Bovine spongiform encephalopathy

BOVINE SPONGIFORM ENCEPHALOPATHY (MAD COW DISEASE) is an afebrile, slowly progressive neurologic disorder affecting adult cattle. It is a subacute Transmissible Spongiform Encephalopathy (TSE )that is uniformly fatal once cattle show signs of nervous disease. TSEs are caused by the accumulation of β-sheets of prion proteins in nervous tissue, leading to slowly progressive neurodegeneration and death. Current knowledge suggests that classical BSE originated from a sporadic spongiform encephalopathy preexisting in the cattle population. The causative prion was fed to genetically susceptible cattle in contaminated animal protein feeds. The disease is of considerable importance mainly because it has zoonotic potential and has spread to many countries. The cost of control is very high

Etiology:

Classical BSE is a prion-related neurodegenerative disease mainly affecting cattle but capable of crossing species barriers, including humans. The large-scale outbreak in the UK during the late 20th century was linked to a single, stable prion strain. This strain likely spread through the consumption of meat-and-bone meal (MBM) made from infected cattle, which was fed back to the herd, creating a self-sustaining transmission cycle.

While early theories suggested the disease may have originated from scrapie in sheep or infected exotic animals processed into feed, these ideas lacked strong scientific backing. Investigations, such as the Phillips and Horn reports, explored these origins but failed to identify a definitive source.

The epidemic was ultimately associated with changes in how MBM was processed, allowing prions to survive and contaminate cattle feed. This led to widespread exposure and disease spread in herds.

Researchers have since identified three forms of BSE:

• Classical BSE (C-type) was the main strain behind the widespread outbreak in the United Kingdom and is known to infect humans, leading to a condition called variant Creutzfeldt-Jakob disease (vCJD).
• Atypical H-type BSE was initially detected in the United States in 2004 and differs from the classical form in its molecular and pathological features.
• Atypical L-type BSE, also known as bovine amyloidotic spongiform encephalopathy, has been reported in aging cattle in countries such as Japan, Italy, and Canada. It is considered a rare, spontaneously occurring form of the disease.

Atypical BSE forms are believed to arise spontaneously in aging cattle, resembling rare spontaneous prion diseases in humans and animals, such as sporadic CJD or Nor98 scrapie in sheep.

Epidemiology of Classical BSE (C-type):

1. Geographic Spread

• First officially identified in Great Britain in 1987, though undetected cases likely existed in southwest England during the 1970s–early 1980s.

• By 1992, the epidemic peaked in the UK with over 37,000 clinical cases in a single year.

• Northern Ireland confirmed cases in 1998, and the Republic of Ireland in 1999.

• The disease later spread across 27 countries by 2015, including Switzerland, Portugal, France, and others.

• BSE was also found in British-imported cattle in Oman, the Channel Islands, and the Falklands.

2. Countries with Native-Born BSE Cases

• Europe: Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, UK.

• Non-Europe: Canada, Israel, Japan, United States.

3. Occurrence in Great Britain

• First clinical signs likely appeared in 1985.

• Disease declared notifiable in 1988 with a ban on feeding ruminant-derived proteins to ruminants.

• The peak of the epidemic was in 1992, and then it declined steadily.

• Most cases appeared in dairy herds (62% by 2002), compared to 17% in beef herds.

• Higher risk was seen in larger herds, and many beef cases originated from dairy herd purchases.

• Most affected region: Southwest England.

• Within-herd outbreaks were rare; less than 2% average incidence per herd.

4. Northern Ireland & Republic of Ireland

• Northern Ireland saw its peak in 1994, with lower case numbers than mainland Britain (about 10%).

• Republic of Ireland experienced a sudden rise between 1996–1998.

• The infection source was likely MBM imported from Great Britain.

• Higher clustering was noted in certain counties linked to local feed suppliers.

5. Continental Europe & Iberia

• Switzerland reported its first case in 1999, followed by Portugal and other EU countries.

• Many earlier cases likely went undetected or misdiagnosed due to a lack of awareness.

• Surveillance was enhanced with Prionics Western blot testing, leading to increased case detection across Europe.

• By 2001, nearly all EU countries (except two) had reported cases.

• France had only 103 reported cases pre-2000, but models estimate over 300,000 infected cattle during that time.

• The first L-type BSE case was reported in Italy in 2004.

6. North America

• Canada reported its first classical BSE case in a UK-imported cow in 1993.

• The first native case appeared in 2003 (Alberta), followed by more in 2005 and beyond.

• The United States confirmed its first atypical H-type case in 2004, involving a cow with a rare E211K prion gene mutation, hinting at possible genetic susceptibility.

7. Japan

• By 2007, Japan had confirmed 33 BSE cases (32 classical, 1 atypical).

• One atypical case occurred in a 16-year-old Japanese Black cow.

• Sources included imported infected cattle and contaminated milk replacer fat.

Method of Natural Transmission of Classical BSE

1. Ingestion of Contaminated Meat-and-Bone Meal (MBM)

• The BSE epidemic in the UK was linked to the consumption of MBM found in commercial cattle feed.

• Studies revealed that MBM acted as a vehicle for a scrapie-like prion agent, especially in proprietary concentrates.

• Beef calves, which were less frequently fed concentrates, showed a lower incidence, supporting this route of infection.

• The oral route is generally inefficient for prion transmission, which explains the low within-herd spread despite widespread feed contamination.

2. Changes in Rendering Practices

• Before the outbreak, MBM was processed using high-temperature solvent extraction.

• A switch to a continuous rendering method without solvent use in the late 1970s–early 1980s may have failed to deactivate prions, allowing infectious agents to survive.

• This allowed early, undetected cases of BSE to recur through cattle feed.

3. Feed Ban and Its Effects

• In 1988, the UK imposed a ban on ruminant-derived protein in cattle feed, resulting in a significant drop in new BSE cases.

• Europe followed with similar bans by 1990.

• The sharp decline in disease incidence after the bans confirmed the central role of MBM ingestion in transmission.

4. Born-After-the-Ban (BAB) Cases

• Cases continued to occur in cattle born after the ban, though at much lower levels.

• Likely caused by residual contaminated feed in mills or farms that was used up post-ban.

• BAB cases often showed geographic clustering, linked to areas with intensive pig and poultry farming, where cross-contamination of feed might have occurred.

5. BARB Cases (Born After Reinforced Ban).

• These cases also lacked evidence of vertical or horizontal transmission, suggesting illegal or accidental exposure to contaminated feed.

6. Horizontal Transmission

• No strong epidemiological evidence for significant horizontal transmission.

• Some minor transmission may occur within birth cohorts, but it is not enough to sustain an outbreak.

• This type of limited transmission is still considered in traceback investigations in the US and Canada due to potential human health risks.

7. Vertical (Maternal) Transmission

• Slightly higher risk exists for calves born after the onset of clinical signs in their dam, possibly due to contact with contaminated birth fluids.

• Placentas and embryos from infected cows have shown no detectable infectivity, and embryo transfer studies support minimal risk.

8. Reproductive Number (R₀)

• Before feed bans, the R₀ was estimated between 10–12, meaning one infected animal could theoretically infect up to 400 others via feed recycling.

• After implementation of feed bans, the R₀ has dropped to below 1 (0–0.25), indicating that the disease cannot sustain itself in the population and will eventually fade out.

Pathogenesis of Bovine Spongiform Encephalopathy (BSE):

• Early research in the UK during the 1990s involved oral dosing of cattle with brain homogenate from naturally infected cows.

• Cattle were euthanized at intervals post-exposure, and tissues were tested for infectivity via injection into mice and cattle.

Key Features

• Long incubation period: ~5 years

• Oral route of infection

• Initial replication in Peyer’s patches (distal ileum)

• Spread to CNS via:

  • Vagus nerve

  • Splanchnic nerves → celiac/mesenteric ganglia → spinal cord

Progression and Tissue Involvement

• Infectivity in Peyer’s patches is detectable at 4 months and persists for at least 24 months.

• CNS involvement begins at ~32 months post-exposure, before histologic changes are seen.

• The trigeminal ganglion and cervical spinal cord were affected around 36–38 months.

• Bone marrow and sciatic nerve show infection only after CNS involvement, suggesting secondary spread.

Prion Accumulation

• Abnormal prion protein slowly accumulates in brain tissue, leading to neuronal damage and death.

• Clinical signs coincide with visible brain pathology.

Infective Dose and Incubation

• 50% infectious dose (ID₅₀) via oral route: 0.15 g of infected brain tissue.

• Higher doses = shorter incubation periods and increased risk of clinical disease.

Clinical Signs of BSE in Cattle:

• Onset and Duration:

  • Gradual onset; disease progresses over 1 to 6 months.

  • Signs can vary daily but steadily worsen.

• General Indicators:

  • A combination of behavioral, sensory, and movement issues raises strong suspicion.

  • Early stages may go unnoticed; animals might be culled for poor production before neurological signs appear.

• Behavioral and Temperament Changes:

  • Nervousness, fearfulness, or aggression

  • Reluctance to be handled or enter familiar areas (e.g., milking parlor)

  • Repetitive behaviors like excessive licking or grooming

  • Head tossing or shaking when touched

• Sensory Abnormalities:

  • Increased sensitivity to light, sound, and touch (hyperesthesia)

  • Startle responses to sudden noise (bang test), light (flash), motion (clipboard), or touch (stick)

• Posture and Movement Disorders:

  • Swaying gait, shortened stride, or difficulty turning

  • Knuckling, stumbling, falling, or trouble rising

  • Progressive muscle weakness and wasting

• Production and Physical Changes:

  • Drop in milk yield

  • Weight loss despite appetite

  • Bradycardia (slow heart rate) unrelated to food intake

• Advanced Neurological Signs:

  • Salivation, snorting, circling, and panic behaviors

  • Staring spells, possibly due to hallucinations

  • In later stages, severe locomotor disability

Diagnostic Clues and Tests:

• No reliable antemortem (before death) test is currently available for routine screening.

• Bang/Flash/Clipboard/Stick tests may detect nervous system sensitivity:

  • Positive reactions include startling, salivating, running, or kicking.

• Atypical BSE Variants (H-type, L-type):

  • Show greater dullness and more difficulty rising, but similar to other signs.

• Neurologic Testing (Experimental/Research Use):

  • Abnormal brainstem auditory evoked potentials (BAEPs)

  • EEG and evoked potentials show promise but aren’t practical for field diagnosis.

  • Retinal changes may occur months before clinical signs in experimental settings.

Differential diagnosis by:

• Hypomagnesemia
•  Nervous acetonemia
• •Rabies
•  Lead poisoning
• Listeriosis
• Polioencephalomalacia
• Tremorgenic toxins

Treatment and Control of BSE:

• There is no known cure or effective treatment for Bovine Spongiform Encephalopathy (BSE).

• Disease control is entirely based on prevention, surveillance, and removal of infected animals.

Zonotic importance:

Bovine Spongiform Encephalopathy (BSE) has been confirmed to transmit to humans, causing a fatal neurodegenerative condition known as variant Creutzfeldt-Jakob Disease (vCJD). Unlike classical CJD, vCJD primarily affects younger individuals and has been linked to the consumption of infected cattle products. All confirmed cases share a specific genetic marker, highlighting both dietary and genetic risk in this zoonotic transmission.

Conclusion:

Bovine spongiform encephalopathy remains a significant health concern due to its link to variant cjd in humans. Prevention relies heavily on strict control of animal feed, removal of high-risk tissues, and routine surveillance. continued awareness and adherence to safety protocols are vital in reducing risks and safeguarding both animal and public health.

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FAQ’S

1. What is the primary cause of BSE in cattle?

BSE is mainly caused by cattle consuming feed contaminated with infectious prions from affected animal tissues.

2. How can humans be affected by BSE?
Humans can develop variant Creutzfeldt-Jakob disease (vCJD) after consuming beef products contaminated with BSE prions.

3. Is there any cure or treatment for BSE or VCDJ?
Currently, no effective treatment exists for either BSE in animals or VCDJ in humans—both are progressive and fatal.

4. How do governments control the spread of BSE?
Measures include feed bans, removing specified risk materials during slaughter, and testing high-risk animals for prions.

5. Why is BSE difficult to eliminate completely?
Prions are unusually resistant to standard disinfection and can survive in the environment, making complete eradication challenging.