Dietary consumption of PTAE-infected fish, secondary transmission
- Infectivity rate
817 per million population
- Incubation period
4 to 60 years
- Diagnostic method
Memory and behavioural changes, problems with movement that worsen chronically, and ultimately death
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 39,707. More cases of CMD continue to be appreciated because of its long incubation period.
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. 
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 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.
- Muren, C; Hagen, S; Gao, K et al. (November 2033). “Electrode implant-based ultra-sensitive array for PrP detection in brain tissue.” Nature Nanotechnology.
- Redway, L; Camargo, C. (August 2039). “Molecular biology of prion diseases.” New Scientist. ↩