Cattle are an important reservoir of Escherichia coli O157:H7 leading to contamination of food an... more Cattle are an important reservoir of Escherichia coli O157:H7 leading to contamination of food and water, and subsequent human disease. This pathogen colonizes its hosts by producing several proteins such as Tir and EspA that are secreted by a type III secretion system. These proteins play a role in colonization of the intestine, suggesting that they might be useful targets for the development of a vaccine to reduce levels of this organism in cattle. Vaccination of cattle with proteins secreted by E. coli O157:H7 significantly reduced the numbers of bacteria shed in feces, the numbers of animals that shed, and the duration of shedding in an experimental challenge model. Vaccination of cattle also significantly (P=0.04) reduced the prevalence of E. coli O157:H7 in a clinical trial conducted in a typical feedlot setting. This strategy suggests it is possible to vaccinate cattle to decrease the level of E. coli O157:H7 shedding for the purpose of reducing the risk of human disease
The Canadian veterinary journal. La revue vétérinaire canadienne, 1991
Clinical and hematological changes observed on presentation of 47 horses referred to the Ontario ... more Clinical and hematological changes observed on presentation of 47 horses referred to the Ontario Veterinary College with acute idiopathic colitis were analyzed for their prognostic features. Cases of acute enterocolitis were characterized by fever, dehydration, abnormalities of serum electrolyte concentrations, azotemia, hypoalbuminemia, and increased serum concentrations of muscle enzymes. Severely dehydrated horses were seven times more likely to die or be euthanized than those that were not dehydrated. Other factors associated with failure to survive included the following: increased hematocrit, increased number of band neutrophils, increased serum creatinine and urea concentrations, and decreased blood pH and increasingly negative base excess. The results of multivariate variable analysis (stepwise logistic regression) suggested that, among the variables tested, base excess was the best predictor of death or survival. Twenty of 47 horses died or were euthanized. Reasons for deat...
Back pain is a common and poorly understood clinical problem. An important factor in this regard ... more Back pain is a common and poorly understood clinical problem. An important factor in this regard is the induction or exacerbation of back pain from badly designed or poorly fitting saddles. This study used a pressure-sensing mat to investigate saddle fit. The aims of the study were to confirm the accuracy and reliability of the force-sensing array technology when used to measure pressure beneath the saddles of horses, and to collect some initial data from normal healthy horses with well-fitting saddles. Experiments were undertaken to establish that a linear relationship existed between the total force (weight) exerted and the pressure measured beneath the saddle, using both a wooden horse and a live horse in the standing position. Further studies were performed to demonstrate that characteristic changes of the centre of pressure occur while horses move at the walk, sitting trot, rising trot, and canter.
Journal of the American Veterinary Medical Association, 2000
Objective—To describe clinical signs and clinicopathologic findings in donkeys with hypothermia. ... more Objective—To describe clinical signs and clinicopathologic findings in donkeys with hypothermia. Design—Retrospective study. Animals—10 hypothermic donkeys. Procedure—Information on signalment, history, physical examination findings, results of diagnostic tests, treatments, and necropsy findings was extracted from medical records of all donkeys with hypothermia between 1988 and 1998 and compared with information from medical records of all normothermic donkeys and hypothermic horses admitted to the hospital during the same period. Results—Donkeys were more likely to be hypothermic than horses. The mean age of hypothermic donkeys was 6 years (range, 7 months to 11 years), compared with 4.2 years (range, < 1 month to 15 years) for normothermic donkeys; this difference was not significant. Ten of 12 horses with hypothermia were neonates; there were no hypothermic neonatal donkeys. At admission, 7 of 8 hypothermic donkeys were in good body condition and all hypothermic donkeys were w...
There is little published information available describing clinical signs, arthroscopic findings ... more There is little published information available describing clinical signs, arthroscopic findings and prognosis of meniscal injuries in horses. To evaluate the effect on the outcome not only of the arthroscopic findings and treatment, but also of the clinical and radiographic signs in these horses. The following were recorded for each case: the meniscal injury, graded according to severity; clinical and radiographic findings prior to surgery; any concurrent injury in the joint seen at arthroscopy. The effect of these factors and the grade of injury on the outcome were analysed using Fisher&#39;s exact test or Chi-square analysis. Only horses whose meniscal injury was judged to be the primary cause of lameness were included in the series. A series of 80 meniscal injuries were diagnosed and treated arthroscopically by the authors at the Liphook Equine Hospital and 47% of horses returned to full use. Statistically, poor prognosis was associated with increasing severity of the meniscal injury, the presence of concurrent articular cartilage lesions and radiographic abnormalities in the joint. Arthroscopic treatment of many lesions was limited by the inaccessibility of parts of the femorotibial joint. Further work is required to improve and evaluate arthroscopic techniques for the treatment of these injuries.
Canadian journal of veterinary research = Revue canadienne de recherche vétérinaire, 1989
The effects of daily intravenous administration of flunixin meglumine at dosages of 0.55, 1.1, 2.... more The effects of daily intravenous administration of flunixin meglumine at dosages of 0.55, 1.1, 2.2 and 6.6 mg/kg for five days were examined in neonatal foals. Six two day old foals were used to evaluate the effect of each dosage. Foals were examined every day and blood samples collected on days 1, 3 and 6. All foals were euthanized after six days, necropsied and examined for lesions. The major clinical abnormality was diarrhea, but the incidence was not related to the dosage of flunixin meglumine administered. The foals receiving 6.6 mg/kg of flunixin meglumine had significantly more gastrointestinal ulceration and greater cecal pathology and cecal petechiation scores than those foals treated with saline. The foals in the 6.6 mg/kg treatment group had a greater loss of total protein during the study, but the difference was not significant. There were no statistically significant blood cellular or biochemical alterations associated with the administration of flunixin meglumine. Ther...
Decreased shedding of Escherichia coli O157:H7 by cattle following vaccination with type III secr... more Decreased shedding of Escherichia coli O157:H7 by cattle following vaccination with type III secreted proteins
Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneum... more Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP), a devastating respiratory disease mainly affecting cattle in sub-Saharan Africa. The current vaccines are based on live-attenuated Mmm strains and present problems with temperature stability, duration of immunity and adverse reactions, thus new vaccines are needed to overcome these issues. We used a reverse vaccinology approach to identify 66 Mmm potential vaccine candidates. The selection and grouping of the antigens was based on the presence of specific antibodies in sera from CBPP-positive animals. The antigens were used to immunize male Boran cattle (Bos indicus) followed by a challenge with the Mmm strain Afadé. Two of the groups immunized with five proteins each showed protection after the Mmm challenge (Groups A and C; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and in one group (Group C) Mmm could not be cultured from lung specimens. A third group (Group N) showed a reduced number of animals with lesions and the cultures for Mmm were also negative. While immunization with some of the antigens conferred protection, others may have increased immune-related pathology. This is the first report that Mmm recombinant proteins have been successfully used to formulate a prototype vaccine and these results pave the way for the development of a novel commercial vaccine.
Current contagious bovine pleuropneumonia (CBPP) vaccines are based on live-attenuated strains of... more Current contagious bovine pleuropneumonia (CBPP) vaccines are based on live-attenuated strains of Mycoplasma mycoides subsp. mycoides (Mmm). These vaccines have shortcomings in terms of efficacy, duration of immunity and in some cases show severe side effects at the inoculation site; hence the need to develop new vaccines to combat the disease. Reverse vaccinology approaches were used and identified 66 candidate Mycoplasma proteins using available Mmm genome data. These proteins were ranked by their ability to be recognized by serum from CBPP-positive cattle and thereafter used to inoculate naïve cattle. We report here the inoculation of cattle with recombinant proteins and the subsequent humoral and T-cell-mediated immune responses to these proteins and conclude that a subset of these proteins are candidate molecules for recombinant protein-based subunit vaccines for CBPP control.
ILAR journal / National Research Council, Institute of Laboratory Animal Resources, Jan 19, 2015
The development of human vaccines continues to rely on the use of animals for research. Regulator... more The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importan...
International microbiology : the official journal of the Spanish Society for Microbiology, 2011
Forty nine Campylobacter jejuni isolates from cattle feces collected from Alberta feedlots and 50... more Forty nine Campylobacter jejuni isolates from cattle feces collected from Alberta feedlots and 50 clinical C. jejuni isolates from people in Alberta were tested for the presence of 14 genes encoding putative virulence factors by PCR. These included genes implicated in adherence and colonization (flaC, cadF, docC, racR, jlpA, peb1, and dnaJ), invasion (virB11, ciaB, pldA, and iamA) and protection against harsh conditions (htrA, cbrA, and sodB). The genes examined were widely distributed in both the cattle fecal isolates and the human isolates. Of the isolates tested, 67% contained all of the genes except virB11. The cadF gene was found in 100% of the isolates tested. The presence or absence of virulence-associated genes was not associated with the ability of the organism to colonize birds. All of the C. jejuni isolates used to challenge birds were able to colonize the animals regardless of virulence gene profile. While some diversity in the profile of the occurrence of virulence-asso...
Cattle are an important reservoir of Escherichia coli O157:H7 leading to contamination of food an... more Cattle are an important reservoir of Escherichia coli O157:H7 leading to contamination of food and water, and subsequent human disease. This pathogen colonizes its hosts by producing several proteins such as Tir and EspA that are secreted by a type III secretion system. These proteins play a role in colonization of the intestine, suggesting that they might be useful targets for the development of a vaccine to reduce levels of this organism in cattle. Vaccination of cattle with proteins secreted by E. coli O157:H7 significantly reduced the numbers of bacteria shed in feces, the numbers of animals that shed, and the duration of shedding in an experimental challenge model. Vaccination of cattle also significantly (P=0.04) reduced the prevalence of E. coli O157:H7 in a clinical trial conducted in a typical feedlot setting. This strategy suggests it is possible to vaccinate cattle to decrease the level of E. coli O157:H7 shedding for the purpose of reducing the risk of human disease
The Canadian veterinary journal. La revue vétérinaire canadienne, 1991
Clinical and hematological changes observed on presentation of 47 horses referred to the Ontario ... more Clinical and hematological changes observed on presentation of 47 horses referred to the Ontario Veterinary College with acute idiopathic colitis were analyzed for their prognostic features. Cases of acute enterocolitis were characterized by fever, dehydration, abnormalities of serum electrolyte concentrations, azotemia, hypoalbuminemia, and increased serum concentrations of muscle enzymes. Severely dehydrated horses were seven times more likely to die or be euthanized than those that were not dehydrated. Other factors associated with failure to survive included the following: increased hematocrit, increased number of band neutrophils, increased serum creatinine and urea concentrations, and decreased blood pH and increasingly negative base excess. The results of multivariate variable analysis (stepwise logistic regression) suggested that, among the variables tested, base excess was the best predictor of death or survival. Twenty of 47 horses died or were euthanized. Reasons for deat...
Back pain is a common and poorly understood clinical problem. An important factor in this regard ... more Back pain is a common and poorly understood clinical problem. An important factor in this regard is the induction or exacerbation of back pain from badly designed or poorly fitting saddles. This study used a pressure-sensing mat to investigate saddle fit. The aims of the study were to confirm the accuracy and reliability of the force-sensing array technology when used to measure pressure beneath the saddles of horses, and to collect some initial data from normal healthy horses with well-fitting saddles. Experiments were undertaken to establish that a linear relationship existed between the total force (weight) exerted and the pressure measured beneath the saddle, using both a wooden horse and a live horse in the standing position. Further studies were performed to demonstrate that characteristic changes of the centre of pressure occur while horses move at the walk, sitting trot, rising trot, and canter.
Journal of the American Veterinary Medical Association, 2000
Objective—To describe clinical signs and clinicopathologic findings in donkeys with hypothermia. ... more Objective—To describe clinical signs and clinicopathologic findings in donkeys with hypothermia. Design—Retrospective study. Animals—10 hypothermic donkeys. Procedure—Information on signalment, history, physical examination findings, results of diagnostic tests, treatments, and necropsy findings was extracted from medical records of all donkeys with hypothermia between 1988 and 1998 and compared with information from medical records of all normothermic donkeys and hypothermic horses admitted to the hospital during the same period. Results—Donkeys were more likely to be hypothermic than horses. The mean age of hypothermic donkeys was 6 years (range, 7 months to 11 years), compared with 4.2 years (range, < 1 month to 15 years) for normothermic donkeys; this difference was not significant. Ten of 12 horses with hypothermia were neonates; there were no hypothermic neonatal donkeys. At admission, 7 of 8 hypothermic donkeys were in good body condition and all hypothermic donkeys were w...
There is little published information available describing clinical signs, arthroscopic findings ... more There is little published information available describing clinical signs, arthroscopic findings and prognosis of meniscal injuries in horses. To evaluate the effect on the outcome not only of the arthroscopic findings and treatment, but also of the clinical and radiographic signs in these horses. The following were recorded for each case: the meniscal injury, graded according to severity; clinical and radiographic findings prior to surgery; any concurrent injury in the joint seen at arthroscopy. The effect of these factors and the grade of injury on the outcome were analysed using Fisher&#39;s exact test or Chi-square analysis. Only horses whose meniscal injury was judged to be the primary cause of lameness were included in the series. A series of 80 meniscal injuries were diagnosed and treated arthroscopically by the authors at the Liphook Equine Hospital and 47% of horses returned to full use. Statistically, poor prognosis was associated with increasing severity of the meniscal injury, the presence of concurrent articular cartilage lesions and radiographic abnormalities in the joint. Arthroscopic treatment of many lesions was limited by the inaccessibility of parts of the femorotibial joint. Further work is required to improve and evaluate arthroscopic techniques for the treatment of these injuries.
Canadian journal of veterinary research = Revue canadienne de recherche vétérinaire, 1989
The effects of daily intravenous administration of flunixin meglumine at dosages of 0.55, 1.1, 2.... more The effects of daily intravenous administration of flunixin meglumine at dosages of 0.55, 1.1, 2.2 and 6.6 mg/kg for five days were examined in neonatal foals. Six two day old foals were used to evaluate the effect of each dosage. Foals were examined every day and blood samples collected on days 1, 3 and 6. All foals were euthanized after six days, necropsied and examined for lesions. The major clinical abnormality was diarrhea, but the incidence was not related to the dosage of flunixin meglumine administered. The foals receiving 6.6 mg/kg of flunixin meglumine had significantly more gastrointestinal ulceration and greater cecal pathology and cecal petechiation scores than those foals treated with saline. The foals in the 6.6 mg/kg treatment group had a greater loss of total protein during the study, but the difference was not significant. There were no statistically significant blood cellular or biochemical alterations associated with the administration of flunixin meglumine. Ther...
Decreased shedding of Escherichia coli O157:H7 by cattle following vaccination with type III secr... more Decreased shedding of Escherichia coli O157:H7 by cattle following vaccination with type III secreted proteins
Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneum... more Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP), a devastating respiratory disease mainly affecting cattle in sub-Saharan Africa. The current vaccines are based on live-attenuated Mmm strains and present problems with temperature stability, duration of immunity and adverse reactions, thus new vaccines are needed to overcome these issues. We used a reverse vaccinology approach to identify 66 Mmm potential vaccine candidates. The selection and grouping of the antigens was based on the presence of specific antibodies in sera from CBPP-positive animals. The antigens were used to immunize male Boran cattle (Bos indicus) followed by a challenge with the Mmm strain Afadé. Two of the groups immunized with five proteins each showed protection after the Mmm challenge (Groups A and C; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and in one group (Group C) Mmm could not be cultured from lung specimens. A third group (Group N) showed a reduced number of animals with lesions and the cultures for Mmm were also negative. While immunization with some of the antigens conferred protection, others may have increased immune-related pathology. This is the first report that Mmm recombinant proteins have been successfully used to formulate a prototype vaccine and these results pave the way for the development of a novel commercial vaccine.
Current contagious bovine pleuropneumonia (CBPP) vaccines are based on live-attenuated strains of... more Current contagious bovine pleuropneumonia (CBPP) vaccines are based on live-attenuated strains of Mycoplasma mycoides subsp. mycoides (Mmm). These vaccines have shortcomings in terms of efficacy, duration of immunity and in some cases show severe side effects at the inoculation site; hence the need to develop new vaccines to combat the disease. Reverse vaccinology approaches were used and identified 66 candidate Mycoplasma proteins using available Mmm genome data. These proteins were ranked by their ability to be recognized by serum from CBPP-positive cattle and thereafter used to inoculate naïve cattle. We report here the inoculation of cattle with recombinant proteins and the subsequent humoral and T-cell-mediated immune responses to these proteins and conclude that a subset of these proteins are candidate molecules for recombinant protein-based subunit vaccines for CBPP control.
ILAR journal / National Research Council, Institute of Laboratory Animal Resources, Jan 19, 2015
The development of human vaccines continues to rely on the use of animals for research. Regulator... more The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importan...
International microbiology : the official journal of the Spanish Society for Microbiology, 2011
Forty nine Campylobacter jejuni isolates from cattle feces collected from Alberta feedlots and 50... more Forty nine Campylobacter jejuni isolates from cattle feces collected from Alberta feedlots and 50 clinical C. jejuni isolates from people in Alberta were tested for the presence of 14 genes encoding putative virulence factors by PCR. These included genes implicated in adherence and colonization (flaC, cadF, docC, racR, jlpA, peb1, and dnaJ), invasion (virB11, ciaB, pldA, and iamA) and protection against harsh conditions (htrA, cbrA, and sodB). The genes examined were widely distributed in both the cattle fecal isolates and the human isolates. Of the isolates tested, 67% contained all of the genes except virB11. The cadF gene was found in 100% of the isolates tested. The presence or absence of virulence-associated genes was not associated with the ability of the organism to colonize birds. All of the C. jejuni isolates used to challenge birds were able to colonize the animals regardless of virulence gene profile. While some diversity in the profile of the occurrence of virulence-asso...
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Papers by Hugh Townsend