Bovine spongiform encephalopathy

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AETIOLOGY

CLASSIFICATION OF THE CAUSATIVE AGENT An unconventional transmissible agent closely similar to that causes scrapie of sheep and goats. Hypothetically termed a prion to denote an infectious protein, because a partially protease resistant isoform of a normal host protein, PrP, is the only detectable macromolecule associated with infectivity.

RESISTANCE TO PHYSICAL AND CHEMICAL ACTION Temperature: Preserved by refrigeration and freezing. Recommended physical inactivation is porous load autoclaving at 134-138C for 18 minutes (this temperature range may not completely inactivate). pH: Stable over a wide range of pH. Disinfectants: Sodium hypochlorite containing 2% available chlorine, or 2 N sodium hydroxide, applied for >1 hour at 20C, for surfaces, or overnight for equipment. Survival: Recommended decontamination measures will reduce titres but may be incompletely effective if dealing with high titre material, when agent is protected within dried organic matter, or in tissue preserved in aldehyde fixatives. Survives in tissues post-mortem after a wide range of rendering processes. Related hamster scrapie infectivity can survive interment in soil for 3 years and dry heat of 1 hour at temperatures as high as 360C

EPIDEMIOLOGY

The incidence during the course of the epidemic in Great Britain has been low. Within affected herds the maximum annual incidence was 3%. BSE is a fatal disease and euthanasia on welfare grounds is necessary.

HOSTS Bovidae (domestic cattle, nyala [Tragelaphus angasi], greater kudu [Tragelaphus strepsiceros] and presumed similar origin for cases in gemsbok [Oryx gazella], Arabian oryx [Oryx leucoryx], eland [Taurotragus oryx], scimitar-horned oryx [Oryx dammah] and bison [Bison bison]). Felidae (domestic cat and presumed bovine origin in cheetah [Acinonyx jubatus], puma [Felis concolor], ocelot [Felis pardalis] and tiger [Panthera tigris]). Experimentally transmissible to cattle, pigs, sheep, goats, mice, mink, marmosets and macaque monkeys.

TRANSMISSION BSE occurs as a result of dietary exposure to feedstuffs containing infected meat and bone meal (MBM). No cases of BSE have been recorded as a result of iatrogenic transmission, but this is a potential means. There is some evidence of a maternally associated risk for calves born to affected cows. The biological mechanisms involved are unknown, but this effect is insignificant in the epidemiology. There is no evidence of horizontal transmission of BSE between cattle. Occurrence of new variant Creutzfeldt-Jakob disease (CJD) suggests zoonotic potential via oral exposure.

SOURCES OF AGENT Central nervous system (including eye) of naturally occurring clinically affected cases. Infectivity detected in the distal ileum of experimentally infected cattle is presumed associated with lymphoreticular tissues.

Prions Normal proteins molecules that became infections when folded into abnormal shapes Invisible to the immune system, yet tough enough to survive harsh solvents and extreme temperature It can be freeze, boil, soak in formaldehyde or carbolic acid or chloroform and most will emerge no less deadly than they were.

Prion diseases in animals Scrapie in sheep has been known for centuries, but it doesn�ft seem to infect humans. Variants in other species have emerged more recently.

Prions diseases in human Creutzfelt Jakob; Begins subtly with depression and memory problems, but in 4 to 6 months progresses to dementia, uncontrollable jerking of muscles and finally death.

OCCURRENCE The primary common source epidemic occurred in Great Britain. Cases of BSE have occurred in a number of other countries as a result of the export of infected cattle or infected MBM from Great Britain. For detailed information on occurrence, see recent issues of World Animal Health and the OIE Web site.

Transmissible Spongiform Encephalopathy (TSE) Stick to single species while others ignore such boundaries Each of them is fatal and untreatable They all ravage the brain usually after long latency periods Cause symptoms that can range from demention to psychosis and paralysis

Kuru Means shaking and shivering 16 months progression well Tremors and unsteady gait Followed by slurred speech Joyless laughter and damily stupor and clean It is transmissible It is an epidemic disease, somehow related to tribes eating habits. The women had recently created a ritual to fill the gap wherein instead of burying dead, they will eat them. They did not eat lepers or those who died of diarrhea, but the flesh of women killed by (Kuru) they considered clean.

Gerstmann-Straussler-Scheinker-Symdrome Damage to motor portions of the brain makes walking, speaking and even swallowing difficult. Dementia comes much later, Death within 2 to 6 years.

Fatal Insomnia Progressive insomnia leads to panic attack, phobias, hallucinations and finally dementia. Patients die within 18 months. Kuru and Variant Creutzfelt Jakob; Anxiety yields to trembling, loss coordination and death after 16 months.

Creutzfelt Jakob disease (CJD) A biochemical fluke, a disease that strikes randomly and infrequently all over the world One of a group of human disease with a similar pattern of brain damage Human counterpart of mad cow disease A human victim on this disease is Allison Williams was 20 yrs, old, living in the coastal village of Caernafon in North Wales, Her personality changed when she was 22. She lost interest in other people. She had grown paranoid and incontinent. A month before she died, she went blind and lost her tongue, she spent her last five days in coma.

DIAGNOSIS

Mean incubation period is 4-5 years.CLINICAL DIAGNOSISBovidae

Subacute or chronic, progressive disorder The main clinical signs are neurological: Apprehension, fear, increased startle, or depression Hyper-aesthesia or hyper-reflexia Adventitial movements: muscle fasciculations, tremor and myoclonus Ataxia of gait, including hypermetria Autonomic dysfunction: reduced rumination, bradycardia and altered heart rhythm. Pruritis, seen in scrapie, occurs also but is not usually a prominent sign. Loss of body weight and condition.

Zoo bovids Similar to cattle but some cases have sudden onset and very rapid progression.

Cats Initial signs frequently behavioural (timidity or aggression). Ataxia is most consistent progressive sign.

LESIONS There are no gross post-mortem changes. A characteristic spongiform encephalopathy is present in most cases.

DIFFERENTIAL DIAGNOSIS Hypomagnesaemia. Nervous ketosis. Encephalic listeriosis and other encephalitides Polioencephalomalacia or cerebro-cortical necrosis. Intra-cranial tumours.

LABORATORY DIAGNOSISProceduresFor details refer to OIE Manual.Identification and isolation of the agent There is no available diagnostic test for the BSE agent. Bioassay of brain tissue of terminally affected cattle or other species by parenteral inoculation of mice is the only method currently available for detection of infectivity. This is impractical because of minimum incubation periods approaching 300 days.

Serological tests The absence of detectable immune responses in BSE or other transmissible spongiform encephalopathies precludes serological tests.

Other tests Histopathological examination of the brain from clinically affected cases for characteristic bilaterally symmetrical spongiform changes of grey matter and subsequent immunohistochemical demonstration of accumulations of disease specific PrP. Examination for fibrils, homologous with scrapie-associated fibrils (SAF) by electron microscopy or electrophoretic separation and immunoblotting for detection of the disease specific isoform of PrP in extracts of unfixed, fresh or frozen brain.

Samples Preferably take whole brain, in a country experiencing initial cases or low incidence and brain stem or medulla (dependent upon BSE incidence in country) as soon as possible after death for histopathological examination. Fresh cervical spinal cord or caudal medulla (3 g) for SAF and PrP detection, frozen as soon as possible after death.

PREVENTION AND CONTROL

There is no effective treatment and clinically suspect cases must be killed by lethal injection to avoid damage to brain tissue sampled for diagnosis.

SANITARY PROPHYLAXIS Free countries Targeted pathological surveillance to occurrences of clinical neurological disease. Safeguards on importation of live ruminant species and their products. Policy and procedures for importation of embryos. Countries with cases in cattle Slaughter and compensation for ascertainment of cases. Controls on recycling of mammalian protein. Effective identification and tracing of cattle.

MEDICAL PROPHYLAXISLaboratory workers handling the tissues of BSE-suspect animals should wear appropriate protective clothing and observe a strict code of practice to avoid exposure to the agent which is highly resistant to physical and many chemical treatments. The recent occurrence of a new variant form of CJD has indicated that the BSE agent may be infectious to humans. BSE is not contagious, therefore laboratory handling aims primarily to avoid accidental iatrogenic, ocular or oronasal exposures.

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