Piscine transmissible amyloidotic encephalopathy: Changes since 2049/10/03


The farming process for Lassgard tuna has been implicated as the likely cause of the PTAE epizootic that led to the CMD pandemic.

Piscine transmissible amyloidotic encephalopathy (PTAE), more commonly known as mad fish disease, is a neurodegenerative disorder that affects the central nervous system of fish. It has to date been described only in farmed tuna developed by Lassgard Bioteknik, though a 2009 study has previously established PTAE infections in gilt-head sea bream.

The transmission of PTAE to humans, primarily via ingestion of infected fish, can result in Cariappa-Muren disease (CMD). Although PTAE entered the food chain in 2034, it went undiscovered until the first cases of CMD were reported in 2039. Since PTAE-affected tuna are considered to be the primary infection vector for the CMD pandemic, it precipitated a dramatic overhaul of food safety regulations and the collapse of the aquaculture industry.



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

Piscine transmissible amyloidotic encephalopathy (PTAE) is classified as a transmissible spongiform encephalopathy (TSE) because its causative agent is considered to be a misfolded protein known as a prion. In the brain, these prions cause the native isoform of major prion proteins (designated as PrPc) to misfold into the same infectious state (designated as PrPSc), which goes on to convert further PrPc in an exponential cascade. This results in dense protein aggregates in the form of amyloid fibres that disrupt the normal tissue structure. [1]

Though there is as yet no consensus on the exact etiology of PTAE, a majority of researchers believes that it is most likely a variant of bovine spongiform encephalopathy (BSE), with an altered pathogenesis due to the cross-species transmission in fish. This finding is largely based on a 2009 research study, which had demonstrated that orally exposing gilt-head sea bream to homogenates with BSE could result in the fish developing a neurodegenerative amyloidosis. The study has since been replicated and found to be broadly consistent with PTAE histopathology. [2]

Signs and symptoms

Fish infected with PTAE will not show any immediate symptoms due to the disease’s long incubation period. The clinical period is further delayed due to the significant potential for neurogenesis in fish. [3] It is thought that the conversion of PrPc into PrPSc is countered, though not outpaced, by the fish brain’s capacity for regenerating a variety of tissues and complete neuronal diversity.

Once the clinical period begins, erratic swimming and behavioural abnormalities will become apparent and grow progressively worse. Death usually follows the onset of hypokinesia, which prevents fish from maintaining the swimming behaviour required to keep pumping water through their gills. Caged fish, as with aquaculture farming sites, have also been known to kill themselves by swimming into walls and nets as a result of ataxia[4] Given the challenging nature of accurately determining anomalous behaviour in individual fish, neuropathological and immunohistochemical examinations of post-mortem brain tissue remain the most reliable diagnosis method of PTAE.



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

PTAE was first described in January 2039 by Sunil Cariappa and Connie Muren. It had been discovered by Cariappa in November 2038 when he linked an increased mortality rate in domestic cats to feeding diets that included Lassgard tuna. When this line of farmed tuna was found to be contaminated with a novel prion agent, the focus shifted to its transmission potential to humans, which led to the discovery of CMD[5]

As a result, research into the origin and pathology of PTAE did not begin in earnest until the World Health Organisation (WHO) was able to conclusively establish a transmission link between PTAE and CMD after internal documentation on Lassgard Bioteknik’s closely guarded production process was leaked to the public in October 2039.


A photo of one of Lassgard Bioteknik's aquaculture farms off the coast of Malta.

One of Lassgard Bioteknik’s aquaculture farms for Lassgard tuna off the coast of Malta in 2039.

Various spatial epidemiology studies have determined that PTAE’s infectivity rate was closely linked to Lassgard Bioteknik’s handling of its tuna as a product:

  • Lassgard Bioteknik maintained high product prices, which led to restaurants and retail outlets processing entire Lassgard tuna, including the heads, in order to cut costs. As a result, processed Lassgard tuna were regularly contaminated with central nervous system tissues, which are more likely to contain a high titre of prions and therefore represent a greater transmission risk to humans. [6]
  • The same risk also applied to the line of canned tuna which Lassgard Bioteknik began marketing and selling in early 2038. These cans generally contained processed fish meat rendered from the less prized parts of Lassgard tuna, such as the heads. Additionally, prions are not destroyed even if the fish or material containing them is canned, cooked, or refrigerated.

See also


  1. Redway, L; Camargo, C. (August 2039). “Molecular biology of prion diseases.” New Scientist
  2. Salta, E; Panagiotidis, C; Konstantinos, E et al. (July 2009). “Evaluation of the Possible Transmission of BSE and Scrapie to Gilthead Sea Bream (Sparus aurata).” PLOS Biology
  3. Zupanc, G. (June 2006). “Neurogenesis and neuronal regeneration in the adult fish brain.” Journal of Comparative Physiology
  4. Daems, A. (October 2039). “Lassgard Bioteknik used AI-powered wildlife cameras to diagnose individual tuna.” World News Wire
  5. Cariappa, S; Muren, C. (July 2039). “Acquired Prionopathic Neurodegeneration Syndrome: Pathology, Transmission, and Epidemiology.” Bulletin of the World Health Organisation
  6. Desai, H. (April 2040). “Zero waste policies in restaurants may have contributed to rapid spread of Cariappa-Muren disease.” World News Wire