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The Race to Understand a Common But Deadly Fungus: Exserohilum rostratum

The deadly multistate fungal meningitis outbreak associated with the injection of tainted medications is unprecedented in scope. Injections associated with infectious diseases are well described in the literature, but fungal meningitis is singularly unusual.

Laboratory analysis to date shows that 52 patients have confirmed meningitis due to the fungal strain known as Exserohilum rostratum (E. rostratum), while two other pathogens, Aspergillus fumigatus and Cladosporium sp., are responsible for one case each.

Injection in patient's backAspergillus species are well-known pathogens, especially in immunocompromised individuals, and Cladosporium infections are uncommon, but well described. In contrast, human infections from Exserohilum species are exceedingly rare.

What many people may not realize is that the fungi associated with this outbreak are common environmental molds. Each day humans and animals inhale massive quantities of fungal spores, but we do not become ill because of our ability to expel the fungi from our lungs and because fungal spores that escape this process are destroyed by our host defense cells. The central nervous system is a “protected” site, one in which there are minimal host defenses to respond to a fungus or other microbial invader. Injection of the spores, therefore, bypasses our host defenses and allows the fungus to cause disease.

The main challenge with E. rostratum is that we have little clinical experience dealing with it. But all resources are being brought to bear to harness what we do know.

For example, we know from studies on drug susceptibility which antifungal compounds are effective in test tubes against E. rostratum. The use of these compounds in a few case reports suggests their utility in the current outbreak.

We are using scientists’ experience dealing with related fungal pathogens to determine the correct dose and length of treatment with antifungal drugs, namely voriconazole and amphotericin B.

From studies of other fungi, we know about factors that make this fungus dangerous to humans, such as the release of enzymes that digest and destroy human tissues. Also, the fungus forms a black pigment (called melanin) in its cell wall. Studies in our laboratories at Einstein (by myself and Arturo Casadevall, M.D., Ph.D.) have shown that the cell-wall melanin acts as a binder for the antifungal drugs (voriconazole and amphotericin B) being used to treat the patients. Black melanin binds to some of the drugs we administer, which supports the use of high drug doses.

Despite the seriousness of this outbreak—to date, 31 have been killed and 424 sickened—it’s important to recognize that our ability to identify the cause of the majority of these infections arises from advances in microbiology diagnostics and a deep understanding of the genetics of fungi. (For the latest information on the fungal outbreak, see http://www.cdc.gov/hai/outbreaks/meningitis.html.) This outbreak highlights the important role that basic scientific investigation plays for healthcare providers, epidemiologists and basic scientists. In order to prepare for future microbiological challenges, we need to advocate for continued support of fundamental scientific exploration.

Joshua D. Nosanchuk, M.D.

Joshua D. Nosanchuk, M.D.

Dr. Nosanchuk, is assistant dean for student affairs and associate professor of medicine (infectious diseases) and of microbiology & immunology at Albert Einstein College of Medicine and attending physician, infectious diseases at Montefiore Medical Center.

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