Rebecca L. Smith

The importance of culling in Johne's disease control

Johnes disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection and results in economic losses in the dairy industry. To control MAP transmission in herds, test-based culling has been recommended and immediate culling of high shedding animals is typically implemented. In this study, we quantified the effects of MAP control in US dairy herds, using the basic reproduction ratio R(0). The effectiveness of culling strategies was evaluated for good and poor herd management (low- and high-transmission rates, respectively) by a phase diagram approach. To establish a quantitative relationship between culling rates and test properties, we defined the average detection times for low and high shedding animals. The effects of various culling strategies and test characteristics, such as test sensitivity, test turnaround time, and testing interval, were analyzed. To understand the overall effect of model parameters on R(0), we performed global uncertainty and sensitivity analyses. We also evaluated the effectiveness of culling only high shedding animals by comparing three test methods (fecal culture, fecal polymerase chain reaction, PCR, and enzyme-linked immunosorbent assay, ELISA). Our study shows that, in the case of good herd management, culling of only high shedding animals may be effective in controlling MAP transmission. However, in the case of poor management, in addition to immediate culling of high shedding animals, culling of low shedding animals (based on the fecal culture test) will be necessary. Culling of low shedding animals may be delayed 6-12 months, however, if a shorter testing interval is applied. This study suggests that if farmers prefer culling only high shedding animals, faster MAP detection tests (such as the fecal PCR and ELISA) of higher sensitivity should be applied with high testing frequency, particularly on farms with poor management. Culling of infectious animals with a longer testing interval is generally not effective to control MAP.

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. Johnes 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 Johnes 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 Johnes disease.

Stochastic simulations of a multi-group compartmental model for Johne's disease on US dairy herds with test-based culling intervention.

Infection elimination may be an important goal of control programs. Only in stochastic infection models can true infection elimination be observed as a fadeout. The phenomena of fadeout and variable prevalence are important in understanding the transmission dynamics of infectious diseases and these phenomena are essential to evaluate the effectiveness of control measures. To investigate the stochastic dynamics of Mycobacterium avium subsp. paratuberculosis (MAP) infection on US dairy herds with test-based culling intervention, we developed a multi-group stochastic compartmental model (a continuous time Markov chain model) with both horizontal and vertical transmission. The stochastic model predicted fadeout and within-herd prevalence to have a large variance. Although test-based culling intervention generally decreased prevalence over time, it took longer than desired by producers to eliminate the endemic MAP infection from a herd. Uncertainty analysis showed that, using annual culture test and culling of only high shedders or culling of both low and high shedders with a 12-month delay in culling of low shedders, MAP infection persisted in many herds beyond 20 years. While using semi-annual culture test and culling of low and high shedders with a 6-month delay in culling of low shedders, MAP infection in many herds would be extinct within 20 years. Sensitivity analysis of the cumulative density function of fadeout suggested that combining test-based culling intervention and reduction of transmission rates through improved management between susceptible calves and shedding animals may be more effective than either alone in eliminating endemic MAP infection. We also discussed the effects of other factors such as herd size, heifer replacement, and adult cow infection on the probability of fadeout.

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 Johnes 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 Johnes 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.

Economic analysis of Mycobacterium avium subspecies paratuberculosis vaccines in dairy herds

Johnes disease, or paratuberculosis, is a chronic infectious enteric disease of ruminants, caused by infection with Mycobacterium avium ssp. paratuberculosis (MAP). Given the absence of a fail-safe method of prevention or a cure, Johnes disease can inflict significant economic loss on the US dairy industry, with an estimated annual cost of over

Environmental contamination with Mycobacterium avium subsp. paratuberculosis in endemically infected dairy herds.

200 million. Currently available MAP control strategies include management measures to improve hygiene, culling MAP serologic- or fecal-positive adult cows, and vaccination. Although the 2 first control strategies have been reported to be effective in reducing the incidence of MAP infection, the changes in herd management needed to conduct these control strategies require significant effort on the part of the dairy producer. On the other hand, vaccination is relatively simple to apply and requires minor changes in herd management. Despite these advantages, only 5% of US dairy operations use vaccination to control MAP. This low level of adoption of this technology is due to limited information on its cost-effectiveness and efficacy and some important inherent drawbacks associated with current MAP vaccines. This study investigates the epidemiological effect and economic values of MAP vaccines in various stages of development. We create scenarios for the potential epidemiological effects of MAP vaccines, and then estimate economically justifiable monetary values at which vaccines become economically beneficial to dairy producers such that a net present value (NPV) of a farms net cash flow can be higher than the NPV of a farm using no control or alternative nonvaccine controls. Any vaccination with either low or high efficacy considered in this study yielded a higher NPV compared with a no MAP control. Moreover, high-efficacy vaccines generated an even higher NPV compared with alternative controls, making vaccination economically attractive. Two high-efficacy vaccines were particularly effective in MAP control and NPV maximization. One was a high-efficacy vaccine that reduced susceptibility to MAP infection. The other was a high-efficacy vaccine that had multiple efficacies on the dynamics of MAP infection and disease progress. Only one high-efficacy vaccine, in which the vaccine is targeted at reducing MAP shedding and the number of clinical cases, was not economically beneficial to dairy producers compared with an alternative nonvaccine control, when herds were highly infected with MAP.

Impact of imperfect Mycobacterium avium subsp. paratuberculosis vaccines in dairy herds: A mathematical modeling approach

Environmental contamination with Mycobacterium avium subsp. paratuberculosis (MAP) is thought to be one of the primary sources of infection for dairy cattle. The exact link between fecal shedding of MAP by individual cows and environmental contamination levels at the herd level was explored with a cross-sectional analysis of longitudinally collected samples on 3 dairy farms. Composite samples from multiple environmental sites in 3 commercial dairy herds in the Northeast US were cultured quarterly for MAP, providing 1131 samples (133 (11.8%) were culture-positive), and all adult animals in the herds were tested biannually by fecal culture (FC), for 6 years. Of the environmental sites sampled, manure storage areas and shared alleyways were most likely to be culture-positive. Environmental sample results were compared to FC results from either the concurrent or previous sampling date at both the herd and the pen level. At the herd level, a 1 log unit increase in average fecal shedding increased the odds of a positive non-pen environmental sample by a factor of 6 and increased the average amount of MAP in non-pen samples by 2.9 cfu/g. At the pen level, a 1 log unit increase in average fecal shedding in the pen increased the odds of a positive environment by a factor of 2.4 and the average amount of MAP was increased by 3.5 cfu/g. We were not able to model the relationship between non-pen environmental sample status and the distance between shedding animals and the samples location, and neighboring pens did not significantly affect the results of the pen-level analysis. The amount of MAP in pen-level samples and the probability of a pen testing positive for MAP were both positively but non-significantly correlated with the number of animals in the pen shedding >30 cfu/g of MAP. At least 6 environmental samples met the criteria for the U.S. Voluntary Bovine Johnes Disease Control Program on 47 of the 72 sampling dates; of these, 19 of the 47 FC-positive sampling dates were positive by the 6-sample environmental testing method, resulting in a herd sensitivity of 0.40 (95% CI: 0.26-0.54). None of the 3 FC-negative sampling dates produced positive environmental samples. Although environmental sampling can be used as a tool in understanding the level of MAP infection in a herd or pen, it did not appear to be a sensitive diagnostic method for herd positivity in these low prevalence herds, and its use may require caution.

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

The objective of this study was to investigate the potential impacts of imperfect Mycobacterium avium subsp. paratuberculosis (MAP) vaccines on the dynamics of MAP infection in US dairy herds using a mathematical modeling approach. Vaccine-based control programs have been implemented to reduce the prevalence of MAP infection in some dairy herds; however, MAP vaccines are imperfect. Vaccines can provide partial protection for susceptible calves, reduce the infectiousness of animals shedding MAP, lengthen the latent period of infected animals, slow the progression from low shedding to high shedding in infectious animals, and reduce clinical disease. To quantitatively study the impacts of imperfect MAP vaccines, we developed a deterministic multi-group vaccination model and performed global sensitivity analyses. Our results explain why MAP vaccination might have a beneficial, negligible, or detrimental effect in the reduction of prevalence and show that vaccines that are beneficial to individual animals may not be useful for a herd-level control plan. The study suggests that high efficacy vaccines that are aimed at reducing the susceptibility of the host are the most effective in controlling MAP transmission. This work indicates that MAP vaccination should be integrated into a comprehensive control program that includes test-and-cull intervention and improved calf rearing management.

Assessing the potential impact of Salmonella vaccines in an endemically infected dairy herd

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.

Economic risk analysis model for bovine viral diarrhea virus biosecurity in cow-calf herds.

Salmonella spp. in cattle contribute to bacterial foodborne disease for humans. Reduction of Salmonella prevalence in herds is important to prevent human Salmonella infections. Typical control measures are culling of infectious animals, vaccination, and improved hygiene management. Vaccines have been developed for controlling Salmonella transmission in dairy herds; however, these vaccines are imperfect and a variety of vaccine effects on susceptibility, infectiousness, Salmonella shedding level, and duration of infectious period were reported. To assess the potential impact of imperfect Salmonella vaccines on prevalence over time and the eradication criterion, we developed a deterministic compartmental model with both replacement (cohort) and lifetime (continuous) vaccination strategies, and applied it to a Salmonella Cerro infection in a dairy farm. To understand the uncertainty of prevalence and identify key model parameters, global parameter uncertainty and sensitivity analyses were performed. The results show that imperfect Salmonella vaccines reduce the prevalence of Salmonella Cerro. Among three vaccine effects that were being considered, decreasing the length of the infectious period is most effective in reducing the endemic prevalence. Analyses of contour lines of prevalence or the critical reproduction ratio illustrate that, reducing prevalence to a certain level or zero can be achieved by choosing vaccines that have either a single vaccine effect at relatively high effectiveness, or two or more vaccine effects at relatively low effectiveness. Parameter sensitivity analysis suggests that effective control measures through applying Salmonella vaccines should be adjusted at different stages of infection. In addition, lifetime (continuous) vaccination is more effective than replacement (cohort) vaccination. The potential application of the developed vaccination model to other Salmonella serotypes related to foodborne diseases was also discussed. The presented study may be used as a tool for guiding the development of Salmonella vaccines.