Assessment of Dietzia subsp. C79793-74 for treatment of cattle with evidence of paratuberculosis

Abstract

The objective of the present investigation was to determine whether the bacterium Dietzia subsp. C79793-74, previously shown to inhibit growth of Mycobacterium subsp. paratuberculosis under in vitro culture conditions, has therapeutic value as a probiotic for adult cattle with paratuberculosis.  Animals were obtained from several herds with evidence of disease based on seropositivity and/or fecal shedding.  Sixty-eight cows with initial evidence of Stage II or III paratuberculosis and 2 with an initial Stage IV disease were evaluated longitudinally.  Animals were either treated daily with variable, disease-dependent doses of Dietzia (n = 48) or left untreated (n = 22).  Clinical aspects of disease (diarrhea, emaciated, cachectic and appetite) were recorded until the animal recovered or required euthanasia due to advanced clinical paratuberculosis or other severe conditions.  Paratuberculosis parameters-antibody serology (ELISA, AGID) and fecal culture-were longitudinally monitored over the lifetime of each animal.  The results indicated that daily treatment with Dietzia was therapeutic for paratuberculosis cows based on: (a) longitudinal decline in ELISA values only occurred in animals that were treated; (b) prolonged survival was dependant upon treatment--the length being directly associated with low initial ELISA values; and (c) treated animals were the only ones cured of disease.  Further investigations are envisaged to determine optimal, long-term dosages that may result in even better therapeutic outcomes as well as to evaluate potential application for therapy of the Johne's disease, human-counterpart, Crohn's disease.

Acknowledgements

This research was funded, in part, by NIH Grant R01AI027331, by Altick Associates, River Falls, WI., and by Paralab, LLC, Eau Claire, WI. We wish to thank William D. Richards for the initial ICON 6 isolate (Dietzia).

Conflict of interest

Both authors are members of Paralab, LLC, which is the assignee of a patent application covering the Dietzia technology presented in this paper, and R.E.C. is a partner in Altick, Associates.

Figures and Tables

Figure 1 Comparison of longitudinal changes in fecal MAP at different doses of Dietzia for cows, R100, Green-4 and Green-1, all initially positive for AGID and all possessing initially high ELISA and MAP values. Solid red line is Dietzia dose and dashed blue line is fecal MAP. (A) Cow, R100. (B) Cow, Green-4. (C) Cow, Green-1.

Figure 2 Longitudinal changes in ELISA values and fecal MAP at different doses of Dietzia for paratuberculosis cows, F16, 1734 and N52, each initially negative for AGID and fecal shedding. (A and B) cow F16. (A) Solid line is ELISA values (best-fit is thin solid line) and dashed line is fecal MAP. Symbol (+) signifies ELISA value was also positive for AGID. (C and D) cows N52 and 1734. Solid lines are ELISA values (best-fit is thin solid line) and dashed lines are fecal MAP. (B and D) Dietzia dose in cfu.

Figure 3 ELISA values of each animal are shown by a specific color (best-fit is thin solid line). Symbol (+) signifies ELISA was also positive for AGID.

Figure 4 Comparison of longitudinal changes in ELISA values for paratuberculosis cows treated with Dietzia. (A) Rapid increases. (B) Moderate increases. (C) Rapid decreases. (D) Moderate decreases. Data for each cow is shown by a specific color.

Figure 5 Kaplan-Meier survival estimates of ELISA-negative and paratuberculosis positive animals. Except for paratuberculosis-free and non-treated paratuberculosis positive animals, survival of treated animals were divided into subgroups (OD intervals of 0.5) based on their initial ELISA values.

Table 1 Parameters of non-treated paratuberculosis cows

Table 2 Parameters of dietzia treated paratuberculosis cows