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The Environmental Reporter
  Volume 11 | Issue 1

I hope you're doing well. I also hope that you'll find the following article about mucormycosis by Dr. Michelle Seidl both interesting and useful.

With best wishes,
Dave Gallup




Mucormycosis and Natural Disasters
By Dr. Michelle Seidl, EMLab P&K Senior Analyst

In 2012, Hurricane Sandy devastated parts of the Eastern seaboard and many areas of the Northern Caribbean. In 2011, a massive tornado wreaked havoc on Joplin, MO and nearby areas. In Southeast Asia in 2005, a tsunami left a destructive wake behind. These and other natural disasters are hotbeds for the occurrence and spread of various diseases.

One example of an uncommon fungal disease that has been associated with various natural disasters is mucormycosis, also known more broadly as zygomycosis. Though the loss of life from this disease is very low when compared to the total loss of life caused by such horrific events, understanding the potential for this kind of infection could potentially save lives.

Several people in Joplin, MO who were injured by the tornado developed a rare and potentially deadly fungal infection caused by a zygomycetous fungus. A recap of the May 22, 2011 event in relation to mucormycosis can be found on the CDC website. The physical and psychological damages the city of Joplin sustained were devastating. On June 3, 2011, a local physician notified the county and state health officials of two patients hospitalized with tornado-related injuries having suspected necrotizing (death of a specific area of tissue) fungal soft-tissue wound infections caused by a zygomycetous (mucoralean) fungus ((MMWR) July 29, 2011/60(29); 992.).

The CDC and Missouri State Health Department immediately began active surveillance for such infections at hospitals and laboratories that were serving patients injured in the tornado. Within a week, eight patients with necrotizing fungal soft-tissue wound infections caused by mucoralean fungi were identified. About a month later, a total of 18 suspected cases of cutaneous (affecting the skin) mucormycosis had been identified, 13 of which were confirmed. A confirmed case here was defined as necrotizing soft tissue infection requiring antifungal treatment or surgical removal of the dead tissue, onset of the illness after May 22, 2011 and a positive fungal culture or histopathology and genetic sequencing consistent with a mucoralean fungus. No additional cases in that specific geographic area were reported after June 17, 2011.

Of the 13 confirmed cases, 7 were female, 6 were male, all were white, and the age range was 13-76. Injuries sustained during the tornado included lacerations, fractures and blunt trauma. Two of the 13 patients had diabetes, none were immunocompromised, 10 required admission to an intensive care unit and 5 died. Specimens from all 13 patients yielded the mucoralean fungus: Apophysomyces trapeziformis.1 This fungus belongs to the fungal phylum Zygomycota, class Zygomycetes, subdivision Mucormycotina, order Mucorales, and classified in the family Mucoraceae. Since this tornado struck in late May during the growing season, spores could have been stirred up by the tornado, then dispersed to the victims through wounds from injuries or by ingestion or inhalation. All of those diagnosed with mucormycosis did have multiple injuries and secondary wound infections (Williams 2011).

Following the Asian tsunami in 2004, a 56-year-old male survivor was diagnosed with an infection caused by another fungus in the same genus: Apophysomyces elegans.2 The survivor escaped broken bones but sustained traumatic wounds (Davis 2005). Despite cleaning and bandaging his wounds, he became feverish within 5 days. He was given broad spectrum antibiotics, the dead tissue cut away, and despite vigilant wound care, the fever remained and his condition worsened (Andreson, et al. 2005). This prompted a warning by doctors that survivors were at risk for this kind of fungal infection.

In 1985, during one of the largest volcanic eruptions in recorded history, over 23,000 people died and 4,500 were seriously wounded. Of those wounded, 8 people were diagnosed with mucormycosis and 6 died. At the time, a plea was made for an early diagnosis, utilizing tissue sampling and microbiological studies, so that prompt and radical treatment could be instituted. This is especially pertinent in situations of natural disasters resulting in massive numbers of casualties and seriously injured survivors (Patiño, et al. 1991).

Zygomycosis vs. Mucormycosis
Zygomycosis is the most broadly encompassing term for a variety of diseases caused by fungi in the class Zygomycetes. Zygomycosis was originally described as a convenient and inclusive term for 2 clinically different diseases: mucormycosis caused by members of the order Mucorales and entomophthoramycosis caused by members of the order Entomophthorales (Kwong-Chun 2012). These two fungal orders comprise distinct lineages within the Zygomycetes (Hibbett et al. 2007; White et al. 2006). Most zygomycete infection cases are classified as mucormycosis.

Of the rare clinical isolates identified as belonging to the Entomophthorales, most are caused by the genera Conidiobolus and Basidiobolus (Sugar 2007; Ribes, et al. 2000). Unfortunately, older literature describing cases of zygomycosis prior to molecular sequencing frequently did not identify the pathogen due to difficulty in culturing and due to lack of expertise needed to identify species using micromorphological methods (Iwen, et al. 2011). The general consensus is to have a combined approach which adopts both morphologic and molecular methods for species identification. In this article, and by definition, the term "mucormycosis" excludes members of the order Entomophthorales.

In the laboratory, mucoralean fungi (e.g. the genus Mucor, see Figure 1), grow well on most standard fungal culture media such as Sabouraud dextrose agar. For a majority of the species associated with human disease, the growth is usually rapid with mycelial elements covering the entire plate within 2 to 3 days of incubation at 30°C. Unfortunately, the recovery of mucoralean fungi from tissue has been described as difficult, with negative results reported despite histological evidence of the presence of a zygomycete.

Mucor spores and sporangia

Figure 1: Mucor spores and sporangia.
Copyright © 2013 EMLab P&K

One reason for this inability to recover the fungus appears to be partly related to aggressive processing of the specimen that may damage the organism. A review by Roden, et al. (2005), described a clear increase in culture positivity over time with 71% of all cases since 2000 diagnosed on the basis of culture results. This improvement was suggested to be due to better training, a greater understanding of specimen processing, improved culture techniques, and increased access to sophisticated reference laboratories.

The vegetative mycelium of all species in the Mucorales is composed of wide diameter, predominantly aseptate (nonseptate), colorless hyphae. The general growth characteristics useful for differentiation of members of this group include colony morphology, the presence of sporangiophores bearing multi-spored sporangia, and the presence or absence of rhizoids. Other methods helpful in identification include maximum temperature at which the isolate will grow and the ability of the organism to assimilate ethanol. Zygospore (sexual spore) formation would be another tool to use but is not always reproducible and can prove difficult. Mating studies require the maintenance of a library of tester strains and are often unrealistic.

Fungal Genera Involved
The most common genus involved in mucormycosis is Rhizopus (Fig. 2). Following is a list of genera that have been associated with this type of human infection:

  • Rhizopus
  • Mucor
  • Rhizomucor
  • Absidia (Lichtheimia)
  • Apophysomyces
  • Saksenaea
  • Cunninghamella
  • Cokeromyces
  • Syncephalastrum

Rhizopus spores and sporangium

Figure 2: Rhizopus spores and sporangium.
Copyright © 2013 EMLab P&K

The Disease
Mucormycosis is a very aggressive and severe infection, but is also very rare (Williams 2011). Organs and areas commonly affected include the sinuses, eyes, skin, brain and lungs. It may also affect the gastrointestinal tract, the skeletal system, the myocardium and endocardium, as well as the kidney (Walsh et al. 2012). It can also occur as a disseminated infection and play a role in allergic fungal sinusitis. The reference to cutaneous mucormycosis, translates to a disease caused by a member of the Mucorales and affecting the skin.

Mucormycosis occurs primarily in people with immune disorders. It can occur, but is generally rare, in immunocompetent hosts. It is considered an opportunistic infection and often affects individuals with pre-existing conditions. Factors or conditions that are known to put humans at risk include: AIDS, diabetes mellitus (usually poorly controlled), lymphoma or leukemia, hematologic malignancy, neutropenia, organ transplants, sustained immunosuppressive therapy, long-term steroid use, metabolic acidosis, iron chelation therapy, broad-spectrum antibiotic use, injection drug use, protein or severe malnutrition and breakdown of the skin barrier such as trauma, surgical wounds, needle punctures or burns. The main risk factors for infection following a natural disaster are spore inhalation, spore ingestion and penetration through injuries that break the skin.

Ibrahim et al. (2012), found that patients with elevated serum levels of available iron are susceptible to mucormycosis. These infections are highly angioinvasive (tendency to invade the walls of blood vessels), as the organism acquires iron from the host. This typically follows traumatic implantation or inhalation of the fungus. The disease is most common in the tropics, with cases reported from India, Australia, USA, Sri Lanka, Thailand, Central America and South America (Alvarez et al. 2010).

Symptoms depend on the condition of the individual and the extent and location of the infection. If not diagnosed early, mucormycosis has an extremely high mortality rate (25% to 80%, averaging 40%). If properly diagnosed, the infection can be treated with antifungal agents (Davis 2005). At the time of this writing, according to the literature and the Mycotic Diseases Branch of the CDC, zero mucormycosis cases were reported as a result of Hurricane Sandy.

Risk assessment is essential in post-disaster situations and the rapid implementation of control measures through re-establishment and improvement of primary healthcare delivery should be given high priority, especially in the absence of pre-disaster surveillance data (Kouadio, et al. 2012). As to whether or not we can say mucormycosis is definitively correlated with natural disasters, the jury is still out and more data will need to be gathered. For now, awareness is critical for prevention and treatment. If the disease is on the "radar screen" of attending physicians and workers following a disaster, the earlier clinical cases can be identified and treated, thereby avoiding this potentially deadly fungal infection from going undiagnosed.

1 Authors of this species: E. Álvarez, A. Stchigel, J. Cano, D. A. Sutton & J. Guarro.

2 Authors of this species: P.C. Misra, K.J. Srivastava & K. Lata.

References:
Alvarez, E, AM Stchigel, J Cano, DA Sutton, AW Fothergill, et al. 2010. Molecular phylogenetic diversity of the emerging, mucoralean fungus Apophysomyces: proposal of three new species. Rev. Iberoam. Micol. 27:80-89.

Andresen, D, A Donaldson, L Choo, et al. 2005. Multifocal cutaneous mucormycosis complicating polymicrobial wound infections in a tsunami survivor from Sri Lanka. The Lancet 365(9462):876-878. doi:10.1016/S0140-6736(05)71046-1.

Davis, K. 2005. Tsunami survivors risk deadly fungal infections. New Scientist 17:48.

Hibbett, DS, M Binder, JF Bischoff, M Blackwell, PF Cannon, et al. 2007. A higher-level phylogenetic classification of the Fungi. Myc. Res. 111(5):509-547.

Ibrahim, AS, Spellberg B, Walsh TJ, Kontoyiannis DP. 2012. Pathogenesis of mucormycosis. Clin Infect Dis. 54 Suppl 1:S16-22. doi: 10.1093/cid/cir865.

Iwen, Peter C, I Thapa & D Bastola. 2011. Review of methods for the identification of Zygomycetes with an emphasis on molecular diagnostics. Lab medicine 42(5):260-266. DOI:10.1309/LMJ8Z0QPJ8BFVMZF

Kouadio, IK, S Aljunid, T Kamigaki, K Hammad & H Oshitani. 2012. Infectious diseases following natural disasters: prevention and control measures. Expert Rev. Anti Infect. Ther 10(1): 95-104.

Kwong-Chun, Kyung J. 2012. Taxonomy of Fungi Causing Mucormycosis and Entomophthoramycosis (Zygomycosis) and Nomenclature of the Disease: Molecular Mycologic Perspectives. Oxford University Press (Infectious Diseases Society of America). Clin Infect Dis. 54 (suppl 1): S8-S15. doi: 10.1093/cid/cir864

Patiño JF, Castro D, Valencia A, Morales P. 1991. Necrotizing soft tissue lesions after a volcanic cataclysm. World J Surg. Mar-Apr;15(2):240-7.

Ribes, JA, CL Vanover-Sams & DJ Baker. 2000. Zygomycetes in human disease. Clin. Microbiol. Rev. 13(2): 236-301.

Roden MM, Zaoutis TE, Buchanan WL, et al. 2005. Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis. 41L634-653.

Sugar, Alan M. 2007. Zygomycosis (Mucormycosis and Entomophthoromycosis). In: Carol A. Kauffman & G. L. Mandell (eds.). Atlas of fungal infections. Springer: Philadelphia.

Walsh, Thomas J, BE Bloom & DP Kontoyiannis. 2012. Meeting the challenges of an emerging pathogen. The Henry Schueler 41 & 9 Foundation International Forum on Mucormycosis. Oxford University Press (Infectious Disease Society of America). Clin Infect Dis. 54 (suppl 1): S1-S4. doi: 10.1093/cid/cir862

White, Merlin M, Timothy Y James, Kerry O'Donnell, Matias J Cafaro, Yuuhiko Tanabe & Junta Sugiyam. 2006. Mycologia 98(6):872-884.

Williams, T. 2011. 8 tornado victims stricken with rare fungal infection. 10 June 2011. The New York Times. http://seattletimes.com/html/health/2015289629_joplinfungus11.html



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