Slow viral or prion diseases

Introduction
Some chronic degenerative diseases of the central nervous system in humans are caused by "slow" or chronic, persistent infections by classic viruses.
subacute sclerosing panencephalitis progressive multifocal leukoencephalopathy

Other diseases known as transmissible spongiform encephalopathieseg, Creutzfeldt-Jakob diseaseappear to be caused by unconventional transmissible agents termed "prions There may be incubation periods of years before clinical manifestations of the infections become evident

Slow Infections In Humans

Viruses SV40-like viruses (PML) measles virus (SSPE) rubella virus Atypical Agents Kuru Creutzfeld-Jakob disease (CJD) (new) variant CJD disease (vCJD=nvCJD)

Progressive Multifocal Leukoencephalopathy

JC virus (JCV), a member of the family Polyomaviridae is the etiologic agent of progressive multifocal leukoencephalopathy A central nervous system complication that occurs in some immunosuppressed individuals Now seen in a significant proportion (about 5%) of patients with AIDS; however, as ART slows pogression of HIV infections, fewer patients develop this disease. Demyelination in the central nervous system of patients with progressive multifocal leukoencephalopathy results from oligodendrocyte infection by polyomaviruses.

SYMPTOMS
weakness speech problems cognitive problems headaches visual problems sensory loss seizures

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Subacute Sclerosing Panencephalitis

A rare disease of young adults caused by measles virus, with slowly progressive demyelination in the central nervous system ending in death Large numbers of viral nucleocapsid structures are produced in neurons and glial cells. There is restricted expression of the viral genes that encode envelope proteins, so the virus persistently infecting neural cells lacks proteins needed for the production of infectious particles. Patients with subacute sclerosing panencephalitis have high titers of antimeasles antibody Reduced efficiency of measles virus transcription in differentiated brain cells is important in maintaining the persistent infection that leads to subacute sclerosing panencephalitis

Transmissible Spongiform Encephalopathy (TSEs)

The Mad Cow Disease in Cows, Scrapie in Sheep, the Creutzfeldt-Jakob Disease in human beings belong to a class of disease called Transmissible Spongiform Encephalopathy (TSEs) Initially thought to be due to slow viruses, due to the long incubation period between time of infection and appearance of disease, these are now known to be caused by agents called prions

Transmissible Spongiform Encephalopathy (TSE) What Are They?

Transmissible Spongiform Encephalopathy (TSEs) are rare forms of progressive neurodegenerative disorders that affect both humans & animals They are caused by similar agents (prions) They are called so because they produce spongiform changes in the brain

Also, the agent causing the disease is found at the highest titre in the brain

Transmissible Spongiform Encephalopathies (Prion Diseases)

Degenerative central nervous system diseases have similar pathologic features
kuru Creutzfeldt-Jakob disease Gerstmann-Strussler-Scheinker syndrome Fatal familial insomnia of humans Scrapie of sheep Transmissible encephalopathy of mink Bovine spongiform encephalopathy of cattle Chronic wasting disease of deer

Transmissible Spongiform Encephalopathies (Prion Diseases)

These diseases are described as transmissible spongiform encephalopathies. The causative agents are not conventional viruses; Infectivity is associated with proteinaceous material devoid of detectable amounts of nucleic acid. The term "prion" is used to designate this novel class of agents. Although the etiologic agent may be recoverable from other organs, the diseases are confined to the nervous system.

Symptoms
Neurodegeneration and spongiform changes Amyloid plaques may be present. Long incubation periods (months to decades) precede the onset of clinical illness and are followed by chronic progressive disease (weeks to years). The diseases are always fatal, with no known cases of remission or recovery. The host shows no inflammatory response and no immune response (the agents do not appear to be antigenic); No production of interferon is elicited; No effect on host B cell or T cell function

Symptoms
Immunosuppression of the host has no effect on pathogenesis chronic inflammation induced by other factors (viruses, bacteria, autoimmunity) may affect prion pathogenesis prions accumulate in organs with chronic lymphocytic inflammation

Scrapie
A protease-resistant protein Can be purified from scrapie-infected brain and is designated prion protein PrP. Preparations containing only PrP and no detectable nucleic acid The level of PrPSc is increased in infected brains because the protein becomes resistant to degradation. Genetic susceptibility to scrapie infection is associated with point mutations in the PrPC gene, and mice genetically altered to be devoid of PrPC are resistant to scrapie.

Mad Cow Disease (BSE)

Scientific Name: Bovine Spongiform Encepalopathy It is found on any type of cloven hoofed animals such as: pigs, sheep, and cattle Sheep: Scrapie Spongiform Encepalopathy. There is a human form called Creutzfeldt-Jakobs Disease

Bovine Spongiform Encephalopathy and New Variant Creutzfeldt-Jakob Disease

A disease similar to scrapie, designated bovine spongiform encephalopathy (BSE), or "mad cow disease," emerged in cattle in Great Britain in 1986. This outbreak was traced to the use of cattle feed that contained contaminated bone meal from scrapie-infected sheep and BSEinfected cattle carcasses. In 1996, a new variant form of Creutzfeldt-Jakob disease (CJD) was recognized in the United Kingdom that occurred in younger people and had distinctive pathologic characteristics similar to those of BSE. It is now accepted that the new variant forms of CJD and BSE are caused by a common agent, indicating that the BSE agent had infected humans. Through 2004, 150 people had been diagnosed with new variant CJD in England, and most had died.

 Bovine Spongiform Encephalopathy (BSE) is so named because of the spongy appearance of the brain tissue of infected cattle (and also in the human beings) when examined under a microscope

Kuru and Classic Creutzfeldt-Jakob Disease

Two human spongiform encephalopathies are kuru and the classic form of CJD. Brain homogenates from patients have transmitted both diseases to nonhuman primates. Kuru occurred only in the eastern highlands of New Guinea and was spread by customs surrounding ritual cannibalism of dead relatives. Since the practice has ceased, the disease has disappeared.

Origins of CJD
Bovine Spongiform Encephalopathy (BSE) was first described in the UK in 1985 as a prion-based disease that affected cattle. In 1996 it was first detected in a human being It was suspected at that time (which turned out to be correct) that humans were contracting the disease from eating cows that had been infected with BSE In humans, it has been named the Creutzfeldt-Jakob Disease (CJD)

Types of CJD
CJD is classified into 2 forms: Classic CJD & Variant CJD

Classic CJD can be transmitted to other species, however other animals cannot carry it.

Sub classified into: Sporadic CJD and Iatrogenic CJD

Sporadic CJD - >85% of Classic CJD cases Most common between 50 75 years Characterized by rapidly increasing dementia Iatrogenic CJD - < 5% Classic CJD cases

Transmission of prion via medications & surgical equipment

vCJD
Variant Creutzfeldtt-Jakob Disease (vCJD), is caused by the consumption of BSE infected meat products The first 10 cases of variant CJD were observed in 1996, ten years after the outbreak of BSE in the UK Variant CJD seems to affect mostly young patients

Clinical Symptoms
CJD causes fatal degradation of brain tissue & the nervous system The symptoms include loss of expressiveness, muscular tremble, spasm, impaired muscle coordination, loss of memory & dementia

vCJD patients also display unusual psychiatric problems

There is no cure for CJD The condition of the patient deteriorates, finally resulting in death

At Present, there is no Cure for the Mad Cow Disease (Bovine Spongiform Encephalitis) and for the Creutzfeldt-Jakob Disease

Prevention is the only available option

Kuru and Classic Creutzfeldt-Jakob Disease

CJD in humans develops gradually, with progressive dementia ataxia myoclonus leads to death in 512 months

Kuru and Classic Creutzfeldt-Jakob Disease

Two familial forms of CJD are
Gerstmann-Strussler-Scheinker syndrome and Fatal familial insomnia.

These diseases are rare (1015% of CJD cases) and are due to inheritance of mutations in the PrP gene.

Kuru and Classic Creutzfeldt-Jakob Disease

Iatrogenic CJD has been transmitted accidentally by contaminated growth hormone preparations from human cadaver pituitary glands by corneal transplant by contaminated surgical instruments cadaveric human dura mater grafts used for surgical repair of head injury. It appears that recipients of contaminated dura mater grafts remain at risk of developing CJD for at least 16 years following receipt of grafts. There is currently no suggestion of CJD transmission by blood or blood products, although the potential is there. A protein very similar to scrapie PrPSc is present in brain tissue infected with classic CJD. It has been speculated that the agent of CJD was derived originally from scrapie-infected sheep and transmitted to humans by ingestion of poorly cooked sheep brains