Putting Crohn's on the MAP: Five Common Questions on the Contribution of Mycobacterium avium subspecies paratuberculosis to the Pathophysiology of Crohn's Disease.

For decades, Mycobacterium avium subspecies paratuberculosis (MAP) has been linked to the pathogenesis of Crohn's disease. Despite many investigations and research efforts, there remains no clear unifying explanation of its pathogenicity to humans. Proponents argue Crohn's disease shares many identical features with a granulomatous infection in ruminants termed Johne's disease and similarities with ileo-cecal tuberculosis. Both are caused by species within the Mycobacterium genus. Sceptics assert that since MAP is found in individuals diagnosed with Crohn's disease as well as in healthy population controls, any association with CD is coincidental. This view is supported by the uncertain response of patients to antimicrobial therapy. This report aims to address the controversial aspects of this proposition with information and knowledge gathered from several disciplines, including microbiology and veterinary medicine. The authors hope that this discussion will stimulate further research aimed at confirming or refuting the contribution of MAP to the pathogenesis of Crohn's disease and ultimately lead to advanced targeted clinical therapies.

Test positivity for Maedi-Visna virus and Mycobacterium avium ssp. paratuberculosis in Sarda ewes: Effects on milk composition and coagulation traits and heritability estimates for susceptibility.

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 (CFt) 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 CFt 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.

Short communication: Vitamin D status and responses in dairy cows naturally infected with Mycobacterium avium ssp. paratuberculosis.

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 D3 (25OHD3) 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 25OHD3 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 25OHD3 for animals with clinical disease may suggest that these cows have reduced innate immune responses, thereby influencing the ability of animals to fight infection.

A synthesis of the patho-physiology of Mycobacterium avium subspecies paratuberculosis infection in sheep to inform mathematical modelling of ovine paratuberculosis.

This literature review of exposure to Mycobacterium avium subsp. paratuberculosis (MAP) in sheep enabled a synthesis of the patho-physiology of ovine paratuberculosis (PTB). These results could be used to inform subsequent modelling of ovine PTB. We reviewed studies of both experimental and natural exposure. They were generally comparable. Possible outcomes following exposure were latent infection, i.e. mere colonization without lesions; active infection, with inflammatory histopathology in the intestinal tissues resulting in mild disease and low faecal shedding; and affection, with severe intestinal pathology, reduced production, clinical signs and high faecal shedding. Latent infection was an uninformative outcome for modelling. By contrast, histological lesions and their grade appeared to be a good marker of active infection and progression stages to clinical disease. The two possible pathways following infection are non-progression leading to recovery and progression to clinical disease, causing death. These pathways are mediated by different immune mechanisms. This synthesis suggested that host-related characteristics such as age at exposure and breed, combined with pathogen-related factors such as MAP dose, strain and inoculum type for experimental infection, have a strong influence on the outcome of exposure. The material reviewed consisted of disparate studies often with low numbers of sheep and study-level confounders. Hence comparisons between and across studies was difficult and this precluded quantitative model parameter estimation. Nevertheless, it allowed a robust synthesis of the current understanding of patho-physiology of ovine PTB, which can inform mathematical modelling of this disease.

The effect of sub-clinical infection with Mycobacterium avium subsp. paratuberculosis on milk production in a New Zealand dairy herd.

BACKGROUND: Johne's disease is a major production limiting disease of dairy cows. The disease is chronic, progressive, contagious and widespread; there is no treatment and there is no cure. Economic losses arise from decreased productivity through reduced growth, milk yield and fertility and capital losses due to premature culling or death. This study attempts to address the effect of subclinical JD on milk production under New Zealand pastoral dairy farming conditions using a new testing approach. Blood samples were taken from all lactating animals from a single seasonally calving New Zealand dairy herd in the autumn of 2013 and 2014. Samples were subject to serological assay for antibodies to Mycobacterium avium subsp. paratuberculosis using a combination of four ELISA tests in parallel followed by selective quantitative fecal PCR to confirm the fecal shedding characteristics of ELISA positive cows. ELISA status was classified as Not-Detected, Low, Moderate or High and fecal PCR status as Not-Detected, Moderate or High. RESULTS: A mixed generalized regression model indicated that, compared to cows where MAP was not detected, daily milk solids production was 4% less for high ELISA positive cows (p = 0.004), 6% less for moderate fPCR cows (p = 0.036) and 12% less for high fPCR cows (p < 0.001). CONCLUSIONS: This study confirms that sub-clinical JD can have a significant impact on milk production and that the testing methodology used stratified the animals in this herd on their likely impact on production and disease spread. This allowed the farmer to prioritize removal of heavily shedding, less-productive animals and so reduce the risk of infection of young stock. This is the first longitudinal study based in New Zealand looking at the effect of Johne's infection status on daily milk production allowing for intermediary and confounding factors.

Association of paratuberculosis sero-status with milk production and somatic cell counts across 5 lactations, using multilevel mixed models, in dairy cows.

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.

Experimental infection with Mycobacterium avium subspecies paratuberculosis resulting in decreased body weight in Holstein-Friesian calves.

Fifty calves inoculated at either 2 weeks or at 3, 6, 9, or 12 months of age with either a low or high dose of Mycobacterium avium subspecies paratuberculosis (MAP) were on average 32 and 39 kg lower in body weight, respectively, compared to negative controls at 17 months of age.

Chute du poids corporel chez des veaux Holstein-Friesian suite à l'infection expérimentale avecMycobacterium aviumsous-espèceparatuberculosis. Cinquante veaux qui ont été inoculés à l'âge de 2 semaines ou à l'âge de 3, 6, 9 ou 12 mois avec soit une dose faible ou élevée de Mycobacterium avium sous-espèce paratuberculosis (MAP) présentaient en moyenne un poids corporel inférieur de 32 kg et de 39 kg respectivement, comparativement aux témoins négatifs à l'âge de 17 mois.(Traduit par Isabelle Vallières).

Analysis of Johne's disease ELISA status and associated performance parameters in Irish dairy cows.

BACKGROUND: Infection with Mycobacterium avium subspecies paratuberculosis (MAP) has been associated with reductions in milk production in dairy cows and sub optimal fertility. The aim of this study was to highlight the production losses associated with testing MAP ELISA positive in Irish dairy cows. Secondary objectives included investigation of risk factors associated with testing MAP ELISA positive. A survey of management practices on study farms was also conducted, with examination of associations between management practices and herd MAP status. Blood samples were collected from 4188 breeding animals on 22 farms. Samples were ELISA tested using the ID Screen Paratuberculosis Indirect Screening Test. Production parameters examined included milk yield, milk fat, milk protein, somatic cell count, and calving interval. The association between MAP ELISA status and production data was investigated using multi-level mixed models. Logistic regression was used to identify risk factors for testing JD blood ELISA positive at individual cow level and to identify associations between farm management practices and herd MAP status. RESULTS: Data were available for 3528 cows. The apparent prevalence recorded was 7.4%. Mixed model analysis revealed no statistically significant association between testing MAP ELISA positive and dairy cow production parameters. Risk factors associated with testing positive included larger sized herds being over twice more likely to test positive than smaller herds (OR 2.4 P = <0.001). Friesians were less likely to test positive relative to other breeds. A number of study farmers were engaged in management practices that have previously been identified as high risk for MAP transmission e.g., 73.1% pooled colostrum and 84.6% of study farmers used the calving area to house sick animals throughout the year. No significant associations however, were identified between farm management practices and herd MAP status. CONCLUSION: No production losses were identified; however an apparent prevalence of 7.4% was recorded. With the abolition of EU milk quotas herd size in Ireland is expanding, as herds included in this study were larger than the national average, results may be indicative of future JD levels if no JD control programmes are implemented to minimise transmission.

The effect of paratuberculosis on milk yield--A systematic review and meta-analysis.

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.

The effects of progressing and nonprogressing Mycobacterium avium ssp. paratuberculosis infection on milk production in dairy cows.

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.

Cow-level association between serum 25-hydroxyvitamin D concentration and Mycobacterium avium subspecies paratuberculosis antibody seropositivity: a pilot study.

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.

Identification of loci associated with tolerance to Johne's disease in Holstein cattle.

Johne's disease, caused by Mycobacterium avium subspecies paratuberculosis (Map), is a fatal disease in cattle. The objective of this study was to identify loci associated with tolerance in cows infected with Map. Tolerance was defined as a cow's fitness at a given level of Map infection intensity. Fitness was measured by Map faecal cultures, and Map infection intensity was measured by culturing four gut tissues. The quantitative phenotype of tolerance was defined by numerical indexes of cultures of peak (peak tolerance, PT) and average (average tolerance, AT) faecal and tissue Map from 245 Holstein cows. The categorical phenotype was defined as: ≥ 100 cfu Map tissue infection, and faecal shedding ≥ 75 cfu (intolerant) or <10 cfu (tolerant cows). In 94 cows, Map was identified in ≥ 1 tissue, including 44 cows with ≥ 100 Map tissue cfu and 36 with ≥ 1 faecal cfu. A genome-wide association analysis was performed after filtering, leaving genotypes for 45,789 SNPs in 90 animals for the quantitative phenotype and 16 cases and 25 controls for the categorical analysis of tolerance. rs41748405:A>C (BTA15) was associated with PT (P = 1.12 × 10(-7)) and AT (P = 2.17 × 10(-6)). Associations were identified with PT and adjacent SNPs ss61512613:A>G and ss61530518:A>G (BTA6) (P < 3.0 × 10(-5)), and with AT for ss61469568:A>G (BTA 2) (P = 3.3 × 10(-5)) and ss86284768:A>G (BTA1) (P = 3.31 × 10(-5)). For the categorical phenotype, an association was found with ss8632653:A>G (BTA6) (P < 5.0 × 10(-5)). This is the first study to identify loci associated with tolerance to Johne's disease.

Associations between paratuberculosis milk ELISA result, milk production, and breed in Canadian dairy cows.

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.

Case-control study: Productivity and longevity of dairy cows that tested positive for infection with Mycobacterium avium ssp. paratuberculosis as heifers compared to age-matched controls.

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.

Association between Mycobacterium avium subspecies paratuberculosis infection and milk production in two California dairies.

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.

Effect of Johne's disease status on reproduction and culling in dairy cattle.

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.

Effect of paratuberculosis on slaughter weight and slaughter value of dairy cows.

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.

A longitudinal study on the impact of Johne's disease status on milk production in individual cows.

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.

Higher non-return rate associated with Mycobacterium avium subspecies paratuberculosis infection at early stage in Holstein dairy cows.

The effects of infection by Mycobacterium avium paratuberculosis (Map) on dairy cows are poorly documented and quite controversial. This retrospective study aimed at quantifying the variation in non-return to service of Holstein dairy cows according to their Map-infection status. Three different statuses were defined based on both individual and herd tests results: ELISA positive cow, all tests negative cow in a negative herd and all tests negative cow in a positive herd. Whatever the age at Map testing, the status was attributed to a cow from its first lactation onwards. Non-return to service was determined at 200 days after first and second services. The study was performed from 1999 to 2007 on 185,950 AI from 48,914 cows in early stage of the infection in 1069 herds by logistic regression controlling for known factors influencing non-return rate. Non-return rate was higher for infected cows compared to negative cows from negative herds (RR of 1.10 or +3.9 points of % of non-return rate). The effect was significant for parities 1 and 2 (RR of 1.11 and 1.12, respectively) but not for higher ones. This effect was lower when comparing positive cows to negative cows in the same herds but relative risks were still above 1. The hypothesis that the effect of Map on non-return depends upon the stage of infection is formulated.

Association between cow reproduction and calf growth traits and ELISA scores for paratuberculosis in a multibreed herd of beef cattle.

The objective of this research was to assess the association between 4 cow reproductive and weight traits, and 2 preweaning calf traits and ELISA scores for paratuberculosis (0 = negative, 1 = suspect, 2 = weak-positive, and 3 = positive) in a multibreed herd of cows ranging from 100% Angus (A) to 100% Brahman (B). Cow data were 624 gestation lengths (GL), 358 records of time open (TO), 605 calving intervals (CI), and 1240 weight changes from November to weaning in September (WC) from 502 purebred and crossbred cows. Calf data consisted of 956 birth weights (BWT), and 923 weaning weights adjusted to 205 d of age (WW205) from 956 purebred and crossbred calves. Traits were analyzed individually using multibreed mixed models that assumed homogeneity of variances across breed groups. Covariances among random effects were assumed to be zero. Fixed effects were year, age of cow, sex of calf, year x age of cow interaction (except WC), age of cow x sex of calf interaction (only for WC), and covariates for B fraction of sire and cow, heterosis of cow and calf, and ELISA score. Random effects were sire (except for TO and CI), dam, and residual. Regression estimates of cow and calf traits on ELISA scores indicated that lower cow fertility (longer TO), lower ability of cows to maintain weight (negative WC), lower calf BWT, and lower calf WW205 were associated with higher cow ELISA scores. Further research on the effects of subclinical paratuberculosis in beef cattle at regional and national levels seems advisable considering the large potential economic cost of this disease.