Dynamics of specific anti-Mycobacterium avium subsp. paratuberculosis antibody response through age.

Mycobacterium avium subsp. paratuberculosis (MAP) causes a chronic infection in cattle. MAP infected cattle with humoral immune (HI) reactions with IgG antibodies are usually those where latency of infection has ceased and their infection is progressing towards reduced milk yield, weight loss and significant bacterial excretion in feces. The proportion of detectable infections among all infected animals that will develop disease is often referred to as 'the tip of the iceberg'. The purpose of this study was to estimate this proportion. Test-records from 18,972 Danish dairy cows with MAP specific IgG antibodies on their final test-record were used to estimate age-specific sensitivities (Se). These cows were the infected ones considered to develop disease in a population with a representative age-distribution and were defined as cases. The specificity (Sp) of the test was estimated based on test-results from 166,905 cows, which had no MAP IgG antibodies in their final four test-records. The Sp, age-specific Se and maximum Se were used to estimate the probability of having HI at a given age resulting in the proportion of infected cows with HI at a given age. For cows 2 years of age, the proportion of detectable cases was 0.33, while it was 0.94 for cows 5 years of age. Thus, there was a significant shift in the tip of the iceberg with aging. This study provided a model for estimating the proportion of latent chronic infections that would progress to disease, and the results can be used to model infection dynamics.

Modeling the effect of direct and indirect contamination of on-farm bulk tank milk with Mycobacterium avium subsp. paratuberculosis.

Mycobacterium avium subsp. paratuberculosis (MAP) in milk of bovine origin is suspected of being implicated in Crohn's disease in humans. Milk can be contaminated via direct excretion of MAP in milk or indirectly via fecal contamination of the milk. This study aimed at estimating the level of MAP in farm bulk tank milk and simulating the effect of direct and indirect contamination with MAP. The effect of discarding milk from test-positive cows at different prevalences was assessed. The concentration of MAP in milk was estimated using a simulation model, while taking direct and indirect contamination with MAP into account. Direct MAP contamination of milk was related to infection stages, while indirect contamination was associated with within-herd prevalence and distribution of cows in different stages of infection. Discarding of milk based on diagnostic test results was included as a control option. Median MAP load in farm bulk tank milk at within-herd infection prevalences from 7.5% to 60% were estimated to be 0.54-7.53 CFU/mL milk. Maximum concentration at the prevalence of 60% could be 1186 CFU/mL caused by shedding of high amounts of MAP in feces. At the prevalence of 15%, discarding milk from test positive cows would result in discarding 11% of milk and reduce the MAP level by 80%. Due to poor sensitivity of the diagnostic test, removing test-positive cows would not further reduce the already low concentration of MAP and it would not guarantee the milk as MAP-free. The model was relatively simple yet capable of capturing true infection status and associated contributions from milk and feces. Further knowledge on distribution of fecal excretion from infected cows is required because very few "super-shedders" might play a major role.

Occurrence of Mycobacterium avium subsp. paratuberculosis in milk at dairy cattle farms: a systematic review and meta-analysis.

Presence of Mycobacterium avium subsp. paratuberculosis (MAP) in milk for human consumption is a concern due to its possible relationship with Crohn's disease in humans. Pasteurization effectively reduces the MAP load by four to five logs, but the efficacy depends on the MAP concentration, which depends on the prevalence among contributing herds and individuals. Considerable variation of MAP in bulk tank milk (BTM) and individual cow's milk (IM) is reported, but factors associated with MAP occurrence in milk at farm level have not been described. This study systematically reviewed published studies aiming at estimating the occurrence of MAP in on-farm BTM and IM by meta-analysis. A total of 692 articles were identified through electronic databases and initially screened using title and abstract. The quality of the 61 potentially relevant articles was assessed using full text and 31 articles were eventually included in the meta-analysis. The apparent prevalence (AP) of MAP in BTM and IM on farm were summarized in relation to strata defined by the test used to identify MAP and the infection status of the herds/animals. There was considerable inconsistency in the reporting, resulting in missing information potentially explaining the dispersion in the estimated AP. The overall AP and 95% confidence intervals based on PCR and culture of MAP were summarized to 0.10 (0.04-0.22) in BTM and 0.20 (0.12-0.32) in IM. Quantifying the MAP load in test-positive milk samples was not possible because very few articles provided quantitative information on individual samples.

Apparent Prevalence of Beef Carcasses Contaminated with Mycobacterium avium subsp. paratuberculosis Sampled from Danish Slaughter Cattle.

Presence of Mycobacterium avium subsp. paratuberculosis (MAP) in beef has been reported as a public health concern because asymptomatically infected cattle may contain MAP in tissues that are used for human consumption. Associations between MAP carcasses contamination and animal characteristics such as age, breed, production type, and carcass classification were assessed. Cheek muscles from 501 carcasses were sampled cross-sectionally at a Danish abattoir and tested for presence of viable MAP and MAP DNA by bacterial culture and IS900 realtime PCR, respectively. Cheek muscle tissues from carcasses of two dairy cows were positive by culture whereas 4% of the animals were estimated with ≥10 CFU/gram muscle based on realtime PCR. Age was found to be associated with carcass contamination with MAP. The observed viable MAP prevalence in beef carcasses was low. However, detection of MAP and MAP DNA in muscle tissues suggested that bacteremia occurred in slaughtered cattle.

Prevalence of Mycobacterium avium subsp. paratuberculosis infection in adult Danish non-dairy cattle sampled at slaughter.

A voluntary, risk-based control program for paratuberculosis in dairy herds was started in 2006 in Denmark. The program does not include non-dairy herds, and the occurrence of Mycobacterium avium subsp. paratuberculosis (MAP) in these herds is unknown. The objective of this study was to establish the prevalence of MAP infected adult non-dairy cattle in Denmark. Serum samples were collected between October, 2008 and January, 2009 from every 6th animal over 24 months of age, sent to slaughter to Danish slaughterhouses from non-dairy herds. The final sample included 2345 cattle of 13 different breeds, with the largest breed group being crossbreds (of unknown breeds) (30%) and three dairy breeds (Danish Holstein, Danish Jersey and Danish Red Cattle) comprising 27% of the samples. The serum samples were tested using a MAP specific antibody ELISA (IDScreen) and positives were defined as the sample-to-positive ratio greater than 0.60. Estimation of the breed-specific apparent prevalences, true prevalences (TP), and true prevalences with a random effect of breed was done in a Bayesian analysis. Information about test sensitivity and specificity were based on literature data and expert information. Regardless of the method of analysis, the estimated prevalences showed similar differences between breeds. The dairy breeds Danish Jersey, Danish Holstein and Danish Red Cattle were ranked highest (i.e. with highest prevalence) (TP medians: 13, 10, and 6, respectively). Combined, the dairy breeds had a significantly higher prevalence than the other breeds, median TP (dairy)=15.7% vs. median TP (non-dairy)=0.8%. For the individual non-dairy breeds, the median estimates were generally higher, illustrating the problems of ranking groups based on relatively small sample sizes.