Epidemiological investigation of bovine tuberculosis causes of herd breakdowns and persistence in Spain

A Espanya, la prevalença de ramats amb tuberculosi ha disminuït del 11,1% el 1986 a 1,3% el 2011. Malgrat aquesta reducció en la prevalença, en els últims anys s'ha moderat el descens i l'actual situació epidemiològica de bTB planteja un desafiament cara a la consecució del estatus de país oficialment indemne de tuberculosi. Entre el 50 i el 60% dels ramats positius detecta cada any, són nous ramats positius, i la resta són ramats on la infecció persisteix des de l'any anterior. No es coneixen quines circumstàncies epidemiològiques condueixen a la introducció o la persistència de la infecció. Per tant, l'objectiu d'aquesta tesi és millorar el coneixement de l'epidemiologia de la bTB a Espanya mitjançant l'avaluació de les causes més probables d'infecció i els factors relacionats amb els ramats infectats de manera persistents. Per a l'estimació de les causes més probables d'introducció de la infecció en un ramat hem desenvolupat una metodologia basada en les diferents vies de transmissió de la bTB entre els ramats. S'han considerat set vies i per cada una s'ha realitzat un arbre de decisió sobre possibles riscos. A cada risc se l'hi ha assignat una probabilitat basada en opinió d'experts. Per a la gestió de dades i per al càlcul de les probabilitats de cada una de les diferents causes possibles s'han creat un parell de macros. D'acord amb els resultats dels 816 ramats estudiats (casos detectades principalment els anys 2010 i 2011), la majoria dels casos serien deguts al ressorgiment d'infeccions residuals que havien afectat anteriorment al ramat (39%, n = 316). La introducció de la infecció es va produir pel contacte amb animals silvestres en el 12% dels casos (n = 98), i a través de ramats veïns en el 10% (n = 85). En el 28% (n = 225) dels brots, no s'ha pogut determinar l'origen de la infecció. En 309 ramats, la diferència entre les dues causes amb la probabilitat més alta era petita (menys d'u), de manera, que per a aquestes granges tant la primera com la segona causa serien possibles. Dins d'aquest grup, la primera opció més freqüent va ser la infecció residual (69%, n = 214) i la segona de les opcions més freqüents era compartir les pastures amb altres granges (36%, n = 112) i la interacció amb la fauna silvestre (30%, n = 94). En comparar aquestes conclusions amb les dels veterinaris oficials que havien fet la investigació epidemiològica sobre el terreny, s'obté una concordança baixa; especialment en el cas de fauna silvestre. Dins del grup dels ramats on el veterinari només considerava una causa (és a dir, 309 ramats), en 124 la fauna silvestre va ser considerada com la causa més probable, mentre que nosaltres només ho varem concloure en 33 granges. Aquestes discordances podrien estar relacionades amb un diferent accés a les dades i també a percepcions diferents sobre la importància atribuïda a cada causa. Per tal d'avaluar els factors relacionats amb la persistència de bTB en granges es va realitzar un estudi de casos i controls on es va comparar granges infectades que es va eliminar fàcilment la bTB amb altres on es va tardar més de 5 anys. Totes les granges eren del sud d'Espanya i es van estratificar per grandària del ramat i la ubicació geogràfica (comarca). Es va omplir un qüestionari mitjançant entrevista personal en 150 ramats (80 controls i 70 casos) de les Comunitats d'Andalusia i de Castilla-la Mancha. D'acord amb els resultats d'aquest estudi, les granges amb més superfície de pastures i amb veïns positius, tenien més dificultats per eradicar la infecció, per tant, eren més propenses a patir un brot de bTB persistent. Les probabilitats de persistència eren entre 1,1 i 5,0 vegades més gran en aquells ramats amb possible contacte amb el bestiar d'un ramat positiu veí. La probabilitat de persistència també es va associar amb la superfície de pastures. Les finques amb àrees de pastura més grans tenien una probabilitat entre 1,2 i 12,7 vegades més alta de tenir dificultats en l'eliminació que les finques amb àrees de pastures més petits. El maneig dels animals positius, com ara utilitzar vedelles de reposició de mares positives o no aïllar els animals positius, així com la presència de cabres dins de la granja semblen tenir també una influència en la persistència de bTB.En España, la prevalencia de rebaños con tuberculosis ha disminuido del 11,1% en 1986 a 1,3% en 2011. A pesar de esta reducción, en los últimos años se ha moderado el descenso de la prevalencia y la situación epidemiológica actual de bTB plantea un desafío cara a la consecución del estatus de país oficialmente indemne de tuberculosis. Entre el 50 y el 60% de los rebaños positivos detectados cada año, son nuevos rebaños positivos, y el resto son rebaños donde la infección persiste desde el año anterior. No se sabe qué circunstancias epidemiológicas están implicadas en la introducción o la persistencia de la infección. Por tanto, el objetivo de esta tesis es mejorar el conocimiento de la epidemiología de la bTB en España mediante la evaluación de las causas más probables de infección y los factores relacionados con los rebaños infectados de forma persistente. Para la estimación de las causas más probables de introducción de la infección en un rebaño hemos desarrollado una metodología basada en las diferentes vías de transmisión de la bTB entre los rebaños. Se han considerado siete vías y por cada una de ellas se ha realizado un árbol de decisión sobre posibles riesgos. A cada riesgo se le ha asignado una probabilidad basada en opinión de expertos. Para la gestión de datos y para el cálculo de las probabilidades de cada una de las diferentes causas posibles se han creado dos macros. De acuerdo con los resultados de los 816 rebaños estudiados (casos detectados principalmente en los años 2010 y 2011), la mayoría de las nuevas infecciones en realidad son debidas al resurgimiento de infecciones que habían afectado anteriormente al rebaño (39%, n = 316). La introducción de la infección se produjo por el contacto con animales silvestres en el 12% de los casos (n = 98), y a través de rebaños vecinos en el 10% (n = 85). En el 28% (n = 225) de los brotes, no se ha podido determinar el origen de la infección. En 309 rebaños, la diferencia entre las dos causas con la probabilidad más alta era escasa (menos de uno), de manera que para estas granjas tanto la primera como la segunda causa serían posibles. Dentro de este grupo, la primera opción más frecuente fue la infección residual (69%, n = 214) y la segunda de las opciones más frecuentes era compartir los pastos con otras granjas (36%, n = 112) y la interacción con la fauna silvestre (30%, n = 94). Al comparar las conclusiones de nuestro estudio con las de los veterinarios oficiales que habían hecho la investigación epidemiológica sobre el terreno, se obtiene una concordancia baja, especialmente en el caso de fauna silvestre. Dentro del grupo de los rebaños donde el veterinario sólo consideraba una causa (es decir, 309 rebaños), en 124 la fauna silvestre fue la causa considerada como más probable para el veterinario, mientras que nosotros sólo lo concluimos en 33 granjas. Estas discordancias podrían estar relacionadas con diferencias en los datos a los que hemos tenido acceso así como a diferentes percepciones sobre la importancia atribuida a cada causa. Para evaluar los factores relacionados con la persistencia de BTB en granjas se realizó un estudio de casos y controles donde se compararon granjas infectadas donde se eliminó fácilmente la bTB con otras donde se tardó más de 5 años. Todas las granjas eran del sur de España y se estratificaron por tamaño del rebaño y ubicación geográfica (comarca). Se rellenó un cuestionario mediante entrevista personal en 150 rebaños (80 controles y 70 casos) de las Comunidades de Andalucía y de Castilla-La Mancha. De acuerdo con los resultados de este estudio, las granjas con más superficie de pastos y con vecinos positivos, tenían más dificultades para erradicar la infección, por lo tanto, eran más propensas a sufrir un brote de BTB persistente. Las probabilidades de persistencia eran entre 1,1 y 5,0 veces mayor en aquellos rebaños con posible contacto con un rebaño positivo vecino. La probabilidad de persistencia también se asoció con la superficie de pastos. Las fincas con áreas de pasto mayores tenían una probabilidad entre 1,2 y 12,7 veces más alta de tener dificultades en la eliminación que las fincas con áreas de pastos más pequeños. El manejo de los animales positivos, tales como utilizar terneras de reposición de madres positivas o no aislar los animales positivos, así como la presencia de cabras dentro de la granja parecen tener también una influencia en la persistencia de la bTB.In Spain, herd prevalence has decreased from 11.1% on 1986 to 1.3% on 2011. Despite this reduction on the prevalence, in the last years there has been just a moderate decline and the current bTB epidemiological situation poses a serious challenge towards the achievement of a national official tuberculosis free (OTF) status. In the country, approximately between 50 and 60% of the total bTB positive herds detected each year, are new positive herds, and the rest of the positives are herds that persist from the previous year. There is not a clear knowledge of the epidemiological circumstances that lead to the introduction or persistence of the infection. Therefore, the aim of this PhD was to improve the understanding of bTB epidemiology in Spain by assessing the most likely causes of infection and factors related with bTB persistent herds. To estimate the most likely causes of introduction of the infection on a herd we developed a methodology based on bTB routes of transmission between herds using decision trees. We considered seven routes as a possible cause of herd breakdown. In order to discriminate among them, probabilities were assigned within each decision tree based on expert opinion. Macros were used for data management and to calculate the probabilities of the different possible causes. According to the results of the 816 studied breakdowns (detected mainly in 2010 and 2011) most of the cases could be resurgence of residual infections that had previously affected the herd (39%, n=316). New introductions of the infection were produced by contact with wildlife in 12% of cases (n=98), and by neighboring herds in 10% of them (n=85). In 28 % (n=225) of the breakdowns, the origin of the infection remained unknown. In 309 herds, the difference between the first and the second cause with the higher probability was small (i.e., less than 1) so, for these herds, first and second possible causes of infection could be considered. Within this group the most frequent first option was residual infection (69%, n=214) and the most frequent second options were sharing pastures with other herds (36%, n=112) and interaction with wildlife (30%, n=94). The results of the comparisons between our conclusions and the ones of the veterinary officers conducting the epidemiological investigation on the field evidenced a low agreement. The lowest agreement was in the case of "wildlife". Within the group of herds where the veterinary officer just considered one cause (i.e., 309 herds) in 124 Wildlife was considered as the most likely cause, while we just found evidences to suspect of this in 33 farms. These discrepancies could be related to differences on access to data and perception about the importance attributed to the different causes. In order to assess factors related to bTB persistence we conducted a case-control study and compared persistent versus transient bTB infected farms from southern Spain. Farms were matched by herd size and geographical location (county). A questionnaire by personal interview was carried on 150 herds (80 controls and 70 cases) from Andalusia and Castilla La Mancha regions. According to the results of this study, farms with large pasture areas and positive neighbors had more difficulties in eradicating the disease and therefore, were more likely to suffer a persistent bTB outbreak. The odds of bTB persistence were between 1.1 and 5.0 times higher in those herds that had the possibility of contact with cattle from a neighbor positive herd. The probability of bTB persistence was also associated with the area of the pasture. Farms with larger pasture areas had odds between 1.2 and 12.7 times higher of having a persistent bTB episode than farms with smaller pasture areas. Management of positive animals such as making replacement from positive herds or not isolating positive animals and the presence of goats within the farm seem to have also an influence on bTB persistence

Epidemiological investigation of bovine tuberculosis herd breakdowns in Spain 2009/2011

We analyzed the most likely cause of 687 bovine tuberculosis (bTB) breakdowns detected in Spain between 2009 and 2011 (i.e., 22% of the total number of breakdowns detected during this period). Seven possible causes were considered: i) residual infection; ii) introduction of infected cattle from other herds; iii) sharing of pastures with infected herds; iv) contiguous spread from infected neighbor herds; v) presence of infected goats in the farm; vi) interaction with wildlife reservoirs and vii) contact with an infected human. For each possible cause a decision tree was developed and key questions were included in each of them. Answers to these key questions lead to different events within each decision tree. In order to assess the likelihood of occurrence of the different events a qualitative risk assessment approach was used. For this purpose, an expert opinion workshop was organized and ordinal values, ranging from 0 to 9 (i.e., null to very high likelihood of occurrence) were assigned. The analysis identified residual infection as the most frequent cause of bTB breakdowns (22.3%; 95%CI: 19.4-25.6), followed by interaction with wildlife reservoirs (13.1%; 95%CI: 10.8-15.8). The introduction of infected cattle, sharing of pastures and contiguous spread from infected neighbour herds were also identified as relevant causes. In 41.6% (95%CI: 38.0-45.4) of the breakdowns the origin of infection remained unknown. Veterinary officers conducting bTB breakdown investigations have to state their opinion about the possible cause of each breakdown. Comparison between the results of our analysis and the opinion from veterinary officers revealed a slight concordance. This slight agreement might reflect a lack of harmonized criteria to assess the most likely cause of bTB breakdowns as well as different perceptions about the importance of the possible causes. This is especially relevant in the case of the role of wildlife reservoirs

The variable prevalence of bovine tuberculosis among dairy herds in Central Ethiopia provides opportunities for targeted intervention.

Bovine tuberculosis (bTB) is an important disease for dairy productivity, as well as having the potential for zoonotic transmission. Previous prevalence studies of bTB in the dairy sector in central Ethiopia have suggested high prevalence, however, they have been limited to relatively small scale surveys, raising concerns about their representativeness. Here we carried out a cross sectional one-stage cluster sampling survey taking the dairy herd as a cluster to estimate the prevalence of bTB in dairy farms in six areas of central Ethiopia. The survey, which to date is by far the largest in the area in terms of the number of dairy farms, study areas and risk factors explored, took place from March 2016 to May 2017. This study combined tuberculin skin testing and the collection of additional herd and animal level data by questionnaire to identify potential risk factors contributing to bTB transmission. We applied the single intradermal cervical comparative tuberculin (SICCT) test using >4mm cut-off for considering an individual animal as positive for bTB; at least one reactor animal was required for a herd to be considered bTB positive. Two hundred ninety-nine dairy herds in the six study areas were randomly selected, from which 5,675 cattle were tested. The overall prevalence of bTB after standardisation for herd-size in the population was 54.4% (95% CI 48.7-60%) at the herd level, and it was 24.5% (95% CI 23.3-25.8) at the individual animal level. A Generalized Linear Mixed Model (GLMM) with herd and area as random effect was used to explore risk factors association with bTB status. We found that herd size, age, bTB history at farm, and breed were significant risk factors for animals to be SICCT positive. Animals from large herds had 8.3 times the odds of being tuberculin reactor (OR: 8.3, p-value:0.008) as compared to animals from small herds. The effect of age was strongest for animals 8-10 years of age (the oldest category) having 8.9 times the odds of being tuberculin reactors (OR: 8.9, p-value:<0.001) compared to the youngest category. The other identified significant risk factors were bTB history at farm (OR: 5.2, p-value:0.003) and cattle breed (OR: 2.5, p-value: 0.032). Our study demonstrates a high prevalence of bTB in central Ethiopia but with a large variation in within-herd prevalence between herds, findings that lays an important foundation for the future development of control strategies

Prevalence of bovine tuberculosis and its associated risk factors in the emerging dairy belts of regional cities in Ethiopia.

Bovine tuberculosis (BTB) has become an economically important disease in dairy herds found in and around Addis Ababa City and is emerging in regional cities like Gondar, Hawassa and Mekelle because of the establishment of dairy farms in the milk sheds of these cities. A cross-sectional study to estimate the prevalence of BTB and identify associated risk factors was conducted between February 2016 and March 2017. A total of 174 herds comprising of 2,754 dairy cattle in the cities of Gondar, Hawassa and Mekelle were tested using the Single Intradermal Comparative Cervical Tuberculin (SICCT) test. Data on herd structure, animal origin, body condition, housing condition, farm hygiene, management and biosecurity practices were collected using a pre-tested structured questionnaire. Generalized Linear Models (GLM) and Generalized Linear Mixed Models (GLMM) were used to analyze the herd and animal level risk factors, respectively. The herd prevalence was 22.4% (95% CI: 17-29%) while the animal prevalence was 5.2% (95% CI: 4-6%) at the cut-off >4 mm. The herd prevalence rose to 65.5% (95% CI: 58-72%) and the animal prevalence rose to 9% (95% CI: 8-10%) when the severe interpretation of >2 mm cut-off was applied. The mean within-herd prevalence in positive farms at the cut-off >4 mm was 22.7% (95% CI: 15-31%). At the herd level, the analysis showed that herd size, farm hygiene, feeding condition and biosecurity were significantly associated with BTB status, while new cattle introductions showed only borderline significance and that age of farm, housing condition, farmers' educational status and animal health care practice were not significant. At the animal level, the results showed that age and animal origin were identified as significant predictors for BTB positivity but sex and body condition score were not related to BTB status. Descriptive analysis revealed that herds having 'BTB history' showed slightly higher likelihood of being BTB positive compared to farms having no previous BTB exposure. In conclusion, this study showed relatively lower average prevalence in the emerging dairy regions as compared to the prevalence observed in and around Addis Ababa City, warranting for implementation of control program at this stage to reduce or possibly stop further transmission of BTB.This work was funded by the Biotechnology and Biological Sciences Research Council, the Department for International Development, the Economic & Social Research Council, the Medical Research Council, the Natural Environment Research Council and the Defence Science & Technology Laboratory, under the Zoonoses and Emerging Livestock Systems (ZELS) programme, ref: BB/L018977/1

Prevalence of bovine tuberculosis and its associated risk factors in the emerging dairy belts of regional cities in Ethiopia

Bovine tuberculosis (BTB) has become an economically important disease in dairy herds found in and around Addis Ababa City and is emerging in regional cities like Gondar, Hawassa and Mekelle because of the establishment of dairy farms in the milk sheds of these cities. A cross-sectional study to estimate the prevalence of BTB and identify associated risk factors was conducted between February 2016 and March 2017. A total of 174 herds comprising of 2,754 dairy cattle in the cities of Gondar, Hawassa and Mekelle were tested using the Single Intradermal Comparative Cervical Tuberculin (SICCT) test. Data on herd structure, animal origin, body condition, housing condition, farm hygiene, management and biosecurity practices were collected using a pre-tested structured questionnaire. Generalized Linear Models (GLM) and Generalized Linear Mixed Models (GLMM) were used to analyze the herd and animal level risk factors, respectively. The herd prevalence was 22.4% (95% CI: 17-29%) while the animal prevalence was 5.2% (95% CI: 4-6%) at the cut-off &gt;4 mm. The herd prevalence rose to 65.5% (95% CI: 58-72%) and the animal prevalence rose to 9% (95% CI: 8-10%) when the severe interpretation of &gt;2 mm cut-off was applied. The mean within-herd prevalence in positive farms at the cut-off &gt;4 mm was 22.7% (95% CI: 15-31%). At the herd level, the analysis showed that herd size, farm hygiene, feeding condition and biosecurity were significantly associated with BTB status, while new cattle introductions showed only borderline significance and that age of farm, housing condition, farmers' educational status and animal health care practice were not significant. At the animal level, the results showed that age and animal origin were identified as significant predictors for BTB positivity but sex and body condition score were not related to BTB status. Descriptive analysis revealed that herds having 'BTB history' showed slightly higher likelihood of being BTB positive compared to farms having no previous BTB exposure. In conclusion, this study showed relatively lower average prevalence in the emerging dairy regions as compared to the prevalence observed in and around Addis Ababa City, warranting for implementation of control program at this stage to reduce or possibly stop further transmission of BTB

Zoonotic tuberculosis in a high bovine tuberculosis burden area of Ethiopia

BackgroundTuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide, caused by species of the Mycobacterium tuberculosis complex (MTBC), with Mycobacterium tuberculosis being the dominant pathogen in humans and Mycobacterium bovis in cattle. Zoonotic transmission of TB (zTB) to humans is frequent particularly where TB prevalence is high in cattle. In this study, we explored the prevalence of zTB in central Ethiopia, an area highly affected by bovine TB (bTB) in cattle.MethodA convenient sample of 385 patients with pulmonary tuberculosis (PTB, N = 287) and tuberculous lymphadenitis (TBLN, N = 98) were included in this cross-sectional study in central Ethiopia. Sputum and fine needle aspirate (FNA) samples were obtained from patients with PTB and TBLN, respectively, and cultures were performed using BACTEC™ MGIT™ 960. All culture positive samples were subjected to quantitative PCR (qPCR) assays, targeting IS1081, RD9 and RD4 genomic regions for detection of MTBC, M. tuberculosis and M. bovis, respectively.ResultsTwo hundred and fifty-five out of 385 sampled patients were culture positive and all were isolates identified as MTBC by being positive for the IS1081 assay. Among them, 249 (97.6%) samples had also a positive RD9 result (intact RD9 locus) and were consequently classified as M. tuberculosis. The remaining six (2.4%) isolates were RD4 deficient and thereby classified as M. bovis. Five out of these six M. bovis strains originated from PTB patients whereas one was isolated from a TBLN patient. Occupational risk and the widespread consumption of raw animal products were identified as potential sources of M. bovis infection in humans, and the isolation of M. bovis from PTB patients suggests the possibility of human-to-human transmission, particularly in patients with no known contact history with animals.ConclusionThe detected proportion of culture positive cases of 2.4% being M. bovis from this region was higher zTB rate than previously reported for the general population of Ethiopia. Patients with M. bovis infection are more likely to get less efficient TB treatment because M. bovis is inherently resistant to pyrazinamide. MTBC species identification should be performed where M. bovis is common in cattle, especially in patients who have a history of recurrence or treatment failure

Epidemiological investigation of bovine tuberculosis causes of herd breakdowns and persistence in Spain

A Espanya, la prevalença de ramats amb tuberculosi ha disminuït del 11,1% el 1986 a 1,3% el 2011. Malgrat aquesta reducció en la prevalença, en els últims anys s'ha moderat el descens i l'actual situació epidemiològica de bTB planteja un desafiament cara a la consecució del estatus de país oficialment indemne de tuberculosi. Entre el 50 i el 60% dels ramats positius detecta cada any, són nous ramats positius, i la resta són ramats on la infecció persisteix des de l'any anterior. No es coneixen quines circumstàncies epidemiològiques condueixen a la introducció o la persistència de la infecció. Per tant, l'objectiu d'aquesta tesi és millorar el coneixement de l'epidemiologia de la bTB a Espanya mitjançant l'avaluació de les causes més probables d'infecció i els factors relacionats amb els ramats infectats de manera persistents. Per a l'estimació de les causes més probables d'introducció de la infecció en un ramat hem desenvolupat una metodologia basada en les diferents vies de transmissió de la bTB entre els ramats. S’han considerat set vies i per cada una s’ha realitzat un arbre de decisió sobre possibles riscos. A cada risc se l’hi ha assignat una probabilitat basada en opinió d'experts. Per a la gestió de dades i per al càlcul de les probabilitats de cada una de les diferents causes possibles s’han creat un parell de macros. D'acord amb els resultats dels 816 ramats estudiats (casos detectades principalment els anys 2010 i 2011), la majoria dels casos serien deguts al ressorgiment d'infeccions residuals que havien afectat anteriorment al ramat (39%, n = 316). La introducció de la infecció es va produir pel contacte amb animals silvestres en el 12% dels casos (n = 98), i a través de ramats veïns en el 10% (n = 85). En el 28% (n = 225) dels brots, no s’ha pogut determinar l'origen de la infecció. En 309 ramats, la diferència entre les dues causes amb la probabilitat més alta era petita (menys d'u), de manera, que per a aquestes granges tant la primera com la segona causa serien possibles. Dins d'aquest grup, la primera opció més freqüent va ser la infecció residual (69%, n = 214) i la segona de les opcions més freqüents era compartir les pastures amb altres granges (36%, n = 112) i la interacció amb la fauna silvestre (30%, n = 94). En comparar aquestes conclusions amb les dels veterinaris oficials que havien fet la investigació epidemiològica sobre el terreny, s’obté una concordança baixa; especialment en el cas de fauna silvestre. Dins del grup dels ramats on el veterinari només considerava una causa (és a dir, 309 ramats), en 124 la fauna silvestre va ser considerada com la causa més probable, mentre que nosaltres només ho varem concloure en 33 granges. Aquestes discordances podrien estar relacionades amb un diferent accés a les dades i també a percepcions diferents sobre la importància atribuïda a cada causa. Per tal d'avaluar els factors relacionats amb la persistència de bTB en granges es va realitzar un estudi de casos i controls on es va comparar granges infectades que es va eliminar fàcilment la bTB amb altres on es va tardar més de 5 anys. Totes les granges eren del sud d'Espanya i es van estratificar per grandària del ramat i la ubicació geogràfica (comarca). Es va omplir un qüestionari mitjançant entrevista personal en 150 ramats (80 controls i 70 casos) de les Comunitats d'Andalusia i de Castilla‐la Mancha. D'acord amb els resultats d'aquest estudi, les granges amb més superfície de pastures i amb veïns positius, tenien més dificultats per eradicar la infecció, per tant, eren més propenses a patir un brot de bTB persistent. Les probabilitats de persistència eren entre 1,1 i 5,0 vegades més gran en aquells ramats amb possible contacte amb el bestiar d'un ramat positiu veí. La probabilitat de persistència també es va associar amb la superfície de pastures. Les finques amb àrees de pastura més grans tenien una probabilitat entre 1,2 i 12,7 vegades més alta de tenir dificultats en l’eliminació que les finques amb àrees de pastures més petits. El maneig dels animals positius, com ara utilitzar vedelles de reposició de mares positives o no aïllar els animals positius, així com la presència de cabres dins de la granja semblen tenir també una influència en la persistència de bTB.En España, la prevalencia de rebaños con tuberculosis ha disminuido del 11,1% en 1986 a 1,3% en 2011. A pesar de esta reducción, en los últimos años se ha moderado el descenso de la prevalencia y la situación epidemiológica actual de bTB plantea un desafío cara a la consecución del estatus de país oficialmente indemne de tuberculosis. Entre el 50 y el 60% de los rebaños positivos detectados cada año, son nuevos rebaños positivos, y el resto son rebaños donde la infección persiste desde el año anterior. No se sabe qué circunstancias epidemiológicas están implicadas en la introducción o la persistencia de la infección. Por tanto, el objetivo de esta tesis es mejorar el conocimiento de la epidemiología de la bTB en España mediante la evaluación de las causas más probables de infección y los factores relacionados con los rebaños infectados de forma persistente. Para la estimación de las causas más probables de introducción de la infección en un rebaño hemos desarrollado una metodología basada en las diferentes vías de transmisión de la bTB entre los rebaños. Se han considerado siete vías y por cada una de ellas se ha realizado un árbol de decisión sobre posibles riesgos. A cada riesgo se le ha asignado una probabilidad basada en opinión de expertos. Para la gestión de datos y para el cálculo de las probabilidades de cada una de las diferentes causas posibles se han creado dos macros. De acuerdo con los resultados de los 816 rebaños estudiados (casos detectados principalmente en los años 2010 y 2011), la mayoría de las nuevas infecciones en realidad son debidas al resurgimiento de infecciones que habían afectado anteriormente al rebaño (39%, n = 316). La introducción de la infección se produjo por el contacto con animales silvestres en el 12% de los casos (n = 98), y a través de rebaños vecinos en el 10% (n = 85). En el 28% (n = 225) de los brotes, no se ha podido determinar el origen de la infección. En 309 rebaños, la diferencia entre las dos causas con la probabilidad más alta era escasa (menos de uno), de manera que para estas granjas tanto la primera como la segunda causa serían posibles. Dentro de este grupo, la primera opción más frecuente fue la infección residual (69%, n = 214) y la segunda de las opciones más frecuentes era compartir los pastos con otras granjas (36%, n = 112) y la interacción con la fauna silvestre (30%, n = 94). Al comparar las conclusiones de nuestro estudio con las de los veterinarios oficiales que habían hecho la investigación epidemiológica sobre el terreno, se obtiene una concordancia baja, especialmente en el caso de fauna silvestre. Dentro del grupo de los rebaños donde el veterinario sólo consideraba una causa (es decir, 309 rebaños), en 124 la fauna silvestre fue la causa considerada como más probable para el veterinario, mientras que nosotros sólo lo concluimos en 33 granjas. Estas discordancias podrían estar relacionadas con diferencias en los datos a los que hemos tenido acceso así como a diferentes percepciones sobre la importancia atribuida a cada causa. Para evaluar los factores relacionados con la persistencia de BTB en granjas se realizó un estudio de casos y controles donde se compararon granjas infectadas donde se eliminó fácilmente la bTB con otras donde se tardó más de 5 años. Todas las granjas eran del sur de España y se estratificaron por tamaño del rebaño y ubicación geográfica (comarca). Se rellenó un cuestionario mediante entrevista personal en 150 rebaños (80 controles y 70 casos) de las Comunidades de Andalucía y de Castilla‐La Mancha. De acuerdo con los resultados de este estudio, las granjas con más superficie de pastos y con vecinos positivos, tenían más dificultades para erradicar la infección, por lo tanto, eran más propensas a sufrir un brote de BTB persistente. Las probabilidades de persistencia eran entre 1,1 y 5,0 veces mayor en aquellos rebaños con posible contacto con un rebaño positivo vecino. La probabilidad de persistencia también se asoció con la superficie de pastos. Las fincas con áreas de pasto mayores tenían una probabilidad entre 1,2 y 12,7 veces más alta de tener dificultades en la eliminación que las fincas con áreas de pastos más pequeños. El manejo de los animales positivos, tales como utilizar terneras de reposición de madres positivas o no aislar los animales positivos, así como la presencia de cabras dentro de la granja parecen tener también una influencia en la persistencia de la bTB.In Spain, herd prevalence has decreased from 11.1% on 1986 to 1.3% on 2011. Despite this reduction on the prevalence, in the last years there has been just a moderate decline and the current bTB epidemiological situation poses a serious challenge towards the achievement of a national official tuberculosis free (OTF) status. In the country, approximately between 50 and 60% of the total bTB positive herds detected each year, are new positive herds, and the rest of the positives are herds that persist from the previous year. There is not a clear knowledge of the epidemiological circumstances that lead to the introduction or persistence of the infection. Therefore, the aim of this PhD was to improve the understanding of bTB epidemiology in Spain by assessing the most likely causes of infection and factors related with bTB persistent herds. To estimate the most likely causes of introduction of the infection on a herd we developed a methodology based on bTB routes of transmission between herds using decision trees. We considered seven routes as a possible cause of herd breakdown. In order to discriminate among them, probabilities were assigned within each decision tree based on expert opinion. Macros were used for data management and to calculate the probabilities of the different possible causes. According to the results of the 816 studied breakdowns (detected mainly in 2010 and 2011) most of the cases could be resurgence of residual infections that had previously affected the herd (39%, n=316). New introductions of the infection were produced by contact with wildlife in 12% of cases (n=98), and by neighboring herds in 10% of them (n=85). In 28 % (n=225) of the breakdowns, the origin of the infection remained unknown. In 309 herds, the difference between the first and the second cause with the higher probability was small (i.e., less than 1) so, for these herds, first and second possible causes of infection could be considered. Within this group the most frequent first option was residual infection (69%, n=214) and the most frequent second options were sharing pastures with other herds (36%, n=112) and interaction with wildlife (30%, n=94). The results of the comparisons between our conclusions and the ones of the veterinary officers conducting the epidemiological investigation on the field evidenced a low agreement. The lowest agreement was in the case of “wildlife”. Within the group of herds where the veterinary officer just considered one cause (i.e., 309 herds) in 124 Wildlife was considered as the most likely cause, while we just found evidences to suspect of this in 33 farms. These discrepancies could be related to differences on access to data and perception about the importance attributed to the different causes. In order to assess factors related to bTB persistence we conducted a case‐control study and compared persistent versus transient bTB infected farms from southern Spain. Farms were matched by herd size and geographical location (county). A questionnaire by personal interview was carried on 150 herds (80 controls and 70 cases) from Andalusia and Castilla La Mancha regions. According to the results of this study, farms with large pasture areas and positive neighbors had more difficulties in eradicating the disease and therefore, were more likely to suffer a persistent bTB outbreak. The odds of bTB persistence were between 1.1 and 5.0 times higher in those herds that had the possibility of contact with cattle from a neighbor positive herd. The probability of bTB persistence was also associated with the area of the pasture. Farms with larger pasture areas had odds between 1.2 and 12.7 times higher of having a persistent bTB episode than farms with smaller pasture areas. Management of positive animals such as making replacement from positive herds or not isolating positive animals and the presence of goats within the farm seem to have also an influence on bTB persistence

Assessment of Major Causes of Calf Mortality in Urban and Periurban Dairy Production System of Ethiopia

A cross-sectional calf mortality study was conducted in urban and periurban dairy farms in Addis Ababa, special zones of Oromia and Amhara regions in July and August 2015. The objectives of the study were to estimate the annual mortality and to assess the major causes of calf mortality in the dairy farms. One-year retrospective data on calf mortality were collected from 330 farms by face-to-face interview using the pretested and structured questionnaire format and direct observation of farm practices. A logistic regression analysis was performed in order to identify the predictor variables associated with early calf mortality. Data were analysed using Statistical Package, Stata SE for Windows, version 12.0. The annual mean calf mortality from birth-to-weaning was reported as 18.5% (95% CI: 12.6, 24.3%). The prenatal loss due to fetal death and stillbirth was 10.1% (95% CI: 6.7, 13.6%). The overall annual loss due to fetal death and calf preweaning mortality was 26.7% (95% CI: 21.2, 32.2%). Age-specific mortality declined with increased age, and the highest mortality was recorded during the first month of life extending up to the third month of age. Disease was the most important causes of calf mortality (73.2%). Among the diseases, diarrhea (63%) and respiratory disorders (17%) were the important causes of calf mortality. Malpractices in calf management were identified, including restricted colostrum and milk feeding, poor care and supplemental feeding, and poor health management. Interventions in dairy cattle health and farm husbandry are recommended to control calf mortality

Epidemiological Investigation of Bovine Tuberculosis Herd Breakdowns in Spain 2009/2011

We analyzed the most likely cause of 687 bovine tuberculosis (bTB) breakdowns detected in Spain between 2009 and 2011 (i.e., 22% of the total number of breakdowns detected during this period). Seven possible causes were considered: i) residual infection; ii) introduction of infected cattle from other herds; iii) sharing of pastures with infected herds; iv) contiguous spread from infected neighbor herds; v) presence of infected goats in the farm; vi) interaction with wildlife reservoirs and vii) contact with an infected human. For each possible cause a decision tree was developed and key questions were included in each of them. Answers to these key questions lead to different events within each decision tree. In order to assess the likelihood of occurrence of the different events a qualitative risk assessment approach was used. For this purpose, an expert opinion workshop was organized and ordinal values, ranging from 0 to 9 (i.e., null to very high likelihood of occurrence) were assigned. The analysis identified residual infection as the most frequent cause of bTB breakdowns (22.3%; 95%CI: 19.4-25.6), followed by interaction with wildlife reservoirs (13.1%; 95%CI: 10.8-15.8). The introduction of infected cattle, sharing of pastures and contiguous spread from infected neighbour herds were also identified as relevant causes. In 41.6% (95%CI: 38.0-45.4) of the breakdowns the origin of infection remained unknown. Veterinary officers conducting bTB breakdown investigations have to state their opinion about the possible cause of each breakdown. Comparison between the results of our analysis and the opinion from veterinary officers revealed a slight concordance. This slight agreement might reflect a lack of harmonized criteria to assess the most likely cause of bTB breakdowns as well as different perceptions about the importance of the possible causes. This is especially relevant in the case of the role of wildlife reservoirs

Most likely causes of bTB breakdowns by type of herd.

<p><i>* 7 farms not included (other types).</i></p