The gut microbiota contributes to the infection of bovine viral diarrhea virus in mice.

Bovine viral diarrhea virus (BVDV) is prevalent worldwide and causes significant economic losses. Gut microbiota is a large microbial community and has a variety of biological functions. However, whether there is a correlation between gut microbiota and BVDV infection and what kind of relation between them have not been reported. Here, we found that gut microbiota composition changed in normal mice after infecting with BVDV, but mainly the low abundance microbe was affected. Interestingly, BVDV infection significantly reduced the diversity of gut microbiota and changed its composition in gut microbiota-dysbiosis mice. Furthermore, compared with normal mice of BVDV infection, there were more viral loads in the duodenum, jejunum, spleen, and liver of the gut microbiota-dysbiosis mice. However, feces microbiota transplantation (FMT) reversed these effects. The data above indicated that the dysbiosis of gut microbiota was a key factor in the high infection rate of BVDV. It is found that the IFN-I signal was involved by investigating the underlying mechanisms. The inhibition of the proliferation and increase in the apoptosis of peripheral blood lymphocytes (PBL) were also observed. However, FMT treatment reversed these changes by regulating PI3K/Akt, ERK, and Caspase-9/Caspase-3 pathways. Furthermore, the involvement of butyrate in the pathogenesis of BVDV was also further confirmed. Our results showed for the first time that gut microbiota acts as a key endogenous defense mechanism against BVDV infection; moreover, targeting regulation of gut microbiota structure and abundance may serve as a new strategy to prevent and control the disease.IMPORTANCEWhether the high infection rate of BVDV is related to gut microbiota has not been reported. In addition, most studies on BVDV focus on in vitro experiments, which limits the study of its prevention and control strategy and its pathogenic mechanism. In this study, we successfully confirmed the causal relationship between gut microbiota and BVDV infection as well as the potential molecular mechanism based on a mouse model of BVDV infection and a mouse model of gut microbiota dysbiosis. Meanwhile, a mouse model which is more susceptible to BVDV provided in this study lays an important foundation for further research on prevention and control strategy of BVDV and its pathogenesis. In addition, the antiviral effect of butyrate, the metabolites of butyrate-producing bacteria, has been further revealed. Overall, our findings provide a promising prevention and control strategy to treat this infectious disease which is distributed worldwide.

Association of bovine viral diarrhea virus, bovine herpesvirus 1, and Neospora caninum with late embryonic losses in highly supplemented grazing dairy cows.

The objectives of this study were: 1- to evaluate the association of Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BoHV-1), and Neospora caninum (N. caninum) with the risk for Late Embryonic Loss (LEL) in grazing dairy cows, 2- to evaluate blood progesterone concentration at the time of LEL occurrence, and 3- to describe a novel ultrasound-guided technique for conceptus sampling. We run a prospective cohort study involving 92 cows (46 LEL and 46 NLEL). An LEL cow was that having an embryo with no heartbeat, detached membranes, or floating structures, including embryo remnants detected at pregnancy check by ultrasonography (US) 28-42 days post-AI, whereas an NLEL cow was that with embryo heartbeats detectable by US at pregnancy check 28-42 d post-IA. We took two blood samples from every cow at pregnancy check by US (the day of LEL detection) and 28 d later to perform serological diagnosis of BVDV, BoHV-1, and N. caninum; and to measure blood progesterone concentration at pregnancy check (28-42 d post-AI). We also sampled the conceptus from all the LEL cows. We performed PCR to detect BVDV, BoHV-1, and N. caninum in sampled conceptuses from LEL cows. Finally, we evaluated the associations of risk factors (serological titers, seroconversion, and progesterone) with LEL odds with logistic models. The risk for LEL was associated with serological titers to BVDV (P = 0.03) and tended to be associated with seroconversion to BVDV, given that 19.6% (9/46) in LEL and 6.5% (3/46) in NLEL cows seroconverted to BVDV (P = 0.09). In addition, BVDV was detected in conceptuses from LEL cows that seroconverted to BVDV but not in LEL cows that did not seroconvert. Conversely, the risk for LEL was not associated with the titers or seroconversion to BoHV-1 and N. caninum. BoHV-1 and N. caninum were not identified in any of the conceptuses. Finally, blood progesterone concentration was similar in LEL and NLEL cows, and it was not associated with the risk for LEL (P = 0.54). In conclusion, BVDV infection is a risk factor for LEL in dairy cows.

Diseases associated with bovine viral diarrhea virus subtypes 1a and 2b in beef and dairy cattle in Uruguay.

Bovine viral diarrhea virus (BVDV, Pestivirus) causes significant economic losses to the livestock industry worldwide. Although serological surveys show that BVDV exposure is widespread in cattle in Uruguay, BVDV-associated diseases are greatly underreported. The aim of this work is to describe the epidemiological, clinical, pathological, and virological findings from spontaneous outbreaks of BVDV-associated diseases in cattle in Uruguay. Diagnostic investigations were performed during 6 spontaneous disease outbreaks on beef and dairy cattle farms in the departments of Colonia, Rio Negro, and Soriano between November 2016 and April 2018. Carcasses of 8 naturally deceased cattle from these outbreaks were necropsied and subjected to histological examination and immunohistochemistry to detect BVDV antigen in the tissues. Reverse transcription real-time PCR and genomic sequencing were also performed to identify BVDV at the species and subtype levels. Other ancillary diagnostic tests, including bacterial cultures, were performed on a case-by-case basis to rule in/out differential diagnoses based on initial clinicopathological presumptive diagnoses. BVDV-associated conditions that were diagnosed in the 8 cases included mucosal disease, transient postnatal BVDV infections associated with digestive/septicemic salmonellosis by Salmonella serovar typhimurium, Histophilus somni bronchopneumonia, urinary tract coinfections with Escherichia coli and Streptococcus sp., enteric coinfection with coccidia, and transplacental fetal infections and abortions with Neospora caninum coinfection. BVDV-1a and BVDV-2b were each identified in four of the eight cases. We conclude that BVDV-1a and BVDV-2b contribute significantly to disease and mortality in cattle in Uruguay. Future research should estimate the economic impact of BVDV in the Uruguayan livestock sector.

Coxiella burnetii associated with BVDV (Bovine Viral Diarrhea Virus), BoHV (Bovine Herpesvirus), Leptospira spp., Neospora caninum, Toxoplasma gondii and Trypanosoma vivax in reproductive disorders in cattle.

This is a cross-sectional study to assess the presence of antibodies in ruminants against selected pathogens associated with reproductive disorders in cattle in four Brazilian states, including the zoonotic agent Coxiella burnetii. The used tests were Virus Neutralization Assay for IBR and BVD, Microscopic Agglutination Test for Leptospira spp., Indirect Fluorescent Antibody Test (IFAT) for C. burnetii and Toxoplasma gondii, and Enzyme-Linked Immunosorbent Assay for Neospora caninum and Trypanosoma vivax. Seropositivity for C. burnetii was 13.7% with titers from 128 to 131,072; 57.8% for BoHV-1, with titers between 2 and 1,024; 47.1% for BVDV-1a, with titers from 10 to 5,120; 89.2% for N. caninum; 50% for T. vivax; and 52.0% for Leptospira spp., with titers between 100 to 800 (the following serovars were found: Tarassovi, Grippotyphosa, Canicola, Copenhageni, Wolffi, Hardjo, Pomona and Icterohaemorrhagiae); 19.6% for T. gondii with titer of 40. This is the first study that has identified C. burnetii in cattle associated with BoHV and BVDV, N. caninum, Leptospira spp., T. gondii and T. vivax. Thus, future studies should be conducted to investigate how widespread this pathogen is in Brazilian cattle herds.

Coxiella burnetii associated with BVDV (Bovine Viral Diarrhea Virus), BoHV (Bovine Herpesvirus), Leptospira spp, Neospora caninum, Toxoplasma gondii and Trypanosoma vivax in reproductive disorders in cattle / Coxiella burnetii associada ao BVDV (Vírus da Diarreia Viral Bovina), BoHV (Vírus do Herpes Bovino), Leptospira spp, Neospora caninum, Toxoplasma gondii e Trypanosoma vivax em distúrbios reprodutivos em bovinos

Abstract This is a cross-sectional study to assess the presence of antibodies in ruminants against selected pathogens associated with reproductive disorders in cattle in four Brazilian states, including the zoonotic agent Coxiella burnetii. The used tests were Virus Neutralization Assay for IBR and BVD, Microscopic Agglutination Test for Leptospira spp., Indirect Fluorescent Antibody Test (IFAT) for C. burnetii and Toxoplasma gondii, and Enzyme-Linked Immunosorbent Assay for Neospora caninum and Trypanosoma vivax. Seropositivity for C. burnetii was 13.7% with titers from 128 to 131,072; 57.8% for BoHV-1, with titers between 2 and 1,024; 47.1% for BVDV-1a, with titers from 10 to 5,120; 89.2% for N. caninum; 50% for T. vivax; and 52.0% for Leptospira spp., with titers between 100 to 800 (the following serovars were found: Tarassovi, Grippotyphosa, Canicola, Copenhageni, Wolffi, Hardjo, Pomona and Icterohaemorrhagiae); 19.6% for T. gondii with titer of 40. This is the first study that has identified C. burnetii in cattle associated with BoHV and BVDV, N. caninum, Leptospira spp., T. gondii and T. vivax. Thus, future studies should be conducted to investigate how widespread this pathogen is in Brazilian cattle herds.

Resumo Este é um estudo transversal para avaliar a presença de anticorpos em ruminantes contra patógenos selecionados e associados a distúrbios reprodutivos em bovinos de quatro estados brasileiros, incluindo o agente zoonótico Coxiella burnetii. Os testes utilizados foram Teste de Vírus-Neutralização para BoHV e BVDV, teste de Aglutinação Microscópica para Leptospira spp., Reação de Imunofluorescência Indireta for C. burnetii e Toxoplasma gondii, e Ensaio de Imunoabsorção Enzimática para Neospora caninum e Trypanosoma vivax. A soropositividade para C. burnetii foi de 13,7% com títulos de 128 a 131.072; 57,8% para BoHV-1, com títulos entre 2 a 1.024; 47,1% para BVDV-1a, com títulos de 10 a 5.120; 89,2% para N. caninum; 50% para T. vivax; e 52,0% para Leptospira spp., com títulos entre 100 a 800 (sorovares encontrados: Tarassovi, Grippotyphosa, Canicola, Copenhageni, Wolffi, Hardjo, Pomona e Icterohaemorrhagiae) 19,6% para T. gondii com título de 40. Este é o primeiro estudo que evidencia a participação de C. burnetii em bovinos associada ao Vírus da Rinotraqueíte bovina infecciosa e da diarreia viral bovina, N. caninum, Leptospira spp., T. gondii e T. vivax em bovinos. Desta forma, futuros estudos devem ser conduzidos a fim de investigar o quão disseminado se encontra este patógeno em rebanhos bovinos brasileiros.

Mechanisms linking bovine viral diarrhea virus (BVDV) infection with infertility in cattle.

Bovine viral diarrhea virus (BVDV) is an important infectious disease agent that causes significant reproductive and economic losses in the cattle industry worldwide. Although BVDV infection is known to cause poor fertility in cattle, a greater part of the underlying mechanisms particularly associated with early reproductive losses are not clearly understood. Previous studies reported viral compromise of reproductive function in infected bulls. In females, BVDV infection is thought to be capable of killing the oocyte, embryo or fetus directly, or to induce lesions that result in fetal abortion or malformation. BVDV infections may also induce immune dysfunction, and predispose cattle to other diseases that cause poor health and fertility. Other reports also suggested BVDV-induced disruption of the reproductive endocrine system, and a disruption of leukocyte and cytokine functions in the reproductive organs. More recent studies have provided evidence of viral-induced suppression of endometrial innate immunity that may predispose to uterine disease. Furthermore, there is new evidence that BVDV may potentially disrupt the maternal recognition of pregnancy or the immune protection of the conceptus. This review brings together the previous reports with the more recent findings, and attempts to explain some of the mechanisms linking this important virus to infertility in cattle.

Assessment of concurrent infection with bovine viral diarrhoea virus (BVDV) and Mycobacterium bovis: A herd-level risk factor analysis from Northern Ireland.

Bovine viral diarrhoea virus (BVDV) is a significant pathogen of cattle, leading to severe economic and animal-welfare impacts. Furthermore, the pathogen has been associated with impacting the progression or spread of other pathogens (e.g. Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB)). During this study we investigated (i) risk factors for BVDV at a herd-level and (ii) whether there was any association between BVDV and herd-level bTB risk. The data for this study were gathered from a voluntary BVDV control programme in Northern Ireland (2013-2015) based on the identification of virus positive animals through tissue tag testing of calves. We assigned a herd-level BVDV status to 2827 participating herds, where a herd was assumed "infected" if one or more animals tested positive for BVDV. Two model suites were developed. Firstly, we assessed risk factors for BVDV herd status using multivariable logit random-effects modelling, aggregating to the calendar year level (2013-2015; n=4828; model 1). Secondly, we aggregated data across the three years of the study to give an overall status for the whole study period (n=2827; logistic model 2). Risk factors included year, herd-type, herd size, number of births, inward trade moves, calf mortality, and region. Furthermore, the herd-level bovine tuberculosis status (based on the single intradermal comparative cervical tuberculin (SICCT) test outcomes, or confirmation at post-mortem), or the size of bTB breakdowns (number of SICCT test positive animals), of herds was also investigated to assess whether there was an association (co-infection) with herd BVDV status. The final models suggested that BVDV herd status was positively associated with increased levels of calf mortality, herd size, number of births, the number of BVDV tests undertaken and the number of animals introduced to the herd. There was a significant univariable positive association between BVDV status, and SICCT breakdown risk, breakdown size and confirmed bTB status in model 2. However, there was no evidence of significant associations between bTB status (using SICTT status, confirmed status or herd breakdown size) and BVDV status in final multivariable models when controlling for other significant confounders. These results provide information for action for the future control and eradication of BVDV in Northern Ireland, though these data provide little support for the hypothesised association between BVDV and bTB status at herd-level. Further animal-level analyses are necessary to investigate whether there is support for a BVD-bTB co-infection association, including the impact of co-infection on the severity of infection.

Methodological challenges to multivariate syndromic surveillance: a case study using Swiss animal health data.

BACKGROUND: In an era of ubiquitous electronic collection of animal health data, multivariate surveillance systems (which concurrently monitor several data streams) should have a greater probability of detecting disease events than univariate systems. However, despite their limitations, univariate aberration detection algorithms are used in most active syndromic surveillance (SyS) systems because of their ease of application and interpretation. On the other hand, a stochastic modelling-based approach to multivariate surveillance offers more flexibility, allowing for the retention of historical outbreaks, for overdispersion and for non-stationarity. While such methods are not new, they are yet to be applied to animal health surveillance data. We applied an example of such stochastic model, Held and colleagues' two-component model, to two multivariate animal health datasets from Switzerland. RESULTS: In our first application, multivariate time series of the number of laboratories test requests were derived from Swiss animal diagnostic laboratories. We compare the performance of the two-component model to parallel monitoring using an improved Farrington algorithm and found both methods yield a satisfactorily low false alarm rate. However, the calibration test of the two-component model on the one-step ahead predictions proved satisfactory, making such an approach suitable for outbreak prediction. In our second application, the two-component model was applied to the multivariate time series of the number of cattle abortions and the number of test requests for bovine viral diarrhea (a disease that often results in abortions). We found that there is a two days lagged effect from the number of abortions to the number of test requests. We further compared the joint modelling and univariate modelling of the number of laboratory test requests time series. The joint modelling approach showed evidence of superiority in terms of forecasting abilities. CONCLUSIONS: Stochastic modelling approaches offer the potential to address more realistic surveillance scenarios through, for example, the inclusion of times series specific parameters, or of covariates known to have an impact on syndrome counts. Nevertheless, many methodological challenges to multivariate surveillance of animal SyS data still remain. Deciding on the amount of corroboration among data streams that is required to escalate into an alert is not a trivial task given the sparse data on the events under consideration (e.g. disease outbreaks).

Effect of timing of challenge following short-term natural exposure to bovine viral diarrhea virus type 1b on animal performance and immune response in beef steers.

Bovine respiratory disease (BRD) is the most common and economically detrimental disease of beef cattle during the postweaning period, causing the majority of morbidity and mortality in feedlots. The pathogenesis of this disease often includes an initial viral infection, which can predispose cattle to a secondary bacterial infection. The objective of this experiment was to determine the effects of timing of an intratracheal (MH) challenge relative to 72 h of natural exposure to bovine viral diarrhea virus (BVDV) type 1b persistently infected (PI) calves on performance, serum antibody production, total and differential white blood cell (WBC) count, rectal temperature, clinical severity score (CS), and haptoglobin (Hp). Steers ( = 24; 276 ± 31 kg initial BW) were randomly allocated to 1 of 3 treatments (8 steers/treatment) in a randomized complete block design. Treatments were steers not exposed to calves PI with BVDV 1b and not challenged with MH (CON), steers intratracheally challenged with MH 84 h after being exposed to calves PI with BVDV 1b for 72 h (LateCh), and steers intratracheally challenged with MH 12 h after being exposed to calves PI with BVDV 1b for 72 h (EarlyCh). Performance (ADG, DMI, and G:F) was decreased ( < 0.001) for both EarlyCh and LateCh from d 0 to 4. From d 5 to 17, LateCh appeared to compensate for this lost performance and demonstrated increased ADG ( = 0.01) and G:F ( = 0.01) compared with EarlyCh. Both EarlyCh and LateCh had decreased platelet counts ( < 0.001) compared with CON. Antibody concentrations of BVDV and MH were higher ( < 0.05) for both EarlyCh and LateCh compared with CON. Rectal temperature, CS, and Hp increased ( < 0.001) across time from h 4 to 48, h 4 to 36, and h 8 to 168, respectively. Within 24 h of MH challenge, WBC and neutrophil concentrations within the blood increased whereas lymphocyte concentrations decreased. The timing of BVDV exposure relative to a MH challenge appears to influence the CS and acute phase response associated with BRD. As typical beef cattle marketing channels allow for variation in the timing of respiratory pathogen exposure, understanding the physiological changes in morbid cattle will lead to improved management of BRD.

Effect of copper, manganese, and zinc supplementation on the performance, clinical signs, and mineral status of calves following exposure to bovine viral diarrhea virus type 1b and subsequent infection.

Research has indicated that trace mineral (TM) supplementation may alter immune function and reduce morbidity associated with bovine respiratory disease. The objective of this experiment was to determine the influence of dietary Cu, Mn, and Zn supplementation on the performance, clinical signs, and TM balance of calves following a bovine viral diarrhea virus (BVDV) and (MH) combination respiratory pathogen challenge. Steers ( = 16; 225 ± 20 kg BW) from a single ranch were processed, weaned, and randomly pairwise assigned to either the TM-supplemented (MIN) or the control (CON) experimental treatments. The MIN calves received an additional 150 mg of Cu, 130 mg of Mn, and 320 mg of Zn daily and the CON calves received the basal diet with no additional Cu, Mn, or Zn supplementation. The basal diet contained sufficient Mn and Zn but inadequate Cu based on published nutrient requirements. After 46 d on the experimental treatments, all calves were naturally exposed to a heifer persistently infected with BVDV type 1b for 4 d and then subsequently intratracheally challenged with MH. Data were analyzed using the GLIMMIX procedure of SAS with sampling time serving as a repeated measure and calf serving as the experimental unit. The respiratory challenge was validated via increased BVDV type 1b antibody concentrations, MH whole cell and leukotoxin antibody concentrations, rectal temperatures (TEMP), and subjective clinical severity scores (CS). Calf performance ( ≥ 0.48) was not affected by TM supplementation. Mineral supplementation also did not impact the CS or TEMP of calves ( ≥ 0.53). There was a treatment × time ( < 0.001) interaction observed for liver Cu concentrations. The concentrations of Cu, Mn, Zn, and Fe within the liver; Cu, Mn, and Zn within the muscle; and Cu, Zn, and Fe within the serum were all impacted by time ( ≤ 0.03). Calves receiving the MIN treatment had greater ( < 0.01) liver Cu and Mn concentrations compared with CON calves. In contrast, serum Cu and Fe concentrations were increased ( ≤ 0.05) in CON calves compared with MIN calves. Mineral supplementation did not impact TM concentrations within the muscle ( ≥ 0.38). The supplementation of Cu, Mn, and Zn can improve the Cu and Mn status within the liver and serum of calves in response to a BVDV and MH challenge. When Cu is supplemented to calves receiving a marginally Cu-deficient diet, Cu status within the body is significantly improved.

Efficacy of bovine viral diarrhea virus vaccination to prevent reproductive disease: a meta-analysis.

Bovine viral diarrhea virus (BVDV) is an important reproductive pathogen of cattle worldwide. The reproductive outcome of BVDV infection is largely dependent on the immune status of the dam and the stage of gestation at the time of infection. Potential sequelae include failure of conception, abortion, a variety of congenital malformations, and fetal infection. Vaccination is a possible tool in the control of BVDV, and there has been a recently renewed focus on providing fetal protection through vaccination. Consequently, the aim of this study was to evaluate the efficacy of BVDV vaccination to prevent reproductive disease by performing a quantitative synthesis of previously published studies. Pertinent articles to be included in the analysis were identified by performing a search in four relevant scientific databases (PubMed, CAB abstracts, National Agricultural Library catalog, and Web of Science) and examining the reference lists of 10 germane review articles. Inclusion criteria for the meta-analysis mandated that the studies were controlled, primary studies that included necessary data for use in the meta-analysis (e.g., group size, number of abortions). Forty-six studies in 41 separate articles matched the inclusion criteria. Risk ratio effect sizes were used in random effects, weighted meta-analyses to assess the impact of BVDV vaccination on three outcomes: risk of fetal infection, abortion risk, and pregnancy risk. Within each outcome, subanalyses were performed to evaluate the effect of a variety of interventions, including modified live, inactivated, polyvalent and monovalent vaccination, homologous, heterologous, or field challenge, and studies with only bovine subjects. The analysis revealed a decrease in abortions of nearly 45% and a nearly 85% decrease in fetal infection rate in cattle vaccinated for BVDV compared with unvaccinated cohorts. Additionally, pregnancy risk was increased by approximately 5% in field trials of BVDV vaccinates. This meta-analysis provides quantitative support for the benefit of vaccination in the prevention of BVDV-associated reproductive disease.

Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves.

Studies in young animals have shown an association between vitamin deficiencies and increased risk of infectious disease; however, there is a paucity of information regarding the effect of acute infection on the vitamin status of the vitamin-replete neonate. To characterize the effects of acute infection on vitamin D and E status of the neonate, 6 vitamin-replete preruminant Holstein bull calves were experimentally infected with bovine viral diarrhea virus (BVDV; strain BVDV2-1373). Six mock-inoculated calves served as controls. Sustained pyrexia, leukopenia, and asynchronous increases in serum haptoglobin and serum amyloid A characterized the response of calves to infection with BVDV. Infection was also associated with increased serum IFN-γ, IL-2, and IL-6 concentrations. During the last 8 d of the 14-d postinoculation period, serum 25-hydroxyvitamin D and α-tocopherol concentrations in infected calves decreased by 51 and 82%, respectively. The observed inverse association between vitamin D and E status and serum amyloid A in infected calves suggests that the infection-induced acute phase response contributed to the reduced vitamin status of these animals. Additional studies are necessary to determine if the negative effect of infection on status are unique to this specific infection model or is representative of preruminant calf's response to acute infection. Studies are also needed to characterize mechanisms underlying infection-related changes in vitamin D and E status and to determine whether additional vitamin D or E supplementation during an acute infection diminishes disease severity and duration in the young animal.

Contribution of Leptospira, Neospora caninum and bovine viral diarrhea virus to fetal loss of beef cattle in New Zealand.

The profitability of beef breeding farms in New Zealand depends principally on optimal reproductive performance. The aim of this study was to estimate the impact of four major pathogens, bovine viral diarrhea virus (BVDV), Neospora caninum (N. caninum), Leptospira borgpetersenii serovar Hardjo (Hardjo), and Leptospira interrogans serovar Pomona (Pomona), on rates of fetal loss in commercial beef breeding herds. Farms reporting fetal loss were recruited, and a blood sample from aborting cows (cases) was collected. Controls were normally calving cows from the same farm. At least four controls were selected from each farm contributing cases. Samples were tested using ELISA for detection of antibodies against BVDV and N. caninum, and microscopic agglutination test (MAT) for detection of antibody against Hardjo and Pomona. A selection of titer cut-offs was conducted to evaluate the relationship between fetal loss and seropositivity to each pathogen using conditional logistic regression. The cut-off titer with the strongest association with fetal loss was included in the multivariate model. A significant increased risk of fetal loss was found for animals seropositive to N. caninum (odds ratio (OR)=3.36; 95% confidence interval (95% CI)=1.27-8.89), Hardjo (OR=1.84; 95% CI=1.01-3.33), and Pomona in non-vaccinated cows (OR=14.91, 95% CI=1.73-128.84) at the ELISA titer ≥ 30, and MAT titers of ≥ 1:384 and ≥ 1:768 for a positive sample, respectively. A marginally non-significant increased risk of fetal loss was found for animals exposed to BVDV (OR=2.01; 95% CI=0.99-4.11) at the ELISA titer of ≤ 1. Vaccination did not affect ORs for Hardjo or BVDV and no herd vaccinated against N. caninum. Approximately 14.0% of all fetal loss in the beef breeding cattle population in New Zealand may be attributable to BVDV (3.5%), N. caninum (3.0%), Hardjo (4.7%), and Pomona (3.6%).

Enterocytozoon bieneusi in Bovine Viral Diarrhea Virus (BVDV) infected and noninfected cattle herds.

Enterocytozoon bieneusi known as a causative agent of opportunistic infections instigating diarrhoea in AIDS patients was identified also in a number of immunocompetent patients and in a wide range of animals, including cattle. In the present study we tested if the Bovine Viral Diarrhea Virus (BVDV), the most common pathogen underlying immunosuppressive Bovine Viral Diarrhoea (BVD), can enhance the occurrence of opportunistic infections with E. bieneusi in cattle. Six dairy farms were investigated using ELISA to detect antibodies against or antigens arising from BVDV in collected sera. A total of 240 individual faecal samples from four age groups were examined for the presence of E. bieneusi by nested PCR. Sequence analysis of six E. bieneusi positive samples revealed the presence of the genotype I of E. bieneusi, previously described in cattle. The hypothesis expecting higher prevalence of E. bieneusi in BVDV positive cattle herds was not confirmed in this study; however this is the first description about E. bieneusi in cattle in the Czech Republic.

Impact of BVDV infection of white-tailed deer during second and third trimesters of pregnancy.

While it has been demonstrated that persistent bovine viral diarrhea virus (BVDV) infections can be established in white-tailed deer (Odocoileus virginianus) following in utero exposure in the first trimester of gestation, there is little to no information regarding the outcome of infection in later stages of pregnancy in deer. Our goal was to observe the impact of infection of white-tailed deer in the second and third trimesters of pregnancy. Five white-tailed deer in the second trimester of pregnancy and four in the third trimester were infected with a BVDV type 2 virus previously isolated from a BVDV-infected deer harvested from the wild. Infection of deer in the second trimester of pregnancy resulted in loss of the pregnancy in three of five deer. Fawns born to the two remaining deer appeared normal and were born BVDV antigen-negative with neutralizing serum antibodies against BVDV. Infection of does in the third trimester of pregnancy did not result in fetal death or persistent infection and all does gave birth to live, healthy fawns that were BVDV antigen-negative and born with antibodies against BVDV. These results, combined with those previously reported regarding BVDV infection in the first trimester of pregnancy, suggest that the impact of BVDV infection of pregnant white-tailed deer is very similar to that observed in pregnant cattle.

Neospora caninum in Estonian dairy herds in relation to herd size, reproduction parameters, bovine virus diarrhoea virus, and bovine herpes virus 1.

Cows infected with the tissue parasite Neospora caninum (Nc) are more likely to abort or give birth to calves with neurological disorders. The known infection routes are transplacentally and by consumption of oocysts shed by the definitive host, the dog. It has been hypothesised, that dormant stages of persistent Nc infection may be reactivated by immunosuppression mechanisms such as pathogenic invasions as bovine herpes virus 1 (BHV1) and bovine virus diarrhoea virus (BVDV). The study was set to give the first prevalence data on Nc from Estonian dairy herds in both animal as well as herd level. In addition, association between herd size and Nc, and association of Nc with abortion incidence (Ab), stillbirth incidence (Sb), insemination index (II), and calving interval (CaI) in the presence of BHV1 and BVDV was studied. Blood samples from 1973 animals from 100 herds were collected in 2006-2008, and 320 bulk tank milk (BTM) samples were collected in 2007. Antibodies against Nc was found in 2.5 ± 0.4% (95% CI) of the animals and at least one positive animal was found in 37.0 ± 4.7% (95% CI) of the herds. In addition, Nc antibodies were detected in 16.3 ± 2.0% (95% CI) of the tested BTM. Large herds (≥ 200 animals) were less likely to have seropositive animals for Nc. Logistic regression models showed that herds with more than one animal seropositive for Nc had significantly higher odds ratio of abortion incidence (OR: 11.92, 1.18-120.18 95% CI, p=0.036) and tendency of having more stillbirths (OR: 5.52, 0.87-35.02 95% CI, p=0.07). On the other hand one Nc seropostive cow in the herd was associated with lower odds ratio (OR: 0.22, 0.05-0.91 95% CI, p=0.04) of higher calving intervals. Estonian prevalence results reflect observations in the region. No evidence was found of the pathogens were affecting fertility variables through interactions but independently BHV1 and Nc had an impact on the abortion.

[Bovine neonatal pancytopenia in German Holstein calves]. / Bovine neonatale Panzytopenie (BNP) bei Deutschen Holstein Kälbern.

Profiles of blood cell counts were evaluated for 15 calves from three different farms. These calves showed petechia in the mucous membranes and in the skin and prolonged secondary bleeding after puncture. The clinical course of the disease could be observed in eleven calves. With exception of one case, the blood cell counts indicated a severe anaemia, leukocytopenia and thrombocytopenia. Out of these 15 calves, six calves survived and the other nine calves died or had to be euthanized due to the severity of the disease. Necropsy of these nine calves revealed petechia in the skin, subcutis, muscles, in inner organs and all serous membranes. Pathohistological examination showed a depletion of the bone marrow and lymphatic tissue in eight calves. These findings confirmed the diagnosis of bovine neonatal pancytopenia (BNP) for eight of these nine calves. Bluetongue virus serotype 8 was tested negatively using PCR. Bovine virus diarrhoea virus (BVDV) was negatively tested using immunofluorescence and cell culture and salmonella species were negatively tested in seven dissected calves. A cluster of toxins was negatively tested in one of the dissected calves. All 15 calves had high antibody titres for BVDV. The BVDV-antibody titres from twelve dams with affected calves were positive in six cases and not detectable in the other six cases. In three of the six dams with not detectable BVDV-antibody titres, calves were fed with colostrum of a further dam with high BVDV-antibody titres. In the further three dams without detectable BVDV-antibody titres, we could not ascertain which colostrum has been fed to the calves. BVDV-specific antigen could not be detected in any of the samples from the calves and dams tested. Using the activity of the gamma-glutamyl-transferase, we assumed a sufficient supply with colostrum for the examined calves.The cause for the occurrence of these BNP cases was due to bone marrow depletion.The reason for the bone marrow depletion remained unclear. However, it was obvious that the BNP described here is highly likely caused by colostrum from cows with positive BVDV-antibody titres.

Fatal congenital anaplasmosis associated with bovine viral diarrhoea virus (BVDV) infection in a crossbred calf.

Clinical disease resulting from the vertical transmission of Anaplasma marginale has only been reported on 5 occasions despite studies demonstrating successful in utero transmission. During the reported experimental induction of congenital anaplasmosis in calves, the outcome was variable but mostly led to inapparent or mild infection. There are previous case reports of fatal congenital anaplasmosis following natural infection. The clinical findings in a 2-day-old calf presented to the Onderstepoort Veterinary Academic Hospital with clinical signs of congenital anaplasmosis, which was unresponsive to treatment, are described. Subsequent post mortem diagnostic tests revealed that this calf was co-infected with bovine viral diarrhoea virus (BVDV). It is postulated that immunosuppression resulting from BVDV infection predisposed to severe, fatal anaplasmosis in this calf.

Bovine viral diarrhea virus (BVDV) infection in relation to fertility in heifers.

In this study, blood serum and leukocyte samples were collected from 400 Holstein heifers, all of which appeared to be healthy. Antibodies (Ab) against bovine viral diarrhea virus (BVDV) were detected in 57 serum samples, and BVDV antigen (Ag) was detected in 38 leukocyte samples. There were statistically important differences between the average first insemination ages (FIT) of the BVDV (Ag-/Ab+) heifers (p<0.0001) (pregnant p<0.05, nonpregnant p<0.0001) and BVDV (Ag-/Ab-) heifers. The average conception rates (CR) of BVDV (Ag-/Ab+) heifers and BVDV (Ag-/Ab-) heifers were not significant statistically. There were statistically important differences in average FIT between persistent infected (PI) BVDV (Ag+/Ab-) heifers (p<0.0001; PI pregnant p<0.05, PI nonpregnant p<0.0001) and BVDV (Ag-/Ab-) heifers. No significant differences in average CR between PI BVDV (Ag+/Ab-) heifers and BVDV (Ag-/Ab-) heifers were found. The differences in average FIT between BVDV (Ag+/Ab+; p<0.0001; nonpregnant p<0.0001) and BVDV (Ag-/Ab-) heifers were important statistically. Although there were no BVDV (Ag+/Ab+) pregnant heifers, the differences in average CR between BVDV (Ag+/Ab+) pregnant heifers and BVDV (Ag-/Ab-) heifers were found to be statistically important (p<0.0001). We conclude that fertility is affected in heifers with BVDV (Ag-/Ab+, Ag+/Ab- and Ag+/Ab+).

Rumen temperature change monitored with remote rumen temperature boluses after challenges with bovine viral diarrhea virus and Mannheimia haemolytica.

Remote rumen temperature monitoring is a potential method for early disease detection in beef cattle. This experiment was conducted to determine if remotely monitored rumen temperature boluses could detect a temperature change in steers exposed to bovine viral diarrhea virus (BVDV) and challenged with a common bovine respiratory disease pathogen, Mannheimia haemolytica (MH). Twenty-four Angus crossbred steers (BW = 313 ± 31 kg) were allotted to 1 of 4 treatments: 1) no challenge (control); 2) challenge by a 72-h exposure to 2 steers persistently infected with BVDV; 3) bacterial challenge with MH; and 4) viral challenge by a 72-h exposure to 2 steers persistently infected with BVDV followed by bacterial challenge with MH (BVDV + MH). Remotely monitored rumen temperature boluses programmed to transmit temperature every minute were placed in the rumen before the time of exposure to steers persistently infected with BVDV. Rectal temperatures were taken before MH challenge (0) and at 2, 4, 6, 12, 18, 24, 36, 48, 72, and 96 h after MH challenge. Rumen temperatures were recorded 3 d before (-72 h; period of BVDV exposure) through 14 d after (336 h) MH challenge. Rumen temperatures were analyzed as a randomized complete block design with a 2 × 2 factorial arrangement of treatments and a first-order autoregressive covariance structure for repeated measures. A treatment × day interaction was observed for average daily rumen temperature (P < 0.01). A treatment difference (P < 0.01) was observed on d 0, when MH-challenged steers had greater rumen temperatures than steers not challenged with MH. There was no BVDV × day interaction (P > 0.01). Rumen temperatures averaged every 2 h resulted in a BVDV × hour interaction (P < 0.01) and an MH × hour interaction (P < 0.01). The BVDV × hour differences occurred at h -18 to -14, 40 to 46, 110, 122, and 144 to 146 (P < 0.01). The MH × hour difference occurred at h 4 to 24 (P < 0.01). Maximum rumen temperature was increased (P < 0.01) for BVDV (0.8 °C), MH (1.2 °C), and BVDV + MH (1.3 °C) compared with the control. On average, rumen temperatures measured by the boluses at the same time points as the rectal temperatures were 0.13 °C less than rectal temperatures, and the 2 body temperatures were highly correlated (r = 0.89). Rumen temperature boluses appear to have potential as a tool for detecting temperature changes associated with adverse health events such as exposure to bovine respiratory disease and BVDV.