Bovine Spongiform Encephalopathy (BSE)- Mad Cow Disease

What is Bovine spongiform encephalopathy?

• Bovine spongiform encephalopathy (BSE), also known as mad cow disease, is a fatal neurodegenerative disease that affects both humans and animals, particularly domestic cattle such as dairy cows. It is caused by a proteinaceous infective agent called a prion, which is a misfolded protein that has changed its conformation through a post-translational modification. This altered protein becomes resistant to inactivation and enzyme degradation.
• The disease leads to neuronal loss, spongiform lesions, astrogliosis, and the disappearance of inflammatory reactions in the affected animals. Symptoms of BSE in cattle include abnormal behavior, trouble walking, and weight loss. As the disease progresses, the cows become unable to function normally. The time between infection and the onset of symptoms is still a subject of conflicting information, but it is estimated to be around four to five years. After symptoms appear, the affected cows usually die within weeks to months.
• BSE is believed to have spread to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The transmission to humans is thought to occur through the consumption of contaminated meat products. The cases of BSE reached a peak of more than 300 cases per week in 1993 in the United Kingdom, raising significant health concerns. However, efforts have been made to prevent the disease by implementing regulations such as not allowing animals older than 30 months to enter the human food or animal feed supply.
• The infection of cattle is primarily attributed to the practice of feeding them meat-and-bone meal (MBM) that contained the remains of cattle infected with BSE or scrapie-infected sheep products. This practice, especially the feeding of MBM to young calves of dairy cows, contributed to the outbreak and spread of the disease in the United Kingdom. The disease is also classified as a transmissible spongiform encephalopathy (TSE), which includes other prion diseases like scrapie in sheep and goat, chronic wasting disease in deer, elk, and moose, and various other forms in different animal species.
• To address the issue, measures were taken, such as testing cattle over 30 months in continental Europe if they are intended for human food, and prohibiting the addition of specified risk material (tissue of concern) to animal feed or pet food in North America. In the UK, a significant eradication program was implemented, leading to the culling of approximately four million cows from 1986 to 2015. While the number of reported cases has decreased significantly over the years, with only four cases reported globally in 2017, it is believed that several million cattle affected by BSE may have entered the food supply during the outbreak.
• Bovine spongiform encephalopathy remains a serious concern due to its impact on animal and human health. Continued surveillance and strict measures are necessary to prevent its recurrence and ensure food safety.

Sources and causes of contamination of Bovine Spongiform Encephalopathy (BSE)

• Bovine spongiform encephalopathy (BSE), commonly known as “mad cow disease,” is caused by the presence of a misfolded protein called a prion. These prions have the ability to cause neurological damage and are resistant to high heat and pressure, making them difficult to eliminate through normal cooking or food processing methods.
• The misfolded prion protein changes the normal alpha-helical structure into a beta-sheet conformation, resulting in the formation of small chains. These chains aggregate and accumulate in the brain, leading to the death of numerous cells and the development of lesions. The progressive destruction of brain tissue ultimately causes various neurological symptoms and, in severe cases, death.
• Contamination of BSE primarily occurs when a healthy animal comes into contact with an infected food source, particularly tainted meat. One of the major sources of contamination is through the consumption of contaminated meat and bone meal (MBM). MBM is a common feed ingredient derived from the rendering process, which involves grinding and processing animal by-products such as bones and offal into a high-protein meal. If the rendering process does not effectively eliminate prions, the resulting MBM can serve as a vector for transmitting BSE to other animals when it is included in their feed.
• In addition to contaminated MBM, another source of BSE contamination is through the feeding of scrapie-infected sheep products to cattle. Scrapie is a prion disease that affects sheep and goats, and when infected sheep materials, such as nervous system tissues, are fed to cattle, it can result in the transmission of BSE.
• It is worth noting that BSE can also be transmitted to humans, leading to a variant form of Creutzfeldt-Jakob disease (vCJD). The primary route of transmission to humans is believed to be the consumption of contaminated meat from slaughtered or dead livestock, particularly from the brain, spinal cord, and digestive tract where prions accumulate at higher concentrations.
• To mitigate the risk of BSE contamination, various measures have been implemented, including stricter regulations on rendering processes, bans on the use of certain animal by-products in animal feed, and surveillance programs to detect and control the disease in cattle populations. These efforts aim to prevent the spread of BSE and reduce the potential transmission of the disease to humans.

Pathogenic mechanism of Bovine Spongiform Encephalopathy (BSE)

• Bovine spongiform encephalopathy (BSE), also known as “mad cow disease,” follows a pathogenic mechanism that involves the ingestion of BSE agents through contaminated meat and bone meal. The disease primarily affects the central nervous system and leads to characteristic lesions in the brain and spinal cord.
• The infection of BSE occurs through the oral route when animals consume meat and bone meal containing BSE agents. These agents, which consist of misfolded prion proteins, reach the digestive tract and cross the mucosal barrier by utilizing specialized macromolecule transporter M-cells located in the epithelium of the gut and tonsils. Additionally, certain proteins like ferritin can also enhance the uptake of BSE agents by dendritic cells, further facilitating their entry into the digestive tract.
• Once inside the digestive tract, the BSE agents accumulate and replicate in the gut-associated lymphoid tissues (GALT), predominantly in the ileum, jejunum, and tonsils. From there, the BSE agent initially infects the neural tissue of the gut, known as the enteric nervous system (ENS). The agent then travels through efferent neuronal pathways, including both parasympathetic and sympathetic routes, to reach various regions of the brain such as the cerebral cortex, cerebellum, hippocampus, basal nuclei, cervical spinal cord, and ultimately the entire brain.
• As the infection progresses, it leads to characteristic brain degenerative changes associated with BSE. These changes include neuronal vacuolation, which is the formation of empty spaces within neurons, as well as degeneration and loss of neurons. Additionally, astrocytic hypertrophy and hyperplasia, an abnormal increase in the size and number of astrocytes (supportive cells in the brain), are also observed.
• These pathological alterations in the brain and spinal cord contribute to the neurological symptoms and ultimately the fatal outcome associated with bovine spongiform encephalopathy. Understanding the pathogenic mechanism of BSE is crucial for implementing effective measures to control and prevent the spread of the disease.

Signs and symptoms of Bovine Spongiform Encephalopathy (BSE)

• Bovine spongiform encephalopathy (BSE), commonly known as “mad cow disease,” exhibits various signs and symptoms in affected cattle. These symptoms are primarily neurological in nature and gradually progress over time.
• Early signs of BSE include nervousness and anxiety, which can be observed as changes in behavior in affected cows within the herd. As the disease progresses, it affects the mental status of the animal, leading to alterations in sensation and increased sensitivity or hyperesthesia to sound and touch.
• Abnormalities in movement and posture are common manifestations of BSE. Affected cattle may exhibit a low head carriage, tremors, and hindlimb ataxia (uncoordinated movement). These neurological deficits can impact the animal’s ability to maintain balance and coordination, resulting in an unsteady gait.
• In addition to neurological symptoms, BSE can also have other effects on the animal’s health and productivity. Mammals infected with BSE may experience a loss of milk yield, reduction in cud-chewing activity, and a slowing of the pulse rate. These systemic changes reflect the impact of the disease on the overall well-being and physiological functioning of the animal.
• As the disease progresses, the symptoms worsen, eventually leading to terminal recumbency (inability to rise) and death. The severity and duration of the disease can vary, with an incubation period ranging from seven days to more than a year, depending on factors such as the level of disease occurrence and its severity.
• It is important to note that the BSE agent has primarily been detected in cattle over 20 months old, and its occurrence in young cattle, particularly those under 20 months old, is relatively rare.
• Managing environmental stresses, such as minimizing stress during transportation, can influence the severity of BSE infection. Reducing these stressors may help alleviate the impact of the disease on affected animals and potentially slow down its progression.
• Monitoring and recognizing the signs and symptoms of BSE are crucial for early detection, appropriate management, and preventing the spread of the disease within cattle populations.

Epidemiology of Bovine Spongiform Encephalopathy (BSE)

• The epidemiology of Bovine Spongiform Encephalopathy (BSE) provides insights into the geographical distribution, affected species, and measures taken to control the disease.
• The United Kingdom has historically reported the highest number of BSE cases, with a peak of 37,280 affected cattle. The spread of the disease to other European countries was primarily attributed to the breeding of infected cattle and the inclusion of contaminated meat-and-bone meals in animal feed.
• Dairy cows are more commonly affected by BSE compared to beef cattle. This is largely due to different rearing systems, as dairy calves are typically separated from their mothers shortly after birth and fed artificial milk. This separation reduces the potential for transmission of the disease from an infected cow to its calf through nursing.
• In addition to cattle, other animal species have been found to be susceptible to BSE infection. These include cats, eland, gemsbok, oryx, puma, cheetah, ocelot, and rhesus monkeys. The transmission of BSE to these species likely occurred through the consumption of contaminated animal products.
• The implementation of bans on the use of certain animal by-products in feed and the removal of specified risk materials from the human food chain had a significant impact on controlling the spread of BSE. Following these measures, BSE cases in many countries declined by approximately 40% per year.
• Outside of Europe, Japan experienced 36 cases of BSE, all of which were non-imported cases. In response to the outbreak, the Japanese government established a Food Safety Commission in 2003 to ensure the safety of food products and prevent the further spread of BSE.
• Various countries, including the United States, Canada, the Falkland Islands, and the Sultanate of Oman, have implemented measures to address BSE cases. When an infection is detected, affected animals are slaughtered, and the carcasses are destroyed to remove the potential risk of transmission.
• The epidemiology of BSE highlights the importance of surveillance, control measures, and international cooperation to prevent the spread of the disease and protect both animal and human health.

Diagnosis of Bovine Spongiform Encephalopathy (BSE)

• The diagnosis of Bovine Spongiform Encephalopathy (BSE) involves multiple techniques and examinations to accurately confirm the presence of the disease. These diagnostic methods focus on the detection of the abnormal prion protein (PrP) and the identification of pathological changes in the brain tissue.
• Clinical diagnosis, based on observed symptoms and neurological abnormalities, can provide an initial indication of BSE with an accuracy of approximately 85%. However, a definitive confirmation of the disease is achieved through microscopic examination of brain tissue.
• Bioassays in animals are conducted to estimate the concentration of BSE prions. These assays involve inoculating susceptible animals with tissue samples from potentially infected animals and monitoring for the development of BSE.
• Enzyme-linked immunosorbent assay (ELISA) is a commonly used technique for BSE diagnosis. It detects the PrP antigen by reacting with specific antibodies. ELISA can also detect antibodies produced by the host against the BSE pathogen, aiding in the identification of infected individuals.
• Histological examination of brain tissue is performed by embedding the tissue in paraffin and staining it with dyes such as hematoxylin and eosin. This technique allows for the visualization of pathological changes using light microscopy.
• Immunohistochemistry is used to specifically detect the presence and distribution of the abnormal prion protein deposits in brain tissue. Secondary antibodies targeting specific PrP epitopes are applied, resulting in a staining pattern that highlights the presence of infection.
• To differentiate strains of prions and enhance diagnostic accuracy, affected tissues may undergo pretreatment techniques. These treatments help in characterizing the specific properties of the prion strains.
• Western immunoblotting, or Western blot, is a technique that detects the PrP antigen. It involves the separation of prion proteins by gel electrophoresis, followed by the application of antibodies that bind to the PrP. The migration pattern of the proteins provides information about their glycosylation state. Different bands are observed, including a high molecular weight band with two sugar molecules (diglycosylated), a middle band with one sugar molecule (monoglycosylated), and a low band with no sugar molecules (unglycosylated). These bands can be used to differentiate isolates and strains, although interpretation can vary depending on laboratory methodologies.
• Combining these diagnostic approaches, including clinical evaluation, histopathology, immunohistochemistry, and molecular techniques, enables accurate diagnosis and identification of BSE. These methods play a crucial role in surveillance programs, disease control, and prevention measures.

Treatment and Vaccination

• Unfortunately, there are no specific treatments or vaccinations available for Bovine spongiform encephalopathy (BSE) at present. BSE is a degenerative neurological disease caused by the presence of misfolded prion proteins, and its treatment remains a significant challenge.
• The nature of prion diseases, including BSE, makes them particularly difficult to treat. Prion proteins are highly resistant to conventional treatments such as antiviral or antibiotic medications. Moreover, the infectious prions are not effectively targeted by the immune system, which further limits the options for therapeutic intervention.
• As a result, the focus in managing BSE primarily revolves around prevention, surveillance, and control measures. Measures implemented to prevent the spread of BSE include strict regulations on animal feed, bans on the use of certain animal by-products in feed, and surveillance programs to detect and control the disease in cattle populations.
• In addition, specific risk materials (SRMs), such as the brain, spinal cord, and certain parts of the digestive tract, are removed from the human food chain to reduce the risk of transmission to humans.
• Efforts are also directed towards implementing strict guidelines and regulations for the proper disposal and rendering of carcasses and potentially contaminated materials, minimizing the risk of environmental contamination.
• Furthermore, international collaboration and information sharing play a crucial role in monitoring and controlling the spread of BSE. Countries have implemented surveillance systems to detect and report cases, which enables the identification of affected animals and helps prevent the further transmission of the disease.
• While research continues to advance our understanding of prion diseases, including BSE, and potential treatment strategies, currently, the absence of effective treatments or vaccinations emphasizes the importance of preventive measures and adherence to regulatory practices to minimize the impact of the disease on animal and human health.

Prevention and control measures of Bovine Spongiform Encephalopathy (BSE)

Prevention and control measures play a crucial role in managing and reducing the spread of Bovine spongiform encephalopathy (BSE). These measures aim to prevent the introduction of BSE agents into the animal feed and human food supply chains, as well as to ensure safe handling and disposal of potentially infected materials. Here are some key prevention and control measures:

1. Exclusion of high-risk materials: BSE can be controlled by excluding all meat and cattle-derived materials from cattle feed products intended for farmed animals. This helps prevent the introduction of infected materials into the animal feed chain.
2. Restriction on import and export: To prevent the transfer of BSE from one country to another, strict regulations are in place to restrict the import and export of live cattle, beef, meat-and-bone meal, and other cattle products. These measures help prevent the introduction of infected animals or materials from BSE-affected regions.
3. Safe disposal of specified risk materials: Slaughterhouses in countries like the US and UK adhere to specific guidelines for the safe disposal of specified risk body materials. These materials include the brain, spinal cord, tonsils, intestines, eyes, and trigeminal ganglia, which are considered high-risk for BSE transmission. Proper disposal methods, such as incineration, are implemented to ensure that these materials are safely removed and do not enter the animal feed or human food supply chains.
4. International regulations: International regulation and cooperation have been established to prevent the entry of BSE prions into the human food supply chain. Countries collaborate on surveillance, reporting, and implementing control measures to detect and manage BSE effectively.
5. Prompt reporting and disposal of infected animals: When a BSE agent is suspected in an animal, it is crucial to inform the competent authority responsible for disease control. The infected animal’s entire body is disposed of following approved methods, such as incineration, to prevent further transmission.
6. Laboratory safety precautions: Laboratory workers who handle infected materials, perform sampling, and conduct testing should strictly follow laboratory safety rules and precautions. This includes using appropriate personal protective equipment (PPE) and following established protocols to minimize the risk of exposure to BSE agents.

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