The pathogenesis of a disease relates to the origin or development of the disease. Different organisms cause disease in different ways and proliferate in varying conditions. An understanding of the mechanisms by which pathogenic agents such as bacteria, viruses, parasites, or fungi cause communicable diseases is essential in creating the best measures of surveillance and control against these diseases.
Bovine Tuberculosis and Anthrax are two important reportable veterinary infectious diseases that are of great economic and public health importance. They are both bacterial infections in animals and an understanding of their basic steps in pathogenesis provides a sound foundation for creating measures of control.
Bovine Tuberculosis is a chronic infectious disease caused by the bacterium Mycobacterium Bovis (M. Bovis) , which affects mainly cattle, but sometimes also other mammals. The disease is zoonotic and can be transmitted to humans through the inhalation of aerosols at the time of slaughter, or the consumption of unpasteurized milk. The most important route of infection in cattle is the respiratory route, by the inhalation of bacteria in aerosol droplets. The secondary route of infection is the oral route, in which calves can become infected by nursing tuberculous cows and cattle may be infected through the ingestion of bacilli from contaminated pastures, fomites and water. Transmission may also occur through saliva and other discharges e.g. semen of infected animals.
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Once infected with M. Bovis, tuberculous lesions form within the lungs and pulmonary lymph nodes. When the immune system recognizes the bacteria, inflammatory cells (macrophages) are sent to destroy the bacteria. The immune system continues to deploy macrophages to destroy the bacteria, resulting in the accumulation of both dead and living macrophages at the site of infection. This accumulation results in the formation of a tubercle. Tubercle bacilli multiply in the alveoli. Granulomas are formed when a thick capsule surrounds the tubercle. These lesions may also be found in the liver and other major organs.
Being a facultative intracellular bacteria, M. Bovis once ingested by the macrophage, survives, replicates intracellularly and eventually kills the macrophage. This is a method of subversion of the hostâ€™s immune response by M. Bovis. Intracellular organisms that multiply within macrophages, like M. Bovis, are able to evade the hostâ€™s natural defenses. Therefore, immune response against M. Bovis is very complex and depends on the activation of the cellular immune defense (CMI), with CD4+ T cells being the most important T Cell evoking a strong recall response when stimulated with mycobacterial antigens in granulomas.
Antibodies play a minor role for protective immunity against Bovine Tuberculosis. This creates a problem in producing an effective vaccine against Bovine TB, as compared to viral infections where producing a vaccine is much less challenging because antibody is often the main component of protective immunity. Currently there are no effective Bovine Tuberculosis vaccines available for cattle. The BCG vaccine created for M. Bovis in the 1920s was not completely successful due to its variable efficacy. The vaccine only reduced the severity of the disease, but failed to prevent infection. Besides that, the occurrence of M. Bovis in wildlife reservoir hosts has always complicated efforts of eradication. Wildlife surveys in the 1970s have revealed a high prevalence of infection in badgers that reside in areas of high incidence of cattle TB in the UK. Culling of badgers to reduce the population density may have decreased transmission of the disease, but has led to unanticipated events such as the spreading and dispersal of the surviving badgers to other areas.
These factors have therefore led to efforts into developing and testing new vaccines for wildlife reservoirs, to prevent the spread of disease to cattle in Great Britain. In 2010, the first injectable badger vaccine was licensed and at the same time, Defra (Department for Environment, Food and Rural Affairs) decided to fund the Badger Vaccine Deployment Project in six different catchment areas in England with high incidence of Bovine TB in cattle in the past. This is part of their program dedicated to vaccinating as many badgers as possible that have access to farms, as well as, developing a cattle vaccine and an oral badger vaccine. However, this is a potential long term option of Bovine TB that is only a risk reduction measure and must be used alongside other disease control and prevention methods.
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Treatment with antibiotics may not be the best option of control due to the fact that mycobacterial diseases, in general, are slow to progress and usually result in a large proportion of infected animals. Therefore, treatment must be long term and is extremely costly. Clinical improvement may also occur with the use of antimicrobials, but without any bacteriological cure. In Bovine Tuberculosis therefore, one of the current and best measures of control is the test-and-slaughter method. Herds are periodically re-tested with the Tuberculin Skin Test in order to identify and cull infected cattle with Bovine TB before they develop any clinical signs. This is due to the fact that the disease progresses very slowly and it can take a long time before clinical signs appear. Hence, a large number of sub-clinically infected animals may go unnoticed. In addition, farms that housed these cattle may be closed and healthy cattle transferred to other farms. Improving sanitary and hygiene in dairy farms can also control the spread of Bovine Tuberculosis, as sanitation and disinfection can reduce the spread of the pathogen within the herd.
Until this very day, the clinical management and control of Bovine Tuberculosis is difficult and complicated, due to the slow growth of the pathogen, difficulty in identifying asymptomatic carriers and the complex immune response of the host to the intracellular bacteria. Hence, the best (and most economical) way to control this disease is through measures of bio-security, as well as test and slaughter methods where necessary, used alongside risk reduction measures such as vaccinations.
Anthrax, unlike Bovine Tuberculosis is an acute infectious disease caused by the bacterium Bacillus Anthracis (B. Anthracis) . Principally, it is a disease of herbivorous animals, as well as carnivores and omnivores who normally contract the disease from eating meat of infected herbivorous animals. It is known to be archetype zoonosis, for no other infectious disease affects such a wide range of species, such as cattle, dogs, cats, horses, pigs and humans. Hoofed animals are most susceptible to this disease. They usually contract it by swallowing anthrax spores while grazing contaminated pastures. Anthrax normally occurs in warmer regions like Africa and Asia, but has spread to southern Europe and several parts of the Americas through trade of infected animals and animal products.
Bacillus Anthracis is part of a group of bacteria that produce spores. Therefore, the main transmissible source of the disease is spores that may remain viable in soil for years. Because of this, outbreaks of disease often occur in areas where animals have previously died of anthrax. These spores enter the host body through lesions, mucosal membranes and inhalation. The inhaled spores enter the alveoli, germinate in macrophages and replicate in lymph nodes. B. Anthracis is able to do this because it possesses a poly-D-glutamate polypeptide that protects the organism from bactericidal components of serum and phagocytic engulfment. Two toxins produced by B. Anthracis, namely, EF (edema factor) and LF (lethal factor) induce cell lysis in macrophages. These factors allow the bacterium to evade the hostâ€™s natural immune defenses.
Within the host, spores germinate, transforming from the resistant form into the growing and multiplying vegetative form. However, these spores may live in the alveoli for weeks without germinating. The vegetative state causes the disease. Antibiotics are effective against the vegetative form of B. Anthracis, but not the spores.
Anthrax spores are known to grow like seeds. If under the right environment, in this case the animal body, they grow into the harmful form of the bacteria that cause the disease. Anthrax spores take an average of 7 days to grow. Therefore, it is recommended that animals suspected of having been exposed to the source of infection be treated with long-acting penicillin. Animals appear to respond well to treatment even if it is at the late stages. However, disease may develop if the antibiotic treatment is discontinued, because complete eradication of the organism might not occur. Some animals may be saved, if treatment starts early and is carried out appropriately. Therefore this is the method of control used if animals show clinical signs of the disease.
Sporulation of B. Anthracis requires oxygen and is therefore inhibited in intact carcasses. Once an animal carcass is opened and the vegetative state of the bacteria is exposed to oxygen, it is able to form spores. These sporulated anthrax organisms are very resistant to temperature (heat and cold), drying and chemical disinfectants. These spores may remain in the soil for more than 50 years and may serve as a source for re-infection of other animals. Therefore, regulations in many countries forbid postmortem examination or necropsy of animals when anthrax is suspected. Carcasses that are not buried and are opened, present and ideal source for the organism to spread, hence, disposal and incineration of carcasses is crucial. They should be isolated from other livestock, pets and scavenger animals. Decontamination of carcass sites, as well as the items used at the time of diagnosis, should also be carried out. Decontamination methods include sterilizing and burning, as disinfecting will not destroy spores.
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Anthrax spores also multiply in wet conditions, and because of that, it is imperative that dead animal carcasses be buried with quicklime. Quicklime reacts quickly with water to form calcium hydrate, and pulls water from bacteria, plants and fungi. Therefore creating a less damp environment in the soil, which is unfavourable for spore multiplication.
A common characteristic of anthrax is that animals in good condition, with no signs of illness, may suddenly die. This is because the progression of the disease is very rapid and cautionary signs may go unnoticed. By the time an animal shows signs of the disease (trembling, convulsions, bleeding), death usually follows very rapidly. As such, important preventive measures must be taken in enzootic areas to control outbreaks. It is important that all animals not showing symptoms be vaccinated with the Anthrax Spore Vaccine, which is a live vaccine that stimulates an immune response but does not cause disease.
The structure and lifecycle of the anthrax spore is well understood today, therefore, proper measures of control have already been identified. There has not been an anthrax outbreak for many years now, but research efforts continue to focus on virulence factors, the anthrax toxin and the immune response to B. Anthracis, which all aid in creating control measures and vaccination protocols.
There has been a lot of research put into the way diseases are transmitted and how they establish infection in their hosts and Bovine Tuberculosis and Anthrax provide good examples for illustrating the relationship between the pathogenesis of a disease and how it may be controlled.
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