Plague Inc.: How to Infect and Eliminate Every Human

To eliminate every human on Earth in Plague Inc., you must keep your pathogen's severity at zero, infect all isolated island territories before they shut their ports, and hoard DNA points for a sudden endgame lethality spike. Never purchase or allow lethal symptoms while healthy people remain. Killing hosts prematurely alerts researchers, speeds up cure production, and permanently locks down sea harbors. Once the game confirms 100% global infection, pause immediately and evolve catastrophic lethal symptoms to destroy the population before the cure finishes.

Step 1: Establish Early Spread from a Central Hub

Begin your infection in a warm, developing nation with dense international transport connections. Saudi Arabia, Egypt, and India provide strong starting positions due to their high populations, warm climates, and extensive airport and seaport links. Saudi Arabia is particularly effective because its air network reaches Europe, Asia, and Africa directly, while its seaports maintain steady traffic through the Indian Ocean and Mediterranean.

Spend early DNA exclusively on transmission upgrades. Prioritize water and air vectors over animal vectors, as abiotic spread delivers broader international range per point spent:

Step 2: Overcome the Island Bottleneck

The primary failure point in an extinction run is an island nation sealing its borders before your disease arrives. Territories like Greenland, Madagascar, Iceland, New Zealand, and the Caribbean rely entirely on single maritime harbors. If global awareness rises, these nations shut their ports, creating uninfectable safe havens that prevent victory.

To ensure your pathogen secures a foothold on isolated islands:

• Evolve Cold Resistance 1 and 2 early: Cold Resistance 2 is mandatory for Greenland and Iceland. Without it, your disease stalls upon arrival and fails to spread among the local population.
• Evolve Drug Resistance 1: Ships traveling to Greenland depart almost exclusively from wealthy Northern European nations such as Norway, Sweden, and the United Kingdom. Drug Resistance ensures your plague spreads efficiently through those source nations.
• Maintain zero visibility: If your disease naturally mutates symptoms like Coughing, Rash, or Cysts, devolve them immediately. Keeping severity at zero ensures port authorities never initiate quarantine measures.

Step 3: Bank DNA and Manage Mutations

Infecting the majority of the world will trigger rapid red and orange DNA bubbles. Do not spend these points on non-essential symptoms during the mid-game. Instead, keep a reserve fund of 45 to 65 DNA points.

How you handle natural mutations depends on your pathogen type:

• Bacteria and Parasite: Pause whenever an unprompted symptom mutates and devolve it. This refunds DNA points while keeping global awareness and cure research at zero.
• Virus: Because devolving symptoms costs DNA for a Virus, leave harmless transmission-assisting traits (such as Sneezing or Sweating) active. However, spend the DNA to devolve any high-lethality mutations that emerge before the entire globe is infected.

Step 4: Trigger Lethal Symptoms at 100% Infection

Wait until the in-game notification displays: "There are no healthy people left in the world." The moment every living human is infected, host mortality no longer risks closing borders or severing transmission paths.

Pause the game and spend your banked DNA to evolve Total Organ Failure, which provides the highest lethality-to-cost ratio in the game. You can reach it quickly through these paths:

• Coughing -> Pneumonia -> Pulmonary Fibrosis -> Total Organ Failure
• Cysts -> Hyper Sensitivity -> Paralysis -> Coma -> Total Organ Failure

If you have leftover DNA, evolve Necrosis via Rash -> Sweating -> Skin Lesions. Necrosis keeps deceased hosts infectious, guaranteeing that population pockets do not survive through fresh birth rates.

Step 5: Counter the Cure Effort

Unleashing lethal symptoms will immediately trigger global cure research. Your goal is not to stop the cure entirely, but to slow it down until the death rate outpaces medical progress:

1. Evolve Genetic Hardening 1 and 2: Purchase these abilities right as you trigger your lethal symptoms to permanently increase the total research work required to finish the cure.
2. Deploy Genetic Reshuffle: Monitor the global cure progress bar. If research climbs past 60%, evolve Genetic Reshuffle 1. Evolve Genetic Reshuffle 2 if the bar approaches completion, which knocks back the overall progress percentage and buys the final weeks needed to eliminate the remaining population.