Bovine Spongiform Encephalopathy (BSE)

Bovine spongiform encephalopathy (BSE), a neurodegenerative disease commonly referred to as mad cow disease, has garnered considerable attention owing to its potential zoonotic risk and its repercussions on animal health and the agricultural industry. Leveraging a profound comprehension of BSE's etiology, epidemiology, and pathogenesis, BioVenic provides its customers with pioneering diagnostics, therapeutic, and preventative solutions.

Etiology

In 1982, Prusiner identified the pathogenic PrP, the pathogen of scrapie, from scrapie-infected hamsters. In his subsequent series of studies, he concluded that pathogenic PrP is also the pathogenic factor that causes BSE.

Pathogenic PrP is a completely new pathogen that is a protein without DNA and RNA. Normal animal and human brain cells and other cells also have PrP, which is called PrP^c. BSE occurs when something causes a change in the spatial configuration of PrP^c. The variant PrP^c after the configuration change is called PrP^sc, which is the pathogenic scrapie protein. PrP^c and PrP^sc have no difference in primary structure, that is, amino acid sequence, but only in spatial configuration and properties. The detailed mechanism of conversion of PrP^c to PrP^sc is still unclear.

Fig. 1 Brain slices of transgenic mice infected with BSE.¹

Epidemiology

BSE was initially identified in the United Kingdom during the 1980s and subsequently extended its presence to various other countries. Its impact on the global bovine industry has been substantial. The disease has been documented in regions across Europe, North America, Asia, and other parts of the world, albeit with differing prevalence rates.

BSE primarily impacts bovines, showing no specific predisposition towards particular breeds or age groups. Nevertheless, it is important to emphasize that other animal species, including sheep, goats, and certain wild animals, can also be susceptible to prion diseases, albeit with variations in specific forms.

Transmission

The transmission of BSE primarily occurs through the ingestion of contaminated feedstuffs. Feed contaminated with PrP^sc from infected animals, especially tissues such as the brain and spinal cord, can introduce PrP^sc into the bovine population. Additionally, vertical transmission from the dam to offspring and, in rare instances, transmission through contaminated surgical instruments or biological products have also been reported.

Fig. 2 Schematic representation of the BSE infection cycle.²

BSE in North America

In North America, BSE has been a focal point of concern for the agricultural industry. The identification of the first native case of BSE in the US in 2003 prompted substantial public health and economic apprehensions. Subsequent to this incident, stringent surveillance measures, reinforced feed regulations, and restrictions on the import of bovine and bovine products have been put in place to forestall the dissemination of BSE and safeguard public health.

It is crucial to emphasize that BSE continues to be a notifiable disease in North America, necessitating prompt reporting of suspected cases by veterinary professionals and farmers.

Pathogenesis

The pathogenesis has not been fully elucidated, but it is generally believed that the prion that enters the body through the mouth first replicates in the lymph nodes, then enters the vagus nerve through the enteric nerve, and finally enters the central nervous system and replicates in the brain. Every time the prions reach a replication point during the above-mentioned transmission process, the normal PrP^c in the nerve cells or on the membrane will be transformed into PrP^sc. It can reduce the antioxidant effect of nerve cells, leading to the death of nerve cells and forming a vacuolated structure, and then cause various signal transduction disorders, so the sick bovine shows neurological symptoms such as voluntary movement disorders and fear.

Types of BSE

According to the characteristics and mode of transmission of the disease, BSE is divided into classical BSE (C-BSE), atypical L-type BSE (L-BSE), and atypical H-type BSE (H-BSE).

• Classical BSE (C-BSE): This is the most common BSE type affecting bovine. It is typically associated with the consumption of feed contaminated with infectious prion protein (PrP^sc). C-BSE primarily affects older bovine and is characterized by long incubation periods, ranging from 2 to 8 years.
• Atypical L-type BSE (L-BSE): This form of BSE is considered to occur spontaneously in bovine, without a clear link to feed contamination. It is characterized by shorter incubation periods compared to C-BSE.
• Atypical H-type BSE (H-BSE): Similar to L-BSE, H-BSE is also regarded as a spontaneous form of BSE. It exhibits distinct characteristics from classical BSE, manifesting a different pattern of accumulation and distribution of the abnormal prion protein in the brain.

Zoonotic Risk

The type of BSE associated with zoonotic transmission is known as C-BSE. Although rare instances of zoonotic transmission have been reported, resulting in variant Creutzfeldt-Jakob disease (vCJD) in humans, it is crucial to emphasize that the overall risk to human health from BSE is considered low.

Signs and Symptoms

The symptoms encompass both neurological and general manifestations.

• Neurological Symptoms
  
  • Fear
  • Manic
  • Aggressive
  • Hindlimb ataxia

  • Unsteady gait
  • Trembling
  • Decreased sense of touch and hearing, etc.
• General Symptoms
  
  • Depression
  • Normal appetite
  • High body temperature
  • Fast breathing

  • Weight loss
  • Reduced milk production
  • Extreme emaciation and death, etc.

Laboratory Diagnosis of BSE

The diagnosis of BSE requires laboratory examination, and the common etiological diagnosis methods are as follows,

• Immunohistochemistry (IHC): Using the brainstem, etc. as a sample
• ELISA: Antigen detection using indirect method and double-antibody sandwich method
• Western Blot: Western blot detection of PrP^sc using BSE bovine brainstem extracts
• Protein Misfolding Cyclic Amplification (PMCA): Detection of misfolded prion

At the same time, the vacuolized structure of the brain should be examined in combination with histopathological staining to assist in the diagnosis. Sick bovines do not produce prion antibodies, so antibody testing is meaningless. We offer highly specific diagnostics development services tailored to the actual conditions and specific needs of our customers.

Treatment and Prevention

There is currently no effective treatment for BSE. For afflicted ruminants, a strengthened nutritional regimen, supportive care, and the use of sulfonamides may be employed. Additionally, there is no vaccine available for the prevention and treatment of BSE.

Therefore, in the prevention and control of BSE, countries worldwide have implemented various coping strategies, including,

• Strengthen the monitoring of this disease, implement isolation observation and quarantine for suspected sick bovine.
• The affected bovine and their herds are all killed and burned, and the environment and utensils are strictly sterilized.
• Importing bovine and related products from countries or regions with BSE is strictly forbidden.
• It is strictly forbidden to feed meat and bone meal.

As a company committed to animal health, BioVenic recognizes the significance of BSE and its impact on the agricultural industry. Our objective is to offer customers cutting-edge diagnostics solutions and vaccine development services to minimize the risk of BSE transmission and safeguard animal and human health. If you want to know more information, please contact us immediately.

References

1. Doherr, Marcus G. "Bovine spongiform encephalopathy (BSE)-infectious, contagious, zoonotic or production disease?." Acta Veterinaria Scandinavica 44.1 (2003): 1-10.
2. Wadsworth, J. D. F., et al. "Contribution of transgenic models to understanding human prion disease." Neuropathology and applied neurobiology 36.7 (2010): 576-597.