The Prion game mode in Plague, Inc. is a very difficult challenge, especially on Brutal difficulty. Because of how slowly it infects people and takes effect, you'll face cure research that often progresses much faster than your infection. By maximizing your infectivity and keeping scary symptoms at a minimum, you'll have a much higher chance of success. This will be a very tough challenge, and may take several tries to pass.

Part 1
Part 1 of 4:

Selecting Genetic Code Modifiers

  1. 1
    Select "ATP Boost" for the DNA Gene. This ability gives you extra DNA to start out with, which is important to get the Prion infection started correctly.
  2. 2
    Select "DNA Mimic" as the Mutation Gene. This will make the Prion infection harder to cure, which will help immensely as it spreads later in the game.
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  3. 3
    Select "Aquacyte" as the Travel Gene. Aquacyte will help get Greenland infected, which is one of the most difficult places for the infection to reach.
  4. 4
    Select "Urbophile" as the Environment Gene. This will help your gene cross closed borders by quickly infecting major urban centers.
  5. 5
    Select "Sympto-Stasis" as the Evolution Gene. Sympto-Stasis will lower the cost of symptoms, allowing you to quickly reach the symptoms that will help you the most. It makes the disease easier to cure, but you'll be making it lethal that the last second, which will kill everyone before a cure can be found. This strategy relies on building a large list of symptoms quickly.
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Part 2
Part 2 of 4:

Starting Your Infection

  1. 1
    Select Saudi Arabia, China, or South Africa. These are the most popular starting countries for Prion, and will result in the best spread for your infection.[1]
  2. 2
    Focus on symptoms that spread your disease. In this initial portion of the game, you'll want to focus on symptoms that will spread your disease, as they'll be cheaper than purchasing transmission upgrades. Focus on getting the following symptoms as soon as you can:
    • Rash
    • Nausea
    • Sweating
    • Vomiting
    • Cysts
    • Hyper Sensitivity
    • Abscesses
    • Coughing
    • Pneumonia
    • Sneezing
  3. 3
    Upgrade a few transmissions to help with infecting Greenland. Upgrade the following three transmissions to help get your infection spread to Greenland and Madagascar:
    • Water 1
    • Air 1
    • Water 2
  4. 4
    Upgrade some abilities to help take Greenland and other difficult countries. The following abilities will help ensure that you are able to get Greenland, which is the country that this plan hinges the most on, as well as some other wealthy countries like Monaco and Sweden:
    • Cold Resistance 1
    • Cold Resistance 2
    • Heat Resistance 1
    • Drug Resistance 1
    • Drug Resistance 2
    • Genetic Hardening 1
    • Genetic Hardening 2
  5. 5
    Devolve anything not listed above. If any evolutions occur, devolve them to prevent your disease from become too deadly or too noticeable. You'll also get a small DNA bonus.
    • Make sure to devolve any symptoms immediately, or your disease may get noticed sooner than you're ready for.[2]
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Part 3
Part 3 of 4:

Increasing Infectivity and Slowing the Cure

  1. 1
    Evolve some more serious symptoms to spread the infection.. The symptoms below will help increase the infectivity of your disease, which will give you more DNA to work with:
    • Pulmonary Oedema
    • Skin Lesions
  2. 2
    Evolve some symptoms to slow the cure. The following symptoms will help slow down work on the cure:
    • Insomnia
    • Paranoia
    • Seizures
    • Paralysis
    • Coma
  3. 3
    Evolve your Prion special abilities. Evolve the following three abilities to put a big hamper on the cure efforts:
    • Neural Atrophy 1
    • Neural Atrophy 2
    • Neural Atrophy 3
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Part 4
Part 4 of 4:

Infecting the World and Becoming Lethal

  1. 1
    Evolve the Necrosis symptom. This symptom will start killing off the hosts, but not too quickly as to end your game. it will also boost your infectivity.
  2. 2
    Evolve the Genetic Reshuffle ability. This will drop the progress of the cure back a few percentage points.
  3. 3
    Evolve Genetic Reshuffle 2 when the cure reaches 25%. The cure will move quickly towards the end, so you'll want to set it back if it reaches 25% or so before you move on to the final few steps.
    • If you are running low on DNA points, you can skip Genetic Reshuffle 2. You should never need Genetic Shuffle 3.
  4. 4
    Wait for all countries to be infected. If you haven't yet, you'll want to wait until every country is infected before you turn your disease into a killing machine.
    • When the last country is infected, wait until it has about 10,000-15,000 people infected before moving on.
  5. 5
    Evolve Total Organ Failure. Make sure your last infected country already has 10,000-15,000 people infected before you evolve this symptom. This is going to start killing people off very quickly.
  6. 6
    Evolve Dysentery. This will help ensure that the disease continues to spread as it is killing people.
    • You'll need to have either Diarrhea or Insanity in order to get Dysentery.
  7. 7
    Evolve Hemorrhagic Shock. This symptom will increase the lethality of your disease as you rush towards the end.
  8. 8
    Wait while the world finishes getting infected and killed off. If you were successful, the entire world should be infected shortly, with death catching up soon after. You can speed things up by getting more symptoms, or evolve Genetic Reshuffle to slow the cure if necessary.[3]
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Community Q&A

  • Question
    The cure keeps rising fast, and I used two of the things next to the pills (not the potion stuff).
    Community Answer
    Community Answer
    If you are talking about genetic shuffle, it does not slow down the cure; it only gets rid of most of the progress. Evolve symptoms that have "significantly makes research harder" in their descriptions.
  • Question
    I followed every single step here carefully, and I lost and only took 40% of the world with me. I evolved every symptom that significantly makes research harder, but the cure still became 100% complete. Why did this happen?
    Community Answer
    Community Answer
    You need to put all available points into stopping the cure, because this type of plague develops symptoms slowly and kills more slowly too. More patience at the start (only plane/ship transmissions and cold 1) means you have more to spend at the end on cure avoidance and developing symptoms, which make a cure harder to research.
  • Question
    What happens if I need the genetic reshuffle 3?
    Community Answer
    Community Answer
    Just buy it if you have enough DNA points to have some left after doing so.
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Updated: March 28, 2019
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