Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus ... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in humans, has a broad host range, and is able to infect domestic and wild animal species. Notably, white-tailed deer (WTD, Odocoileus virginianus), the most widely distributed cervid species in the Americas, were shown to be highly susceptible to SARS-CoV-2 in challenge studies and reported natural infection rates approaching 40% in free-ranging WTD in the U.S. Thus, understanding the infection and transmission dynamics of SARS-CoV-2 in WTD is critical to prevent future zoonotic transmission to humans and for implementation of effective disease control measures. Here, we demonstrated that following intranasal inoculation with SARS-CoV-2, WTD fawns shed infectious virus up to day 5 post-inoculation (pi), with high viral loads shed in nasal and oral secretions. This resulted in efficient deer-to-deer transmission on day 3 pi. Consistent a with lack of infectious SA...
Supplemental Material, DS1_VET_10.1177_0300985819833454 for Early Pulmonary Lesions in Cattle Inf... more Supplemental Material, DS1_VET_10.1177_0300985819833454 for Early Pulmonary Lesions in Cattle Infected via Aerosolized <i>Mycobacterium bovis</i> by Mitchell V. Palmer, Jayne Wiarda, Carly Kanipe, and Tyler C. Thacker in Veterinary Pathology
The bovine tuberculoid granuloma is the hallmark lesion of bovine tuberculosis (bTB) due to Mycob... more The bovine tuberculoid granuloma is the hallmark lesion of bovine tuberculosis (bTB) due to Mycobacterium bovis infection. The pathogenesis of bTB, and thereby the process of bovine tuberculoid granuloma development, involves the recruitment, activation, and maintenance of cells under the influence of antigen, cytokines and chemokines in affected lungs and regional lymph nodes. The granuloma is key to successful control of bTB by preventing pathogen dissemination through containment by cellular and fibrotic layers. Paradoxically, however, it may also provide a niche for bacterial replication. The morphologic and cellular characteristics of granulomas have been used to gauge disease severity in bTB pathogenesis and vaccine efficacy studies. As such, it is critical to understand the complex mechanisms behind granuloma initiation, development, and maintenance.
Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major ... more Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major economic burden associated with production losses and a public health concern due to its zoonotic nature. As with other intracellular pathogens, cell-mediated immunity plays an important role in the control of infection. Characterization of such responses is important for understanding the immune status of the host, and to identify mechanisms of protective immunity or immunopathology. This type of information can be important in the development of vaccination strategies, diagnostic assays, and in predicting protection or disease progression. However, the frequency of circulating M. bovis-specific T cells are often low, making the analysis of such responses difficult. As previously demonstrated in a different cattle infection model, antigenic expansion allows us to increase the frequency of antigen-specific T cells. Moreover, the concurrent assessment of cytokine production and proliferat...
While Mycobacterium tuberculosis is the primary cause of tuberculosis in people, multiple other m... more While Mycobacterium tuberculosis is the primary cause of tuberculosis in people, multiple other mycobacteria are capable of doing so. With the World Health Organization's goal of a 90% reduction in tuberculosis by 2035, all tuberculous mycobacteria need to be addressed. Understanding not only the similarities, but importantly the differences between the different species is crucial if eradication is ever to be achieved. Mycobacterium bovis, while typically thought of as a disease of cattle, remains a possible source of human infection worldwide. Although this species' genome differs from Mycobacterium tuberculosis by only 0.05%, significant differences are present, creating unique challenges to address. This review focuses on features which distinguish this bacterium from Mycobacterium tuberculosis, including differences in origin, structure, environmental persistence, host preferences, infection and disease, host immune response, diagnostics and treatment.
Mycobacterium bovis is the cause of tuberculosis in most animals, most notably cattle. The stereo... more Mycobacterium bovis is the cause of tuberculosis in most animals, most notably cattle. The stereotypical lesion of bovine tuberculosis is the granuloma; a distinct morphological lesion where host and pathogen interact and disease outcome (i.e., dissemination, confinement, or resolution) is determined. Accordingly, it is critical to understand host-pathogen interactions at the granuloma level. Host-pathogen interactions within individual granulomas at different stages of disease have not been examined in cattle. We examined bacterial burden and cytokine expression in individual pulmonary granulomas from steers at 30, 90, 180, and 270 days after experimental aerosol infection with M. bovis. Bacterial burdens within individual granulomas examined 30 days after infection were greater and more heterogenous (variable) than those examined 90 to 270 days after infection. Bacterial burdens did not correlate with expression of IFN-γ, TNF-α, TGF-β, granuloma stage, or lung lesion score, althou...
Fading elk syndrome, or chronic ill-thrift of elk, is a disease associated with abomasal parasiti... more Fading elk syndrome, or chronic ill-thrift of elk, is a disease associated with abomasal parasitism with Ostertagia species, of which elk appear to be particularly susceptible. While this syndrome has been extensively reported to affect wapiti-type red deer hybrids farmed in New Zealand since the mid 1980's, there is only a single report of this disease in North America. Here, we report a case of fading elk syndrome in a herd of 34 elk (Cervus elaphus) in Ames, Iowa, at the National Animal Disease Center. Analysis of complete blood counts were unremarkable, but blood chemistry demonstrated a severe hypoalbuminemia. Fecal floatations were also unremarkable, and non-diagnostic. Histological examination of tissues collected at necropsy revealed proliferative abomasitis and nematodes consistent with Ostertagia spp. Anthelmintic treatment consisting of a combination of pour-on Cydectin ® and injectable Noromectin Plus ® , at double the recommended dose for cattle, showed positive results, as all remaining animals in the herd recovered. The work presented here is the first report of naturally-acquired disease in a herd of captive elk used for research and sheds light on this seldomly-reported disease in North America.
To assess the effects of challenge dose and stage of gestation on infection and abortion, 35 elk ... more To assess the effects of challenge dose and stage of gestation on infection and abortion, 35 elk were conjunctivally challenged with virulent Brucella abortus strain 2308 (S2308) during pregnancy. Seventeen elk were experimentally challenged early in the second trimester of gestation (December) with high (approximately 108 CFU) or low challenge (approximately 107 CFU) treatments having 8 and 9 pregnant elk, respectively. Other pregnant elk were experimentally challenged at a later challenge time (approximately early third trimester, February), with high and low challenge treatments having 8 and 10 elk, respectively. Conjunctival swabs from all animals were culture positive for the S2308 strain at 7 days after experimental challenge. All animals seroconverted on a B. abortus ELISA but optical density readings were not influenced (P > 0.05) by time of challenge or by challenge dosage. In the early challenge group, abortions occurred in 2 of 9 (22%) in the low challenge treatment and 3 of 8 (37%) in the high challenge treatment, whereas in the later challenge group, 1 of 8 (12.5%) in the low challenge treatment and 2 of 10 (20%) in the high challenge treatment aborted. The ability to recover B. abortus from samples obtained at necropsy did not differ (P > 0.05) between early and late challenges or between high and low challenge treatments. Despite the lack of abortions observed after experimental challenge, recovery from maternal tissues ranged from 50% (low dose, late challenge) to 77% (low dose, early challenge). Our data suggests that naïve elk do not abort as frequently after experimental infection with B. abortus strain 2308 as compared to similar data in cattle and bison.
Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycoba... more Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and 'omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts. Larsen et al.
Whole blood based assays, particularly interferon gamma (IFN-γ) release assays (IGRAs), are used ... more Whole blood based assays, particularly interferon gamma (IFN-γ) release assays (IGRAs), are used for the diagnosis of both bovine and human tuberculosis (TB). The aim of the current study was to evaluate a panel of cytokines and chemokines for potential use as diagnostic readouts indicative of Mycobacterium bovis (M. bovis) infection in cattle. A gene expression assay was used to determine the kinetics of the response to M. bovis purified protein derivative and a fusion protein consisting of ESAT-6, CFP10, and Rv3615c upon aerosol infection with ∼10 4 cfu of M. bovis. The panel of biomarkers included: IFN-γ, CXCL9, CXCL10, CCL2, CCL3, TNF-α, IL-1α, IL-1β, IL-1Ra, IL-22, IL-21 and IL-13. Protein levels of IFN-γ, CXCL9, and CXCL10 were determined by ELISA. Findings suggest that CXCL9, CXCL10, IL-21, IL-13, and several acute phase cytokines may be worth pursuing as diagnostic biomarkers of M. bovis infection in cattle.
Journal of Veterinary Diagnostic Investigation, 2019
Paratuberculosis (Johne’s disease) is caused by Mycobacterium avium ssp. paratuberculosis (MAP), ... more Paratuberculosis (Johne’s disease) is caused by Mycobacterium avium ssp. paratuberculosis (MAP), and affects both domestic and wild ruminants, including cattle, goats, sheep, and deer. In cattle, most infections occur during calfhood followed by a prolonged incubation period of 1–2 y or more before cows shed culturable numbers of MAP bacilli in their feces. As disease progresses, infected animals develop protein-losing enteropathy, intractable diarrhea, and weight loss. In a cohort of 32 clinically normal deer from a herd with a history of periodic clinical paratuberculosis, we found that subclinical infection was characterized by high rates of infection, common involvement of mesenteric lymph nodes, minimal lesion formation, few intralesional acid-fast bacilli, and low-level fecal shedding of MAP. The characteristics of subclinical paratuberculosis in white-tailed deer resemble those of cattle and red deer, although microscopic lesions were less common in subclinical deer than repo...
Brucellosis is a bacterial zoonosis and a significant source of economic loss and a major public ... more Brucellosis is a bacterial zoonosis and a significant source of economic loss and a major public health concern, worldwide. Bovine brucellosis, as caused primarily by Brucella abortus, is an important cause of reproductive loss in cattle. Vaccination has been the most effective way to reduce disease prevalence contributing to the success of control and eradication programs. Currently, there are no human vaccines available, and despite the success of commercial vaccines for livestock, such as B. abortus strain RB51 (RB51), there is need for development of novel and safer vaccines against brucellosis. In the current study, we report the fabrication of and immune responses to an implantable single dose polyanhydride-based, methanol-killed RB51 antigen containing delivery platform (VPEAR) in cattle. In contrast to animals vaccinated with RB51, we did not observe measurable RB51-specific IFNγ or IgG responses in the peripheral blood, following initial vaccination with VPEAR. However, following a subsequent booster vaccination with RB51, we observed an anamnestic response in both vaccination treatments (VPEAR and live RB51). The magnitude and kinetics of CD4þ IFN-γ-mediated responses and circulating memory T cell subpopulations were comparable between the two vaccination treatments. Additionally, IgG titers were significantly increased in animals vaccinated with VPEAR as compared to live RB51-vaccinated animals. These data demonstrate that killed antigen may be utilized to generate and sustain memory, IFN-γ-mediated, CD4þ T cell and humoral responses against Brucella in a natural host. To our knowledge, this novel approach to vaccination against intracellular bacteria, such as Brucella, has not been reported before.
Mycobacterium bovis is a serious zoonotic pathogen and the cause of tuberculosis in many mammalia... more Mycobacterium bovis is a serious zoonotic pathogen and the cause of tuberculosis in many mammalian species, most notably, cattle. The hallmark lesion of tuberculosis is the granuloma. It is within the developing granuloma where host and pathogen interact; therefore, it is critical to understand host-pathogen interactions at the granuloma level. Cytokines and chemokines drive cell recruitment, activity, and function and ultimately determine the success or failure of the host to control infection. In calves, early lesions (ie, 15 and 30 days) after experimental aerosol infection were examined microscopically using in situ hybridization and immunohistochemistry to demonstrate early infiltrates of CD68+ macrophages within alveoli and alveolar interstitium, as well as the presence of CD4, CD8, and γδ T cells. Unlike lesions at 15 days, lesions at 30 days after infection contained small foci of necrosis among infiltrates of macrophages, lymphocytes, neutrophils, and multinucleated giant c...
Mycoplasma bovis, a frequent contributor to polymicrobial respiratory disease in cattle, has rece... more Mycoplasma bovis, a frequent contributor to polymicrobial respiratory disease in cattle, has recently emerged as a major health problem in North American bison. Strong circumstantial evidence suggests it can be the sole pathogen causing disease manifestations in outbreaks of mortality in bison, but direct evidence is lacking. The goal of this study was to compare clinical signs and lesions in bison and cattle experimentally infected with field isolates of M. bovis recovered from bison. Bison (n = 7) and cattle (n = 6), seronegative for anti-M. bovis IgG, were exposed intranasally to M. bovis and necropsied 4-6 weeks later. Blood and nasal swabs were collected on day 0 (before exposure), day 11 and at necropsy. Samples of lung, lymph node, liver and spleen were also collected at necropsy. The only clinical sign observed was an elevation in the core body temperature of bison during the first few weeks post-exposure. Grossly visible lesions were apparent at necropsy in the lungs of fiv...
To report the successful surgical treatment of a comminuted left acetabular fracture, a dorsally ... more To report the successful surgical treatment of a comminuted left acetabular fracture, a dorsally luxated left femoral head, and avulsion of the ligament of the femoral head by femoral head ostectomy (FHO) and physical therapy in a companion Potbelly pig. Case report. A 1-year-old, 13 kg, castrated male, companion Potbelly pig. The pig presented with a nonweight bearing left pelvic limb lameness of 3 weeks' duration that was noticed shortly after the pig got caught under a fence. Under general anesthesia a lateral approach was made to the fractured limb. A FHO was performed as described for dogs. Following surgery, a period of physical therapy was initiated based on protocols described for dogs. The canine surgical procedure with the approach modified for pigs was successfully performed in our pig. Following surgery, the pig was comfortable and weight bearing. A physical therapy regimen of supervised activity, stairs, and water therapy was used to rehabilitate the leg, as well as...
Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infecte... more Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex (MTC) pathogen, Mycobacterium mungi. We evaluated gross and histologic lesions in 62 infected mongooses (1999-2017). Many tissues contained multifocal irregular, lymphohistiocytic to granulomatous infiltrates and/or multifocal or coalescing noncaseating to caseating granulomas with variable numbers of intralesional acid-fast bacilli. Over one-third of nasal turbinates examined had submucosal lymphohistiocytic to granulomatous infiltrates, erosion and ulceration of the nasal mucosa, bony remodeling, and nasal distortion. Similar inflammatory cell infiltrates expanded the dermis of the nasal planum with frequent ulceration. However, even in cases with intact epidermis, acid-fast bacilli were present in variable numbers among dermal infiltrates and on the epidermal surface among desquamated cells and debris, most commonly in small crevices o...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus ... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in humans, has a broad host range, and is able to infect domestic and wild animal species. Notably, white-tailed deer (WTD, Odocoileus virginianus), the most widely distributed cervid species in the Americas, were shown to be highly susceptible to SARS-CoV-2 in challenge studies and reported natural infection rates approaching 40% in free-ranging WTD in the U.S. Thus, understanding the infection and transmission dynamics of SARS-CoV-2 in WTD is critical to prevent future zoonotic transmission to humans and for implementation of effective disease control measures. Here, we demonstrated that following intranasal inoculation with SARS-CoV-2, WTD fawns shed infectious virus up to day 5 post-inoculation (pi), with high viral loads shed in nasal and oral secretions. This resulted in efficient deer-to-deer transmission on day 3 pi. Consistent a with lack of infectious SA...
Supplemental Material, DS1_VET_10.1177_0300985819833454 for Early Pulmonary Lesions in Cattle Inf... more Supplemental Material, DS1_VET_10.1177_0300985819833454 for Early Pulmonary Lesions in Cattle Infected via Aerosolized <i>Mycobacterium bovis</i> by Mitchell V. Palmer, Jayne Wiarda, Carly Kanipe, and Tyler C. Thacker in Veterinary Pathology
The bovine tuberculoid granuloma is the hallmark lesion of bovine tuberculosis (bTB) due to Mycob... more The bovine tuberculoid granuloma is the hallmark lesion of bovine tuberculosis (bTB) due to Mycobacterium bovis infection. The pathogenesis of bTB, and thereby the process of bovine tuberculoid granuloma development, involves the recruitment, activation, and maintenance of cells under the influence of antigen, cytokines and chemokines in affected lungs and regional lymph nodes. The granuloma is key to successful control of bTB by preventing pathogen dissemination through containment by cellular and fibrotic layers. Paradoxically, however, it may also provide a niche for bacterial replication. The morphologic and cellular characteristics of granulomas have been used to gauge disease severity in bTB pathogenesis and vaccine efficacy studies. As such, it is critical to understand the complex mechanisms behind granuloma initiation, development, and maintenance.
Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major ... more Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major economic burden associated with production losses and a public health concern due to its zoonotic nature. As with other intracellular pathogens, cell-mediated immunity plays an important role in the control of infection. Characterization of such responses is important for understanding the immune status of the host, and to identify mechanisms of protective immunity or immunopathology. This type of information can be important in the development of vaccination strategies, diagnostic assays, and in predicting protection or disease progression. However, the frequency of circulating M. bovis-specific T cells are often low, making the analysis of such responses difficult. As previously demonstrated in a different cattle infection model, antigenic expansion allows us to increase the frequency of antigen-specific T cells. Moreover, the concurrent assessment of cytokine production and proliferat...
While Mycobacterium tuberculosis is the primary cause of tuberculosis in people, multiple other m... more While Mycobacterium tuberculosis is the primary cause of tuberculosis in people, multiple other mycobacteria are capable of doing so. With the World Health Organization's goal of a 90% reduction in tuberculosis by 2035, all tuberculous mycobacteria need to be addressed. Understanding not only the similarities, but importantly the differences between the different species is crucial if eradication is ever to be achieved. Mycobacterium bovis, while typically thought of as a disease of cattle, remains a possible source of human infection worldwide. Although this species' genome differs from Mycobacterium tuberculosis by only 0.05%, significant differences are present, creating unique challenges to address. This review focuses on features which distinguish this bacterium from Mycobacterium tuberculosis, including differences in origin, structure, environmental persistence, host preferences, infection and disease, host immune response, diagnostics and treatment.
Mycobacterium bovis is the cause of tuberculosis in most animals, most notably cattle. The stereo... more Mycobacterium bovis is the cause of tuberculosis in most animals, most notably cattle. The stereotypical lesion of bovine tuberculosis is the granuloma; a distinct morphological lesion where host and pathogen interact and disease outcome (i.e., dissemination, confinement, or resolution) is determined. Accordingly, it is critical to understand host-pathogen interactions at the granuloma level. Host-pathogen interactions within individual granulomas at different stages of disease have not been examined in cattle. We examined bacterial burden and cytokine expression in individual pulmonary granulomas from steers at 30, 90, 180, and 270 days after experimental aerosol infection with M. bovis. Bacterial burdens within individual granulomas examined 30 days after infection were greater and more heterogenous (variable) than those examined 90 to 270 days after infection. Bacterial burdens did not correlate with expression of IFN-γ, TNF-α, TGF-β, granuloma stage, or lung lesion score, althou...
Fading elk syndrome, or chronic ill-thrift of elk, is a disease associated with abomasal parasiti... more Fading elk syndrome, or chronic ill-thrift of elk, is a disease associated with abomasal parasitism with Ostertagia species, of which elk appear to be particularly susceptible. While this syndrome has been extensively reported to affect wapiti-type red deer hybrids farmed in New Zealand since the mid 1980's, there is only a single report of this disease in North America. Here, we report a case of fading elk syndrome in a herd of 34 elk (Cervus elaphus) in Ames, Iowa, at the National Animal Disease Center. Analysis of complete blood counts were unremarkable, but blood chemistry demonstrated a severe hypoalbuminemia. Fecal floatations were also unremarkable, and non-diagnostic. Histological examination of tissues collected at necropsy revealed proliferative abomasitis and nematodes consistent with Ostertagia spp. Anthelmintic treatment consisting of a combination of pour-on Cydectin ® and injectable Noromectin Plus ® , at double the recommended dose for cattle, showed positive results, as all remaining animals in the herd recovered. The work presented here is the first report of naturally-acquired disease in a herd of captive elk used for research and sheds light on this seldomly-reported disease in North America.
To assess the effects of challenge dose and stage of gestation on infection and abortion, 35 elk ... more To assess the effects of challenge dose and stage of gestation on infection and abortion, 35 elk were conjunctivally challenged with virulent Brucella abortus strain 2308 (S2308) during pregnancy. Seventeen elk were experimentally challenged early in the second trimester of gestation (December) with high (approximately 108 CFU) or low challenge (approximately 107 CFU) treatments having 8 and 9 pregnant elk, respectively. Other pregnant elk were experimentally challenged at a later challenge time (approximately early third trimester, February), with high and low challenge treatments having 8 and 10 elk, respectively. Conjunctival swabs from all animals were culture positive for the S2308 strain at 7 days after experimental challenge. All animals seroconverted on a B. abortus ELISA but optical density readings were not influenced (P > 0.05) by time of challenge or by challenge dosage. In the early challenge group, abortions occurred in 2 of 9 (22%) in the low challenge treatment and 3 of 8 (37%) in the high challenge treatment, whereas in the later challenge group, 1 of 8 (12.5%) in the low challenge treatment and 2 of 10 (20%) in the high challenge treatment aborted. The ability to recover B. abortus from samples obtained at necropsy did not differ (P > 0.05) between early and late challenges or between high and low challenge treatments. Despite the lack of abortions observed after experimental challenge, recovery from maternal tissues ranged from 50% (low dose, late challenge) to 77% (low dose, early challenge). Our data suggests that naïve elk do not abort as frequently after experimental infection with B. abortus strain 2308 as compared to similar data in cattle and bison.
Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycoba... more Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and 'omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts. Larsen et al.
Whole blood based assays, particularly interferon gamma (IFN-γ) release assays (IGRAs), are used ... more Whole blood based assays, particularly interferon gamma (IFN-γ) release assays (IGRAs), are used for the diagnosis of both bovine and human tuberculosis (TB). The aim of the current study was to evaluate a panel of cytokines and chemokines for potential use as diagnostic readouts indicative of Mycobacterium bovis (M. bovis) infection in cattle. A gene expression assay was used to determine the kinetics of the response to M. bovis purified protein derivative and a fusion protein consisting of ESAT-6, CFP10, and Rv3615c upon aerosol infection with ∼10 4 cfu of M. bovis. The panel of biomarkers included: IFN-γ, CXCL9, CXCL10, CCL2, CCL3, TNF-α, IL-1α, IL-1β, IL-1Ra, IL-22, IL-21 and IL-13. Protein levels of IFN-γ, CXCL9, and CXCL10 were determined by ELISA. Findings suggest that CXCL9, CXCL10, IL-21, IL-13, and several acute phase cytokines may be worth pursuing as diagnostic biomarkers of M. bovis infection in cattle.
Journal of Veterinary Diagnostic Investigation, 2019
Paratuberculosis (Johne’s disease) is caused by Mycobacterium avium ssp. paratuberculosis (MAP), ... more Paratuberculosis (Johne’s disease) is caused by Mycobacterium avium ssp. paratuberculosis (MAP), and affects both domestic and wild ruminants, including cattle, goats, sheep, and deer. In cattle, most infections occur during calfhood followed by a prolonged incubation period of 1–2 y or more before cows shed culturable numbers of MAP bacilli in their feces. As disease progresses, infected animals develop protein-losing enteropathy, intractable diarrhea, and weight loss. In a cohort of 32 clinically normal deer from a herd with a history of periodic clinical paratuberculosis, we found that subclinical infection was characterized by high rates of infection, common involvement of mesenteric lymph nodes, minimal lesion formation, few intralesional acid-fast bacilli, and low-level fecal shedding of MAP. The characteristics of subclinical paratuberculosis in white-tailed deer resemble those of cattle and red deer, although microscopic lesions were less common in subclinical deer than repo...
Brucellosis is a bacterial zoonosis and a significant source of economic loss and a major public ... more Brucellosis is a bacterial zoonosis and a significant source of economic loss and a major public health concern, worldwide. Bovine brucellosis, as caused primarily by Brucella abortus, is an important cause of reproductive loss in cattle. Vaccination has been the most effective way to reduce disease prevalence contributing to the success of control and eradication programs. Currently, there are no human vaccines available, and despite the success of commercial vaccines for livestock, such as B. abortus strain RB51 (RB51), there is need for development of novel and safer vaccines against brucellosis. In the current study, we report the fabrication of and immune responses to an implantable single dose polyanhydride-based, methanol-killed RB51 antigen containing delivery platform (VPEAR) in cattle. In contrast to animals vaccinated with RB51, we did not observe measurable RB51-specific IFNγ or IgG responses in the peripheral blood, following initial vaccination with VPEAR. However, following a subsequent booster vaccination with RB51, we observed an anamnestic response in both vaccination treatments (VPEAR and live RB51). The magnitude and kinetics of CD4þ IFN-γ-mediated responses and circulating memory T cell subpopulations were comparable between the two vaccination treatments. Additionally, IgG titers were significantly increased in animals vaccinated with VPEAR as compared to live RB51-vaccinated animals. These data demonstrate that killed antigen may be utilized to generate and sustain memory, IFN-γ-mediated, CD4þ T cell and humoral responses against Brucella in a natural host. To our knowledge, this novel approach to vaccination against intracellular bacteria, such as Brucella, has not been reported before.
Mycobacterium bovis is a serious zoonotic pathogen and the cause of tuberculosis in many mammalia... more Mycobacterium bovis is a serious zoonotic pathogen and the cause of tuberculosis in many mammalian species, most notably, cattle. The hallmark lesion of tuberculosis is the granuloma. It is within the developing granuloma where host and pathogen interact; therefore, it is critical to understand host-pathogen interactions at the granuloma level. Cytokines and chemokines drive cell recruitment, activity, and function and ultimately determine the success or failure of the host to control infection. In calves, early lesions (ie, 15 and 30 days) after experimental aerosol infection were examined microscopically using in situ hybridization and immunohistochemistry to demonstrate early infiltrates of CD68+ macrophages within alveoli and alveolar interstitium, as well as the presence of CD4, CD8, and γδ T cells. Unlike lesions at 15 days, lesions at 30 days after infection contained small foci of necrosis among infiltrates of macrophages, lymphocytes, neutrophils, and multinucleated giant c...
Mycoplasma bovis, a frequent contributor to polymicrobial respiratory disease in cattle, has rece... more Mycoplasma bovis, a frequent contributor to polymicrobial respiratory disease in cattle, has recently emerged as a major health problem in North American bison. Strong circumstantial evidence suggests it can be the sole pathogen causing disease manifestations in outbreaks of mortality in bison, but direct evidence is lacking. The goal of this study was to compare clinical signs and lesions in bison and cattle experimentally infected with field isolates of M. bovis recovered from bison. Bison (n = 7) and cattle (n = 6), seronegative for anti-M. bovis IgG, were exposed intranasally to M. bovis and necropsied 4-6 weeks later. Blood and nasal swabs were collected on day 0 (before exposure), day 11 and at necropsy. Samples of lung, lymph node, liver and spleen were also collected at necropsy. The only clinical sign observed was an elevation in the core body temperature of bison during the first few weeks post-exposure. Grossly visible lesions were apparent at necropsy in the lungs of fiv...
To report the successful surgical treatment of a comminuted left acetabular fracture, a dorsally ... more To report the successful surgical treatment of a comminuted left acetabular fracture, a dorsally luxated left femoral head, and avulsion of the ligament of the femoral head by femoral head ostectomy (FHO) and physical therapy in a companion Potbelly pig. Case report. A 1-year-old, 13 kg, castrated male, companion Potbelly pig. The pig presented with a nonweight bearing left pelvic limb lameness of 3 weeks' duration that was noticed shortly after the pig got caught under a fence. Under general anesthesia a lateral approach was made to the fractured limb. A FHO was performed as described for dogs. Following surgery, a period of physical therapy was initiated based on protocols described for dogs. The canine surgical procedure with the approach modified for pigs was successfully performed in our pig. Following surgery, the pig was comfortable and weight bearing. A physical therapy regimen of supervised activity, stairs, and water therapy was used to rehabilitate the leg, as well as...
Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infecte... more Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex (MTC) pathogen, Mycobacterium mungi. We evaluated gross and histologic lesions in 62 infected mongooses (1999-2017). Many tissues contained multifocal irregular, lymphohistiocytic to granulomatous infiltrates and/or multifocal or coalescing noncaseating to caseating granulomas with variable numbers of intralesional acid-fast bacilli. Over one-third of nasal turbinates examined had submucosal lymphohistiocytic to granulomatous infiltrates, erosion and ulceration of the nasal mucosa, bony remodeling, and nasal distortion. Similar inflammatory cell infiltrates expanded the dermis of the nasal planum with frequent ulceration. However, even in cases with intact epidermis, acid-fast bacilli were present in variable numbers among dermal infiltrates and on the epidermal surface among desquamated cells and debris, most commonly in small crevices o...
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