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The study of pathogenesis of veterinary infectious diseases aims to understand how a disease develops, spreads and manifests, which is important in the development of effective measures and controls to identify, contain, control and eradicate the diseases. By using the understanding of the pathogenesis of veterinary infectious diseases, all available and reliable control methods can be developed and considered for execution in animal management and husbandry.
There are multiple controls that can be directed either at the agent, the route of transmission, the host or the environment and sometimes it is necessary to use several control strategies at the same time.
Vaccination is a powerful control method. It provides the ultimate measure for individual protection against veterinary infectious diseases. However, vaccines are not available for every veterinary infectious disease. This may be due to the failure in developing a vaccine or either a vaccine is not available to the public due to expense, production interruption, ineffectiveness to a rapid evolving disease, such as HIV, or it causes too many side effects. In these cases, controls mainly focused upon animal husbandry and management are deployed.
The understanding of the pathogenesis has rendered successful results in predicting how the development of the disease will change when induced by certain drug treatments; which will result in the production of vaccines. The purpose of a vaccine is to improve the immunity of either an animal or human, to a particular disease. Canine Lyme disease is an example of a veterinary infectious disease that utilises the understanding of pathogenesis in the creation of vaccines.
Lyme disease, also called Lyme borreliosis, is an emerging infectious disease that occurs in many species, including dogs and humans. In canine, the disease may manifest within the body for weeks to months after infection, without showing any symptoms. The causative agents are bacteria belonging to the genus Borrelia: B. burgdorferi, B. afzelii, B. garinnii and B. japonica (Straubinger 2000). B. burgdorferi is the main cause of Lyme disease in the United States, and B. afzelii and B. garinnii are the main cause in Europe. B. burgdorferi are Gram-negative, long, spiral-shaped and motile organisms that belong to the order Spirochaetales.
The spirochete that causes Lyme disease cannot survive outside the body of a host. It must live within either a mammal or a tick. The primary method of transmission is by tick bites. In North America, Ixodes scapularis (commonly known as the deer tick) is the primary vector of Lyme disease. In Europe, it is Ixodes ricinus (the sheep tick). In a mammal's body, the spirochete expresses different outer surface proteins (Osps). There are different Osps expressed at various phases in a tick's feeding cycle. When an unfed tick initially attaches to a dog, high amounts of an outer surface protein called OspA are expressed by the spirochete in the tick's midgut. As the tick starts to feed on the dog, the spirochete starts to replicate rapidly. Instead of expressing OspA, OspC are now expressed in the mammal's connective tissue (Mar Vista Animal Medical Center 2010). By changing its Osps, the spirochete is able to disguise itself to escape the mammalian host's immune system. With this knowledge of the spirochete's pathogenesis, vaccines can be created to control the infectious disease.
Lyme disease in canine has three possible vaccines available: LymeVaxÂ®, NobivacÂ® Lyme and Recombitek LymeÂ®.
LymeVax, an inactivated vaccination manufactured by Fort Dodge, is a two-strain, multi-antigen vaccine that contains intact dead spirochetes. By using the entire spirochete, the host is exposed to parts of the organism that are not useful in immunization, which may lead to a vaccine reaction. Nobivac, manufactured by Intervet/Schering-Plough, applies the knowledge of the Lyme spirochete by targeting the proteins OspA and OspC. Older vaccinations stimulate a protective immune response to only OspA; therefore they do not prevent live Borrelia that are expressing OspC from escaping and infecting the dog. Nobivac stimulates OspC antibodies to kill any Borrelia that have not been de-activated by the OspA antibodies, thus providing enhanced protection. Finally, Recombitek, manufactured by Merial, is a recombinant vector vaccine and happens to be the most popular vaccine. It provides a clear example of applying the understanding of Lyme disease's pathogenesis. The vaccine is "to block the transmission, from tick to dog, of the spirochete that causes Lyme disease (Merial n.d)." Spirochetes reside primarily in the midgut of the tick. When a tick begins to feed on blood, the spirochetes are stimulated and migrate to the tick's salivary glands to be injected into the dog. Recombitek blocks the spirochete's migration route by generating antibodies specifically against OspA (Anti-OspA antibodies). When the tick takes a blood meal, it is full of Anti-OspA antibodies and the spirochete is unable to exit the tick.
Not all veterinary infectious diseases have vaccines available. An appropriate example would be bovine tuberculosis; its controls are mainly focused upon animal husbandry and management. This may include: routinely cleaning of housing and feeding, identifying and culling infected animals and limiting exposure to species that may harbour the bacteria.
The understanding of the pathogenesis of bovine tuberculosis dictates that a live infected cow is the major source of infection to non-infected cattle and thus, the current strategy to prevent the disease is by the continuous identification and removal of diseased cattle.
Bovine tuberculosis is a deadly infectious disease that primarily infects the respiratory system of cattle and humans. It is a worldwide occurrence that generates severe economic losses. Mycobacterium bovis (M. bovis) is the causal agent, and is a filamentous, acid fast, curved rod. This agent enters the respiratory system of cattle, settles in the lungs and uses alveolar macrophages as the primary host cell for intracellular growth. Large abscesses then form in the lung, causing respiratory disease.
M. bovis is predominantly transmitted through the inhalation of aerosolised droplets. In a controlled experiment, the dose required to establish an infection via aerosol route was approximately 1000 times less than the dose needed to establish an infection via oral route (Collins & Grange 1983). A mathematical model created by Neill et al. (2001) states that the inhalation of a single bacillus in an aerosolised droplet is capable of establishing an infection. Furthermore, Francis (1958) conducted an experiment that cattle outdoors spread of bovine tuberculosis occurs at a lower rate compared to the cattle that share a confined airspace. From this understanding of the primary route of transmission of bovine tuberculosis, specific and efficient measures of control have been created to prevent the infection.
Tuberculin skin testing is the most significant method used to control the disease. This test is more sensitive than others, such as ELISA, and does not confuse M. bovis with M. avium or M. paratuberculosis. Tuberculin skin testing's purpose is to assess the T-cell response to mycobacterial proteins. If the cow responds to the injection of 0.10cc of a purified protein derivative, it is classified as positive. Once a cow is tested positive, it will be culled to prevent the spread of infection via aerosol route to non-infected cattle. Another preventive measure is to eliminate the exposure of the cattle to white-tailed deer (Palmer et al. 2000) and badgers. This is because white-tailed deer and badgers are known to harbour and excrete large quantities of M. bovis, which can be spread through aerosol droplets.
There is a vaccination for bovine tuberculosis, created in the 1920s by Calmette and Guerin, but has undergone examination due to its variable capability. The vaccine has been proven to reduce the severity of the disease; however it does not prevent infection. Additionally, it may cause false-positive caudal fold skin tests resulting in culling non-infected cows. Therefore, preventive measures are the most successful current method of control for bovine tuberculosis.
In the case of Lyme disease, the understanding of pathogenesis rendered successful results in predicting how the development of the disease will change when induced by certain drug treatments; which resulted in the production of vaccines. In bovine tuberculosis however, when vaccines are not available, the understanding of pathogenesis proved to be invaluable in the creation of efficient animal husbandry and management methods to control the infectious disease. Whilst different solutions, both control methods have been generated from the understanding of pathogenesis of veterinary infectious diseases. It can provide new insights into the vital mechanisms shared with the disease and facilitate the rational design of efficient control methods.