Cariappa-Muren disease: Changes since 2049/09/30

Cariappa-Muren disease (CMD)
Media
An electron micrograph of 35kD membrane glycoprotein that shows amyloid fibres from its prion structure.

Micrograph of 35kD membrane glycoprotein that has formed amyloid fibres from its prion structure.

Type

Acquired

Cause

Dietary consumption of PTAE-infected fish, secondary transmission

Infectivity rate

817 per million population

Incubation period

4 to 60 years

Diagnostic method

Medical colloid

Symptoms

Memory and behavioural changes, problems with movement that worsen chronically, and ultimately death

Treatment

Supportive care

Prognosis

80% die within 3 months of becoming symptomatic, 100% within 6 months

Cariappa-Muren disease (CMD), previously known as acquired prionopathic neurodegeneration syndrome (APNS), is a universally fatal neurodegenerative disorder resulting from the transmission of piscine transmissible amyloidotic encephalopathy (PTAE) to humans. It is estimated that over three million people were infected with CMD after a popular line of farmed tuna contaminated with PTAE was introduced to the food chain in 2034 and went undiscovered until 2039.

CMD is classified as a transmissible spongiform encephalopathy (TSE) due to the causative role played by prions, though it is considered a subtype because its pathogenesis lacks any apparent spongiosis. CMD prions exponentially convert adjacent proteins into the same abnormal conformation, resulting in the disruption of neuronal cell function.

Symptoms of CMD are behavioural and psychiatric impairments with progressive decline in cognitive and motor functions. There are some available treatments that offer relatively small symptomatic benefit as the search for a cure continues. The number of confirmed infections stands at 1,620,450 with a current death toll of 39,70739,709. More cases of CMD continue to be appreciated because of its long incubation period.

The World Health Organisation (WHO) has determined that the feeding practices of Lassgard Bioteknik, the company that developed the contaminated tuna, were the likely origin of the CMD pandemic, though this remains a controversial matter of debate amongst a minority of researchers.

Table of contents

  1. Nomenclature
  2. Pathology
    1. Etiology
    2. Pathogenesis
    3. Symptoms
  3. Diagnosis
  4. See also
  5. References

Nomenclature

  1. A photo of Sunil Cariappa looking off to the side, smiling slightly. He's wearing a suit and has a lanyard around his neck.
    Epidemiologist Sunil Cariappa, pictured in 2047.
  2. A portrait of Connie Muren, dressed formally and looking at the camera.
    Neurologist Connie Muren, pictured in 2039.

Sunil Cariappa and Connie Muren.

Cariappa-Muren disease (CMD) is named after Sunil Cariappa and Connie Muren, who described the disease in July 2039 after their individual avenues of investigation led them to its shared discovery. [1]CMD was originally given the medical name acquired prionopathic neurodegeneration syndrome (APNS), but the eponymous name was ultimately chosen to avoid confusion with the simultaneous description of piscine transmissible amyloidotic encephalopathy (PTAE) as a causative agent.

Pathology

Etiology

Cariappa-Muren disease (CMD) is one of a small number of diseases known as transmissible spongiform encephalopathies (TSEs), which are caused by prions. Unlike viruses, which essentially are tightly coiled packages of DNA or RNA, prions can affect hosts in different ways without using DNA to pass along different sets of instructions to living cells. CMD prions cause major prion proteins (PrP) to misfold their normal conformation (designated as PrPc) into an infectious isoform (designated as PrPSc), which is able to convert other PrP proteins in an exponential cascade. [12]

Pathogenesis

A simplified ribbon diagram of protein structures of both normal and diseased prion proteins.

A ribbon diagram of the protein conformations of normal and diseased major prion proteins.

When CMD prions are introduced to the body, they travel to the brain and spinal cord, where they begin to convert PrPc into polymers of PrPSc that act as seeds to propagate the conversion of more prions. When they aggregate extracellularly within the central nervous system, they form amyloid plaques that disrupt the normal tissue structure. In other TSEs, this accumulation process tends to be characterised by holes in the tissue with resultant spongy architecture, but CMD causes no spongiosis in the neurons due to the cross-species transmission between fish and humans.

Symptoms

CMD progresses rapidly once symptoms appear, leading to brain damage and death within three to six months. Initial psychiatric and behavioural symptoms may include aggression, anxiety, apathy, ataxia, depression, emotional lability, insomnia, loss of memory, poor concentration, paranoid delusion, recklessness, and withdrawal. Some patients may also show signs of sensory disturbance such as pain, paresthesia, and dysesthesia.

Neurologic symptoms occur at least two months after the onset of psychiatric symptoms and include cognitive impairment, difficulty speaking, involuntary spasms, and unsteadiness. Urinary incontinence and akinetic mutism are the late onset signs. Most people eventually lapse into a coma. Heart failure, respiratory failure, pneumonia, or other intercurrent infections are generally the cause of death.

Diagnosis

A promotional photo of a reusable neural colloid injector.

The standard method of continuous testing for CMD is a medical colloid monitored by G6.

Standard testing for CMD is accomplished by fitting neural colloids with chemical sensors that can detect PrPSc in brain tissue, even when initially present at only one part in a hundred billion (10−11). The sensors were developed in 2033 by a research team at the University of Düsseldorf as a diagnosis method for variant Creutzfeldt-Jakob disease (vCJD), which acts on the same PrP protein that is affected by CMD. [3] Medical colloids administered through G6 are now used worldwide to continuously screen for latent CMD infections.

See also

References

  1. Muren, C; Hagen, S; Gao, K et al. (November 2033). “Electrode implant-based ultra-sensitive array for PrP detection in brain tissue.” Nature Nanotechnology.
  2. Cariappa, S; Muren, C. (July 2039). “Acquired Prionopathic Neurodegeneration Syndrome: Pathology, Transmission, and Epidemiology.” Bulletin of the World Health Organisation. ↩
  3. Redway, L; Camargo, C. (August 2039). “Molecular biology of prion diseases.” New Scientist. ↩
  4. Muren, C; Hagen, S; Gao, K et al. (November 2033). “Electrode implant-based ultra-sensitive array for PrP detection in brain tissue.” Nature Nanotechnology. ↩