Cariappa-Muren disease

Cariappa-Muren disease (CMD)

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




Dietary consumption of PTAE-infected fish, secondary transmission

Infectivity rate

817 per million population

Incubation period

4 to 60 years

Diagnostic method

Medical colloid


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


Supportive care


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 1,620,470 with a current death toll of 39,713. 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.


  1. Image
    Epidemiologist Sunil Cariappa, pictured in 2047.
  2. Image
    Neurologist Connie Muren, pictured in 2039.

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.



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. [2]



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.


CMD has a relatively long incubation period during which there are no apparent symptoms, even though the conversion of PrPc into PrPSc has started. As with most TSEs, the incubation period varies depending on, among others, the exponential growth rate of PrPc concentration, brain weight, and genetic quantitative trait loci[3]

Determining the mean and range of CMD’s incubation period is further complicated by species-barrier effects delaying the clinical period. The shortest documented time elapsed between exposure and onset of symptoms is a little over four years, and it is estimated that CMD can incubate for up to 60 years based on available data from the second wave of variant Creutzfeldt-Jakob disease (vCJD) cases recorded in Europe[4]

Once symptoms do appear, CMD progresses rapidly, 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.


The major transmission route of PTAE to humans, causing CMD, is widely considered to be dietary consumption of PTAE-infected fish. The World Health Organisation (WHO) eliminated this primary infection vector with the ban of Lassgard tuna, but secondary transmissions remain a pressing concern.

CMD prions have been identified in bodily fluids such as blood, saliva, milk, urine, and feces as early as nine months after infection, and successful transmission has been demonstrated via the nose, mouth, eyes, open wounds, and cuts and abrasions. [5] Consequently, there is continued awareness of the potential that some individuals may be asymptomatic “silent carriers” who can transmit and perpetuate CMD in susceptible hosts. [6]



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 vCJD, which acts on the same PrP protein that is affected by CMD[7] Medical colloids administered through G6 are now used worldwide to continuously screen for latent CMD infections.


The WHO and the International CMD Society (ICS) are working at all levels to find a treatment for CMD, which has to date resulted only in several therapeutic strategies that extend life and provide relief in patients. Supportive care generally includes administering vCJD-effective drugs such as daunocycline to prolong the preclinical period, and neurostimulation via colloids to mitigate psychiatric and behavioural symptoms in the clinical period. These strategies have been known to increase life expectancy by as much as 20%.

See also


  1. Cariappa, S; Muren, C. (July 2039). “Acquired Prionopathic Neurodegeneration Syndrome: Pathology, Transmission, and Epidemiology.” Bulletin of the World Health Organisation
  2. Redway, L; Camargo, C. (August 2039). “Molecular biology of prion diseases.” New Scientist
  3. Ngai, L; Mishra, S; Verheiden, K et al. (August 2045). “Identification of Multiple Quantitative Trait Loci Linked to Cariappa-Muren Disease Incubation Period.” International Journal of CMD Studies
  4. Muren, C. (February 2024). “Overall incidence of variant Creutzfeldt-Jakob disease expected to double after second wave of cases.” News Medical
  5. Da Costa Dias, B; Weiss, S. (June 2010). “A Kiss of a Prion: New Implications for Oral Transmissibility.” The Journal of Infectious Diseases
  6. Mathiason, C. (December 2015). “Silent Prions and Covert Prion Transmission.” PLOS Biology
  7. Muren, C; Hagen, S; Gao, K et al. (November 2033). “Electrode implant-based ultra-sensitive array for PrP detection in brain tissue.” Nature Nanotechnology