Elsevier

Journal of Theoretical Biology

Volume 254, Issue 1, 7 September 2008, Pages 135-146
Journal of Theoretical Biology

The importance of culling in Johne's disease control

https://doi.org/10.1016/j.jtbi.2008.05.008Get rights and content

Abstract

Johne's 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 R0. 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 R0, 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.

Introduction

Johne's disease is a chronic, progressive, and infectious intestinal disease caused by infection with Mycobacterium avium subsp. paratuberculosis (MAP). MAP spreads in herds primarily through fecal–oral transmission (Clarke, 1997), contaminated water and soils, in utero transmission, and infected milk and colostrum (Streeter et al., 1995). The typical symptoms of Johne's disease in cattle include reduced milk production, weight loss despite a normal appetite, and, in advanced cases, chronic diarrhea. There is no treatment available at present (National Research Council of the National Academies, 2003).

Johne's disease is globally widespread, and is currently among of the most important infectious disease of domestic ruminants in modern agricultural systems (NAHMS, 1997). Johne's disease is especially important to the dairy industry, due to the impact of the disease on milk production. It has been estimated to cost US dairy producers more than $200 million each year (Ott et al., 1999). Thus, MAP control is an important economic consideration for dairy producers.

In addition to the economic impact, a potential causative link between MAP and a chronic intestinal disease of humans, Crohn's disease, is being investigated (Collins, 1997, Feller et al., 2007, Mpofu et al., 2007, Behr and Kapur, 2008). As MAP is secreted in the milk of infected cattle and is highly prevalent in the US dairy industry, control of MAP transmission may be an important issue from a public health perspective.

Control of MAP spreading within and across herds is difficult, however, as Johne's disease has a long incubation period, and MAP can survive in the environment for a year or more (Whittington et al., 2004). In cattle, infection by MAP occurs at an early age (<1 year), and infected animals typically start to shed MAP several years after initial infection. When animals begin to shed MAP, generally as adults, the amount of the pathogen that is shed gradually increases. Clinical signs of Johne's disease only develop months to years after shedding of MAP starts (Whitlock et al., 2000).

To control the spread of MAP, test-based culling intervention is typically recommended. Current diagnostic tests, such as fecal culture test, fecal polymerase chain reaction (PCR) test, and enzyme-linked immunosorbent assay (ELISA) have high test sensitivities for detecting infectious animals shedding high levels of MAP, but relatively low test sensitivities for detecting infectious animals shedding low levels of MAP (Whitlock et al., 2000, Whitlock et al., 2007, Collins, 2005, Collins et al., 2006). A general practice on many dairy farms is to immediately cull animals shedding high levels of MAP, as they are considered to be a greater risk for spreading MAP. For animals shedding low levels of MAP, culling is generally delayed or not done at all; culling low shedding animals may be more costly to the herd than the infections they cause (Dorshorst et al., 2006).

In addition to culling of infectious animals, changes to management practices can reduce the transmission rates due to direct contacts between the susceptible and infectious animals. In the present study, we consider good and poor herd management as two extremes of a wide spectrum. Poor management signifies a failure to control the physical spread of MAP organisms between animal groups. This commonly includes using pooled colostrum for calves and poorly cleaned and/or shared calving pens. Good management involves cleaning calving pens between usage, housing calves separate from cows, and individual housing of calves (Nielsen and Toft, 2007). On real-life dairy farms, the implementation of these management procedures will vary and a wide range in good and poor managements may be observed. The goal of our research is to study the impact of culling strategies over the full range of observed management strategies.

The work presented here focuses on the efficacy of test-based culling strategies for MAP control in US dairy herds. First, we quantified the effect of MAP control by using the concept of the basic reproduction ratio R0. The expression of R0 was derived from a mathematical model which we developed and published earlier for studying infection dynamics of MAP on US dairy herds (Mitchell et al., 2008). We applied a phase diagram approach to determine the effectiveness of test-and-cull strategies for good and poor herd managements (low- and high-transmission rates, respectively). Second, we derived the average detection time for infectious animals and described culling rates in terms of test characteristics such as test sensitivity, test turnaround time, and producer decisions such as testing interval and delayed culling. The effects of different test strategies and culling decisions for low shedding animals, based on the fecal culture test, were directly addressed. Third, we performed global uncertainty analysis (UA) and sensitivity analysis (SA) to understand the overall effect of all model parameters on R0. Fourth, we evaluated the impact of culling of only high shedding animals on MAP control by comparing three test methods (fecal culture, fecal PCR, and ELISA).

Section snippets

Model description

Mathematical models of Johne's disease have been developed to study infection dynamics on dairy farms (Collins and Morgan, 1992, Groenendaal and Galligan, 1999, Beyerbach et al., 2001, Groenendaal et al., 2003, Kudahl et al., 2007). We used the mathematical model proposed by Mitchell et al. (2008) for US dairy herds. In this model (Fig. 1), all animals are classified into six compartments according to their infection status: susceptible animals (X1), animals resistant to MAP infection due to

Phase diagrams of R0 for farms with good and poor management

Phase diagrams of R0 provide an overview to evaluate the effectiveness of culling strategies for MAP control (Anderson and May, 1999, Hethcote, 2000). In Figs. 3(a) and (b), the phase plane is defined as the culling plane formed by culling rates δ1 and δ2. The critical curve R0(δ1,δ2)=1 divides the culling plane into two regions, disease free (R0<1), and endemic equilibrium (R0>1). The constraint culling rates δ1=0.5 and δ2=0.85, for low and high shedders, respectively, were calculated by

Conclusions

The results given in this work, based on the simple mathematical model for US dairy herds, show that for farms with good management, culling of only high shedding animals is effective in controlling MAP transmission, but for farms with poor management, in addition to immediate culling of high shedding animals, culling of low shedding animals (based on the results of the fecal culture test), is necessary. Culling of low shedding animals is more efficient than that of high shedding animals to

Acknowledgments

This work was supported by USDA-CSREES/2004-35605-14243, Johne's Disease Integrated Program in Research, Education and Extension, and by USDA-ARS under the Regional Dairy Quality Management Alliance (RDQMA) Specific Cooperative Agreement. We thank Robert H. Whitlock, Cristina Lanzas, Renata Ivanek, Abani Pradhan, and Patrick Ayscue for helpful discussions and suggestions.

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