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Maedi-Visna virus (MVV) and Mycobacterium avium ssp. paratuberculosis (MAP) are two pathogens that cause chronic, production-limiting diseases in dairy sheep. Although they are present worldwide, there are no detailed reports on their actual effects on milk traits in the literature. This study was designed to investigate the effects of test positivity to MVV and MAP on ovine milk yield, composition and coagulation properties, and curd-firming over time (CF t ) variables in clinically healthy animals at the field level. The additive genetic variation and heritabilities of MVV and MAP positivity were also estimated. Milk samples were collected from 1,079 Sarda sheep kept on 23 farms, and pedigree information was obtained from the flock book. Milk yield was also recorded on the sampling date. Positivity for MVV and MAP was determined from milk samples using indirect ELISA test kits. Milk composition traits were measured by spectroscopy, milk coagulation properties were measured with a Formagraph (Foss Italia, Padua, Italy), and CF t traits were calculated using the data from the Formagraph diagram. The effects of MVV and MAP positivity on milk traits were determined through a set of mixed linear models, which took into account various sources of variation, such as days in milk, parity, and flock effects, and included the effects (positive or negative) of the 2 pathogens. A Bayesian threshold sire model with sire relationship was used to estimate genetic variation and heritability. The overall animal prevalence of MVV-positive ewes was 43.6%; on only 1 farm of the 23 tested were all sampled ewes negative. An overall animal prevalence of 10.6% was recorded for MAP, with 4 farms at 0%. Positivity for MVV significantly affected the logarithmic score of the bacterial count, curd firmness after 30 min and 45 min, and the curd-firming instant rate constant. We found significant effects of MAP infection on milk composition, pH, and rennet coagulation time. The mean of the posterior distributions of heritability estimates on the liability scale was 0.15 for MAP and 0.07 for MVV. Our results demonstrate that only a few traits are negatively affected by MVV and MAP positivity, and that there is exploitable genetic variation in MVV and MAP susceptibility in dairy sheep., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Serum samples were obtained from Holstein dairy control cows and cows naturally infected with Mycobacterium avium ssp. paratuberculosis (MAP) to evaluate the effects of disease status on serum 25-hydroxyvitamin D 3 (25OHD 3 ) levels. Disease status was stratified for infected cows into asymptomatic, subclinical infection (n = 25), and cows demonstrating clinical signs (n = 20), along with noninfected control (n = 12) cows for comparison. In addition, portions of the ileocecal valve were taken from a subsample of cows (n = 5 per treatment group) at necropsy and processed for RNA sequencing gene transcription studies. Genes associated with vitamin D metabolism were queried to determine any association between infection and gene expression. Serum 25OHD 3 levels were significantly lower in cows in the clinical stage of disease compared with either cows in the subclinical stage and noninfected control cows. Differential expression for genes associated with the vitamin D pathway such as CYP27A1, CYP27B1, vitamin D-binding protein (DBP), and IFNG was dependent upon infection status. An upregulation of CYP27A1 was noted for cows in subclinical status, whereas CYP27B1 expression was enhanced for clinical cows. Increased expression of vitamin D-binding protein was observed for infected cattle, regardless of infection status. In summary, decreases in circulating 25OHD 3 for animals with clinical disease may suggest that these cows have reduced innate immune responses, thereby influencing the ability of animals to fight infection., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The aim of this work was to investigate associations between individual cow Mycobacterium avium ssp. paratuberculosis (MAP) seropositivity, 305-d corrected milk production, and somatic cell count during 5 lactations lifespan in Portuguese dairy herds using multilevel mixed models. We used MAP serum ELISA (Idexx MAP Ac, Idexx Laboratories Inc., Westbrook, ME) results (n = 23,960) from all the 20,221 adult cows present in 329 farms and corresponding 47,586 lactation records from the National Dairy Improvement Association. Cows and farms were classified as positive or negative. Multilevel mixed models were used to investigate the association of cow MAP status with variation in milk production and somatic cell count. Cow MAP status, farm status, and lactation number were considered as independent variables. A quadratic function of lactation number was used to mimic the effect of lactation order on milk production. The models considered 3 levels: measurement occasion (level 1) within cow (level 2) and cow within farm (level 3). Four final models were produced, including all herds and cows, to address the effect of farm status (models 1 and 2) or the effect of cow status (models 3 and 4) on the outcome variables. Our results show that MAP status affects milk production. Losses are detectable from third lactation onward. During the first 5 lactations, positive cows accumulated an average loss of 1,284.8 kg of milk when compared with the negative cows. We also observed that somatic cell counts were higher in positive cows and a positive interaction occurs between cow status and lactation number, suggesting a positive association between MAP infection and increased somatic cell counts. Our results are in line with previous studies, suggesting a possible positive relation between cow milk production and susceptibility to MAP infection., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Longitudinal data from 3 commercial dairy herds in the northeast United States, collected from 2004 to 2011, were analyzed to determine the effect of Mycobacterium avium ssp. paratuberculosis (MAP) infection status and progression path on milk production. Disease status, as indicated by MAP test results, was determined through quarterly ELISA serum testing, biannual fecal culture, and culture of tissues and feces at slaughter. Milk production data were collected from the Dairy Herd Information Association. Animals with positive MAP test results were categorized, based on test results over the full course of the study, as high path (at least one high-positive culture) or low path (at least one positive culture or ELISA). The cumulative numbers of positive ELISA and culture results were recorded. The effects of both MAP infection path, status, and number of positive tests on milk production were analyzed using a mixed linear model with an autocorrelation random effect structure. Low- and high-path animals produced more milk before their first positive test than always-negative animals, especially high-path animals. Although mean production decreased after a first positive test, low-path animals were shown to recover some productivity. High-path animals continued to exhibit a decrease in milk production, especially after their first high-positive fecal culture. These results show that not all animals that test positive for MAP will have long-term production losses. Milk production decreased significantly with each additional positive test. Ultimately, production loss appeared to be a function of MAP infection progression., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Bovine paratuberculosis is a disease characterized by chronic granulomatous enteritis causing protein-losing enteropathy. Adverse effects on animal productivity are key drivers in the attempt to control paratuberculosis at the farm level. Economic models require an accurate estimation of the production effects associated with paratuberculosis. The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of paratuberculosis on milk production. A total of 20 effect estimates from 15 studies were included in the final meta-analysis. Substantial between-study heterogeneity was observed. Subgroup analysis by case definition and study design was carried out to investigate heterogeneity. The majority of between-study variation was attributed to studies that defined cases on serology. Calculation of a pooled effect estimate was only appropriate for studies that defined cases by organism detection. A reduction in milk yield, corrected for lactation number and herd of origin of 1.87 kg/d, equivalent to 5.9% of yield, was associated with fecal culture or PCR positivity in individual cows., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Vitamin D deficiency has been associated with various human diseases. Therefore, the objective of this study was to evaluate the cow-level association between serum 25-hydroxyvitamin D [25(OH)D] concentration and Mycobacterium avium ssp. paratuberculosis (MAP) seropositivity of dairy cows, adjusting for diet, breed, hair coat color, stage of lactation, reproductive status, and cow age. The sera of 80 MAP antibody ELISA-positive and 80 test-negative herd mates from 5 Minnesota dairy herds were analyzed for 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. The cows' age, production records, and hair coat color were recorded. Additionally, feed samples were obtained and analyzed for vitamin D(2) and vitamin D(3) content. A linear mixed model was used to identify potential predictors for serum 25(OH)D concentration, accounting for herd of origin. The majority of rations analyzed had over 22,000 IU of vitamin D/day (maximum: 52,000 I U/d) and the study cows' average serum 25(OH)D concentration was 62.5 ± 13.8 ng/mL. Serum ELISA-positive cows had, on average, 5.3 ng/mL lower 25(OH)D serum levels than test-negative herd mates. The reproductive status of cows was also associated with the 25(OH)D levels, with fresh cows having the lowest serum concentration. In this cross-sectional study, a temporal or causal association between MAP antibody ELISA status and serum 25(OH)D concentration could not be evaluated. In addition, the high levels of vitamin D in the rations of participating farms and the average 25(OH)D serum concentration suggest that additional supplementation with vitamin D in the ration is likely to be ineffective., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

A case-control study was performed to determine if dairy heifers testing positive for Mycobacterium avium ssp. paratuberculosis (MAP) before 2 yr of age by either fecal culture or serum ELISA had decreased productivity and longevity as cows compared with age-matched herdmates. Cases were individually matched with 4 controls. Survival analysis was conducted to determine differences in longevity between cases and controls. Conditional logistic regression was used to assess differences in mean 3.5% fat-corrected 305-d mature-equivalent milk, milk fat, and milk protein production, linear somatic cell count, and MAP test and clinical status as mature cows. No significant difference was found between cases and controls for any parameter assessed. Herd production performance and longevity did not appear to be impaired; therefore, testing immature dairy heifers for MAP is not economically justifiable, using currently available culture methods and commercial serum ELISA tests., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The 3 objectives of this study were (1) to quantify milk production differences among cows with different paratuberculosis (ParaTB) milk ELISA results; (2) to determine if production differences existed in lactations preceding the test among cows with different ParaTB milk ELISA results; and (3) to assess whether Channel Island breeds were more likely to test positive with the ParaTB milk ELISA than other dairy breeds. Current and completed lactation records from 35,591 dairy cows in Ontario and western Canada that had been tested with a commercial ParaTB milk ELISA were included in the analysis. The first occurrence of the highest categorical test result was used to classify the cow. Cows were then grouped by the lactation in which the first high-positive (HTP), low-positive, or negative milk ELISA occurred, and comparisons were made within lactation groups. High test-positive cows were defined as those that had an optical density ≥ 1.0 on at least 1 ParaTB milk ELISA. The associations between ParaTB milk ELISA status and milk production, as measured by the 305-d milk yield, were assessed with a series of linear mixed models. The effect of breed on the likelihood of testing positive with the milk ELISA was assessed using a logistic mixed model for the lactation in which the first negative or positive ParaTB milk ELISA occurred. Test-positive cows produced on average 2.9 to 6.8% less milk than negative herdmates in the lactation in which they were tested. The HTP cows produced on average 466, 514, and 598 kg less milk than low-positive herdmates in lactations 1, 2, and 4, respectively. Cows testing low-positive in their second lactation had, on average, a 218-kg higher milk yield in their first lactation than their test-negative herdmates. Otherwise, no association was found between test result and milk production in preceding lactations. Differences in milk production among negative, test-positive, and HTP cows increased with increasing parity. Cows of the Channel Island breeds had 1.4 to 8.3 times the odds to test positive compared with other dairy breeds. The findings of this study are consistent with previous studies that have reported that milk production is lower in test-positive animals. The differences in milk production increased with increasing ELISA optical density scores and parity in which the animal tested positive. However, with the exception of second-lactation cows, no differences in milk production were observed in tests preceding lactations. The differences in milk ELISA status among dairy breeds support the need for further studies investigating the genetic component of ParaTB susceptibility., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Among the costs attributed to Mycobacterium avium ssp. paratuberculosis (MAP) infection in dairy cattle, the effects on reproduction and culling are the least documented. To estimate the cost of MAP infections and Johne's disease in a dairy herd, the rates of calving and culling were calculated for cows in each stage of MAP infection relative to uninfected cows. Data from 6 commercial dairy herds, consisting of 2,818 cows with 2,754 calvings and 1,483 cullings, were used for analysis. Every cow in each study herd was tested regularly for MAP, and herds were followed for between 4 and 7 yr. An ordinal categorical variable for Johne's disease status [test-negative, low-positive (low-shedding or ELISA-positive only), or high-shedding] was defined as a time-dependent variable for all cows with at least 1 positive test result or 2 negative test results. A Cox regression model, stratified on herd and controlling for the time-dependent infection variable, was used to analyze time to culling. Nonshedding animals were significantly less likely to be culled in comparison with animals in the low-shedding or ELISA-positive category, and high-shedding animals had nonsignificantly higher culling rates than low-shedding or ELISA-positive animals. Time to calving was analyzed using a proportional rates model, an analog to the Andersen-Gill regression model suitable for recurrent event data, stratifying on herd and weighted to adjust for the dependent censoring caused by the culling effects described above. High-shedding animals had lower calving rates in comparison with low-shedding or ELISA-positive animals, which tended to have higher calving rates than test-negative animals., (Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The association between Mycobacterium avium ssp. paratuberculosis (MAP) and milk production was estimated on 2 California dairies using longitudinal data from 5,926 cows. Both study herds had moderate MAP seroprevalence, housed cows in freestalls, and had Johne's disease control programs. Cow MAP status was determined using both serum ELISA and fecal culture results from cows tested at dry-off and from whole-herd tests. Potential confounders were evaluated based on a causal diagram. Mixed models with 2 functions (splines) for days in milk (DIM) representing milk production pre- and postpeak used in similar studies were further modified to use each cow's observed DIM at peak and lactation length. Cows that were seropositive produced 2.5kg less 4% fat-corrected milk (FCM) per day than their seronegative herdmates. In addition, cows that were fecal-culture positive by liquid culture and confirmed by PCR produced 2.2kg less 4% FCM per day than their fecal-culture negative herdmates. The decrease in milk production in MAP test-positive compared with test-negative cows started in the second lactation. A switch in MAP status in either ELISA or fecal culture results from positive to negative had no significant association with milk production. Modified DIM functions that used the observed DIM at peak had better model fit than another function that assumed a fixed peak at 60 DIM. Cows that tested positive for MAP on serum ELISA or fecal culture produced less milk than cows that tested negative, and the association between MAP and milk production was not confounded by mastitis, elevated somatic cell counts, or uterine or metabolic cow conditions.

The effect of infection with Mycobacterium avium ssp. paratuberculosis (MAP) on slaughter weight and slaughter value of dairy cows was evaluated. Two data sets were analyzed: 1) recordings from 1,031 cows from herds in a pilot study to control MAP infections, and 2) recordings from 36,455 cows from herds participating in the Danish MAP control program. The effect of stage of MAP infection on carcass weight and slaughter value was assessed by ANOVA. Infection stage was diagnosed by repeated milk antibody ELISA in both data sets. Furthermore, repeated fecal culture was recorded in data set 1 and occurrence of enteritis or enteric edema found at slaughter was recorded in data sets 1 and 2. Compared with presumably unaffected cows with at least 2 ELISA negative tests, slaughter weight and value were reduced by 10 and 17%, respectively, in cows with positive ELISA at slaughter. If the cow was also positive using fecal culture, slaughter weight and value were reduced up to 15 and 31%, respectively. The slaughter weight and value were reduced an additional 20 and 31%, respectively, for cases with recorded enteritis or edema. Thereby, summarized weight losses of up to 31% and slaughter value losses up to 48% occurred. Cows with negative fecal cultures had reduced slaughter results only if they were ELISA-positive in the last 2 tests. Losses of both slaughter weight and slaughter value caused by MAP were more severe than previously estimated. These losses could be predicted by repeated milk ELISA tests with or without confirmation with fecal culture.

Longitudinal data from 3 commercial dairy herds in the northeast United States were collected from 2004 to 2007. Johne's disease status, as indicated by Mycobacterium avium ssp. paratuberculosis infection levels, was determined through quarterly ELISA serum testing, biannual fecal culture, and culture of tissues at slaughter. Milk production data were collected from the Dairy Herd Improvement Association. The effect of Johne's disease status on milk production was analyzed using a mixed linear model with an autocorrelation random effect structure. Infected animals produced more milk than uninfected cows before they began shedding M. avium ssp. paratuberculosis. Cows infected with M. avium ssp. paratuberculosis had monthly decreases of 0.05 to 1 kg in daily milk production relative to uninfected animals, with greater decreases in progressive disease categories. Animals with fecal culture results of >30 cfu/g produced approximately 4 kg less milk per day compared with uninfected cows. These results will be valuable in calculating the economic effect of Johne's disease.

The primary purpose of this research was to determine associations among seropositivity for bovine leukemia virus (BLV), bovine viral diarrhea virus (BVDV), Mycobacterium avium ssp. paratuberculosis (MAP), and Neospora caninum (NC) and each of 3 outcome variables (305-d milk, fat, and protein production) in Canadian dairy cattle. Serum samples from up to 30 randomly selected cows from 342 herds on monthly milk testing were tested for antibodies against BLV (IDEXX ELISA; IDEXX Corporation, Westbrook, ME), MAP (IDEXX or Biocor ELISA; Biocor Animal Health, Inc., Omaha, NE), and NC (IDEXX or Biovet ELISA; Biovet Inc., St. Hyacinthe, Quebec, Canada). Up to 5 unvaccinated cattle over 6 mo of age were tested for virus-neutralizing antibodies to the Singer strain of type 1 BVDV. Dairy Herd Improvement records were obtained electronically for all sampled cows. Linear mixed models with herd and cow as random variables were fit, with significant restricted maximum likelihood estimates of outcome effects being obtained, while controlling for potential confounding variables. Bovine leukemia virus seropositivity was not associated with 305-d milk, 305-d fat, or 305-d protein production. Cows in BVDV-seropositive herds (at least one unvaccinated animal with a titer > or =1:64) had reductions in 305-d milk, fat, and protein of 368, 10.2, and 9.5 kg, respectively, compared with cows in BVDV-seronegative herds. Mycobacterium avium ssp. paratuberculosis seropositivity was associated with lower 305-d milk of 212 kg in 4+-lactation cows compared with MAP-seronegative 4+-lactation cows. Neospora caninum seropositivity in primiparous cows was associated with lower 305-d milk, fat, and protein of 158, 5.5, and 3.3 kg, respectively, compared with NC-seronegative primiparous cows. There were no interactions among seropositivity for any of the pathogens and their effects on any of the outcomes examined, although the low MAP seroprevalence limited this analysis. Results from this research will contribute to understanding the economic impacts of these pathogens and justify their control.

Paratuberculosis (Johne's disease) is a significant animal health problem. Evaluation of diagnostic tests for Johne's disease has been difficult due to lack of a gold standard test. In recent years, there has been interest in receiver operating characteristic (ROC) curve estimation without any gold standard test. Typically, either Bayesian or maximum likelihood methods are proposed. Although these methods overcome the lack of a gold standard test in ROC curve estimation, little work has been done to incorporate covariates in the analysis. In this paper, we propose a method for estimation of ROC curves based on statistical models to adjust for covariate effects when the true disease states of test animals are unknown. The covariates may be correlated with the disease process or with the diagnostic testing procedure, or both. We propose a 2-part Bayesian model: first, a logistic regression model for disease prevalence is used to fit the covariates; second, a linear model is used to fit the covariates to the distribution of test scores. We used Markov chain Monte Carlo methods to compute the posterior estimates of the sensitivities and specificities that provide the groundwork for inference concerning the diagnostic procedure's accuracy. We applied the methodology to milk ELISA scores from several dairy-cow herds for the diagnostic testing of paratuberculosis. We found that both milk yield and its interaction with age had significant effects on the disease process whereas only milk yield was significant on the testing procedure.

Paratuberculosis, which is also known as Johne's disease, is a chronic, progressive enteric disease of ruminants caused by infection with Mycobacterium paratuberculosis. Cattle become infected with M. paratuberculosis as calves but often do not develop clinical signs until 2 to 5 yr of age. The clinical disease is characterized by chronic or intermittent diarrhea, emaciation, and death. Although animals with clinical disease are often culled from the herd, animals with subclinical paratuberculosis may cause economic losses because of reduced milk production and poor reproductive performance. Although the economic impact of paratuberculosis on the national cattle industry has not been determined, it is estimated to exceed $1.5 billion/yr. The diagnosis of subclinical paratuberculosis is difficult. Bacteriologic culture is the most definitive method of diagnosis, but culture is time consuming and labor intensive. Serological assays are not very useful because animals do not develop an antibody response until the clinical stages of disease. Development of assays to measure cell-mediated immunity is critical to accurate detection of paratuberculosis in subclinically infected animals. Although not considered a zoonotic agent, M. paratuberculosis has been identified in intestinal biopsy tissue from patients with Crohn's disease, an inflammatory enteritis in humans. Currently, the potential human health risk is being addressed by research evaluating pasteurization of dairy products in the US.