6 terrifying fictional diseases and their real-life inspirations

As a health reporter and avid horror fan, there are few things I love more than seeing a fictional infectious disease take center stage as the villain — especially when they’re inspired by actual germs or parasites.

Fortunately, there’s no shortage of horror movies with terrifying invasions or diseases to choose from. We’re not even three months away from 2026, and there are already two infection-themed movies released so far, each with their own distinct bent (28 Years Later: Temple of Bones and Cold storage). So here are some of my personal favorite or particularly interesting fictional illnesses featured in movies and TV shows, along with their real-life inspirations.

1. The last of us

Now both a hit video game and HBO TV series, The last of us involves a fungus-induced apocalypse. But not just any mushroom, but one that turns its victims into aggressive zombies.

Dead ant affected by Ophiocordyceps unilateralis infection. © Walt Sturgeon (Mycowalt) (Wikimedia Commons)

This villain is based on two actual related mushroom families: Cordyceps and Ophiocordyceps. Like the show, these species spread by manipulating the behavior of their insect or arachnid hosts. Infected animals also tend to be very distinctive, with stalks or growths protruding from their bodies or heads; these growths are full of spores, ready to burst and infect others.

Fortunately, fungi are generally selective about their hosts, and there is no chance that Cordyceps fungi will jump the species barrier and start infecting humans, at least not anytime soon. Unfortunately, part of the show’s basic premise is actually happening. Thanks to climate change, some fungi have begun to adapt to higher temperatures, and we may already be seeing the emergence of new fungal diseases in humans as a result.

This year Cold storagemeanwhile, features more generic but B-movie-like mold fungi that zombify (and explode) both humans and animals. Also, Liam Neeson is his best gritty action hero.

2. 28 days/months/years later

The germ in this long-running series (hopefully a fifth is on the way) has an established name: the rage virus. Based on that, you’d think it was a fictional take on rabies. But no, canonically the Rage virus is a lab-made modified version of the Ebola virus that apparently went horribly wrong.

Rabies victims show some of the signs of severe Ebola infection, such as vomiting blood and bloodshot eyes (they are also, as the name suggests, incredibly, uncontrollably aggressive). It might stretch credulity to think that anyone with these symptoms could go after uninfected people for very long, like the Rage-infected carriers in these movies do. To those movies’ credit, though, the infected aren’t treated like zombies invulnerable to anything but a headshot, and the latest movies even provide a justification for how they’ve managed to survive all these 28 years later.

3. REC/Quarantine

Now, if you want a real rabid villain, there’s the REC series, along with its lesser quality but still fun American remakes Quarantine 1 and 2.

The first films in both series involve the quarantine of an apartment complex due to a mysterious epidemic that turns the residents into ferocious zombies. At one point, a health official even stated that the outbreak was started by an infected dog, a very real carrier of rabies. However, without going into too many spoilers, the infections in these films end up being dramatically different from rabies in their own ways.

Actual rabies infection can cause animals and humans to become aggressive towards others, although this is hardly the only symptom. Muscle twitching, confusion, and a reflexive fear of water are other common signs. And by the time these symptoms appear, death is almost 100% certain. Fortunately, pet and livestock vaccination programs have made rabies rare in much of the world, although cases in humans and dogs are still rare in the U.S.

4. Boxes

Staying in the zombie thread, there is a 2014 movie Boxes. This fictional disease exceptionally turns pre-pubescent children into zombie-like infected while giving everyone older the stomach flu (hence the film’s name). Zombification aside, this is actually a very real feature of many foodborne infections. While most people will experience mild but limited gastrointestinal distress from norovirus or Salmonella infection, younger children (and those with weakened immune systems) are more vulnerable to severe complications. These complications don’t usually involve zombification, but that’s movie magic for you.

5. The bay

The 2000s and early 2010s were littered with films that tried to cash in on the found footage craze. Few have captured my attention as much as The bayreleased in 2012, it did.

The antagonist, who runs through the fictional town of Claridge, Maryland, is not a microbe, but a species of voracious isopod mutated by the release of toxins (including growth hormones) into the Chesapeake Bay from a shady chicken farm.

Isopods are a very real order of crustaceans. And the movie version is based on Get yourself together a littleaka tongue-eating louse. These isopods will cut off the fish’s tongue and set up shop as a replacement organ. Unlike the isopods in the film, which prove fatal to many unlucky infected humans, fish can often live for years with C. little lice attached to their mouths. Only certain types of isopods are also parasitic, and the ones you’ll most often encounter are harmless pill bugs, also known as rolly skirts.

6. Contagion

2011 Contagion is not outwardly a horror film, but the pandemic-causing disease depicted in it may be the scariest because it is deliberately designed to be as real as possible.

According to the film’s technical consultants, Meningoencephalitis Virus 1 (MEV-1) was modeled after Nipah virus, an emerging zoonotic disease that occurs naturally in bats. In the movie, MEV-1 initially reaches the human population through contact with pigs infected by bats, an actual scenario that occurred with Nipah outbreaks.

Since its discovery in 1998, Nipah has continued to cause outbreaks, even this year. The virus is most easily spread through contact with infected animals, but it can also spread directly between people. At least so far, the outbreaks have generally been contained (the largest so far involving about 300 people), but have a fatality rate of about 40% to 50%. And it is certainly possible that Nipah or similar viruses may one day develop and cause the next pandemic.

For a slightly less realistic 1990s thriller, the 1995 film Outburstwhich includes an Ebola-like virus.