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Fungal meningitis: How a wimpy, ubiquitous black mold turned to the dark side

Exserohilum rostratum is the scary character responsible for the multi-state outbreak of fungal meningitis cases linked to tainted steroid preparations.

A sample of Cladosporium species, one of the fungi diagnosed in the fungal meningitis outbreak sweeping the United States.
REUTERS/Harrison McClary

If your Halloween costume didn’t end up scaring anybody this year, maybe you should have dressed up as Exserohilum rostratum. It’s the black mold that’s responsible for the multi-state outbreak of fungal meningitis cases linked to tainted steroid preparations.

Exserohilum is indeed a scary character  — 28 people have died since the first case was reported in mid-September — but this current homicidal rampage is historically unprecedented. Although Exserohilum is a ubiquitous mold, found commonly in soils and on plants, it doesn’t find humans to be particularly appetizing or easily boarded, and so human infections are rare.

If you’re frightened of fungi, the best advice is to come out with your hands up: You are surrounded. Like morticians, fungi make their living off the dead, but they don’t embalm or cremate — they simply digest. This “saprophytic” function serves to recycle important nutrients back into the biological revenue stream, and keeps the world from looking like a teenager’s bedroom, littered with debris.

Fortunately for us, fungi focus most of their saprophytic powers on the dead, but some do have the capability to infect living plants or people. Human fungal infections are typically minor skin-related infections, such as athlete’s foot, jock itch, or ringworm (no worm at all); vaginal yeast infections can occur after a course of antibiotics pathologically alters the normal symbiotic mix of bacteria and fungi in the vagina.

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Occasionally a fungal infection can go beyond skin deep, most commonly in people whose immune systems are impaired, typically because of HIV or chemotherapy. If healthy folks do get a deeper fungal infection, it’s usually precipitated by a heavy inhalation of spores, such as “Valley Fever” in the Southwest, where desert winds can sometimes kick up the spores of a fungus called “coccidioides.” The Midwest’s version of Valley Fever is from histoplasmosis, perhaps better known as “Bob Dylan Fever,” after the rock legend contracted a particularly bad case of it in 1997.

There are a few other fungi that can cause serious human infections, and with rare exceptions, they all enter the body through the lungs. In the current outbreak, Exserohilum rostratum entered through the back, literally, through the spine via a needle. But if Exserohilum is so ubiquitous, shouldn’t we all have antibodies against it, and shouldn’t that protect us from getting a serious infection, even in the spine?

I put that question to Dr. Kirsten Nielsen, a mycologist (fungal specialist) at the University of Minnesota, who’s studied how another fungus — Cryptococcus neoformans — finds it way into the brain. Because Exserohilum has such a short rap sheet when it comes to humans, it hasn’t been studied very much, but Nielsen could tell me this:

“Because the primary source of exposure to fungi is through the lungs, most of our immune defenses are poised for action at the pulmonary level,” Nielsen explained. “If the fungus does manage to move through the lungs and deeper into the body, at least we’ve already been alerted to their presence, and the body is able to escalate its immune response to the invader.”

But according to Nielsen, when something like Exserohilum rostratum gains a back-door entry into the central nervous system, it has two distinct advantages. The first is anonymity.

“Because the vast majority of human pathogens cannot cross the blood-brain barrier, the immune cells of the central nervous system (CNS) have never seen Exserohilum, and so it takes a while to recognize the fungus and begin mounting an immune response,” said Nielsen. The second advantage has to do with food and fuel. “The CNS is a very rich environment for fungi — it has all the nutrients that fungi need, and so they are able to grow quite rapidly.” The infective battle is no longer about access, but rather momentum, the ability of the fungus to outflank and out-produce the immune system.

Autopsy results published in the New England Journal of Medicine and Annals of Internal Medicine showed that the fungal infection involved the entire spinal cord and brain, and not just the site of the injection. Of note, spinal injections aren’t supposed to be into the central nervous system, but rather just outside of it, above the “dura mater,” a heavy covering that surrounds both the brain and the spinal cord, and holds in the spinal fluid. Most of these “epidural” (i.e., above the dura) injections are performed under X-ray control, where X-ray dye is used to confirm that the tip of the needle is in the epidural space, and not any deeper.

At autopsy, no perforation of the dura was noted, but it may be that the fungus infected the dura to the point that it began to leach its way into the spinal fluid. The steroids that were injected with purpose of calming an inflamed nerve root as it exits out of the dura would also have had the effect of blunting any immune response at the site of injection. Once Exserohilum reached the spinal fluid, it then had easy access to the entire spinal cord and brain. Eventually it began infecting some of the blood vessels supplying the brain, leading to stroke symptoms.

This outbreak of fungal meningitis, an otherwise rare event, is a sobering reminder that even a fairly routine procedure like an epidural injection can be a risky proposition if routine measures are not taken during the manufacture of the injection itself.

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And it’s a reminder that we are not alone. Mushrooms might be fungi’s most recognizable form, but fungi play a critical role in the vast cauldron of life, most of it unseen. And as Dr. Nielsen pointed out, biologically speaking, they’re closer to us than you think:

“Almost any way you want to look at fungi — in terms of metabolism, genome sequencing, etc. — humans are much more closely related to fungi than we are to plants,” she explained. “We share a basal lineage: as life developed, plants split off into their own kingdom, well prior to humans’ and fungi’s branching off. That’s why we’ve had a hard time developing anti-fungal drugs for humans: it’s hard to create a drug that is toxic to the fungus without being toxic to the patient.”