Carole Sala

Modelling BSE trend over time in Europe, a risk assessment perspective

BSE is a zoonotic disease that caused the emergence of variant Creuzfeldt-Jakob disease in the mid 1990s. The trend of the BSE epidemic in seven European countries was assessed and compared, using Age-Period-Cohort and Reproduction Ratio modelling applied to surveillance data 2001–2007. A strong decline in BSE risk was observed for all countries that applied control measures during the 1990s, starting at different points in time in the different countries. Results were compared with the type and date of the BSE control measures implemented between 1990 and 2001 in each country. Results show that a ban on the feeding of meat and bone meal (MBM) to cattle alone was not sufficient to eliminate BSE. The fading out of the epidemic started shortly after the complementary measures targeted at controlling the risk in MBM. Given the long incubation period, it is still too early to estimate the additional effect of the ban on the feeding of animal protein to all farm animals that started in 2001. These results provide new insights in the risk assessment of BSE for cattle and Humans, which will especially be useful in the context of possible relaxing BSE surveillance and control measures.

Individual factors associated with L- and H-type Bovine Spongiform Encephalopathy in France

BackgroundCattle 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.ResultsThe 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.ConclusionTo 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.

Modelling the trend of bovine spongiform encephalopathy prevalence in France: Use of restricted cubic spline regression in age-period-cohort models to estimate the efficiency of control measures.

An age-period-cohort (APC) analysis was used to assess the trend in prevalence of bovine spongiform encephalopathy (BSE) in France over time in relation to the control measures adopted since onset of the epidemic. Restricted cubic regression splines were used to model the functional forms of the non-linear effects of age at screening, birth cohort and date of diagnosis of the tested animals. The data of the 2001-2007 period of surveillance was analysed using 1-year categorisation. A categorical analysis was performed as control to check the accuracy of the sets of knots in the spline models, which were selected according to the Akaike Information Criterion (AIC). Knot selection was based on a priori knowledge of the disease and the dates of implementation of the five main BSE control measures. It was assumed that disease prevalence was a function of exposure to BSE and that changes in the exposure of cattle to BSE were mainly due to the control measures. The effects of the five main control measures were discussed in relation to the trend in BSE risk for the successive birth cohorts. The six selected models confirmed that all measures participated in disease control. However, characterization of the respective effect of individual measures was not straightforward due to the very low disease prevalence, incompletely tested cohorts and probably cumulative and overlapping effects of successive measures. The ban of importation of meat and bone meal (MBM) from the UK and the ban of use of MBM in bovines were insufficient to control the epidemic. The decline in the BSE epidemic more likely originated from implementation of the ban of MBM use in all ruminants in 1994, whose effect was probably reinforced by the evolution in perception of the BSE risk following evidence of BSE transmission to humans. Finally, the respective effects of the last two measures (prohibition of the use of specific risk material in 1996 and total MBM ban in 2000) could not be characterized as they were implemented when the disease trend was already in strong decline.

Assessment of fallen equine data in France and their usefulness for epidemiological investigations

Quantitative information about equine mortality is relatively scarce, yet it could be of great value for epidemiology purposes. Several European projects based on the exploitation of data from rendering plants have been developed to improve livestock surveillance. Similar data are available for equines in France but have never been studied to date. The objective of this research was to evaluate the potential of the French Ministry of Agricultures Fallen Stock Data Interchange (FSDI) database to provide quantitative mortality information on the French equine population. The quality of FSDI equine data from 2011 to 2014 was assessed using complementary data registered in the French equine census database, SIRE. Despite a perfectible quality, the FSDI database proved to be a valuable source for studying the basal patterns of mortality over time in the French equine population as illustrated by the spatial representation of the number of deaths. However, improvements in the FSDI database are needed, in particular regarding the registration of animal identification numbers, in order to detail equine mortality for epidemiology purposes.

Fallen stock data: An essential source of information for quantitative knowledge of equine mortality in France

Summary Background Quantitative information about equine mortality is relatively scarce, yet it could be of great value for epidemiological purposes. In France, data from rendering plants are centralised in the Fallen Stock Data Interchange database (FSDI), managed by the French Ministry of Agriculture, while individual equine data are centralised in the French equine census database, SIRE, managed by the French horse and riding institute (IFCE). Objectives To evaluate whether the combined use of the FSDI and SIRE databases can provide representative and accurate quantitative information on mortality for the French equine population and to propose enhancements of these databases to improve the quality of the resulting demographic information. Study design Descriptive study. Methods Mortality ratios for the French equine population were calculated per year between 2011 and 2014 and temporal variations in equine mortality modelled during the same period. Survival analyses were performed on a sample of equines traceable in both the FSDI and SIRE databases. Results Estimates of the annual mortality ratios varied from 3.02 to 3.40% depending on the years. Survival rates of equines 2‐years‐old and over differed according to breed categories with the highest median age at death for the ponies. The weekly description of mortality highlighted marked seasonality of deaths whatever the category of equines. Modelling temporal variations in equine mortality also brought to light excess mortality. Main limitations Insufficient traceability of equines between the two databases. Conclusion The FSDI database provided an initial approach to equine death ratios on a national scale and an original description of temporal variations in mortality. Improvement in the traceability of equines between the FSDI and SIRE databases is needed to enable their combined use, providing a representative description of equine longevity and a more detailed description of temporal variations in mortality.

A Non Parametric Exact Test Based on the Number of Records for an Early Detection of Emerging Events: Illustration in Epidemiology

Facing the first times of occurrence of events of a new type, such as seismic events, arrivals of individuals of a unknown species, occurrences of cases of a new disease, etc., it is crucial to predict if these events are only “sporadic,” or if they announce an emerging phenomenon (earthquake, emergence of a population, epidemic). We propose here an exact non parametric test statistic based on the number of lower records Nn in {ΔTk}1 ⩽ k ⩽ n, ΔTk being the waiting time between two successive events. Under H0 (sporadic events), the {ΔTk} are assumed i.i.d., while under H1 (emergent events), the {ΔTk} are assumed independent with cdf’s (cumulative distributions functions) {Gk} increasing with k. Under H0, the distribution of Nn is independent of Gk, thus allowing a non parametric test of H0. To calculate the power of the test under the alternative hypothesis H1, we assume the particular family of cdf, , , where G is a continuous cdf on (0, ∞) and a > 1. These distributions represent an exponential occurrence rate of events. We show that the distribution of Nn under H1 depends only on a (and not on G). We estimate a by the maximum likelihood estimator, and give the asymptotic properties of this estimator, as n → ∞. Finally, we illustrate the test on simulations and then on data concerning the atypical bovine spongiform encephalopathy in France.

Time trends in exposure of cattle to bovine spongiform encephalopathy and cohort effect in France and Italy: value of the classical Age-Period-Cohort approach

BackgroundThe Age-Period-Cohort (APC) analysis is routinely used for time trend analysis of cancer incidence or mortality rates, but in veterinary epidemiology, there are still only a few examples of this application. APC models were recently used to model the French epidemic assuming that the time trend for BSE was mainly due to a cohort effect in relation to the control measures that may have modified the BSE exposure of cohorts over time. We used a categorical APC analysis which did not require any functional form for the effect of the variables, and examined second differences to estimate the variation of the BSE trend. We also reanalysed the French epidemic and performed a simultaneous analysis of Italian data using more appropriate birth cohort categories for comparison.ResultsWe used data from the exhaustive surveillance carried out in France and Italy between 2001 and 2007, and comparatively described the trend of the epidemic in both countries. At the end, the shape and irregularities of the trends were discussed in light of the main control measures adopted to control the disease. In Italy a decrease in the epidemic became apparent from 1996, following the application of rendering standards for the processing of specific risk material (SRM). For the French epidemic, the pattern of second differences in the birth cohorts confirmed the beginning of the decrease from 1995, just after the implementation of the meat and bone meal (MBM) ban for all ruminants (1994).ConclusionThe APC analysis proved to be highly suitable for the study of the trend in BSE epidemics and was helpful in understanding the effects of management and control of the disease. Additionally, such an approach may help in the implementation of changes in BSE regulations.

Is The Age-Period-Cohort Model Well Suited to an Epidemic Context? The Case of the French BSE Epidemic

Abstract Although Age-Period-Cohort (APC) models are routinely used in time-trend analyses of chronic diseases, few examples of their application to epidemic diseases are available. APC analyses of the French bovine spongiform encephalopathy (BSE) epidemic revealed an unexpected period effect, which was attributed to the design of the study, in connection with low BSE prevalence and a short surveillance period. The aim of our study was to evaluate the relevance of this hypothesis, the behaviour of the APC model in an epidemic context (e.g. the BSE epidemic) and the impact of including the period effect in an APC model on the estimate of birth cohort effects. We simulated datasets mimicking the French BSE epidemic and its variable pattern, as well as duration and the surveillance time period, and analysed them with a categorical APC model. Results showed a period effect in 44% of analysed datasets, although no period effect had been introduced in the data simulation process. This type of artefactual period effect was detected when a sudden change in cohort prevalence occurred over a short period of time. Additionally, in the context of BSE, including a period effect in the model may dramatically affect the estimation of cohort prevalence, depending on epidemic pattern and, as expected, duration and the surveillance time period according to the year in which highly infected birth cohorts are detected as BSE cases.