Investigating Fungal Outbreaks in the 21st Century

What Causes Fungal Outbreaks?Public attention has been drawn to recent high-profile outbreaks of mycotic diseases, such as those of fungal meningitis and other infections linked to contaminated steroids [1] and an outbreak of necrotizing cutaneous mucormycosis linked to a tornado [2].However, fungal outbreaks are more common than most people appreciate, and reports of outbreaks caused by unusual fungal pathogens are increasing.The Mycotic Diseases Branch at the Centers for Disease Control and Prevention (CDC) investigates 3-6 fungal outbreaks per year, many of which are caused by rare fungi with limited diagnostic and treatment options.This is a considerable increase from the 1990s, when the Branch investigated 1-2 hospital-based outbreaks per year, generally caused by yeast and traced to a single source.Although the exact reasons for this increase are unknown, the increased number of patients with impaired immune system may have contributed to this trend.The majority of fungal outbreaks can be attributed to either environmental exposure or a contaminated product (Table 1).For example, two recent outbreaks were linked to contaminated medications.In 2012, two medications produced by a single compounding pharmacy in Florida were contaminated with Fusarium sp. and Bipolaris sp., respectively, shipped to 15 states, and injected into the eyes of patients undergoing vitrectomies.As a result, 47 patients developed endophthalmitis, and most lost vision [3].In the 2012 fungal meningitis outbreak, methylprednisolone acetate (MPA) contaminated with Exserohilum rostratum and several other microorganisms was shipped to 23 states, potentially exposing nearly 14,000 individuals to this contaminated medication.As a result, 752 people developed meningitis, arachnoiditis, or spinal/ paraspinal abscesses, and 64 patients died, making this the deadliest fungal outbreak to date [1].Environmental exposure is the other common cause of fungal outbreaks [2,4].For example, a recent cluster of Rhizopus delemar infections in a children's hospital in New Orleans was linked to contaminated linens [4].In this outbreak, five children died from cutaneous mucormycosis, and R. delemar was isolated from linens, linen shelves, and bins at the hospital [4].In another example, 13 people developed necrotizing cutaneous mucormycosis caused by Apophysomyces trapeziformis after receiving puncture wounds caused by flying debris during a tornado [2].Although A. trapeziformis was not recovered from the local environment, whole genome sequence typing (WGST) of the isolates showed that at least three different strains were involved, suggesting environmental exposure [2,5].In addition, many other outbreaks and clusters caused by dimorphic and other fungal pathogens have been linked to environmental exposure [6][7][8].