtype-Based Real-Time PCR Strategy for Specific Detection of Shiga Toxin-Producing Escherichia coli Serotypes O157:H7, O26:H11, O103:H2, O111:H8, and O145:H28 in Cattle Feces 
Shiga toxin-producing Escherichia coli (STEC) strains belonging to serotypes O157:H7, O26:H11, O103:H2, O111:H8, and O145:H28 are known to be associated with particular subtypes of the intimin gene (eae), namely, γ1, β1, ε, θ, and γ1, respectively. This study aimed at evaluating the usefulness of their detection for the specific detection of these five main pathogenic STEC serotypes in cattle feces. Using real-time PCR assays, 58.7% of 150 fecal samples were found positive for at least one of the four targeted eae subtypes. The simultaneous presence of stx, eae, and one of the five O group markers was found in 58.0% of the samples, and the five targeted stx plus eae plus O genetic combinations were detected 143 times. However, taking into consideration the association between eae subtypes and O group markers, the resulting stx plus eae subtype plus O combinations were detected only 46 times. The 46 isolation assays performed allowed recovery of 22 E. coli strains belonging to one of the five targeted STEC serogroups. In contrast, only 2 of 39 isolation assays performed on samples that were positive for stx, eae and an O group marker, but that were negative for the corresponding eae subtype, were successful. Characterization of the 24 E. coli isolates showed that 6 were STEC, including 1 O157:H7, 3 O26:H11, and 2 O145:H28. The remaining 18 strains corresponded to atypical enteropathogenic E. coli (aEPEC). Finally, the more discriminating eae subtype-based PCR strategy described here may be helpful for the specific screening of the five major STEC in cattle feces.
doi:10.1128/AEM.03161-13
PMCID: PMC3911233  PMID: 24296503
8.  Assessment of the Impact of the 2003 and 2006 Heat Waves on Cattle Mortality in France 
PLoS ONE  2014;9(3):e93176.
Objectives
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.
Methods
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.
Results
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.
doi:10.1371/journal.pone.0093176
PMCID: PMC3965539  PMID: 24667835
9.  Overall Decrease in the Susceptibility of Mycoplasma bovis to Antimicrobials over the Past 30 Years in France 
PLoS ONE  2014;9(2):e87672.
Mycoplasma (M.) bovis is frequently implicated in respiratory diseases of young cattle worldwide. Today, to combat M. bovis in Europe, only antimicrobial therapy is available, but often fails, leading to important economical losses. The antimicrobial susceptibility of M. bovis is not covered by antimicrobial resistance surveillance networks. The objectives of this study were to identify resistances that were acquired over the last 30 years in France and to determine their prevalence within comtemporary strains. The minimum inhibition concentration (MIC) values of 12 antimicrobials, considered active on M. bovis, were compared, using an agar dilution method, between 27 and 46 M. bovis isolates respectively obtained in 1978–1979 and in 2010–2012 from 73 distinct respiratory disease outbreaks in young cattle all over France. For eight antimicrobials, resistances were proven to be acquired over the period and expressed by all contemporary strains. The increase of the MIC value that inhibited 50% of the isolates (MIC50) was: i) substantial for tylosin, tilmicosin, tulathromycin and spectinomycin, from 2 to >64, 2 to >128, 16 to 128 and 4 to >64 µg/mL, respectively, ii) moderate for enrofloxacin, danofloxacin, marbofloxacin and oxytetracycline, from 0.25 to 0.5, 0.25 to 0.5, 0.5 to 1, 32 to >32 µg/mL, respectively. No differences were observed for gamithromycin, tildipirosin, florfenicol and valnemulin with MIC50 of 128, 128, 8, <0.03 µg/mL, respectively. If referring to breakpoint MIC values published for respiratory bovine pathogens, all contemporary isolates would be intermediate in vivo for fluoroquinolones and resistant to macrolides, oxytetracycline, spectinomycin and florfenicol.
doi:10.1371/journal.pone.0087672
PMCID: PMC3913625  PMID: 24503775
10.  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.
doi:10.1371/journal.pone.0085444
PMCID: PMC3897431  PMID: 24465562
11.  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.
doi:10.1371/journal.pone.0063246
PMCID: PMC3653928  PMID: 23691004
12.  Defining syndromes using cattle meat inspection data for syndromic surveillance purposes: a statistical approach with the 2005–2010 data from ten French slaughterhouses 
Background
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.
Results
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.
Conclusion
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.
doi:10.1186/1746-6148-9-88
PMCID: PMC3681570  PMID: 23628140
Syndromic surveillance; Animal health; Meat inspection; Slaughterhouses; Cattle
13.  Phylogenetic Grouping and Virulence Potential of Extended-Spectrum-β-Lactamase-Producing Escherichia coli Strains in Cattle 
Applied and Environmental Microbiology  2012;78(13):4677-4682.
In line with recent reports of extended-spectrum beta-lactamases (ESBLs) in Escherichia coli isolates of highly virulent serotypes, such as O104:H4, we investigated the distribution of phylogroups (A, B1, B2, D) and virulence factor (VF)-encoding genes in 204 ESBL-producing E. coli isolates from diarrheic cattle. ESBL genes, VFs, and phylogroups were identified by PCR and a commercial DNA array (Alere, France). ESBL genes belonged mostly to the CTX-M-1 (65.7%) and CTX-M-9 (27.0%) groups, whereas those of the CTX-M-2 and TEM groups were much less represented (3.9% and 3.4%, respectively). One ESBL isolate was stx1 and eae positive and belonged to a major enterohemorrhagic E. coli (EHEC) serotype (O111:H8). Two other isolates were eae positive but stx negative; one of these had serotype O26:H11. ESBL isolates belonged mainly to phylogroup A (55.4%) and, to lesser extents, to phylogroups D (25.5%) and B1 (15.6%), whereas B2 strains were quasi-absent (1/204). The number of VFs was significantly higher in phylogroup B1 than in phylogroups A (P = 0.04) and D (P = 0.02). Almost all of the VFs detected were found in CTX-M-1 isolates, whereas only 64.3% and 33.3% of them were found in CTX-M-9 and CTX-M-2 isolates, respectively. These results indicated that the widespread dissemination of the blaCTX-M genes within the E. coli population from cattle still spared the subpopulation of EHEC/Shiga-toxigenic E. coli (STEC) isolates. In contrast to other reports on non-ESBL-producing isolates from domestic animals, B1 was not the main phylogroup identified. However, B1 was found to be the most virulent phylogroup, suggesting host-specific distribution of virulence determinants among phylogenetic groups.
doi:10.1128/AEM.00351-12
PMCID: PMC3370483  PMID: 22522692
14.  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.
doi:10.1371/journal.pone.0043360
PMCID: PMC3419712  PMID: 22916249
15.  Comparative assessment of two commonly used commercial ELISA tests for the serological diagnosis of contagious agalactia of small ruminants caused by Mycoplasma agalactiae 
Background
Contagious agalactia (CA) of sheep and goats caused by Mycoplasma agalactiae is a widely occurring economically important disease that is difficult to control. The ELISA is commonly used for the serological detection of CA but it has some limitations and the performance of the available tests have not been properly evaluated.
Two commercial ELISA kits are widely used, one involving a fusion protein as target antigen and the other a total antigen. The objectives were to compare these tests by evaluating:
i. Their diagnostic sensitivity and specificity, the relevance of the recommended cut-off points, the correlation between the two tests, and, the correlation between serology data and the milk shedding of M. agalatiae;
ii. The influence of extrinsic factors such as the targeted animal species, geographical origin of the samples, intra-specific variability of M. agalactiae and concurrent mycoplasma infections.
A sample of 5900 animals from 211 farms with continuous CA monitoring for 20 years and no prior vaccination history was used. The infection status was known from prior bacteriological, epidemiological and serological monitoring with a complementary immunoblotting test.
Results
The average diagnostic sensitivity was 56% [51.8–59.8] for the fusion protein ELISA and 84% [81.3–87.2] for the total antigen ELISA, with noteworthy flock-related variations. The average diagnostic specificity for the fusion protein ELISA was 100% [99.9–100], and for the total antigen ELISA differed significantly between goats and sheep: 99.3% [97.4–99.9] and 95.7% [93.8–97.2] respectively.
Experimental inoculations with different M. agalactiae strains revealed that the ELISA kits poorly detected the antibody response to certain strains. Furthermore, test performances varied according to the host species or geographical origin of the samples.
Finally, the correlation between milk shedding of M. agalactiae and the presence of detectable antibodies in the blood was poor.
Conclusions
These serological tests are not interchangeable. The choice of a test will depend on the objectives (early detection of infection or disease control program), on the prevalence of infection and the control protocol used. Given the variety of factors that may influence performance, a preliminary assessment of the test in a given situation is recommended prior to widespread use.
doi:10.1186/1746-6148-8-109
PMCID: PMC3439703  PMID: 22776779
16.  Individual factors associated with L- and H-type Bovine Spongiform Encephalopathy in France 
Background
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.
Results
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.
Conclusion
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.
doi:10.1186/1746-6148-8-74
PMCID: PMC3514362  PMID: 22647660
Atypical bovine spongiform encephalopathy; L-BSE; H-BSE; Spatial analysis; Risk factors; France

Results 1-16 (16)