Assessment of the utility of routinely collected cattle census and disposal data for syndromic surveillance

Census and disposal data provide a multipurpose source of information on cattle mortality. The retrospective analyses we conducted on the data gathered in the National Cattle Register produced relevant information for describing and modelling the cattle mortality baseline and evaluating the impact of the 2007-2008 Blue Tongue epidemic on the French cattle population. This work was conducted retrospectively but showed that monitoring cattle mortality near real time could help detecting unexpected events. We are thus currently working on a timely and automated system to monitor cadaver disposal requests received by rendering plants, thanks to a data interchange system recently implemented between the Ministry of Agriculture and the fallen stock companies. Besides technical and methodological challenges, using these data for surveillance purposes raises epidemiological questions that still need to be answered. The question remains notably as to whether an abnormal increased mortality is a sensitive and timely signal for detecting unexpected health events. It appears also very challenging to identify the most adequate surveillance scale (time, space and population) and the most adequate anomaly detection algorithms to apply when the characteristics of the signals to be detected (shape, amplitude, etc.) are not known a priori. In Human health, similar systems have not yet proven their ability to detect unexpected events earlier than classical surveillance systems currently in place, but they have already demonstrated their value for real time assessment of identified and potentially dangerous events. Combined with traditional surveillance systems, we think that monitoring routinely collected data could improve the surveillance of the animal population health. Even if not used for detection purposes, cattle mortality monitoring could be used to rapidly produce information on the impact and evolution of identified events, what would facilitate decision-making regarding management measures and improve the communication.     

Estimating spatial and temporal variations of the reproduction number for highly pathogenic avian influenza H5N1 epidemic in Thailand

Since 2003, highly pathogenic avian influenza (HPAI) H5N1 virus has spread, causing a pandemic with serious economic consequences and public health implications. Quantitative estimates of the spread of HPAI H5N1 are needed to adapt control measures. This study aimed to estimate the variations of the reproduction number R in space and time for the HPAI H5N1 epidemic in Thailand. Transmission between sub-districts was analyzed using three different and complementary methods. Transmission of HPAI H5N1 was intense (R(t)>1) before October 2004, at which point the epidemic started to progressively fade out (R(t)<1). The spread was mainly local, with 75% of the putative distances of transmission less than 32km. The map of the mean standardized ratio of transmitting the infection (sr) showed sub-districts with a high risk of transmitting infection. Findings from this study can contribute to discussions regarding the efficacy of control measures and help target surveillance programs.     

A field study on estrus detection in lactating beef cattle

Estrus detection efficacy and heat detection protocol were studied by means of a field study carried out on 878 lactating beef cows in 60 French herds. Average herd size was 48, and 75% of the farmers partly or exclusively used artificial insemination. The cows were calved between October 1992 and March 1993. Estrus was recorded daily by the farmers. Cycling status was determined by progesterone radioimmuno-assay 2 months after calving. The relationship between the estrus detection protocol and the delay period from calving to first observed estrus was analysed using survival curves and the Cox proportional hazard model, adjusting for confounders. Seventy-one percent of the cows were seen in estrus by the farmers; the interval between calving and the first observed estrus ranged from 9 days to more than 5 months and the median was 56 days. Two months after calving, 44% of the cycling cows had not been seen in heat by the farmers and 11% of the non-cycling cows had been reported to have been in estrus. The heat detection protocol varied widely between farmers, depending on the considered estrus signs, schedule and time spent looking for signs. Two factors were significantly related to a shorter interval from calving to first observed heat: the use of artificial insemination (which relates to the farmer's interest in heat detection) and an overall daily time spent for heat detection greater than 1 h. Cows in tie stalls had a delayed interval to the first observed estrus. These results show that many farmers did not adapt their reproduction practice sufficiently to an earlier calving period. There is room for improvement since in many cases the heat detection protocol does not match the required standards for optimal heat detection.     

Review on the epidemiology and dynamics of BSE epidemics

The paper describes how the comprehensive surveillance of bovine spongiform encephalopathy (BSE) and studies carried out on these data has enhanced our knowledge of the epidemiology of BSE. Around 7, 000 BSE cases were detected through the screening of about 50 million cattle with rapid tests in Europe. It confirmed that the clinical surveillance had a poor capacity to detect cases, and also showed the discrepancy of this passive surveillance efficiency between regions and production types (dairy/beef). Other risk factors for BSE were being in a dairy herd (three times more than beef), having a young age at first calving (for dairy cattle), being autumn-born (dairy and beef), and being in a herd with a very high milk yield. These findings focus the risk on the feeding regimen of calves/heifers. Several epidemiological studies across countries suggest that the feedborne source related to meat and bone meal (MBM) is the only substantiated route of infection - even after the feed ban -, while it is not possible to exclude maternal transmission or milk replacers as a source of some infections. In most European countries, the average age of the cases is increasing over time and the prevalence decreasing, which reflects the effectiveness of control measures. Consistent results on the trend of the epidemic were obtained using back-calculation modelling, the R(0) approach and Age-Period-Cohort models. Furthermore, active surveillance also resulted in the finding of atypical cases. These are distinct from previously found BSE and classified in two different forms based on biochemical characteristics; their prevalence is very low (36 cases up to 1st September 2007), affected animals were old and some of them displayed clinical signs. The origin and possibility of natural transmission is unknown.     

Characterization of metabolites of fungicidal cymoxanil in a sensitive strain of Botrytis cinerea

The metabolism of cymoxanil [1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea] by a very sensitive strain of Botrytis cinerea toward this fungicide was studied by using [2-(14)C]-cymoxanil. Labeled cymoxanil was added either in a culture of this strain or in its enzymatic extract. The main metabolites, detected in biological samples, were isolated and identified by mass and NMR spectrometry. Their identification allowed us to show that this strain quickly metabolized cymoxanil according to at least three enzymatic pathways: (i) cyclization leading, after hydrolysis, to ethyl parabanic acid, (ii) reduction giving demethoxylated cymoxanil, and (iii) hydrolysis and reduction followed by acetylation leading to N-acetylcyanoglycine. In a cell-free extract of the same strain, only the first and the second enzymatic reactions, quoted above, occurred. Biological tests showed that, among all the metabolites, only N-acetylcyanoglycine is fungitoxic toward this sensitive strain.     

Spatial heterogeneity of the risk of BSE in France following the ban of meat and bone meal in cattle feed

In France, meat-and-bone meal (MBM) has been prohibited for cattle feeding since 1990, but bovine spongiform encephalopathy (BSE) cases, called 'NAIF', appeared in animals born after this feed ban. Furthermore, in 1996 a new measure was taken: removal of cadavers and specified risk materials (SRM) from the processing of MBM dedicated to animal feed. Nevertheless, BSE cases (called 'super-NAIF') appeared in cattle born after this measure was in force. We analysed the spatial distribution of 445 'NAIF' and 58 'super-NAIF' cases detected in France from July 1, 2001 to July 31, 2003. The detection of BSE was based both on the mandatory reporting system (MRS) and the systematic test screening of cattle at the abattoir and at the fallen-animal plant with rapid tests. The background population was based on the adult-cow census. The disease mapping of the BSE risk was based on the standardised incidence ratio (stochastic Poisson process). A spatial component, which takes into account the spatial dependence between the geographical units by a notion of adjacency was used to eliminate the over-dispersion in the risk assessment. The geographical units were defined by hexagons with a side of 23km (France had 1264 hexagons). The parameters were estimated by a Metropolis Gibbs sampling algorithm using the Markov-chain Monte Carlo methods. The BSE cases were not randomly distributed. Furthermore, the areas at risk for the 'super-NAIF' matched part of the areas at risk for the 'NAIF' cases-which suggests that it might be a common source of contamination.     

A spatio-temporal analysis of BSE cases born before and after the reinforced feed ban in France

A spatio-temporal analysis was carried out to see how the risk distribution of bovine spongiform encephalopathy (BSE) in France changed depending on the period of birth. The data concerned the 539 BSE cases born in France after the ban (BAB) of meat and bone meal (MBM) in 1990 and detected between July 1, 2001 and December 31, 2003, when the surveillance of BSE was comprehensive. Seventy-two of these cases were born after the reinforced (second) ban (BASB) in 1996, which involved the removal of BSE-risk materials and cadavers from the processing of MBM. The Ederer-Myers-Mantel (EMM) time and space cluster test was applied, after classifying the cases by trimester and region of birth, BAB or BASB status, and dairy or beef status. Then disease mapping was performed for four successive birth periods, three for the BAB cases (January 1991 through June 1994, July 1994 through June 1995, July 1995 through June 1996), and one for the BASB (July 1996 through October 1998). It was elaborated with the Bayesian graphical modelling methods and based on a Poisson distribution with spatial smoothing. The parameters were estimated by a Markov Chain Monte Carlo (MCMC) simulation method. The main finding was that the areas with the highest risk of BSE changed largely from one birth period to another; from the west, it reached the east of France for birth cohort 1994-1995 and the southwest for birth cohort 1995-1996. The EMM test identified a peak risk in this region both for dairy and beef cattle in the fall 1995. The spatial distribution of the risk for the BASB cases matched the spatial pattern of risk for the preceding BAB birth cohort quite well; this was in favour of a common origin of the infection of the BAB and BASB cases, despite the complementary control measures.     

Questionnaire analysis of BSE cases in France detected by active surveillance and the reasons for non-notification

A mandatory reporting system (MRS) was set up in France in December 1990 to detect animals showing clinical signs of bovine spongiform encephalopathy (BSE). Since June 2000, four active surveillance programmes dedicated to fallen stock and slaughtered cattle have been implemented to reinforce the MRS. The clinical status of the cases detected through these programmes was investigated to understand why the MRS had failed to detect them. Up to September 1, 2002, 181 cases had been analysed (126 fallen stock and 55 slaughtered cattle). Almost all the fallen stock cases were animals which had been showing clinical signs, and two thirds of them had shown signs which should have led to a suspicion of BSE. No clinical signs had been reported for two thirds of the slaughtered cattle cases and 10 (8 per cent) of the fallen stock cases.     

Estimating the trend of the French BSE epidemic over six birth cohorts through the analysis of abattoir screening in 2001 and 2002

A bovine spongiform encephalopathy (BSE) testing programme at the abattoir started in 2001 in France. A total of 5 281 293 bovines were tested in 2001 and 2002; 87 were found positive in 2001--37 per million (95% CI 30-46)--, whereas only 71 in 2002--24 per million (95% CI 19-30). Logistic regression models were run to compare the prevalence of BSE on successive birth cohorts, using a pair-wise method of controlling for age at testing; the prevalence on the first one, determined on animals slaughtered in 2001, was compared to the prevalence on the following one determined on animals slaughtered in 2002. Five models were performed in order to compare the birth cohorts preceding and following the months of June 1993 (i.e. July 92-June 93 birth cohort compared to July 93-June 94 birth cohort) (8.5 years old cattle), June 1994 (7.5 years old cattle), June 1995 (6.5 years old cattle), June 1996 (5.5 years old cattle) and June 1997 (4.5 years old cattle). The models were adjusted for the production type of cattle and the test used. The results showed a significant increase (OR = 2.31, 95% CI 1.08-4.9) of the BSE prevalence between the July 93-June 94 and July 94-June 95 cohorts, and then a significant decrease over the next two birth cohorts; the July 95-June 96 birth cohort was significantly less affected than the July 94-June 95 one (OR = 0.46, 95% CI 0.27-0.78), and the July 96-June 97 birth cohort was significantly less affected than the July 95-June 96 one (OR = 0.17, 95% CI 0.07-0.37). The increase in BSE prevalence between the July 93-June 94 and July 94-June 95 cohorts was in agreement with modelling studies, but needs to be confronted to the data on fallen stock at the national level. The decrease in BSE prevalence on the birth cohorts born after June 1995 was in agreement with the findings on the fallen stock in the western part of France and matches the implementation of the removal of specified risk materials (SRM) and dead animals from the processing of meat and bone meal (MBM) since June 1996.