A greater understanding of the biological and genetic basis of rhodococcal pneumonia and the development of a vaccine to be administered to foals will greatly reduce the incidence of symptoms in foals and minimize mortality.
Equine Related Hero: Dr. Prescott emphasizes that he "really loves horses" and states that the horse "is such an interesting animal and I find the whole relationship with humankind interesting. My heroes are the draft horses, the work horses".
Horse Background: Dr. Prescott has enjoyed much pleasure riding and hopes to resume this when time allows. He looks forward to trips to friends' farms where he takes great joy in visiting their workhorses.
Research Focus: Since arriving at the University of Guelph three decades ago, Dr. Prescott has been investigating rhodococcal pneumonia, an important, widespread and often fatal disease of foals up to the age of six months. His interest in the disease started during his vet studies in Cambridge and his commitment to researching the disease was established when he again, saw the disease in foals at Guelph. Clinical symptoms of the pneumonia in foals include coughing, and elevated temperature. The causal agent is the ubiquitous bacterium R. equi that readily grows and multiplies in soil and feces of many herbivores. Occasional R. equi -induced pneumonia in humans is associated with lowered immune function, for example following organ transplantation or HIV-infection. Treatment is difficult, expensive and usually involves prolonged antibiotic therapy, however early recognition boosts survival rate.
The highly variable level of incidence of rhodococcal pneumonia on farms has been correlated positively to the number of pathogenic bacteria on the properties. The pathogen can survive and multiply in soil and manure for prolonged periods, is relatively resistant to environmental stress and can be impossible to eradicate on site. Hot temperatures, dust and dryness favor multiplication and dispersal of the pathogen. Crowding of foals, increases disease incidence.
R. equi enters an animal's airways through inhalation on contaminated dust, soil, manure and other particles. R. equi , like the closely related Mycobacterium tuberculosis that produces tuberculosis in humans, multiplies and spreads inside the lungs in macrophages, which are cells of the immune system that normally kill and digest bacteria. Decreased bactericidal capacity of the macrophages allows R. equi to attack and kill these and release the pathogen. Alveolar (lung) lesions and inflammation form and the animal's immune response is lowered. Filling of the lungs with dead macrophages leads to pneumonia symptoms and fatalities are associated with slow suffocation due to reduced oxygen availability. Infected foals may also ingest the mucous associated with the disease and re-infect their intestines, where the bacterium is also able to multiply.
Macrophage filled with pathogen
All horses are exposed to R. equi , however, adult horses and non-equine species are rarely diseased. Disease is most prevalent in 4-12 week old foals, coinciding with the transitional period from passive immunity to active immunity. During this time the antibody titer in the dam's colostrum is relatively low and the foal has not had time to build up its own immunity. Symptom development is influenced by the inherent susceptibility of an animal and promoted by high quantities of the bacterium in its environment. Affected foals often appear healthy until the disease reaches an advanced stage after abscesses and lesions have formed in the lungs.
In order to confer pathogenicity, a strain of R. equi must posses a large plasmid (circular piece of DNA exterior to the chromosome) that contains genes on a pathogenicity island (site with genes for virulence) that encode specific pathogenicity-associated proteins. Dr. Prescott and his team have noted that VapA (a specific gene) plays a major role in macrophage attack. Following ingestion of R. equi , expression of Vaps is regulated by environmental conditions in the alveolar (lung) macrophages including temperatures (optimum around 37ºC for VapA), pH and low iron concentration. Pathogenicity is based on the ability of R. equi to infect, replicate within and destroy the macrophages. Dr. Prescott and his team are determining which genes are critical for survival of the bacterium inside the macrophages and how the pathogen alters the macrophage immune response. He is excited about completed sequencing of the R. equi genome (around 5000 genes), as it will greatly contribute to his research on the biology and virulence of the pathogen.
Prevention and control of rhodoccocal pneumonia on farms requires good management and sanitation practices to minimize bacterial levels as well as prompt treatment of clinical cases with antibodies. Foals and mares should be kept in well-ventilated, non-crowded areas that have little dust or manure. Parasite control in mares, regular health monitoring for warning signs in foals and isolation of infected foals help decrease cases. Birth of foals during cooler seasons decreases their exposure to optimum disease for exposure to the disease.
Dr. Prescott's research led to the development of current antibiotic treatment protocols that involves the oral administration of erythromycin and rifampin, two antibiotics that are able to penetrate the alveolar macrophages and work synergistally to kill R. equi . This treatment is prolonged and expensive, but greatly reduces mortality. Prevention of infection can be addressed by intravenous injections with commercially available hyperimmune plasma (HIP) given to young foals, which provides passive immunity. The plasma contains antibodies produced in adult horses that have been vaccinated against genes encoding for Vaps. This procedure is costly and time consuming, however greatly decreases the incidence of disease.
Dr. Prescott is devoted to developing a commercially available vaccine against rhodococcal pneumonia that would be given to foals in their first few weeks of life. The vaccine will provide a protective immune response to Vap proteins. He is optimistic that his vaccine will be 100% effective. He notes that this is "quite challenging because trying to immunize foals by 3 weeks of age is a huge challenge in young animals because young animals mostly have the predisposition to the wrong type of immune response; the right type of response would be to kill the organism with macrophages". At this time the foals also have immature immune cells and a delayed immune response.
Dr. Prescott's research is funded by the Natural Sciences and Engineering Research Council and Equine Guelph.
Area of Specialty: Bacterial diseases in animals; clinical bacteriology; effective antimicrobial drug use
Degrees: MA, Vet. MB, PhD (University of Cambridge
Position: Chair & Faculty Member, Department of Pathobiology, Ontario Veterinary College, University of Guelph
Responsibilities:
Additional Accomplishments: Dr. Prescott enjoys writing and has published extensively in scientific journals, especially on the topic of rhodococcal pneumonia in horses, and has edited several books including Antimicrobial Therapy in Veterinary Medicine. He also wrote a book on the intriguing life of the famous Guelph-born physician, poet and soldier, Dr. John McCrae entitled In Flanders Fields: The Story of John McCrae . Dr. Prescott was the recipient of awards including the Research Excellence Award and is a member of numerous associations and committees including the Canadian Committee on Antibiotic Resistance for the Canadian Veterinary Medical Association. He also played a role in the materialization of the new Centre for Public Health and Zoonoses to be built at the University of Guelph.
- Coralie Sopher
