The Last of Us: Separating Fungal Fact From Fiction

Head Shot Anne Menegetti
Head Shot Dr Anne Menegetti
Anne Meneghetti, MD, juxtaposes the portrayal of fungal infections in HBO’s The Last of Us with real-world concerns about rising rates of antimicrobial resistance.

The Last of Us, HBO’s popular new show about a fungal infection that turns humans into flesh-eating zombies, is spurring conversation.1 Although a zombie apocalypse-inducing fungal outbreak is improbable, fungal infections do pose a very real and significant threat.

Fungal infections and toxins are common, ranging from superficial infections, such as seborrheic dermatitis, oropharyngeal and vaginal candidiasis, tinea corporis and tinea pedis, and onychomycosis, to deadly invasive infections that penetrate deep into body tissues. One such example is Candida auris, an emerging global health threat that affects hospitalized patients and is often resistant to multiple types of drugs.2

Fungal infections can be transmitted through the air, the digestive tract, or direct contact with humans, animals, the environment, or contaminated materials. Mycotoxins can cause many different adverse reactions in humans, including hallucinations and behavioral changes if a person inhales, ingests, or has skin-to-skin contact with them in sufficient amounts. Mycotoxins also can spread and contaminate food sources, leading to harmful effects. However, mycotoxins themselves will not lead to new infections because transmission requires live fungus or spores.

The Last of Us Is Sci-Fi With an Emphasis on the “fi”

The show has dominated pop culture and raised suspicion about the dangers posed by fungi. However, the show takes significant leaps with its portrayal of the manifestations of a fungal infection.

  • Interspecies spread: It is true that some types of infections can jump from one species to another; for example, from infected bats or birds to humans or passively from mosquito or tick bites. Infectious agents can mutate in a variety of ways — as we have seen with COVID-19 — and may become more or less suitable to various host species. However, the jump of an infection from an ant to a human, as suggested in The Last of Us, is a huge biological leap — even with a series of mutations.
  • Zombie puppets: Infections of the brain can cause behavioral changes. Dogs infected with rabies can become aggressive and more prone to bite or lethargic and unusually quiet. Although individuals, such as those with rabies encephalitis, may also experience neurologic and behavioral changes, the concept of a zombie that specifically bites other humans with the purpose-driven intent to spread infection, directed by the fungus, is far-fetched. High-speed chasing and biting are complex coordinated actions that require multiple working motor and sensory functions and abundant caloric intake and hydration. Mycotoxins may cause similar effects such as hallucinations or neurologic and behavioral changes, none of which are coordinated or predictable.
  • Hive mentality: The concept of disturbing a fungus in the ground leading to trigger and coordinate specific physical actions in nearby infected hosts is not based in evidence.

Fungal Infection Treatment Options

There are multiple categories of antifungal agents worth trying, alone or in combination, against a fungal infection new to humans. However, there are known fungal infections, like some strains of C auris, that are resistant to multiple drug classes, and certain mutations can lead to drug resistance.2 In contrast to fungi, new viruses are more likely to have no known treatment options until specific antiviral therapies are developed. It is noteworthy that the major epidemics and pandemics since 2000 have all been viral, including SARS, H1N1, Zika, Ebola, Middle East respiratory syndrome, and SARS-CoV-2.

One reason many of us turn to dystopian themes during a pandemic is that this form of entertainment serves as a controlled and contained outlet for our reality-based fears.

One reason many of us turn to dystopian themes during a pandemic is that this form of entertainment serves as a controlled and contained outlet for our reality-based fears. I can turn the screen off at any moment and remind myself that it is only fiction. Am I actually concerned that there is a mutated fungus lurking in my kitchen cupboards, ready to transform me into a carnivorous zombie? Not in the least. Am I enjoying The Last of Us? Yes — immensely. For me, the ideal pandemic-era dystopian show has just enough internal logic and scientific factoids to avoid being laughable or absurd, but not so much scientific realism to be truly frightening.

If I want to be truly concerned by science-based emerging infectious disease threats, I need look no further than a report on antimicrobial resistance report from the Centers for Disease Control and Prevention.3 The report highlights the worsening death toll from antimicrobial-resistant bacterial and fungal infections.

Supporting Clinicians in Infection Management

Infection management is a dynamic area of concern for clinicians. One recent area of evolution in fungal disease involves Valley Fever (coccidioidomycosis), an airborne fungal infection caused by Coccidioides.4 The fungus has far outgrown San Joaquin Valley, California, for which it was named; the infection has become prevalent outside desert regions in the Southern and Western United States, appearing in other parts of the country. Whether climate change is responsible for its spread is unknown. Fungi such as blastomycosis and histoplasmosis are already common in the environments of multiple regions throughout the country. A United Nations’ report, “Bracing for Superbugs,” highlights potential links between environmental changes and drug-resistant infectious organisms.5

Antibiotics and other infection disease therapeutics have historically been among the top drug look-ups in epocrates, and infections are among the top expert guidance algorithm topic queries as well. To support clinicians in identifying the bacteria relevant to their patients in the ambulatory setting, epocrates created the patented Bugs + Drugs technology to support optimal antibiotic prescribing decisions. The Bugs + Drugs tool is available for free in the epoc­­rates mobile app. The epocrates+ app, available by subscription­, includes detailed guidance on diagnosis and treatment of numerous fungal diseases, from superficial infections to serious invasive infections.

Anne Meneghetti, MD, is the physician executive who leads the Medical Information Team at epocrates. After training in internal medicine, pulmonary, and critical care specialties, she worked in health care policy before joining the epocrates team in 2006. Her team creates and curates clinical decision support tools for the moments of care.


1. Mazin C, Druckmann N. The Last of Us [Television series]. United States: HBO; 2023.

2. Centers for Disease Control and Prevention. Candida auris. Accessed February 23, 2023.

3. Centers for Disease Control and Prevention. COVID-19 & antibiotic resistance. Accessed February 23, 2023.

4. Centers for Disease Control and Prevention. Valley fever (coccidioidomycosis). Accessed February 23, 2023.

5. United Nations Environment Programme. Bracing for superbugs: strengthening environmental action in the one health response to antimicrobial resistance. UNEP. Accessed February 23, 2023.