Intestinal infection following aerosol challenge of calves with Mycobacterium avium subspecies pa... more Intestinal infection following aerosol challenge of calves with Mycobacterium avium subspecies paratuberculosis Eisenberg et al.
ii Preface iv Acknowledgements vii Dedication ix Table of contents x List of Tables xiii List of ... more ii Preface iv Acknowledgements vii Dedication ix Table of contents x List of Tables xiii List of Figures xiv List of Abbreviations xv CHAPTER 1. GENERAL INTRODUCTION 1 1.1. Pathogenesis and stages of MAP infection 2 1.1.1. Stage I: ‘silent’ infection 3 1.1.2. Stage II: subclinical disease 4 1.1.3. Stage III: clinical disease 4 1.1.4. Stage IV: advanced clinical disease 5 1.2. Importance of age at infection and infection dose 5 1.3. Prevalence of MAP infection in dairy cattle in Canada 7 1.4. Diagnostics 9 1.4.1. MAP Culture from feces and tissues 9 1.4.2. Direct PCR on fecal samples 10 1.4.3. Detection of a humoral immune response 11 1.4.4. Detection of a cellular immune response 11 1.5. Epidemiology and control programs 13 1.6. Hypotheses 14 1.7. Objectives of the study 15 1.8. Outline of thesis 15 1.9. References 17 CHAPTER 2: EVALUATION OF AGE-DEPENDENT SUSCEPTIBILITY IN CALVES INFECTED WITH TWO DOSES OF MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS USING PATHOLOGY AND TISSUE C...
The primary objectives of paratuberculosis control programs are reducing exposure of calves to My... more The primary objectives of paratuberculosis control programs are reducing exposure of calves to Mycobacterium avium subspecies paratuberculosis (MAP), reducing herd infection pressure and regular testing of cattle >36 months of age. Although control programs based on these principles have reduced prevalence of MAP infection in dairy herds, they have generally not eliminated the infection. Recent infection trial(s) have yielded new knowledge regarding diagnostic testing and age- and dose-dependent susceptibility to MAP infection. Calves up to 1 year of age are still susceptible to MAP infection; therefore, control programs should refrain from referring to specific ages with respect to susceptibility and prevention of new infections. Notwithstanding, lesions were more severe when calves were inoculated at 2 weeks versus 1 year of age. Furthermore, a high inoculation dose resulted in more pronounced lesions than a low inoculation dose, especially in young calves. Consequently, keepin...
Fifty calves inoculated at either 2 weeks or at 3, 6, 9, or 12 months of age with either a low or... more 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.
Five calves were inoculated orally at 2 weeks of age with a dose of 5 x 10 9 colony-forming units... more Five calves were inoculated orally at 2 weeks of age with a dose of 5 x 10 9 colony-forming units of Mycobacterium avium subspecies paratuberculosis (MAP) on 2 consecutive days. Two calves developed clinical Johne's disease at 12 and 16 months of age after being consistently positive for MAP on fecal culture and antibody enzyme-linked immunosorbent assay (ELISA), starting 2 to 3 weeks and 4 to 5 months after inoculation, respectively.
Although substantial fecal shedding is expected to start years after initial infection with Mycob... more Although substantial fecal shedding is expected to start years after initial infection with Mycobacterium avium subspecies paratuberculosis (MAP), the potential for shedding by calves and therefore calf-to-calf transmission is underestimated in current Johne's disease (JD) control programs. Shedding patterns were determined in this study in experimentally infected calves. Fifty calves were challenged at 2 weeks or at 3, 6, 9 or 12 months of age (6 calves served as a control group). In each age group, 5 calves were inoculated with a low and 5 with a high dose of MAP. Fecal culture was performed monthly until necropsy at 17 months of age. Overall, 61% of inoculated calves, representing all age and dose groups, shed MAP in their feces at least once during the follow-up period. Although most calves shed sporadically, 4 calves in the 2-week and 3-month high dose groups shed at every sampling. In general, shedding peaked 2 months after inoculation. Calves inoculated at 2 weeks or 3 mo...
Veterinary immunology and immunopathology, Jan 15, 2014
The interferon-gamma (IFN-γ) release assay is considered useful for diagnosis of subclinical para... more The interferon-gamma (IFN-γ) release assay is considered useful for diagnosis of subclinical paratuberculosis. However, interpretation can be subjective and complex; therefore, additional information regarding the course of the cellular immune response and effects of age and dose at infection would be helpful. Thirty-three calves were randomly allocated to 10 challenge groups and a negative control group. Calves were inoculated orally at 2 weeks or at 3, 6, 9, or 12 months of age. Within each age group, calves received either a high or low dose of Mycobacterium avium subspecies paratuberculosis (MAP). Monthly blood samples were collected, stimulated with Purified Protein Derivative (PPD) Johnin in vitro, and the subsequent release of IFN-γ measured. Calves inoculated with a high dose had earlier and stronger IFN-γ responses than low-dose calves. Furthermore, calves inoculated at 2 weeks of age produced less IFN-γ compared to those inoculated later in life. The IFN-γ response peaked ...
The longstanding assumption that calves of more than 6 months of age are more resistant to Mycoba... more The longstanding assumption that calves of more than 6 months of age are more resistant to Mycobacterium avium subspecies paratuberculosis (MAP) infection has recently been challenged. In order to elucidate this, a challenge experiment was performed to evaluate age- and dose-dependent susceptibility to MAP infection in dairy calves. Fifty-six calves from MAP-negative dams were randomly allocated to 10 MAP challenge groups (5 animals per group) and a negative control group (6 calves). Calves were inoculated orally on 2 consecutive days at 5 ages: 2 weeks and 3, 6, 9 or 12 months. Within each age group 5 calves received either a high – or low – dose of 5 × 109 CFU or 5 × 107 CFU, respectively. All calves were euthanized at 17 months of age. Macroscopic and histological lesions were assessed and bacterial culture was done on numerous tissue samples. Within all 5 age groups, calves were successfully infected with either dose of MAP. Calves inoculated at < 6 months usually had more cu...
Intestinal infection following aerosol challenge of calves with Mycobacterium avium subspecies pa... more Intestinal infection following aerosol challenge of calves with Mycobacterium avium subspecies paratuberculosis Eisenberg et al.
ii Preface iv Acknowledgements vii Dedication ix Table of contents x List of Tables xiii List of ... more ii Preface iv Acknowledgements vii Dedication ix Table of contents x List of Tables xiii List of Figures xiv List of Abbreviations xv CHAPTER 1. GENERAL INTRODUCTION 1 1.1. Pathogenesis and stages of MAP infection 2 1.1.1. Stage I: ‘silent’ infection 3 1.1.2. Stage II: subclinical disease 4 1.1.3. Stage III: clinical disease 4 1.1.4. Stage IV: advanced clinical disease 5 1.2. Importance of age at infection and infection dose 5 1.3. Prevalence of MAP infection in dairy cattle in Canada 7 1.4. Diagnostics 9 1.4.1. MAP Culture from feces and tissues 9 1.4.2. Direct PCR on fecal samples 10 1.4.3. Detection of a humoral immune response 11 1.4.4. Detection of a cellular immune response 11 1.5. Epidemiology and control programs 13 1.6. Hypotheses 14 1.7. Objectives of the study 15 1.8. Outline of thesis 15 1.9. References 17 CHAPTER 2: EVALUATION OF AGE-DEPENDENT SUSCEPTIBILITY IN CALVES INFECTED WITH TWO DOSES OF MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS USING PATHOLOGY AND TISSUE C...
The primary objectives of paratuberculosis control programs are reducing exposure of calves to My... more The primary objectives of paratuberculosis control programs are reducing exposure of calves to Mycobacterium avium subspecies paratuberculosis (MAP), reducing herd infection pressure and regular testing of cattle >36 months of age. Although control programs based on these principles have reduced prevalence of MAP infection in dairy herds, they have generally not eliminated the infection. Recent infection trial(s) have yielded new knowledge regarding diagnostic testing and age- and dose-dependent susceptibility to MAP infection. Calves up to 1 year of age are still susceptible to MAP infection; therefore, control programs should refrain from referring to specific ages with respect to susceptibility and prevention of new infections. Notwithstanding, lesions were more severe when calves were inoculated at 2 weeks versus 1 year of age. Furthermore, a high inoculation dose resulted in more pronounced lesions than a low inoculation dose, especially in young calves. Consequently, keepin...
Fifty calves inoculated at either 2 weeks or at 3, 6, 9, or 12 months of age with either a low or... more 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.
Five calves were inoculated orally at 2 weeks of age with a dose of 5 x 10 9 colony-forming units... more Five calves were inoculated orally at 2 weeks of age with a dose of 5 x 10 9 colony-forming units of Mycobacterium avium subspecies paratuberculosis (MAP) on 2 consecutive days. Two calves developed clinical Johne's disease at 12 and 16 months of age after being consistently positive for MAP on fecal culture and antibody enzyme-linked immunosorbent assay (ELISA), starting 2 to 3 weeks and 4 to 5 months after inoculation, respectively.
Although substantial fecal shedding is expected to start years after initial infection with Mycob... more Although substantial fecal shedding is expected to start years after initial infection with Mycobacterium avium subspecies paratuberculosis (MAP), the potential for shedding by calves and therefore calf-to-calf transmission is underestimated in current Johne's disease (JD) control programs. Shedding patterns were determined in this study in experimentally infected calves. Fifty calves were challenged at 2 weeks or at 3, 6, 9 or 12 months of age (6 calves served as a control group). In each age group, 5 calves were inoculated with a low and 5 with a high dose of MAP. Fecal culture was performed monthly until necropsy at 17 months of age. Overall, 61% of inoculated calves, representing all age and dose groups, shed MAP in their feces at least once during the follow-up period. Although most calves shed sporadically, 4 calves in the 2-week and 3-month high dose groups shed at every sampling. In general, shedding peaked 2 months after inoculation. Calves inoculated at 2 weeks or 3 mo...
Veterinary immunology and immunopathology, Jan 15, 2014
The interferon-gamma (IFN-γ) release assay is considered useful for diagnosis of subclinical para... more The interferon-gamma (IFN-γ) release assay is considered useful for diagnosis of subclinical paratuberculosis. However, interpretation can be subjective and complex; therefore, additional information regarding the course of the cellular immune response and effects of age and dose at infection would be helpful. Thirty-three calves were randomly allocated to 10 challenge groups and a negative control group. Calves were inoculated orally at 2 weeks or at 3, 6, 9, or 12 months of age. Within each age group, calves received either a high or low dose of Mycobacterium avium subspecies paratuberculosis (MAP). Monthly blood samples were collected, stimulated with Purified Protein Derivative (PPD) Johnin in vitro, and the subsequent release of IFN-γ measured. Calves inoculated with a high dose had earlier and stronger IFN-γ responses than low-dose calves. Furthermore, calves inoculated at 2 weeks of age produced less IFN-γ compared to those inoculated later in life. The IFN-γ response peaked ...
The longstanding assumption that calves of more than 6 months of age are more resistant to Mycoba... more The longstanding assumption that calves of more than 6 months of age are more resistant to Mycobacterium avium subspecies paratuberculosis (MAP) infection has recently been challenged. In order to elucidate this, a challenge experiment was performed to evaluate age- and dose-dependent susceptibility to MAP infection in dairy calves. Fifty-six calves from MAP-negative dams were randomly allocated to 10 MAP challenge groups (5 animals per group) and a negative control group (6 calves). Calves were inoculated orally on 2 consecutive days at 5 ages: 2 weeks and 3, 6, 9 or 12 months. Within each age group 5 calves received either a high – or low – dose of 5 × 109 CFU or 5 × 107 CFU, respectively. All calves were euthanized at 17 months of age. Macroscopic and histological lesions were assessed and bacterial culture was done on numerous tissue samples. Within all 5 age groups, calves were successfully infected with either dose of MAP. Calves inoculated at < 6 months usually had more cu...
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