Person:
Pozo Piñol, Pilar

First Name

Pilar

Last Name

Pozo Piñol

URI

https://hdl.handle.net/20.500.14352/85580

Affiliation

Universidad Complutense de Madrid

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Now showing 1 - 10 of 12

Accuracy of Tests for Diagnosis of Animal Tuberculosis: Moving Away from the Golden Calf (and towards Bayesian Models)
(Transboundary and Emerging Diseases, 2023) Álvarez Sánchez, Julio; Pozo Piñol, Pilar; Gómez-Buendía, Alberto; Picasso-Risso, Catalina; Branscum, Adam; Pérez, Andrés
The last decades have seen major efforts to develop new and improved tools to maximize our ability to detect tuberculosis-infected animals and advance towards the objective of disease control and ultimately eradication. Nevertheless, there is still uncertainty regarding test performance due to the wide range of specificity and especially sensitivity estimates published in the scientific literature. Here, we performed a systematic review of the literature on studies that evaluated the performance of tuberculosis diagnostic tests used in animals through Bayesian Latent Class Models (BLCMs), which do not require the application of a (fallible) reference procedure to classify animals as infected with tuberculosis or not. BLCM-based sensitivity and specificity estimates deviated from those obtained using a reference procedure for certain antemortem tests: an overall lower sensitivity of skin tests and serology and a higher sensitivity of interferon-gamma (IFN-γ) assays was reported. In the case of postmortem diagnostic tests, sensitivity estimates from BLCMs were similar to estimates from studies based on other methodologies. For specificity, the range of BLCM-based estimates was narrower than those based on a reference test, reaching values close to 100% (but lower in the case of IFN-γ assays). In conclusion, Bayesian methods have been increasingly applied for the evaluation of tuberculosis diagnostic tests in animals, yielding results that differ (sometimes substantially) from previously reported test performance in the literature, particularly for in vivo tests and sensitivity estimates. Newly developed models that allow adjustment for relevant factors (e.g., age, breed, region, and herd size) can contribute to the generation of more unbiased estimates of test performance. Nevertheless, although BLCMs for tuberculosis do not require the use of an imperfect reference procedure and are therefore not influenced by its limited performance, they require careful implementation, and transparent systematic reporting should be the norm.
Once bitten twice shy: Risk factors associated with bovine tuberculosis recurrence in Castilla y León, Spain
(Research in Veterinary Science, 2023) Grau, Anna; Nácar, Jesús; Sáez-Lorente, José Luis; Mínguez, Olga; Pozo Piñol, Pilar; Bezos Garrido, Javier; Romero Martínez, Beatriz; Álvarez Sánchez, Julio
Persistence of bovine tuberculosis (bTB) in cattle herd remains a major challenge in disease elimination due to the ineffectual removal of all infected animals in a bTB breakdown. Characterization of herds with a higher probability of experiencing further bTB breakdowns can help to implement specific risk-based policies for disease control and eradication. Here, our aim was to identify herd- and breakdown-level risk factors in bTB infected herds in Castilla y Leon, Spain, associated with a decreased time to recurrence and an increased risk of recurrence using a mixed effects Cox proportional hazards model and a multivariable logistic regression model, respectively. Results revealed that location (province), herd size and number of incoming animals/contacts were good predictors of a decreased time to bTB recurrence and an increased risk of becoming a recurrent herd. Additionally, the duration of the previous outbreak and the number of IFN-γ herd-tests applied in it were associated with increased odds of (an early) recurrence. Risk factors identified here can be used for early identification of herds in which bTB eradication may be more challenging and that should thus be subjected to increased control efforts. The characterization of high-risk herds may help to minimize the risk of reinfection and emphasize early detection and removal of bTB positive animals in the herd.
Use of Whole-Genome Sequencing to Unravel the Genetic Diversity of a Prevalent Mycobacterium bovis Spoligotype in a Multi-Host Scenario in Spain
(Frontiers in Microbiology, 2022) Pozo Piñol, Pilar; Lorente Leal, Víctor; Robbe-Austerman, Suelee; Hicks, Jessica; Stuber, Tod; Bezos Garrido, Javier; Juan Ferré, Lucía De; Sáez-Lorente, José Luis; Romero Martínez, Beatriz; Álvarez Sánchez, Julio
Despite the efforts invested in the eradication of bovine tuberculosis in Spain, herd prevalence has remained constant in the country during the last 15 years (~1.5–1.9%) due to a combination of epidemiological factors impairing disease control, including between-species transmission. Here, our aim was to investigate the molecular diversity of Mycobacterium bovis isolates belonging to the highly prevalent SB0339 spoligotype in the cattle-wildlife interface in different regions of Spain using whole-genome sequencing (WGS). Genomic data of 136 M. bovis isolates recovered from different animal species (cattle, wild boar, fallow deer, and red deer) and locations between 2005 and 2018 were analyzed to investigate between- and within-species transmission, as well as within-herds. All sequenced isolates differed by 49–88 single nucleotide polymorphisms from their most recent common ancestor. Genetic heterogeneity was geographic rather than host species-specific, as isolates recovered from both cattle and wildlife from a given region were more closely related compared to isolates from the same species but geographically distant. In fact, a strong association between the geographic and the genetic distances separating pairs of M. bovis isolates was found, with a significantly stronger effect when cattle isolates were compared with wildlife or cattle-wildlife isolates in Spain. The same results were obtained in Madrid, the region with the largest number of sequenced isolates, but no differences depending on the host were observed. Within-herd genetic diversity was limited despite the considerable time elapsed between isolations. The detection of closely related strains in different hosts demonstrates the complex between-host transmission dynamics present in endemic areas in Spain. In conclusion, WGS results a valuable tool to track bTB infection at a high resolution and may contribute to achieve its eradication in Spain.
Contribution of herd management, biosecurity, and environmental factors to the risk of bovine tuberculosis in a historically low prevalence region
(Animal, 2024) Pozo Piñol, Pilar; Isla, Julio; Asiaín, A.; Navarro, D.; Gortázar, Christian
Eradication of bovine tuberculosis (bTB) in certain historically low-prevalence regions remains elusive. A complete characterisation of the husbandry practices, biosecurity, and environment where farms are located is crucial to implement targeted in-farm risk mitigation protocols. Here, a detailed survey performed in 94 dairy cattle farms located in Navarra, a low-prevalence region of Spain between 2016 and 2020 was carried out. Data on 73 biosecurity, farm-, and environmental-level factors potentially associated with the risk of bTB occurrence were evaluated using an ordinal logistic regression model: farms were classified based on their prevalence index, a score linked to each farm to account for the severity and recurrence of bTB cases: 22.3% of the farms had a score of 1, 21.3% a score of 2, 26.6% a score of ≥ 3, and 29.8% were negative herds. A statistically significant association between a higher prevalence index and the frequency of badger sightings along with the lease of pastures to sheep during Winter was identified. Farms that detected badgers on a monthly to daily basis in the surroundings and those that leased pastures for sheep flocks during Winter were four [odds ratio, 95% CI (4.3; 1.1–17.5)] and three (3.1; 1.0–9.9) times more likely to have the highest prevalence index, respectively (predicted probabilityprevalence index≥3 = 0.7; 95% CI 0.3–0.9). Conversely, farms that used a vehicle to transport animals from holdings to pastures were less likely (0.1; <0.1–0.3) to present higher levels of prevalence index compared with farms that used none (on foot). Results suggested that the combined effect of farm- and environmental-level risk factors identified here may be hampering disease eradication in Navarra, highlighting the need to implement targeted protocols on farms and grazing plots. An increased awareness of monitoring sheep and wildlife in direct or indirect contact with cattle herds in historically low bTB prevalence areas should be raised.
Use of epidemiological analytic tools and molecular characterization techniques to inform bovine tuberculosis eradication programs
(2021) Pozo Piñol, Pilar; Álvarez Sánchez, Julio; Romero Martínez, Beatriz; Bezos Garrido, Javier
Bovine tuberculosis (bTB) is an infectious disease with a complex epidemiology at the human-animal-environment interface which, despite the application of extensive control measures, is still prevalent in livestock and wildlife in several regions of Spain. The disease, caused by Mycobacterium bovis (and to a lesser extent M. caprae), remains a concern due to its negative impact on animal health and welfare, together with the important consequences for production and animal trade that its presence imposes. Eradication programs of bTB in cattle in Spain are based on a combination of regular test and slaughter policies using mostly the single intradermal test (SIT), the interferon-gamma (IFN-γ) assay as an ancillary test in infected herds, and abattoir post-mortem inspection. Disease eradication at the herd level is challenging due to several factors including the limitations in the sensitivity of available diagnostic techniques, the risk of introduction of undetected infected animals, the proximity to positive farms, and the contact with infected wildlife reservoirs. This thesis is based on the application of different analytic tools such as social network analysis, epidemiological models and whole genome sequencing (WGS) to quantify the relative importance of risk factors impairing disease control in Spain using a multidisciplinary approach...
Evaluation of Risk Factors Associated With Herds With an Increased Duration of Bovine Tuberculosis Breakdowns in Castilla y Leon, Spain (2010–2017)
(Frontiers in Veterinary Science, 2020) Pozo Piñol, Pilar; Romero Martínez, Beatriz; Bezos Garrido, Javier; Grau, Anna; Nácar, Jesús; Sáez-Lorente, José Luis; Mínguez, Olga; Álvarez Sánchez, Julio
The persistence of bovine tuberculosis (bTB) in certain cattle herds is a major concern in countries pursuing disease eradication worldwide. The chronic nature of the disease, the lack of performance of diagnostic tools, and the presence of wildlife reservoirs may lead infected herds to require longer periods to achieve the officially tuberculosis-free (OTF) status. Here, we evaluated the impact of farm and breakdown characteristics on the probability of disease persistence in infected farms in Castilla y Leon, a bTB-endemic region of Spain, using survival and logistic regression models. Data from bTB breakdowns occurring in 3,550 bTB-positive herds detected in 2010–2017 were analyzed. A multivariable Cox proportional hazards model was fitted using time to recover OTF status as the response variable, and a multivariable logistic regression model using the chronic status (yes/no) for herds experiencing particularly long breakdowns as the outcome variable was also used. Both analyses revealed that county-level bTB herd prevalence, herd size, number of incoming animals in the previous 3 years, number of skin test reactors in the disclosing test, and number of days between the disclosing and follow-up tests were associated with increased breakdown duration. Production type was not consistently associated with chronic infection, suggesting that once infected, it is not a significant predictor of outbreak duration beyond the initial stages of the breakdown. Province-level location and number of animals that are bacteriology-positive also affected significantly the expected herd breakdown duration, but their effect became less significant over time. Risk factors identified in this study may help to identify herds more prone to suffer chronic bTB infection that may require additional control measures early on in a breakdown.
Assessment of the sensitivity of the bovine tuberculosis eradication program in a high prevalence region of Spain using scenario tree modeling
(Preventive Veterinary Medicine, 2019) De la Cruz, María Luisa; Pozo Piñol, Pilar; Grau, Anna; Nacar, Jesús; Bezos Garrido, Javier; Pérez, Andrés; Domínguez Rodríguez, Lucas José; Sáez, José Luís; Mínguez-González, Olga; Juan Ferré, Lucía De; Álvarez Sánchez, Julio
In spite of the efforts invested to eradicate bovine tuberculosis (bTB) in cattle, the disease is still present in several developed countries, including Spain. Among the factors related with disease persistence in high prevalence areas, the lack of sensitivity of the screening test for detection of infected herds [single intradermal tuberculin (SIT) test] can play a major role. Here, a scenario tree model mimicking the diagnostic test scheme in place in the region of Castilla y Leon (Spain) was developed to estimate the probability of detecting bTB in an infected-non detected officially tuberculosis free (OTF) herd (herd sensitivity, HSe). In order to do so the probability of detecting at least one positive animal in the SIT test with/without post-mortem (detection of lesions and culture) confirmation in an infected herd was estimated using Monte Carlo simulation through @ RISK (Palisade Co, NY, USA). Uncertainty on the accuracy of the diagnostic tests was introduced in the model using distributions based on the literature. The performance of the model was evaluated by comparing the predicted number of SIT/post-mortem positive animals in infected herds with those observed in newly detected bTB-infected herds in the region in 2011–2015. The estimated HSe of the SIT test was 76.2% (95% probability interval: 19.8–97.6). According to the model, bTB infection would be then confirmed through culture in 65.3% (95% PI: 50.0–82.3) of the herds detected through the SIT test, so that overall the proportion of infected-non detected OTF herds in which the infection could be confirmed after the initial SIT test was 49.6% (95% PI: 9.75–80.3). The predicted HSe of both SIT test and culture was directly correlated with herd size. Results from the model suggest a moderate but highly variable HSe of the current surveillance system in place for bTB detection in OTF herds located in high prevalence areas, that could be maximized by performing multiple tests within a year as indicated in the Spanish eradication program (with a median SIT HSe of 87% when two consecutive tests were considered). In addition, these results highlight the usefulness of performing subsequent SIT tests to rule out infection in SIT-positive herds even when the causative agent cannot be isolated.
Liver Transudate, a Potential Alternative to Detect Anti-Hepatitis E Virus Antibodies in Pigs and Wild Boars (Sus scrofa)
(Microorganisms, 2020) Navarro Gómez, Alejandro; Bárcena Asensio, María Carmen; Pozo Piñol, Pilar; Díez Guerrier, Alberto Antoine; Martínez Alares, Irene; Polo, Coral; Duque, Clara; Rodríguez-Lázaro, David; Goyache Goñi, Joaquín; García Benzaquén, Nerea
In recent years, cases of hepatitis E virus (HEV) infection have increased in Europe in association with the consumption of contaminated food, mainly from pork products but also from wild boars. The animal’s serum is usually tested for the presence of anti-HEV antibodies and viral RNA but, in many cases such as during hunting, an adequate serum sample cannot be obtained. In the present study, liver transudate was evaluated as an alternative matrix to serum for HEV detection. A total of 125 sera and liver transudates were tested by enzyme-linked immunosorbent assay at different dilutions (1:2, 1:10, 1:20), while 58 samples of serum and liver transudate were checked for the presence of HEV RNA by RT-qPCR. Anti- HEV antibodies were detected by ELISA in 68.0% of the serum samples, and in 61.6% of the undiluted transudate, and in 70.4%, 56.8%, and 44.8% of 1:2, 1:10, or 1:20 diluted transudate, respectively. The best results were obtained for the liver transudate at 1:10 dilution, based on the Kappa statistic (0.630) and intraclass correlation coefficient (0.841). HEV RNA was detected by RT-qPCR in 22.4% of the serum samples and 6.9% of the transudate samples, all samples used for RT-qPCR were positive by ELISA. Our results indicate that liver transudate may be an alternative matrix to serum for the detection of anti-HEV antibodies.
Analysis of the cattle movement network and its association with the risk of bovine tuberculosis at the farm level in Castilla y Leon, Spain
(Transboundary and Emerging Diseases, 2019) Pozo Piñol, Pilar; Bezos Garrido, Javier; Álvarez Sánchez, Julio; VanderWaal, Kimberly; Grau, Anna; de la Cruz Conty, María Luisa; Nácar, Jesus; Pérez, Andrés; Mínguez, Olga
Between-farm transmission of bovine tuberculosis (bTB) occurs mostly through fence-to-fence contact between neighbouring farms, endemic infected wildlife or movement of infected animals. Unfortunately, bTB detection is frequently delayed and identification of the source of introduction is often difficult, particularly in endemic regions. Here, we characterized the cattle movement network of Castilla y Leon, a high bTB-prevalence (1.9% at the farm level in 2015) region in Spain, over six years and analysed the distribution of bTB to ultimately assess the likelihood of spatial and movement-mediated transmission. We analysed movement and bTB data from 27,633 units located in the region, of which 87% were involved in ~1.4 million movements of ~8.8 million animals. Network-level connectivity was low, although a few highly connected units were identified. Up to 15% of the herds became bTB-positive at some point during the study, with the highest percentage found in bullfighting and beef herds. Although bTB-positive herds had a significantly higher degree and moved more cattle than negative herds. Results of the k-test, a permutation-based procedure, suggested that positive farms were not significantly clustered in the movement network. Location was a likely risk factor as bTB-positive farms tended to be located within 5 km from each other. Results suggested that movements may be a source of bTB in cattle in Castilla y Leon, although local factors may be more influential in determining risk of disease at the farm level. The description of the movement network in Castilla y Leon may be valuable for bTB surveillance in Spain. Moreover, results are useful to assess the movement-associated risk for multiple diseases.
Evaluation of the performance of slaughterhouse surveillance for bovine tuberculosis detection in Castilla y Leon, Spain
(Preventive Veterinary Medicine, 2021) Pozo Piñol, Pilar; Cardenas, Nicolas Cespedes; Bezos Garrido, Javier; Romero Martínez, Beatriz; Grau, Anna; Nacar, Jesus; Saez, Jose Luis; Minguez, Olga; Álvarez Sánchez, Julio
Post-mortem inspection (PMI) of routinely slaughtered cattle in abattoirs is an extremely valuable tool for detecting bovine tuberculosis (bTB) infected herds that can supplement active surveillance activities. However, its true performance is difficult to assess due to the multiple factors that may affect it. Here, we determined relative efficiencies in the detection of bTB-compatible lesions and probabilities of subsequent laboratory confirmation of abattoirs located in Castilla y Leon, one of the regions with the largest cattle population in Spain, between 2010 and 2017. The slaughtered animal population was split based on the results of the ante-mortem tests (reactors or non-reactors), and two generalized linear multivariable mixed models were fitted to each subpopulation to calculate the risk of lesion detection and laboratory confirmation per abattoir while accounting for the effect of potential confounding variables. Throughout the 8-year period, ~30,000 reactors and >2.8 million non-reactor animals in the ante-mortem tests were culled in the abattoirs under study. Bovine TB compatible lesions were detected in 4,710 (16%) reactors and 828 (0.03%) non-reactor animals, of which >95% were confirmed as infected through bacteriology. The probability of disclosure of bTB-like lesions was associated with the animal subpopulation, type of source unit, the herd size, the year of slaughter, the breed and age of the animal, and/or the season of slaughter. The probabilities of detection of bTB-like lesions varied largely depending on the abattoir in both subpopulations, ranging from 603 to 3,070 per 10,000 animals for the reactors and 0.2–16.1 per 10,000 animals for the nonreactor animals. Results obtained here will help to quantify the performance of PMI in abattoirs in Castilla y Leon and the between-abattoir variability, and to identify animals at increased risk of having bTB-like lesions detected during PMI based on animal- and farm-related factors.