Bovine spongiform encephalopathy

bovine spongiform encephalopathy (also, popularly, mad cow disease or mad cow disease) is a disease caused by by prions, and which can be transmitted to humans through the consumption of infected animal parts, especially nerve tissue.

Bovine spongiform encephalopathy (BSE) or mad cow disease is a disease that belongs to a mysterious family of related diseases, most of which are very rare. The first cases of sick animals were reported in the United Kingdom in 1986. In 1996, a new disease, a variant of Creutzfeldt-Jakob disease, was detected in humans and was associated with the BSE epidemic in cattle..^{[citation required]}

Signs and symptoms

Symptoms are not immediately seen in cattle due to the extremely long incubation period of the disease. Some cattle have been observed to have an abnormal gait, behavioral changes, tremors, and hyperactivity to certain stimuli. Hind limb ataxia affects the animal's gait and occurs when muscle control is lost. This results in poor balance and coordination. Behavior changes can include aggression, nervousness, and a general change in temperament. Some neurological symptoms are an irregular gait and persistent licking. In addition, non-specific symptoms including weight loss, decreased milk production, lameness, ear infections, and teeth grinding due to pain have also been observed. Some animals may show a combination of these symptoms, while others only show one of the many reported. Once clinical symptoms emerge, they generally worsen over the following weeks and months, eventually leading to recumbency, coma, and death.

Diagnosis

The diagnosis of BSE remains a practical problem. It has an incubation period of months to years, during which no symptoms are noted, although the pathway to convert normal brain prion protein (PrP) to the disease-associated toxic form of PrPSc has been initiated. At present, virtually no way to reliably detect PrPSc is known except by examination of postmortem brain tissue using neuropathological and immunohistochemical methods. Accumulation of PrPSc in the form of abnormally folded PrP is a hallmark of the disease, but it is present at very low levels in easily accessible body fluids such as blood or urine. Investigators have attempted to develop methods to measure PrPSc that have not been fully accepted for use in materials such as blood.

The traditional method of diagnosis is based on histopathological examination of the medulla oblongata of the brain and other tissues, post mortem. Immunohistochemistry can be used to demonstrate accumulation of prion protein.

In 2010, a New York team described detecting PrPSc even when it was initially present in only one part in a hundred billion (10-11) in brain tissue. The method combines amplification with a new technology called fiberoptic envelope immunoassay and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, samples are labeled with a fluorescent dye using an antibody for specificity and then loaded into a microcapillary tube. This tube is placed in a specially constructed apparatus, totally surrounded by optical fibers to capture all the light emitted once the dye is excited using a laser. The technique allowed detection of PrPSc after much fewer conversion cycles than others achieved, substantially reducing the possibility of artifacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that developed scrapie. The animals' brains were analyzed once symptoms became apparent. The researchers could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals' lives, and from uninfected animals. The results showed very clearly that PrPSc could be detected in the animals' blood long before symptoms appeared. After further development and testing, this method could be of great value in surveillance as a blood or urine-based screening test for BSE.

Scientific facts

It is a degenerative disease of the bovine central nervous system, characterized by the appearance of nervous symptoms in adult animals that progressively ends with the death of the animal.

The disease is caused by a protein that has modified its three-dimensional structure (in biochemistry, they are called secondary and tertiary structures of proteins), due to a process called conformational change, and that turns it into a pathological agent. These infectious proteins are called prions. The incubation period for the disease is 4-5 years. This protein is Prp, which in its normal variant (Native conformation) is c, but when it comes into contact with the protein in the non-native conformation it becomes Prp (Sc) and in chain. This, when it comes into contact with the normal protein (c) of the organism, induces a conformational change and causes the passage to the Sc. It is a physiological protein and it has not been possible to eliminate it from the organism.

The symptoms observed are caused by prion accumulation in neuronal cells, causing cell death. Microscopic examination reveals vacuole-like lesions that give nerve tissue a sponge-like appearance.

The route of transmission of this disease known to date is the ingestion of food contaminated with the prion, the administration of drugs of bovine origin and from sick animals (typically growth hormone) and possibly from mother to child. The only method available to detect end-stage infection is parenteral inoculation of brain tissue into mice. However, this technique is not usable in practice since the incubation periods are about 300 days.

The disease accumulates primarily in the skull (including the brain and eyes), tonsils, spinal cord, intestine (duodenum to rectum), and spleen.

Alan Colchester of the University of Kent proposed in the September 2005 medical journal The Lancet that the disease may have originated through cattle feed from India contaminated with human remains. The Indian government strongly denied this, calling the investigation "misleading, malicious; figment of the imagination; absurd," adding that India maintains constant controls and that they have not had any cases of BSE or vCJD. Most scientists believe that the disease originated from the animals themselves and from the consumption of non-human remains.

Scientists^[who?] have accepted that the appearance of this disease was determined by the supplementary feeding of cattle with remains of sheep and goats (which already had the disease, but it was not transmitted to humans, called scrapie), which led to the slaughter and incineration of animals suspected of having acquired the disease in the United Kingdom in 1998.

Pathogenesis

The pathogenesis of BSE is not as well understood or documented as other diseases of this nature. Although BSE is a disease that produces neurological defects, its pathogenesis occurs in areas residing outside the nervous system. There was heavy deposition of PrPSc initially localized to Peyer's patches of the small intestine. The lymphatic system has been identified in the pathogenesis of cuttings. However, it has not been determined to be an essential part of the pathogenesis of BSE. Peyer's patches have been the only organ in this system found to play an important role in pathogenesis. Peyer's patch infectivity has been observed 4 months after inoculation. PrPSc accumulation was found to occur mainly in tangible body macrophages of Peyer's patches. Tangible bodily macrophages involved in PrPSc clearance are believed to play a role in the accumulation of PrPSc in such Peyer's patches. PrPSc accumulation was also found in follicular dendritic cells although to a lesser degree. Six months after inoculation, infectivity was not observed in any tissue except the ileum. This led the researchers to believe that the disease agent reproduces here. In naturally confirmed cases, there have been no reports of infectivity in Peyer's patches. Generally, in clinical experiments, high doses of the pathogen are administered. In natural cases, low doses of the agent were hypothesized to be present and therefore infectivity could not be observed.

Incidence

Bovine spongiform encephalopathy arrived in Spain in the year 2000 when it was detected in a cow. In 2001 it reached the summit causing a health crisis that would be controlled a year later thanks to European control of the epidemic. In the year 2000, the first case of BSE was detected in Spain, Carballedo (Lugo), followed by the creation of an Interministerial Commission for Food Safety accompanied by a series of measures for the massive destruction of specific risk materials. On December 22 a plan of measures against BSE is approved at a cost of 60 million pesetas. The residents of Mesía (La Coruña) spend New Year's Eve concentrated at the entrance of a mine protesting the burial of cows. On January 1, 2001, the obligation to carry out BSE tests on bovines over 30 months of age intended for consumption and the prohibition of animal meal for cattle feed entered into force. On January 16, the Special Committee on Transmissible Spongiform Encephalopathy is created. On March 31, the European standard that orders the withdrawal from the food chain of the spine of bovines over one year old enters into force, which joins the list of Specific Risk Materials along with the brain, spinal cord, intestines, eyes and tonsils. On April 28, Spain lifts the beef embargo from France and Ireland. On January 3, 2002, a law came into force that establishes fines of up to 1.2 million euros for the offender in matters of transmissible spongiform encephalopathies. In 2003, a case was confirmed in the Canary Islands, which affects the other autonomous communities. In 2005, a 26-year-old woman died. In 2007 the Ministry of Agriculture and Livestock reported in Spain a total of 713 cases of "mad cows" since the first was recorded.

Up to and including 2007, 336,799 cattle were declared sick with BSE in the European Union and 516 more in the rest of the world, the vast majority in the United Kingdom: 98.38%. In Great Britain alone, more than 2 million cattle were slaughtered.

On the other hand, until June 2010, 220 human patients affected by the new variant of Creutzfeldt-Jakob Disease were diagnosed, 217 primary cases and 3 secondary (by a blood transfusion).

On 18 October 2018 the Scottish Government confirmed the identification of a BSE case on a farm in Aberdeenshire.