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The Plague

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Sometimes you can see death on the horizon. Sometimes it's microscopic.

"You have to admire its simplicity. It's one billionth our size, and it's beating us."
Sam Daniels, Outbreak

An epidemic (or even pandemic) disease with lethal or at least very serious consequences for the infected. The Plague stories come in several different types. In the first, the protagonists are usually trying to find a cure or preventing it from spreading further. Expect Storyboarding the Apocalypse and a Spreading Disaster Map Graphic from such stories. The second is where the Plague is the cause of an After the End plot. Either the disease happened before the beginning of the story or the story begins with The End of the World as We Know It. In both cases the heroes are usually just naturally immune and are unable to stop the Plague killing everyone who isn't.

Sometimes, the Plague overlaps with The Virus and turns its victims into horrible degenerate mutants. It's also a common cause of the Zombie Apocalypse, if the story wants to empty the world and then fill it with monsters.

For artificially and magically created diseases, see Synthetic Plague and Mystical Plague, respectively. For a being whose main ability is to spread similar diseases, see Plaguemaster. Compare Depopulation Bomb and Sterility Plague.

Needless to say, this sort of thing has been sadly Truth in Television for centuries, although the rise of modern medicine has greatly helped.

As an aside, the word "plague" originally described a specific disease, The Black Death. While the Black Death is still called "plague", the word's definition has expanded to describe any widespread disease.


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    Anime & Manga 
  • 7 Seeds has the Ryugu Shelter arc that has a parasitoid break out, first among the cattle and finally on the humans.
  • 20th Century Boys has a plague used by the Big Bad that causes all of the blood in its victims' bodies to be drained out. The plague ends up causing both of the mentioned plots at different times.
  • A bad plague hits Midland soon after the Eclipse goes down in Berserk. The plague is spread by rats that have been possessed by Conrad, one of the God Hand.
  • An episode of the Cyborg 009 2001 series has the Cyborgs finding out that a villain wants to drop a biological bomb, containing a mortal virus that he re-discovered, over Cairo, so he can sell the cure to huge prices. It's up to them to first find out what virus did he work with, then stop him.
  • Emerging centers around an Ebola-like plague that is emerging in the middle of Tokyo.
  • Final Fantasy VII: Advent Children has Geostigma, a painful, incurable disease caused by Sephiroth infesting the Lifestream.
  • King of Thorn has the disease Medusa, which causes victims to be Taken for Granite. The main characters are chosen by lottery to be turned into Human Popsicles until a cure is found, only to wake up After the End with no cure in sight and in the middle of a Garden of Evil to boot.
  • The Gendercide plague Redface Pox in Ōoku: The Inner Chambers, that only affected males and left feudal Japan a (predominantly) Lady Land. Bears are carriers for the plague, apparently.
  • Red River (1995) has as one of its subplots a terrible plague that affected the Hitite empire. In actual history, the plague raged in Hattusha for some 20 years and killed a large portion of the population, including King Suppiluiuma, King Arnuwanda, and Gassalawiya, Mursili's wife (who Yuri's character is partially based upon).
  • In Rurouni Kenshin, it is revealed that Shinta later called Kenshin Himura was the Sole Survivor when his village was hit with cholera. He was taken in by Hiko Seijuro, and trained in the art of swordsmanship.
  • The back-story of Yuki Yuna is a Hero involves this. A virus devastated the world 300 years ago but Shinju-Sama protected the people of Shikoku by putting a protective barrier around the island and providing them with water and food. However, this is a fabrication. The outside world was actually destroyed by the Vertex, which were sent by the Heavenly Gods to wipe out humanity. This happened 300 years ago and the people still live like that, in a sheltered protective dome where the Shinju-sama and its representatives, the Taisha, have complete authority.

    Comic Books 
  • Warhol Fever from The Authority. Named because at its peak, gives the victim 15 minutes of feral superpowers and berserk rage before they explode and spread the infection even more.
  • Baltimore is set in an Alternate History where World War I ends in a stalemate as a terrible vampiric plague sweeps across Europe.
  • The Ebola Gulf-A, a.k.a. The Clench from Batman: Contagion, originally unleashed in Gotham City by the Saint Duma's Order but later revealed to have been created by Ra's al Ghul.
  • A subplot of the Lost Year storyline in Batwoman (Rebirth) involves the investigation into a mysterious disease that's decimating the fox population of the island of Coryana.
  • The backstory to the Alternate History of Chassis involves the outbreak of a virulent disease known as 'the Virus' to scientists, and as the 'Perfect Plague' during The Great War. This virus forces hasty peace talks and a speedy end to the war in 1916.
  • The Hourman Virus spread by Solaris in DC One Million was particularly insidious. Caused by Nanomachines, it acted like both a biological virus and a computer virus, and could be spread to each type of victim by the other type. And it was capable of wiping out humanity in twenty-four hours.
  • The Morbus Gravis from Italian comic book Druuna is the horrible degenerate mutant version. There's no known cure, although certain medicines can slow down the mutation or temporarily reverse its progress.
  • Green Lantern: One of the members of the Green Lantern Corps is actually a sentient smallpox virus named Leezle Pon, who stays out of meetings because it would infect the other Green Lanterns. The Sinestro Corps, on the other hand, has its own sentient virus known as Despotellis, who is responsible for killing Kyle Rayner's mother.
  • Killtopia: A "nano-plague" has spread across the globe in the world of the comic, killing humans everywhere.
  • Legacy: Vul Isen creates one to be unleashed against the galaxy
  • Martian Manhunter: Hronmeer's Curse is the reason that the eponymous hero is the Last of His Kind.
  • In Nth Man: The Ultimate Ninja , after the Soviets and the United States launch biological warheads at each other, a powerful Reality Warper tries to neutralize them. Instead, he turns the lethal virus into a nonlethal mutagen that turns infected humans into disfigured "moots" with a taste for flesh.
  • In Sweet Tooth, a plague known as The Affliction decimated the entire human population seven years before the start of the series.
  • Superman:
    • The Plague of the Antibiotic Man: A strange plague of unknown origin and nature -whose symptoms include loss of consciousness, fever and odd purple splotches all over the skin- is decimating the population of Central City, and Superman suspects it has been caused by one of his enemies.
    • In The Leper from Krypton, Lex Luthor engineers a strain of Virus-X, a dangerous and incurable alien pathogen which had scourged Krypton several centuries before, and then he spreads it with the aim to kill Superman and blackmail the world into paying him a fortune for a non-existent cure.
    • The Condemned Legionnaires: Subverted. The Big Bad claims she has infected the female members of the Legion of Super-Heroes with a pathogen called the "Crimson Virus", but she eventually reveals she caused their sickness by secretly exposing them to lethal doses of radiation.
    • In The Fall of Metropolis, Superman's city is seemingly inflicted by a malady that has inflicted the likes of Lex Luthor II, Superboy and the Newsboy Legion. Cadmus Project ultimately learns this was from fallout created by Engine City and is ultimately fixed, however not before Luthor's locked in his body for a good while.
  • X-Men: The Legacy Virus killed off a few mutants. One strain of it was capable of infecting ordinary humans too; Moira McTaggert was the most well-known non-mutant victim.
  • Y: The Last Man: A plague that wipes out every single mammal with a Y chromosone with the exception of one human Sole Survivor and his pet monkey.

    Fan Works 
  • Present in the background of the Robotech/Babylon 5 spin-off A Different Kind of Contact and its prequel: a codex entry explains how any first contact could unleash one on one or both parties due them not having immunity to the other party's illnesses, and provides examples such as the (historical) smallpox epidemics unleashed by the Spaniards in America completely by accident, the Xon invasion of Centauri lands being halted by an outbreak of the Centauri equivalent of common cold, and an epidemics of actual common cold killing 10% of Kumlakshi's population before being contained by anti-virals. That's why first contact is handled in such way to avoid it, unprotected first contact is universally a death sentence, and the Centauri consider the allegation of them trying to exterminate the Narn as completely ridiculous: if they wanted, they wouldn't spend so much on a vaccination program aimed precisely to prevent their extinction by plague.
  • In Empath: The Luckiest Smurf, an unknown incurable disease Only Fatal to Adults causes all the Smurfs in Papa Smurf's generation except for himself to perish, leaving him with about a hundred young Smurfs to take care of, leading to his A Father To His Smurfs role.
  • Guardians, Wizards, and Kung-Fu Fighters: The first epilogue chapter reveals that, centuries ago, Meridian was afflicted by one called the "White Death", which was caused by a white insect that infected crops, causing white spots, fevers, convulsions, and in many cases, death. Once they discovered the source, they burned their crops to kill the insects, even if it meant causing famine once the plague was gone, and it prompted Jonathan Ludmoore to create a new order to revitalize medical knowledge in Meridian, especially after seeing how the survivors fared, and learning that the remaining side effects could be heritable.
  • The Familiar of Zero Crossover with Bloodbourne, Lady of Blood, a one shot where Louise summon a hunter from Yharnam, and along with it the plague of knowledge. The story follows Louise in her research of unconventional magic while the professors of the academy study the hunter. Eventually Louise realizes that the hunter brought something with her, a plague of understanding, but not until after her one of her professors had turned herself into a monster. The story ends with Louise realizing she needs to stop the plague from getting out of the school, resulting in her attempting to quarantine the entire school with ritual magic. The other students, or rather monsters, try and stop her until she is saved by Colbert, who sets the entire school on fire to stop the spread and save the world.
  • My Dream Is Yours has a downplayed example with Dream-Transfer-itis, which isn't lethal in nature but it does cause Sleep Deprivation in its victims and can spread rapidly in offices and other close-knit areas. Considering Odd Squad Headquarters in general are also Dangerous Workplaces that can cause someone's premature death in an instant, sleep deprivation is a very dangerous thing to have.
  • In the Animal Crossing fanfic My Name Is Molly, a plague threatened to lead to the extinction of all of humanity. Healthy children were shipped off to far-off villages, but only after they were changed into Funny Animals and removed of their memories.
  • The Pokemon fanfic Pokémon Reset Bloodlines mentions in it a equivalent plague to the Black Death known as the Dark Pestilence that once ravaged Kalos and other European equivalent regions. It is said to have killed half the entire population and is hinted in the narrative to have originated from Ultra Space.
  • In Tales of the Hunger Games, the Capitol is ravaged by a measles outbreak around the time of the talent competition for District One's 100th Hunger Games. President Gaul is reluctant to cancel any of the related festivities and the outbreak worsens throughout that Games and the Grand Final. The historians chronicling the Hunger Games also agree that it's one of the reasons why the post-Games riots were violent and horrific.
    • The lore episode of Panem Reborn, a fan-created continuation of the series, mentions that the Capitol still suffered from the measles epidemic a year later, as seen with Emilia Cardew's 101th Hunger Games.
  • The Glee and Avatar: The Last Airbender Fusion Fic Solar Winds has a mysterious plague spreading across the entire world. Most, if not all of the still-living victims have been quarantined on an abandoned island in the Fire Nation. Fire Lord Sue plans to get rid of the plague by simply blowing up the volcano on the island.
  • What a Wonderful World has the Black Vein that caused the "Epidemic of 756". Qrow, Raven and Summer were infected by it in the past.
  • Wishing Well: A plague known as the "Three Day Drop" devastated Ponyville, killing all but eleven of the ponies. As a result of the plague, there are no pegasi or unicorn left in Ponyville. The surrounding kingdoms also refused to help Queen Sunsparkle and her people for fear of getting ill themselves.

    Film — Animation 
  • In The Mysterious Geographic Explorations of Jasper Morello, the city of Gothia is ravaged by a plague that leaves its victims bedridden with painful, glowing orange pustules. The protagonists are sent out on an expedition in search of a potential cure. They find one in the boiled blood of a giant insect that eats humans.

    Film — Live-Action 
  • The virus from 12 Monkeys, which is virulent enough to force the remaining survivors underground.
  • The Rage virus turns people into Infected in 28 Days Later and 28 Weeks Later.
  • The Andromeda Strain is about a team of scientists trying to avert a deadly disease which has wiped out a town (except for two survivors) from breaking into a worldwide pandemic.
  • The Bay revolves around a coastal town being almost wiped out by what appears to be a disease but turns out to be an infestation of mutated fish parasites eating the victims from the inside out.
  • In Breakheart Pass, the train is racing vitally needed medical supplies and personnel to Fort Humboldt, which is experiencing an outbreak of diphtheria. There is no outbreak. The villains faked it to allow a train to be sent in which they were smuggling weapons.
  • In Cabin Fever, the flesh-eating disease will eventually reach pandemic levels.
  • The unnamed virus in Carriers has already decimated humanity when the movie starts.
  • Castaways: A devastating pandemic has struck the world in the backstory of the film. Cara and Emily both tried to escape through getting on a boat away from the affected areas of the US. However, it sinks and they're then left stranded on an island together.
  • The MEV-1 virus from Contagion (2011), which starts in Hong Kong with the Patient Zero being Beth Emhoff. The final scene reveals that the virus started when an infected bat dropped a bit of banana it was eating, a pig ate it and became infected, the pig was slaughtered by a chef at a casino, and the chef didn't wash his hands before shaking hands with Beth.
  • The Crazies (1973) and its 2010 remake feature "Trixie", a biological weapon which causes violent psychosis and death within a matter of days.
  • In Day of the Evil Gun, Warfield and Forbes arrive in a small frontier town where they are hoping to resupply, only to find it is gripped by a cholera outbreak.
  • The Reaper Virus from Doomsday.
  • In Faust, the demon Mephisto brings a plague to Faust's town. Faust's despair at being unable to save the plague victims is what leads him to make a Deal with the Devil.
  • A deadly epidemic strikes New Spain in The Holy Office. The Jews are blamed for it.
  • The Zombie Plague from I Am Legend. Neville even breaks it down into how many people it killed: 90% simply died and 9% turned into zombie vampire things. Neville's in the "lucky" 1%.
  • James Bond:
    • On Her Majesty's Secret Service: The "Omega Virus". While it doesn't affect human beings, it is a germ-warfare agent that Ernst Stavro Blofeld plans to spread to create total infertility in plants and animals. It can destroy whole strains forever across entire continents in what Bond calls "epidemics of sterility".
    • No Time to Die: "Heracles" combines the fast spreading of a virus via touch and Nanomachines to devastating effects, causing certain death for the people it's genetically coded to affect.
  • Johnny Mnemonic: Nerve Attenuation Syndrome (aka NAS, "The Black Shakes") infects half the world's population by 2021. In Spider's words, this is a consequence of the overabundance of Wi-Fi electronic signals "poisoning the airwaves".
  • In The Killer That Stalked New York, health officials struggle to vaccinate the city's populace while police track down the diamond smuggler who'd unwittingly brought smallpox into the country. Meanwhile, the smuggler unknowingly spreads the sickness as she dodges the cops she assumes want to arrest her. (This was Inspired by… a Real Life incident in which NYC engaged in an emergency vaccination campaign after a visitor to the city was diagnosed with smallpox.)
  • In L: change the WorLd, a terrorist group create a virus that is a mix of Ebola and influenza, highly contagious, and quick to mutate. Naturally finding a cure before it wipes everybody out is the main plot of the movie.
  • Les Misérables (2012) mentions a plague on "At The End Of The Day". Nineteenth century France's squalid conditions make this unsurprising.
  • While Mimic is about Giant Mutant Bugs, it's a child-killing Plague which prompts the bugs' creation in the first place.
  • The Omega virus from The Ωmega Man. It kills most of the human race, and turns most of the rest into zombie vampires.
  • The Ebola-like Motaba virus from Outbreak.
  • Riot Girls: This is what adults died from, a wasting disease beginning as a black stomach rot that slowly killed them.
  • In Rise of the Planet of the Apes, a virus created to combat Alzheimer's mutated to be fatal to humans, but give apes sentience. By the time Dawn of the Planet of the Apes begins only ten percent of the human population remains, those with a natural immunity to the plague. War for the Planet of the Apes reveals that it's mutating to affect the remaining population: it robs them of the ability to speak. The Colonel claims it also robs them of their intelligence, but, as seen on the film's YMMV page, there's room for debate on that.
  • Tomb Raider (2018) features a deadly contagion instead of usual supernatural events. Himiko, an ancient Japanese empress (whose Tomb is Raided in the movie) was an asymptomatic, infectious carrier for the disease, which made her people think she possessed dark magical powers.

  • The eponymous Andromeda Strain from Michael Crichton's novel is an extraterrestrial micro-organism against which Earthborn life has no natural or scientific defense. When the lab in which it's being studied is compromised, a nuclear device is armed to obliterate it. It's realized almost too late that the strain can convert energy directly into matter and vice versa, and that a nuclear explosion would only cause it to proliferate uncontrollably.
  • Area 51: In The Mission an engineered strain of the Black Plague is released to cull humanity of all except those who obey the Airlia.
  • The germ-bomb used by the Soviets on the Midlands and spread by wind to cover 2/3's of England and Wales in Breaking Glass, by Brian Morse.
  • Circleverse: Briar's Book deals with a plague sweeping through the city, and the main characters' work to heal the sick, discover its origin, and try to find a cure.
  • In Clade, a pandemic with a 25% mortality rate ravages the world. Adam, Noah, and Lijuan hide out for as long as possible in an isolated house in the country. They occasionally visit the nearby town, which has been thoroughly looted, so there's not much to scavenge. When rioters start a wildfire, the three have to flee to the beach. Eventually scientists learn how to synthesize antibodies, ending the pandemic.
  • Just about every ailment in the world of Clocks that Don't Tick has evolved to the point of causing near-certain death. There’re super AIDS, super flues, super rabies, and that’s just scratching the surface.
  • Colas Breugnon has a plague halfway through the book. The protagonist, always carefree, accidentally catches it and nearly dies, but still keeps his cool — except for when his grand-daughter nearly dies, and when his old house and everything inside is burned down by other townspeople for fear of plague.
  • In Robert E. Howard's Conan the Barbarian novel The Hour of the Dragon, a plague is used to eliminate a king and his immediate heirs, to allow his young brother Tarascus to ascend the throne. Since the plague stops with the king's death, Tarascus is acclaimed as the chosen of the gods.
  • In a nonlethal variant, H. G. Wells' "The Country of the Blind" is set in an isolated Andean community where a disease that targets the eyes had blinded the entire population long ago.
  • Crusade in Jeans: The crusade is beset by a plague that claims the lives of quite a lot of children. Dolf, being from the future, understands germ theory and implements quarantine and hygiene measures to stop the disease.
  • Dolphin Trilogy: In Destiny and the Dolphins, World War III breaks out, and although the war never turns nuclear, genetically modified strains of typhoid fever and bubonic plague are released into the population as part of biological warfare. These illnesses have a fatality rate of nearly 100%, and despite the efforts of most countries to close their borders, they spread all over the world. One by one, radio broadcasts from each country fall silent, leaving John, Vinca, and Syn on Crab Island as possibly the only humans alive.
  • Connie Willis's Doomsday Book has two plagues. Influenza ravages Oxford, while a time travelling historian gets stuck in the Black Death.
  • Possibly the original world-killing-disease novel is Earth Abides by George R. Stewart from 1949, where humanity is cut down by a plague once mentioned as a kind of "super-measles".
  • The Fourth Empire from Empire from the Ashes — a huge, incredibly-advanced, galactic civilization — was completely annihilated (only the descendants of Dahak's crew and an isolated planet (Pardal) in the third book were shown to have survived) by the accidental release of an experimental bio-weapon. Said weapon halted the critical chemical reactions of any life it encountered, rapidly evolved, had a very long dormancy period, and could survive for centuries outside of a host. Holy shit.
  • In the Farsala Trilogy, a "swamp fever" that regularly decimates the Kadeshi population is mentioned. Kavi and Soraya use it to their advantage when they are captured — they promise that, if they are released, they will convince the Suud to find a cure.
  • The Festering by Guy N. Smith concerns a hideous skin disease that comes with copious amounts of Body Horror. It's dug up out of the earth by contractors digging a well.
  • The disease that killed all the adults in O.T. Nelson's The Girl Who Owned a City.
  • In Eye of the Falcon, the third part of the Gods and Warriors series, one of the misfortunes that has brought the island of Keftiu to its knees is some sort of a bubonic plague that has killed a great portion of the populace, including Pirra's mother, High Priestess Yassassara. The gods drive it away at the end of the book when Kreon's death appeases the ghosts of the plague's victims.
  • Bone Fever and Fat Death in Helliconia. Bone Fever causes people to lose their bodily fat rapidly, while Fat Death forces them to gorge themselves. They are actually adaptative mechanisms, allowing survivors and their offspring to live through long summer and long winter, respectively.
  • Honor Harrington: A major part of the Backstory is a plague that ravaged Manticore and Sphinx a couple decades after the first settlers arrived, when a native microbe mutated enough to jump the species barrier and infect humans. As a result, the government was reorganized into a monarchy with a system of noble titles, and the recruitment drive for new colonists brought Honor's ancestors to Sphinx.
  • Household Gods: A pestilence sweeps through Carnantum near the end of the book, killing thousands. This includes Aurelia, Julia and Titus.
  • In Richard Matheson's I Am Legend, a disease turns most of humanity into zombie vampires. Three times adapted for the movies.
  • Idlewild has Black Ep, the subject of the Ten's medical education which has already slain more than 99% of Earth's ape populations when the book starts.
  • Kadingir's prequel The Queen of Kigal describes the Signishra, a disease brought upon the planet Ki by a space cloud it came in contact with. Not only did the disease bring one of the races to the brink of extinction, but to make matters worse the cloud entered a 25-year orbit, meaning the heroes need to find a way to counter Signishra before it comes back.
  • Kane Series: An unnamed plague appears in the Back Story to "The Cold Light". Brought by a traveller on a caravan, it ravaged the rich and green land of Demornte, drastically reducing its population. The few survivors all gathered in the capital Sebbei, where they spend the rest of their lives in despair and despondency, while the rest of the country is practically deserted.
    Dead Demornte. Demornte whose towns lie empty, whose farms are slowly returning to forest. Demornte where death has lain and life will no more linger. Land of death where only shadows move in empty cities, where the living are but a handful to the countless dead.
  • Syphilis, known commonly as the Italian Fire, is devastating Europe in The Kingdom of Little Wounds. The royal family is all ill, an affliction everyone is calling Morbus Lunediernus. It's syphilis, though the queen refuses to accept this.
  • A mutation of the avian flu [A(H5N1)] that can infect humans steps in for this trope in John Ringo's The Last Centurion.
  • In 1826, Mary Shelley wrote The Last Man, which depicted a future in which humanity is wiped out by a plague. It might be the first work of fiction to feature a plague as the premise.
  • In L: change the WorLd, a former Wammy's student unleashes a genetically-engineered virus on Thailand, with the goal of eventually destroying the human race, on the grounds that Humans Are Bastards. One particular village ended up being used as a "testing site", successfully; only one little boy survived. (L eventually renames him Near, although he doesn't seem to actually be in any way related to the Near from the Death Note series proper.) L has to stop her from unleashing more of the virus.
  • The eponymous Red Death in Edgar Allan Poe's "The Masque of the Red Death", which appears to be a cross between Tuberculosis and the Bubonic plague, both of which were known in Poe's time, although Ebola, which would spring up more than a century after Poe's time, probably fits the bill too.
  • In Book 3 of The Mallorean, a nasty plague is seen initially passing from a prostitute to a sailor going AWOL, and its eventual path toward the capital of Mallorea, the largest city in the world. It becomes a massive complication for the protagonists, as Emperor Zakath refuses to let them continue on their journey until the plague has run its course, but ends up aiding them as they find a way to escape, and Zakath is unable to pursue them. The most disturbing part of the disease is the victims are left with a hideous rictus grin on the faces of their corpses.
  • The disease known as the Flare in The Maze Runner Trilogy. It was a population control virus used so that certain governments would have less overflow to deal with in the aftermath of the super-solar flare strike on the Earth. Unfortunately, it targeted everyone.
  • Anne McCaffrey has used this more than once.
  • TimeRiders: The genetically engineered Kosong-ni Virus.
    • In the short story "The Ship Who Mourned", a plague has wiped out most of a planet's population. The handful of survivors of this disease are either immune or are left paralyzed. Helva supports Theoda in an attempt to demonstrate that physiotherapy may be effective for the latter.
    • In the Dragonriders of Pern books Moreta and Nerilka's Story, a plague ravages Pern.
  • In Hermann Hesse's book Narcissus and Goldmund, while Goldmund is wandering about Europe, the Black Death breaks out, and he meets several characters who lives have been transformed by the plague, Robert and Rebecca, to name a few.
  • Subverted by Harry Turtledove in his short story Nasty, Brutish And..., part of a wider sci-fi universe. The Foitani, a race of galactic conquerors, find out which planets are likely to later produce potential enemies and hit them with an engineered virus that will constantly mutate to ensure their life forms will never be free of it. However, it turns out that Earth was one of these planets, and the virus turns out to be... the common cold.
  • Andre Norton:
    • Subverted in Android at Arms: The "epidemic" which led to the planet being quarantined — and thus cut off from any possibility of further outside interference in an ongoing civil war — was actually due to one of the rebel leaders' poisoning of the water supply of the main mercenary outpost.
    • Breed to Come: The story opens After the End; the plague that wiped out the humans (called the Demons in-story) led to the development of intelligence in several other species, including that of the protagonist.
    • Dark Piper: The planet Beltane, a lightly settled planet dedicated to biological research, developed some biological weapons, as some would-be invaders learn to their cost.
    • Ordeal in Otherwhere: An epidemic has decimated the Cult Colony on Demeter, leaving few male survivors. The protagonist, the now-orphaned daughter of the colony's education officer, is on the run as the story opens, since the survivors have become viciously xenophobic and she is an outsider.
    • The novella and short story "Outside": All the adults died years ago.
    • Plague Ship: Fear of this trope means that the titular ship can't seek help through legitimate channels, as they will be destroyed without trial if their status is known.
    • The Zero Stone: In the Back Story, a plague ship crashed on planet, and since they both survived, his parents did much better after than before. Also, he comes down with something, which causes the Free Traders to panic, because they might be labeled a plague ship.
  • Touched upon in Orson Scott Card's Pastwatch: The Redemption of Christopher Columbus. In the original timeline, Columbus didn't go to America, but went east on a Crusade. As a result, a ruthless Mayincatec empire forms that soon encounters Portuguese sailors, develops immunities to their diseases, and proceeds to conquer an unprepared Europe — which has no defense against the American diseases. An interesting reversal of how it went in our history. A more benign version is spread among the new, less bloodthirsty Mayincatec and Caribbean cultures by the time-travelers in the end, giving them immunity to European diseases.
  • The Plague, a novel by Albert Camus, is about a plague outbreak of the Algerian city of Oran.
  • The Real Boy: A devastating plague struck the island of Aletheia long ago, killing not only people but also animals and even plants. Large swathes of Aletheia are still uninhabitable wastelands.
  • The Reynard Cycle: The Red Death, a disease which causes the Incurable Cough of Death, as well as Blood from the Mouth. The disease is so feared that sufferers of it in The Baron of Maleperduys are locked aboard prison barges and left to starve. Given its general description, it's probably meant to be Tuberculosis.
  • The Roman Mysteries features an historic pandemic that starts at the end of The Twelve Tasks of Flavia Gemina and becomes one of the main plot points of The Enemies of Jupiter.
  • The Scarlet Plague by Jack London takes place in 2037, 60 years after the "Red Death" (which started in San Fran, USA) killed off most of the planet. By a point, our narrator, James Smith starts to wonder if he's and worries about being the last person to remember life before the plague.
  • The Sickenesse in Septimus Heap is a plague that was brought forward by Ghost Queen Etheldredda's pet animal the Aie-Aie and plays a background role in Physik.
  • Amoridere's Sneezing Blood and its sequels tells a narrative of a mysterious "blood plague", where the outbreak starts with the Patient Zero sneezing and then the spread continues from there. Three things that are clear is what it does (and it's not pretty), no treatments can help, and, by Blood at the Borders, the country is on the verge of collapse because of it.
  • The Great Spring Sickness in the backstory to A Song of Ice and Fire, which killed tens of thousands in the Seven Kingdoms, including 40% of the population of King's Landing, the High Septon and king Daeron II Targaryen and his heirs Valarr and Matarys.
    • In Meereen, Daenerys has to deal with an outbreak of "the pale mare" threatening to enter her city — it seems to be dysentery. Barristan says he's seen it destroy entire armies.
  • In Stephen King's book The Stand, America (and it's presumed, the rest of the world) is devastated by "Captain Trips", a genetically altered super variety of influenza.
  • Star Wars Legends:
    • In the X-Wing Series, the Krytos Plague is engineered by Imperial elements to kill only nonhumans. The Imperial throneworld, previously known as Coruscant, is infected with the plague just before the Rebel Alliance takes it, so that not only will nonhuman populations be decimated, but the Alliance will have to spend limited resources treating the victims, and nonhumans will be bitter at perceived favoritism.
    • Galaxy of Fear: The Planet Plague. The people of Ghobindi were wiped out long ago by a big plague, and an Imperial interest on that world is looking into tailoring a new one from samples which turns people into Blob Monsters.
  • Starsnatcher features an extraterrestrial After the End variation. A plague which is, appropriately, known as the Plague wiped out an entire extraterrestrial civilization and it's going to wipe out humanity next. It was originally designed to infect machines. Via radio wave transmissions, it travels from solar system to solar system and forces the computers it hijacks to print biological pathogens which infect organic life. Those infected tend to turn into omnicidal, super-durable zombies.
  • Station Eleven has Georgia Flu, a pandemic which annihilates 99% of humanity in the space of about five weeks.
  • The plot of the fourth book of The Sword of Truth is driven by a magical plague unleashed by the Imperial Order.
  • Victoria: The New Orleans Flu wipes out a substantial portion of the US population, leading to panic migrations and harsh border controls, and contributes to the general breakdown of society. Later, the titular American successor state engages in a bioweapon exchange with a Middle Eastern Coalition, leading to millions of casualties.
  • It's thanks to The Spanish Flu that Twilight's Edward Cullen became a vampire. More exactly, he and his mother contracted it; with her last energies, she took him to Dr. Carlisle Cullen and made the doc swear he'd save her son. And to do this, Carlisle turned Edward into a vampire.
  • The Underland Chronicles: Gregor and the Curse of the Warmbloods has the disease known Curse of the Warmbloods.
  • The War Against the Chtorr: The invading Chtorrans unleash a series of these to successfully soften up humanity before larger Chtorran lifeforms begin appearing.
  • There are two major examples in the Warrior Cats series: greencough, a deadly, contagious pneumonia; and an unnamed sickness that crops up in ShadowClan from them eating rats (later referred to as ShadowClan's Great Sickness): it only comes once in a great while and wipes out a good chunk of the Clan, and it doesn't have a cure until Cinderpelt discovers one.
  • The Water and the Wild: There's a deadly disease in the fairy world that has spread like wildfire, and has no known cure. Currently, it's been isolated to the wisp forest, but the wisp species are now in danger of extinction. Lottie's parents were claimed by the plague years ago, too.
  • One of the many things the rabbits of Watership Down have to fear is the dreaded "white blindness", a fast-acting disease that causes fatigue, fever and, well, blindness, but most terrifyingly leaves you oblivious to Everything Trying to Kill You. Humans know it as myxomatosis.
  • The White Plague by Frank Herbert has it where mad scientist, after the deaths of his family, creates a virus that's only fatal to women but can be carried by men. This plague has the effect of almost ending the human race creating a Gender Rarity Value.
  • Geraldine Brooks' Year Of Wonders. However, the protagonist wasn't trying to find a cure (it was the Black Death), rather, her village was purposely isolating itself in order to stop the plague from spreading more than it had to. Something of a Heroic Sacrifice... Most of them died.
  • The Years of Rice and Salt depicts an alternate Earth where The Black Death was even more destructive than in our timeline. Europe is so badly depopulated that the entire continent looks a bit like Fallout, with the only surviving Europeans being a handful of poor cretins scratching a living out of tiny enclaves on a dead continent. Though there is still an industrial revolution, there's no huge era of mass European expansion, leading to the future world being dominated by Muslim and Chinese culture over the following centuries.
  • The works of Max Brooks involve a virus — named "Solanum" in The Zombie Survival Guide and unnamed in World War Z. In either case, the virus is present globally — in the Guide, it's present in low enough levels to escape detection by the public at large, but not so much in World War Z.

    Live-Action TV 
  • Babylon 5:
    • War criminal Jha'dur from "Deathwalker" became infamous for creating them during the Dilgar War. Whatever they did, the plagues were so terrible that relatives of at least one survivor, after seeing how he died, sworn to kill her... and when she's revealed to have survived her supposed death during the Dilgar War, one of said relatives beats her within an inch of her life with a fire extinguisher before the security stops her.
    • The Markab get wiped out by a long-dormant disease in "Confessions and Lamentations". They could have survived it... except it's culturally associated with immorality to the point that individuals refuse to seek treatment and the government bans attempts at finding a cure.
  • The Barrier: The noravirus is apparently a death sentence to whoever catches it and one of the story's plotlines involves looking for a cure for it. Anyone showing symptoms at a checkpoint is taken away and the Canned Orders over Loudspeaker are frequently reminding people to avoid forming too large groups to limit risks of transmission.
  • Cathedral of the Sea: Barcelona is ravaged by the Black Death, and the citizens blame the Jews.
  • Reality show The Colony is about ten contestants trying to build a working, self-sustaining colony after a fictional worldwide viral outbreak kills off the majority of the population.
  • CSI: In "Bad Blood", the Victim of the Week was suffering from a hemorrhagic fever before being shot. The bacteria had been stolen from a local lab. Greg and Sarah are exposed to the blood while processing the scene and are quarantined while the rest of the team races to prevent further outbreak.
  • Doctor Who:
    • "The Empty Child"/"The Doctor Dances" has an interesting version: "physical injuries as plague", as Dr. Constantine puts it.note 
    • "Gridlock": The Bliss virus that wiped out everyone on New Earth except for those in New New York's undercity, Novice Hame and the Face of Boe.
  • Earth: Final Conflict had some sort of plague on humans that was caused by the Taelons after their arrival on Earth.
  • Jeremiah had the Big Death, which was Only Fatal to Adults.
  • The Last Man on Earth is an After the End story about a couple of the very, very few survivors of "the Virus" that wiped out humanity in 2018.
  • The Last Ship is all about a US Navy ship, the Nathan James, on a desperate mission to find a cure for a virus known as the "Red Flu", which is ravaging the world, and to keep that cure out of the hands of people who would use it for their own agendas.
    • By Season 4, the cure has been successfully distributed everywhere, but this has just caused the virus to mutate and jump hosts. Now known as the "Red Rust", it begins targeting the world's crop plants, triggering a global famine.
  • The Lazarus Project opens with a deadly mutated strain of MERS (Middle Eastern Respiratory Syndrome) ravaging the world. It takes the Lazarus Project a few tries to create the conditions necessary to stop it.
  • An episode in the fifth season of Leverage features the team fighting to stop a terrorist from unleashing the historical Spanish flu on modern-day Washington, D.C.
    • A season three episode features a variation: An agricultural company attempts to unleash a blight, a disease that would destroy any wheat crop other than their own, which was genetically engineered to survive it.
  • Little House on the Prairie: A localized typhus plague hits Walnut Grove and Hero Township in the first-season episode "Plague." There, a warehouse manager stores cornmeal inside his warehouse, but the lack of pest control allows a swarm of rats to get inside and infect the cornmeal. Several people die from the illness and others are on the brink of death as the church is used as a makeshift hospital to quarantine and treat the ill. In the end, Charles and several farmers trace the source and burn down the warehouse.
  • Motive: In "Index Case", the Victim of the Week is suffering from a rare tropical virus. Betty is infected while conducting the autopsy. The murder case takes on a new urgency as it is discovered that the killer is also infected, and is spreading the disease as he moves around the city.
  • This Trope is played for laughs in the Roger Miller episode of The Muppet Show, where the theater is swept with an epidemic of "Cluckitus", a disease that causes anyone infected to turn into a chicken. By the end of the show, everyone except Gonzo and Miller has it. Kermit is pretty relieved to hear from Miller (who claims to have had it once) that it's no more longer lasting than the mumps. (Which is presumably why he and Gonzo avoided it; catching it grants an immunity.)
  • The Outer Limits (1995):
    • In "Resurrection", every last human on Earth was killed in a biological war on July 24, 1997.
    • In "The Vaccine", the vast majority of humanity was killed by the Berlin C virus, which was genetically engineered by a doomsday cult, within three months.
    • In "Lithia", in the aftermath of the Great War which killed seven billion people (99% of the world's population), a plague known as the Scourge killed all the remaining males. Preserved genetic material, enough to last generations, is used to propagate humanity, but the Scourge remained in the atmosphere and all of the male children died within weeks of birth.
    • In "Essence of Life", billions of people were killed by the HR2 virus in 2003. In this episode, humanity is not quite as badly affected as in the others since civilization is in the process of being rebuilt in 2014. It is predicted that the population will grow in 2015 for the first time since the outbreak of the virus.
    • In "Final Appeal, Part One", the time traveler Dr. Theresa Givens testifies before the US Supreme Court in 2076 that a plague will wipe out humanity — at least the 20% that remains after the War of 2059 — in 2105. Clips from "The Vaccine" are used to depict the devastated world of 2105.
    • In "Patient Zero", the Gehenna Strain killed 500 million people within two months of its outbreak in New York City in 2001. By 2015, the death toll stood at more than three billion. As with "Final Appeal", clips from "The Vaccine" are used to represent the devastation.
  • Stargate-verse:
    • The plague that almost killed the Ancients in the universe is an important part of the setting. It wasn't enough to kill them all, but the first time they encountered it they said "screw it, we're out of here".
    • The same or a similar plague was used by the Ori against unbelievers in the Milky Way. It was the first and only time when a weapon of mass destruction was successfully used against Earth in the primary universe.
  • In the Starsky & Hutch two-parter "The Plague," Hutch is one of the victims, and Starsky tears the city apart looking for a man whose body might have developed antibodies so a cure can be developed.
  • Star Trek: The Original Series:
    • The disease that killed all the adults in "Miri".
    • Rigelian Fever in "Requiem for Methuselah".
    • The disease from "The Naked Time" (and its sequel "The Naked Now") is apparently non-fatal, but is highly contagious and, in both episodes, adversely affects the crew in the midst of a disaster which could destroy the ship.
    • The macrovirus in the Voyager episode "Macrocosm". Especially nightmarish because of the monsters that exist solely as vectors, and are produced by the comatose sufferers.
      • Also in "Phage" an entire alien species struck with a plague, and is forced to steal body-parts from other species. Their weapons teleport organs right out of you. Fortunately, the only major character it happens to could be kept alive until his lungs are retrieved. If you're a Red Shirt you may not be so lucky — Torres and a nameless crew member are captured, and their captor comes back wearing the Red Shirt's face to replace his own diseased skin.
    • In one episode of Star Trek: Deep Space Nine, the Dominion infected an entire planet which resisted them with a plague that they call the Blight. Everyone is born with it, and it lives dormant in their bodies until "quickening", the phase in which the disease becomes active, which can occur at any time, and once a victim has "quickened", death is inevitable and there's nothing that doctors can do except give them a quick death. This has caused the complete collapse of their society, turning what was once a space-faring civilization into something resembling the Dung Ages (it doesn't help that the disease escalates much faster around any kind of electro-magnetic power source), and their population has dwindled as many do not live long enough to have children of their own. By the time Dax and Bashir find them, the people have resigned themselves to the idea that this will be a part of their society forever. When Dr. Bashir discovers a vaccine that will prevent future generations from being infected by inoculating them in the womb, even though he feels that he has failed because he can't save the generation that is currently infected, it's nothing short of a miracle to them.
      • The Federation's "Section 31" also created a plague to kill the Changelings and win the war. Dr. Bashir was also involved in countering this plague in the series' last season.
  • Both versions of Survivors deal with the aftermath of such a disease.
  • In the Torchwood episode "End of Days", it was feared that people coming from other centuries would spread diseases for which the modern population had no immunity. Interestingly enough, although there were cases, the actual bubonic plague was the least of their concerns.
  • The Tribe, a show based around a world in which a mysterious virus wipes out all adults seemingly overnight, leaving the children and teenagers to fend for themselves.
  • "The Night of the Plague" and "The Night of the Gruesome Games" from The Wild Wild West involve the main characters attempting to stop the spread of a deadly disease.

    Tabletop Games 
  • In Exalted's backstory, a plague known as the "Great Contagion" wiped out 9/10ths of all life in Creation. The really scary part? No one knows why it didn't finish off the last tenth, which is what it was designed to do.
  • Magic: The Gathering has Phyrexia, which specializes in this. There's even a keyword called infect.
  • The card game Nuclear War features the SuperGerm card, which immediately eliminates 25 million people when played; the Nuclear Retaliation expansion introduces the SuperVirus card, which moves around the board and eliminates each player's population on their turn.
  • In Pandemic (where you fight disease, not like in the flash game of the same name, where you are the disease) you have not only one, but four (or even five with the expansion) plagues.
  • The VITAS (Viral-Induced Toxic Allergy Syndrome - essentially a super-COVID) plague cut back the planet's population by about 1/4, then another 1/10, in the future timeline of the Shadowrun game setting. Ironically, the second outbreak actually helped society; it came not long after goblinization first broke out (turning people into orcs and trolls), and seeing orcs and trolls catch VITAS made it clear that they were humans, not some sort of body-stealing monsters.
  • In Traveller Intersteller Wars the Vilani not only find that they cannot cope with Terran diseases but that Terrans can. Some of them surrender just so Terran Medics can arrive faster.
  • Warhammer and Warhammer 40,000: This is Nurgle's domain, and he's always cooking up new and horrible concoctions to try out. Some of his creations include Nurgle's Rot, which had the worst aspects of every disease in existence, and plague zombies, which... yeah. Despite this, he's definitely the cheeriest of all Chaos gods, genuinely loving his followers, and they in turn know him as Grandfather Nurgle. See, he loves all life, and bacteria and vermin count as life...

    Video Games 
  • In the backstory of a Nintendo 64 game, BattleTanx, a plague killed 99.99% of women (later revealed to be all women who didn't have the power of "The Edge"). Which is the reason the remaining men are tear-assing around in tanks.
  • In Blood Omen: Legacy of Kain it's implied that Kain had escaped from his hometown due to an outbreak. After his resurrection as a vampire, he gets the chance to return there, and things are about as bad as you'd expect — the streets are littered with piles of corpses, some of which acting as obstacles to force you to take the long way underground through basements and dungeons. One of the last houses contains proof that the plague was actually unleashed by some cultists, although this is never commented upon by Kain or anyone else.
  • Candy Mountain Massacre: The Cake Queen released a deadly plague that turned all the inhabitants of Candy Mountain aside from the cupcakes into evil monsters.
  • Plagues can show up as random events in the Conquests expansion to Civilization III. They kill a number of citizens in a city and only disappear after a certain number of turns; building certain city improvements can reduce their impact or eliminate them entirely.
  • Code 7 has the "Phantom Plague". In contrast to most cases listed here, the Phantom Plague is very un-gory, quick and always 100% lethal. The very few symtoms at most a minute or two before death are mania, berserker-like behaviour and then calling for "Alex" before simply collapsing.
  • The original Plague and many other "lesser" epidemics are found in Crusader Kings II, and are the focus of The Reaper's Due. The Black Death in particular has a way of cutting through the most intricate plots by showing up at exactly the wrong time, killing off or forcing into hiding most major individuals in the affected areas.
  • Danganronpa V3: Killing Harmony has a plague which began to kill much of Japan’s population, helping prompt the beginning of the Gofer Project. Like everything else in the game’s story, the plague never actually happened — it’s revealed to be made up through Fake Memories as part of the "Truman Show" Plot surrounding the central characters.
  • Gray Death from Deus Ex. Later revealed to be a nano-mechanical virus formed by MJ12 to take control of the world.
  • The Pandyssian rat plague is a key backdrop of the original Dishonored, affecting every level of Dunwall society. It is extremely virulent and deadly, with several stages progressing from a simple cough and Tears of Blood, through Zombie-like state (people in this stage are referred as "weepers"), to an extremely painful death. Towards the end of the game, it is revealed that the plague was introduced to Dunwall from Pandyssia on purpose by the future Big Bad (back when he was just The Spymaster), as part of a plot to Kill the Poor.
  • Dragon Quest IX has the town of Coffinwell afflicted by one, which turns out to be a magical curse rather than a natural illness. Once the party beats up and seals away the Ragin' Contagion with the help of Dr. Phlegming, everyone gets better. Except for Phlegming's wife.
  • The Elder Scrolls:
  • Fallen Legion Revenants centers around a pandemic respiratory illness -> Zombie Plague called "The Miasma", with the social conditions of the time modeled after 1918 England.
  • In Fallout 4, one sidequest has you find a cure for a child who contracted a plague from the Mole Rats in the Abandoned Laboratory of Vault 81. There's only one dose of the medicine, so if you get infected by the Mole Rats, you're either stuck with a -10 max HP debuff for the rest of the game, or you fail the quest due to using the cure on yourself and cause the vault dwellers to hate you.
  • EINDS from Fear Effect 2.
  • The Time Plague that drives the plot to Find the Cure!! is an asymptomatic disease that transmits through proximity and kills its victims exactly 25 years after contracting it. The extremely long incubation period is why nobody realized what was happening before almost the entire world was already infected.
  • In Guild Wars the human kingdom of Elona was devastated by the Scarab Plague, a disease which caused scarabs to grow inside the victim's body before erupting out and spreading to others. The Primeval Dynasty fell as a result and the great city of Fahranur, the epicenter of the plague, was sealed off permanently. In Guild Wars 2 the Inquest was able to recreate the Plague only for Palawa Joko to steal it in order to unleash it on his enemies.
  • In Hatoful Boyfriend, one of the things Iwamine Shuu is doing, is creating a virus called the Charon Virus that is an airborne virus fatal to any human exposed to it.
  • The plague, referred to by name, is present in both inFAMOUS games, but is a significantly larger threat in the second. It's caused by ray sphere radiation, a contagious plague that's 100% lethal, but conduits are immune to it, choosing to ease nature along and create a world of superhumans or sacrificing yourself and every other superhuman to cure it is the penultimate karmic choice of the game.
  • Kolibri's story uses the Gaia Hypothesis and presents all life on Earth as part of a single 'body', with each living organism one of its 'cells'. The dark crystal's influence is likened to a cancer, corrupting the 'cells' and threatening to see them destroy their own 'body'. This mostly comes from the manual, but is also reflected in level names like "Metastasis" and "Remission".
  • The entire plot of Left 4 Dead revolves around this — the main characters are some of the only people with natural immunity to The Virus that turns everyone else into crazed killing machines. There Is No Cure — they can only run for their lives.
    • It's worse than that. They're asymptomatic carriers, like Typhoid Mary.
  • It's small potatoes compared to the rest of the plot, but there's a plague on Omega in Mass Effect 2 which is rapidly lethal towards everyone but vorcha and humans, the latter of which are accused of creating and spreading it. Vorcha are seen as too short-lived and unintelligent to do anything of the sort. Professor Mordin Solus, who develops a cure, believes it was created by the Collectors.
  • In Medieval II: Total War, cities can suffer from the plague when they grow too large, but at a certain point in the timeline, the Black Death strikes and nearly all cities have a few years of plague. It is possible for units to survive for some time while infected, allowing them to spread the plague when they conquer uninfected cities or for spies to (accidentally, ahem) introduce it to cities they infiltrate. Your economy tanks meanwhile, though it may well recover after as half your army is suddenly no longer pestering you for wages.
  • Metal Gear Solid V: The Phantom Pain has the vocal chord parasites, a virulent biological weapon that matures when the larvae are exposed to the unique vibrations in vocal chords created by speaking a specific language, at which point it attacks the victim's lungs, killing them quickly, but not before causing them to revert to zombie-like dementia to spread the disease to other victims. Skull Face intends to use one specific strain of the parasites, attuned to the English language, in his plot to Take Over the World by robbing humanity of their dominant language.
  • In Mortal Kombat 1, following a Cosmic Retcon, Tarkatans are no longer a distinct race in Outworld, but victims of a virulent illness known as "Tarkat". Symptoms include mutating into creatures with mouths lined with razor-sharp teeth, red eyes with slitted pupils, blade-like protrusions from the arms and diminishing sanity that eventually gives way to ravenous violence.
  • Mutant Year Zero: Road to Eden is set a couple hundred years after a disease called the Red Plague devastated humanity (with a global thermonuclear war nearly finishing it off completely). Its symptoms included paranoia, rashes, and bleeding from the eyes.
  • The entire plot of the original Neverwinter Nights campaign. It turns out that the plague is magical in nature and designed to harvest life force that gets send to power an Ancient Evil.
  • P.A.M.E.L.A. is set in a futuristic city where a horrific disease has wiped out much of the population.
  • In Pandemic and its sequel, you play as a disease attempting to infect the entire planet. Infamously difficult to get 100% Completion on, since Madagascar does not hesitate to close its ports, and it doesn't have an airport or land boundaries with other countries.
  • Pathologic and Pathologic 2 have the Sand Plague, named due to its victims’ skin drying up like sand. It can kill anyone infected within the space of a day, prompting the player character to find a cure (or die trying).
  • Pharaoh: a non-specific plague is a possible disaster/divine punishment if you don't ensure good citywide health (access to physicians and clean water) or piss off Bast. It instantly kills a group of houses, and releases walkers that spread their infection across the houses they pass (though they can be stopped by apothecaries or a priestess of Bast if she's the patron god).
  • Phoenix Point has the Pandoravirus, which is revealed early on to be an alien bioweapon that fell onto Earth in prehistory and was sequestered in permafrost until global warming allowed it to spread into the oceans in the late 2020s. Many of the infected who didn't die walked into the sea. The second major outbreak came with fogbanks of Mysterious Mist carrying the disease covering coastal cities and swarms of mutant creatures coming back out of the sea, bringing about the collapse of global civilization. At the game's starting point in the After the End era there are signs that the virus is gearing up to infect the Earth's remaining land biomass.
  • Plague Inc. started out as a Pandemic clone, but, a number of updates later, has surpassed the original. One of the main changes is that, in Pandemic, the world searches for a vaccine, which can be a moot point if everyone is already infected. In Plague Inc, the world searches for a cure, which is distributed within days to everyone in the world and is a nearly-instant game over. There are many different types of plague the player can choose with different strengths, weaknesses, and challenges, including:
    • Bacteria, a well-balanced plague that can evolve to resist medication and hostile conditions.
    • Virus, a rapidly-mutating disease that can be difficult to control.
    • Fungus, a slow-spreading plague that can be carried by wind currents, circumventing the need for ships and planes to spread.
    • Parasite, an organism that cannot gain DNA points as quickly as the other disease types that can evolve to remain hidden in its hosts.
    • Prion, a slow-killing cerebral illness that excels at impeding research into a cure.
    • Nano-Virus, an artificial disease that must evolve, infect, and kill quickly to prevent being deactivated.
    • Bio-weapon, an escaped pathogen that kills quickly, necessitating careful evolution to keep humans alive long enough to outlast humanity.
    • Neurax Worm, a brain parasite with two paths to victory: total human extinction, or total human assimilation.
    • Necroa Virus, a disease that can reanimate the dead, leading to a war between humans and an impending Zombie Apocalypse.
    • Simian Flu, an attempt at expanding intelligence and curing Alzheimer's disease that kills humans while mentally elevating apes.
    • Shadow Plague, a sentient disease that can transform humans into vampires.
  • Persona 3 had the city believe that Apathy Syndrome was caused by a plague.
    • In Persona 4, the fog that envelops Inaba by the end of the year and causes every last (non-named) inhabitant to slowly go insane with nihilism at best, or collapse in inexplicable, incurable illness at worst.
  • [PROTOTYPE] deals with a Synthetic Plague infecting Manhattan and turning everyone in the city into mutated monsters under the control of Elizabeth Greene. It turns out that the protagonist, Alex Mercer, is the result of the original Doctor Alex Mercer's enhancing of the original "Redlight" plague virus into the current "Blacklight" virus, up until the point where he was shot and killed and the virus infected his corpse, resulting in the entity that would become the avatar of the Blacklight virus that thinks it is Alex Mercer.
  • The T-Virus from Resident Evil, which transforms infectees into hardy, dangerous zombies. Humans aren’t the only vulnerable ones…
  • Roadwarden has an unnamed plague which strikes the western village of Old Pagos, dooming its population unless the player does something about it.
  • The "Prometheus Virus" of Sid Meier's Alpha Centauri works essentially the same way as the Civ III Plagues; again certain base facilities (Research Hospitals and Nanohospitals) prevent them. Also, your Probe Teams (read: spies) can spread the disease as a form of biological warfare.
  • In The Silent Age the reason of efficient extinction of the mankind is a type of avian flu, brought from the future and amplified by the effects of Time Travel.
  • Spider-Man (PS4) has "Devil's Breath", a prototype healing serum that was meant to eradicate genetic diseases, but instead attacks a person's immune system. Doctor Octopus unleashes it upon New York City as part of his revenge scheme against Norman Osbourn, and the resultant plague kills many in the city, including Aunt May, before an antiserum can be made.
  • Subnautica features the Khaara bacterium which did quite a number on the Precursors' interstellar society after they encountered it on an unexplored world. Their reports indicate a death toll of over 140 billion across their species, and resulted in them very forcefully quarantining any planet on which the bacterium had spread. Unfortunately, the planet the game takes place on is one such planet...
  • Sword of the Stars features a number of different bioweapons that ships with Biowar modules can deploy against enemy planets. Allowing a player to kill everyone in the colony with minimal damage to infrastructure and terraforming. A specialty of the Liir.
    • Though the Zuul in the first expansion are both immune to bioweapons and unable to research them.
  • The Trauma Center series has a man made one in the GUILT and Stigma diseases (Though the latter is due to technology gone wrong) Trauma Team kind of follows in the tradition by having the Rosalia virus, which is comparable to the Ebola virus, only deadlier and with a dose of Ax-Crazy. The last arc focuses on a widespread outbreak of the disease.
  • In Virtue's Last Reward, there's Radical-6, a disease that slows the brain function of its victims and eventually causes them to become insane and suicidal. Over the course of the game it is gradually revealed that the game takes place many years after the player thought it did, after the pandemic has killed most of Earth's population, and that the point of the game is to fix that. Also, all of you were deliberately infected with Radical-6 before the game began so that you wouldn't realize you're actually on the Moon, since your slower brain function made the Moon's lower gravity feel like Earth's normal gravity.
  • In Warcraft III, and again in World of Warcraft in a pre-expansion event, you have the plague of undeath, a plague which turn people into undead. The Forsaken later successfully created the Blight, a plague capable of killing both the living and the undead.
    • The Forsaken are also the result of the Scourge's Plague. As well as the majority of most undead.
    • The "Corrupted Blood Plague" was an incident involving a raid boss named Hakkar the Soulflayer. He came equipped with the Corrupted Blood debuff, which drained HP over time and could spread to other players... as well as their pets and minions. Not only that, but thanks to quality foresight, infected pets remained so even after the raid was over. The trouble began when some players used pets to collect the ailment and then unleashed them in cities. As it turned out, NPCs were vulnerable to Corrupted Blood, too. This basically broke the game for about a week as entire cities were depopulated and low-level players died in droves. Interestingly, this incident attracted the attention of both epidemiologists and anti-terrorism units, the former because of how similar the spread of Corrupted Blood was to real-life diseases, and the latter because quite a few infectees tried to deliberately spread the virus.
  • In The Outer Worlds, the First Town of Edgewater suffers from a terrible, deadly plague. Except not really, it's actually just malnutrition because literally the only thing the town eats is saltuna from the local cannery... which might not be so bad if the cans actually contained saltuna. Saltuna aren't native to that particular planet, so the cannery just fills its cans with pretty much whatever it can find. Mostly sawdust.

  • A plague wiped out 99% of all human males in the universe of Angels 2200. A plague we find out was created by Earth's central government as a way to pacify the off-world colonies.
  • The Rash Illness in Stand Still, Stay Silent, which started off as a harmless virus but quickly turned lethal, after which the Nordic countries closed off their borders. The Rash is still considered such a danger that there are certain jobs which non-immune people are barred from, and in the case of one person caused her to kill herself rather than suffer after she contracts it.
  • Unsounded: Illness is a major issue in Kasslyne because the human healers have no understanding of it, with cold and flu analogs being very deadly. They're better at treating infection, only because the Tains left words that casters can use to kill bacteria. The problem is with the Gefendur culling of the Tains as heretics and destruction of their culture modern Kasslynians don't even know what bacteria actually are, thinking them ghosts.

    Web Original 
  • The Chaos Timeline has the Black Death, happening somewhat later and spread through longer time than in our world.
  • The Fire Never Dies has the historical 1918 influenza outbreak, here known as the American Flu rather than the Spanish Flu. While it infects Red and White soldiers indiscriminately, the Reds are better off due to a stronger response from their leadership and more industry to produce medical supplies.
  • A big part of Lands of Red and Gold concerns the fact that the Alternate History Australian civilisation has its own pandemic diseases which make their way back to the Old World after contact is made in the early 1600s, basically decapitating half the political leadership of Europe among other things.
  • The plague of Swampbreak in There is no GATE; we did not fight there is described as a disease that causes pus-filled boils to rise all over the bodies of the afflicted, while causing their flesh to rot. It is only the intervention of Julianne and Hestia, through a simple yet heartfelt shrine, that manages to cure the plague in a grand pulse of energy. Before the divine miracle, their faithful were barely able to make any progress at all.

    Western Animation 
  • In the Futurama episode "Cold Warriors", the plague is the common cold, which was eradicated in the 25th Century but reintroduced by Fry after a dormant strain of it was reactivated. Now with no vaccine or natural immunity, drastic measures are taken, mainly quarantining the entire island of Manhattan and hurling it into the sun for good measure.
  • Super Noobs:
    • The main premise of the series involves a pathogen called the virus attempting to turn living organism into rampaging monsters designed to cause chaos. The virus also seeks to infect entire planets as its revealed in " A Noob World Order" that it has managed to do so to one planet. Several soldiers called Virus Warriors seek to prevent the virus from infecting the whole universe and desire to find those responsible for creating it
    • A downplayed version of this trope is used in "License To Noob" in the form of a contagious space oriented eye infection called swink eye, which causes blindness, discharge, and itchiness in many aliens and is more severe than regular pink eye. The hive world, which is home to bee like people, fell victim to a swink eye outbreak which infected all the soldiers there and its queen and the queen claimed that all of her people had the infection as well and in the process accidentally declared war on another planet. This outbreak is heavily implied to have spread outside of the hive world and to other aliens, including Memnock and Zenblock, who are the alien tutors to the Noobs and had the infection at the same time the entire hive world had it.
  • Star Wars: The Clone Wars gives us the Blue Shadow Virus. It is described as a deadly disease with no one in the galaxy being immune and the Separatist Doctor Vindi is making the repercussions worse, since the disease is normally not airborne, but Vindis tempering caused a more aggressive strain. It's toned down a bit, as it's the villains intent to cause a pandemic, but it never comes that far. In the following episode though, it's spread in Vinds bunker due to some virus bombs getting into the wrong hands, causing Padmé Amidala, Ahsoka Tano, Captain Rex and all the remaining clones to be infected. All the scenes in the bunker just ooze dread, from Ahsoka trying to keep everybody's spirits high, to Padmés concern for everyone and the clones themselves just being resigned to their fates, as they are mostly considered expendable and believe no one would cure them anyways.

    Real Life 
Truth in Television far, far more often than we'd like it to be.
  • The Plague of Athens in 430 BC, probably typhus or typhoid but possibly a hemorrhagic fever distantly related to Ebola, struck during The Peloponnesian War, crippling Athens' ability to fight the Spartans, killed Pericles, and led to general anarchy on the streets.
  • The Antonine Plague in AD 165-80, probably smallpox but possibly measles, left Rome's legions undermanned, setting up a century of nearly fatal external threats. In addition, the plague may have caused the death of Marcus Aurelius, the last of the "Five Good Emperors".
  • The Plague of Cyprian around AD 250, essentially a repeat of the Antonine, and also claiming the life of an Emperor.
  • Justinian's Plague, almost certainly the same Yersinia plague that caused the Black Death, absolutely devastated the Roman and Persian empires. It was one of the main reasons the intact Eastern Roman Empire wasn't able to reestablish the Western Empire. Later recurrences of the plague were probably one of the reasons Islam spread as far as it did.
  • The Black Death, also Yersinia plague, began in China and had spread to Europe by the 1300s, killed a sizable fraction of the Eurasian population: estimates vary wildly, but some place the death rate as high as 60%. Europe's population would not recover for 150 years.
    • Smaller Yersinia epidemics would continue to recur once every few decades in Europe and Asia until the early 18th Century.
  • The H1N1 flu pandemic of 1918, which may have had an even higher death toll. Modern estimates peg the death toll at 100 million people, or what was at the time five percent of the world population. By contrast, the death toll for World War I (which, keep in mind, was raging at the same time) was "only" about 10-15 million. Unusually, this strain of flu hit young adults and adults the hardest—children and older people often did okay. It's thought that it killed by causing a cytokine storm, a fatal overreaction of the immune system. Because of this flu it was the second world war that was the first in history where more people didn't die afterwards of disease than died during the war.
    • 91 years later, the H1N1 only made a minor dent on worldwide death statistics with "barely" 284,500 dead, thanks to 2009's medicine and the swift measures taken worldwide to prevent its spread, as well as the fact that the swine-based A/H1N1 subtype of 2009 was probably less lethal than the 1918 subtype of unknown origin. The memories of 1918, however, were still enough to keep the entire world scared, and indeed many people thought it would be the end of the human race. [1]
    • 1918's H1N1 killed 22% of Samoa within two months. Victor Vaughan, the head of the U.S. Army's division of communicable diseases, said that year: "If the epidemic continues its mathematical rate of acceleration, civilization could easily disappear from the face of the Earth within a matter of a few more weeks."
  • Native Americans suffered from a number of major epidemics, many of which were lost to history due to lack of writing by most native peoples and the fact that disease often preceded extensive European penetration into a region.
    • Smallpox epidemics were common, and due to the fact that no one in the population was immune due to previously catching smallpox (or cowpox, a virus closely enough related that infections with it provided immunity from smallpox), resulting in the entire population falling ill at the same time. Contrary to its portrayal in popular culture, the Native Americans died no more often from smallpox than Europeans did (typically averaging a 30-40% fatality rate, about the same as Europeans), but the fact that the entire population got sick at the same time could put other stresses on them.
    • The worst epidemics on record in the Americas, however, were a series of epidemics in Mexico in the 1500s. An initial population of approximately 22 million was reduced by about 8 million by the 1520 smallpox epidemic (a fairly standard death rate from smallpox, which had a fatality rate of 30-40%), followed by 12-15 million deaths from the 1545 cocoliztli epidemic, then by another 2 million deaths from the 1576 epidemic. Between the three epidemics, the population was reduced by over 90%, which is the source of the oft-quoted claim that 90% of the population of *all* of the Americas died from epidemics. Interestingly, cocoliztli is thought to be a native, rat-borne disease which was some manner of hemorrhagic fever rather than an imported European disease.
    • Importation of diseases to the Americas was not just one-way deal: the Europeans got syphilis as an exchange. Whilst there had been similar diseases earlier in Europe, the American strand was extremely virulent, and it killed a lot of people, and rendered even more sterile. The majority of old European Medieval noble families died out and several royal houses (Valois, Tudor, Trastamara, Rurik) became extinct. The syphilis meant also a drastic change on sexual behavior — and, unfortunately, hygiene. Since Treponema pallidium thrived in public baths and saunas, they all but disappeared in Europe. The following centuries were the real Dung Ages, not Middle Ages.
  • As many as 500 million people died from smallpox in the 20th century alone; it had a 30% fatality rate.note  However, it typically existed in endemic rather than epidemic form, circulating amongst the population continuously rather than killing large numbers of people in a single wave.
  • Throughout history, disease epidemics killed far more people than wars ever did. It was a source of horror for people, as a plague could strike without much warning and kill a majority of the people in the village. The phrase "a pox on your house" may seem quaint to us now, but it was essentially wishing that a person and his entire family would be killed by a plague, which was a very real possibility. This is one reason children in Medieval Europe were fostered to other families at an early age: if (say) an epidemic of diphtheria struck your community, you could lose all your children in the space of a few days. Fostering children in another community at least helped to ensure that some of your descendants might outlive you.
  • War tends to foster quite a nice set of plague conditions: disruptions of infrastructure, especially anything that will reduce people's ability for nursing; overwork because all the men are away fighting; disruption of food supplies leading to a poorer diet; dead bodies lying around; people resistant to the bugs in one area travelling to a second area where they are not resistant, picking up the bugs and then travelling to a third area where no one is resistant. Oh, and people not being aware of it due to censorship of reports of it happening.
    • Up to and including the US Civil War, the vast majority of deaths in wartime (even among the military) were from disease and not from fighting. Even some of the "minor" wounds one would get on a battlefield (if you can call getting your bones smashed beyond recognition or repair "minor") could be fatal because surviving even a "routine" amputation was basically nothing but luck as disinfection of wounds was not really understood at the time.
    • The US Civil War deserves special mention because of the approximately 600,000 casualties sustained (still the largest loss of American life in battle), about 2/3rds, or 400,000 were victims of disease. Mostly due to the conditions of camps with poor sanitation and even poorer medical care. However an important factor was the concentration of a mostly rural population into (relatively) small areas, meaning all those farmboys who lived alone were exposed to every single disease from across the nation.
    • Several wars were decided by which army was less malnourished, disease-ridden and overall miserable. The Haitian Revolution arguably only had the outcome it did because the French Army came down with a major case of yellow fever at the worst possible time — granted Haiti had some skilled military leaders and much more to gain from winning, but still.
    • While modern medicine has since the late 19th century greatly reduced the number of disease deaths during most wars, wars taking place in less developed parts of the world can still display the old pattern of far more people dying from disease than from fighting. For example, the Second Congo War, which took place in the Democratic Republic of the Congo from 1998-2003, is estimated to have caused the deaths of more than 5 million people mostly from disease and starvation.
    • The 1918 flu pandemic was especially virulent precisely because it was pretty much the first war in history where troops were being constantly and efficiently transported all around the world, spreading the disease. Also, it's surmised that the conditions of the war itself made it easier for the virus to spread: Soldiers with only mild symptoms would stay in the trenches at the front line, while those with severe symptoms were transported to field hospitals... thus transmitting the disease further (which is the opposite of what happens normally, ie. people with severe symptoms tend to stay home, slowing the spread of the disease.) Oh, and the Allied and Central Powers were suppressing reports of it to prevent it from affecting morale, exacerbating the spread because people didn't know it existed. This led to it being called Spanish flu even though it didn't originate in Spain because Spain was neutral, meaning Spanish journalists were allowed to do their job. It has been suggested that it wasn't anything about the supposedly "Spanish" flu itself that caused it to be so deadly but rather superinfections caused by malnourishment, overcrowded hospitals, and shitty hygiene, all a result of the war since getting away from death would take priority over eating and washing and an absurd number of people would be injured or fall ill.
  • The Other Wiki has a very nice list of historical plagues.
  • Ebola. As a virus, it's innately difficult to treat and it's rare enough that there are no specific drugs for it. A vaccine that works on humans courtesy of MSD was in development since the mid-2000s, but it's approved for medical use since late 2019-early 2020. Oh, and it makes your innards dissolve into a bloody pulp that you then bleed out. Thankfully, it had been confined to Africa ...had. note  An important point is that Ebola is so virulent that it kills its victims before they can get very far — it's not airborne (you need to come into contact with the bodily fluids of a visibly-infected person in order to catch it), making transmission easily prevented by proper hygiene, which tends to keep it in isolated villages (until the 2014 outbreak — which is itself mostly confined to a few desperately poor West African countries with extraordinarily weak public health systems).
    • However, in the case of Ebola, it's not the disease itself that kills the host, but the cytokine storm that does. A protein in Ebola allows the virus to avoid the dendritic cells (a type of macrophage: they eat the disease and use a sample of it to generate antibodies by presenting it to the immune system). It then latches onto an organ and causes necrosis. When the immune system detects this, it causes a massive immune system assault in an attempt to kill off the virus, thus causing the hemorrhaging because the immune system attacks the organs as well.
  • For a more slow-moving plague, there's the HIV-AIDS pandemic, which involves a virus that slowly kills the immune system. It has killed millions and infected millions more. Medicine and treatment can keep a victim alive for years. Currently the only known cure for AIDS is to receive a bone marrow transplant from somebody who has a mutation that makes them resistant to it, which is such a dangerous operation that living with the disease is a far safer option, and it does not work against all strains of AIDS.
  • While estimates of the worldwide population at any given time in history tend to vary widely, most agree on two or three major times the otherwise steady trend of growth was interrupted: the middle of the 14th century (Black Death), the early 16th century (Columbian exchange), just after World War I (H1N1), and during the "Great Leap Forward" in China. Wars, catastrophes and all that had nothing on disease and malnourishment. Just let that sink in for a while.
  • Notice how often smallpox is mentioned on here? Well, humanity finally won that fight. It was the first disease for which there was a vaccination, and as it is not known to survive in non-human animals, it was actually possible to eradicate this scourge of mankind. By the late 1970s, what had once been one of the deadliest things on earth was no more. In 1980, it became the first disease to be declared officially extinctnote .
  • In addition to the many plagues that have directly impacted humans, there's the cattle plague known as rinderpest. Since domestic cattle have long been a primary food source for humans, outbreaks of rinderpest tended to cause famine and mass starvation. Mass vaccination of cattle resulted in it being declared eradicated in 2010, becoming the second virus that has been eliminated in that manner. The laboratory samples of the virus are now being destroyed, so that it will not only be gone from the wild but completely erased from existence.
  • There's also Panama disease, a wilting disease caused by a fungus that almost completely wiped out the Gros Michel banana, at the time the most popular banana on the market (this, incidentally, is why banana flavoring tastes so different from actual bananas). Not helping matters is Panama disease is resistant to fungicides and it spread so easily because, due to bananas being reproduced asexually in order to be suitable for consumption, all Gros Michel bananas were genetically identical. The scariest part? This could very well happen again: there's a new strain of Panama disease affecting the current most popular banana on the market, the Cavendish.
  • COVID-19, a disease pandemic caused by the coronavirus SARS-CoV-2, was first identified in the city of Wuhan, Hubei province, China and spread globally in the first half of 2020. This in turn led to significant increases in mortality around the world and rolling lockdowns globally. Late 2020 saw the advent of vaccines to inoculate the population against the disease, but in turn the virus has started mutating to be more contagious and at least one variant can get around vaccines, so the fight continues. Its not helped by the fact that paranoid conspiracy theorists refuse to get the vaccine.


Video Example(s):


Klay World: DISEASE

A deadly disease is spreading throughout Klay World!

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Main / ThePlague

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