Face to Face

The scene reminded me of similar frightening news reports and panel discussions during our recent COVID pandemic. Like all of us before COVID, no one ever experienced a pandemic — where the whole world is sick at the same time. We knew the theory, but COVID brought it to reality. And, just as the best fiction holds up a mirror to fact, it makes The Last of Us more believable today than it would have been five years ago – with a few notable differences. There are no vaccines for fungal infections. Many serious fungal infections are multidrug resistant, and some do not have any forms of treatment. As the climate warms, the gap between the preferred temperature of fungi and humans narrows, putting us at even greater risk. In The Last of Us, we cynically view fungus growing out of the heads of those infected. The specific organism in the show, Ophiocordyceps unilateralis, is a fungus that in real life infects ants. It hijacks the ant’s motor neurons to gain control of its muscles making it seek higher ground to improve its chances of spreading its spores farther. Once the body of the ant is dead, stalks grow out of the body, then release spores into the air and attach to more ants to do the same thing. Fascinating. In the real world, we do know that certain fungi can cause hallucinatory effects on the human central nervous system, causing changes in a person’s behavior. Direct invasion into the brain can also cause neurocognitive changes as well. Acute Invasive Fungal Sinusitis (AIFS) in particular is an invasive fungus growing rapidly inside the nose and sinuses frequently invading the brain as its thrombosis arteries create more dead tissues where it prefers to thrive. In its most invasive form, it does cause significant tissue necrosis that can extend “outside the head” and through the skin or palate. If we allowed it to, it could also lead to spore formation that can be spread outside of the body. Thus, to an otolaryngologist, there remains enough plausibility to keep the show interesting. At the recent 2023 Combined Otolaryngology Spring Meetings (COSM) in Boston for the American Rhinologic Society (ARS) I served on a panel discussion of “Acute Invasive Fungal Sinusitis (AIFS): Management in the Current Era.” At Houston Methodist we see a lot of this as we conduct more multi-organ transplants than almost every hospital in the United States. Ironically our medical successes of prolonging the life of the immunosuppressed and utilizing immunosuppression to treat diseases, such as organ failure, is placing more of our population at risk for fungal diseases. Our goal at the recent conference was to try to unify diagnoses, management, and treatment of patients with invasive fungal sinusitis. Our discussion was not near as dramatic as The Last of Us, but we agreed that diligence in research is the only way to clear our paths toward a healthier future and to discover new treatments and future cures. Research continues to evolve identifying different mold species causing AIFS under different conditions. For example, it is known that Mucor tends to be the causative agent in more cases that involved diabetic ketoacidosis and steroid immunosuppression. More studies are being done on leukocyte, monocyte and granulocyte stimulating factors to help improve patient outcomes. A new theory is also developing suggesting the potential for noninvasive fungal sinusitis to transform into AIFS under certain situations and status post-surgery. Another factor that we are actively investigating at our institution is the timing after differing organ transplantation when AIFS peaks as well as identifying why the timing varies from one organ transplantation to another (i.e., kidney vs liver vs lung, etc.). What is our current solution? So far, it’s prevention. And if that is not possible, early identification of the pathogen with initiation of directed therapy has been shown to decrease mortality. The answer also is in the diligence of continued research. So, are we worried about the end of the world, like in The Last of Us? Always. Are we worried it will be because of a Zombie apocalypse caused by evil fungi. Probably not. And certainly not if we do our part. Diligent research is the way toward more successful treatments and cures.