Fungal Infections After Joplin Tornado Proved Deadly

Joanna Broder

December 05, 2012

After a natural disaster, physicians should be aware that fungi can cause those injured in the incident to develop soft tissue infections, which are most likely to occur if the injured party sustains penetrating wounds.

These findings come from a case-control study published in the December 6 issue of the New England Journal of Medicine. All 13 of the case patients in the study were determined to have necrotizing cutaneous mucormycosis, a rare infection resulting from molds in which vascular invasion and thrombosis lead to tissue death.

"The timely diagnosis of mucormycosis is essential for guiding therapy, because the early initiation of appropriate antifungal medication and aggressive surgical débridement are associated with improved outcomes," study authors Robyn Neblett Fanfair, MD, MPH, an epidemic intelligence service officer in the Mycotic Disease Branch at the Centers for Disease Control and Prevention in Atlanta, Georgia, and colleagues write.

On May 22, 2011, a devastating tornado touched down in Joplin, Missouri. After the disaster, local and regional hospitals and reference laboratories from local and state health departments conducted active surveillance for fungal infections. Researchers investigated all fungal infections in those injured in the tornado.

They found a cluster of 13 cases of mucormycosis among the injured people, who were housed at 6 different area hospitals. The first positive murcormycetes cultures came from 6 to 24 days following injury. Of the 13 patients, 5 ultimately died, from 0 to 5 days following their first positive culture.

The researchers conducted an investigation to identify the causative agents of infection, to define how the patients presented clinically, and to isolate risk factors. They performed an unmatched 1:3 case-control study in which a case patient was a person who had been injured during the tornado and who later developed a necrotizing soft tissue infection. Researchers ascertained that the organism responsible for the infection was mucormycetes either by culture or by histopathology plus genetic sequencing, . A control patient was a person who was injured during the tornado and who sustained a resulting break in the skin. Each control patient received a culture of his or her wound between May 22 and June 15, and the scientists found no evidence of mucormycosis in those cultures.

The researchers reviewed medical records and held interviews with case patients and control patients or their surrogates. They also conducted DNA sequencing or whole-genome sequencing to assess differences among species and strain levels.

Results showed that all of the 13 case patients had been in the area where the tornado wreaked the most havoc. According a multivariate analysis, those patients with penetrating trauma were 8.8 times more likely than those without such trauma to develop the fungal infection (95% confidence interval [CI], 1.1 - 69.2), and those with an increased number of wounds were twice as likely to develop the infection (95% CI, 1.2 - 3.2) as those with fewer wounds.

The multivariate analysis controlled for variables found to be statistically significant with a P value of 0.2 or less in preliminary analyses. These variables included the number of wounds, whether they were puncture wounds, whether there were crush injuries, and whether the patient was admitted to the intensive care unit or had sepsis.

When scientists sequenced the D1-D2 region of 28S ribosomal DNA, they found Apophysomyces trapeziformis in each case patient. When they performed whole-genome sequencing, they found 4 separate strains of Apophysomyces isolates.

"It is likely that one or more environmental sources of apophysomyces existed along the tornado path and that spores were aerosolized, carried along with debris, and inoculated along with the debris after penetrating trauma," the authors write.

Physicians irrigated the wounds of all the case patients, each of whom received extensive surgical debridement. All case patients also received systemic antifungal therapy to treat their incident wound.

At this time, there are only 2 antifungal drugs that the US Food and Drug Administration has approved to treat mucormycetes: amphotericin B and posaconazole.

"In this cluster of cases, antifungal agents that are not active against mucormycetes were initially used in six case patients; in some patients, treatment was switched to amphotericin B when culture results became available," the authors write. "It is not known whether the outcomes for these case patients would have been different if mucormycete-active agents had been used initially."

In prior outbreaks of mucormycosis, investigators thought that medical equipment might have been to blame, according to authors, but equipment contamination did not occur in this case. "[T]he 13 case patients received medical attention at six different hospitals, making a common nosocomial source unlikely," they write.

When disaster strikes in the future, the authors encourage public health officials to consider surveying for cutaneous mucormycosis among people who sustain multiple penetrating trauma wounds. They also encourage officials to develop emergency tornado preparedness such as early-warning systems and emergency shelter plans to decrease the risk for injury.

The authors have disclosed no relevant financial relationships.

N Engl J Med. 2012;367:2214-2225.