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REVIEW 10.1111/j.1469-0691.2009.02972.x

The ecology of the Zygomycetes and its impact on environmental exposure

M. Richardson The University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester, Manchester, UK and Regional Laboratory, Wythenshawe Hospital, Manchester, UK

Abstract

Zygomycetes are unique among filamentous fungi in their great ability to infect a broader, more heterogeneous population of human hosts than other opportunistic moulds. Various members of the Zygomycetes have been implicated in , although those belonging to the are isolated more frequently than those of any other family. The environmental microbiology litera- ture provides limited insights into how common zygomycetes are in the environment, and provides a few clues about which ecological niches these fungi are found in. are thermotolerant moulds that are supposedly ubiquitous in nature and widely found on organic substrates, including bread, decaying fruits, vegetable matter, crop debris, soil between growing seasons, compost piles, and excreta. The scientific and medical literature does not support this generalization. Sporangiospores released by mucorales range from 3 to 11 lm in diameter, are easily aerosolized, and are readily dispersed throughout the environment. This is the major mode of transmission. However, there are very few data concerning the levels of zygomycete sporangiospores in outdoor and indoor air, espe- cially in geographical areas where zygomycosis is particularly prevalent. Airborne fungal are almost ubiquitous and can be found on all human surfaces in contact with air, especially on the upper and lower airway mucosa. Inhalation of sporangiospores must be a daily occurrence. Surprisingly, members of the Mucorales are very rarely found in nasal mucus, suggesting that spores in the mucus of airway mucosa are cleared by mucociliary transport or that there is a low level of airborne contamination. Zygomycetes are found occasionally in water-damaged buildings, as demonstrated by air-sampling, and analysis of settled dust by quantitative PCR. Moreover, inhalation of sporangiospores in dust has been linked to outbreaks of rhinocerebral or pulmonary zygomycosis due to excavation, con- struction, or contaminated air-conditioning filters. Whereas most zygomycete are community-acquired, nosocomial acquisition due to percutaneous routes of exposure is very important. Sporadic cases, and pseudo-outbreaks, have been linked to contaminated bandages and adhesive dressings, needles, and tongue depressors used to construct splints for intravenous and arterial cannulation sites in preterm infants. Insect bites or stings have been implicated in disease transmission in cases of cutaneous and subcutaneous zygomy- cosis, e.g. diseases caused by the . Traumatic implantation of spores in dirt or in contaminated water, e.g. as occurred during the Asian tsunami, has led to in multiple patients.

Keywords: Entomophthoromycosis, environmental exposure, , , zygomycosis Clin Microbiol Infect 2009; 15 (Suppl. 5): 2–9 namely, the small group Entomophthorales, members of Corresponding author and reprint requests: M. Richardson, which have forcibly discharged spores, and the Mucorales Regional Mycology Laboratory, Education and Research Centre, University Hospital of South Manchester (Wythenshawe Hospital) and , in which the spores arise by cleavage of Southmoor Road, Manchester M23 9LT, UK the sporangial plasma and are passively liberated. E-mail: [email protected] Zygomycosis (mucormycosis) is caused by moulds belong- ing to the Mucorales [1]. The order Mucorales is divided into six families of significance in human or animal dis- ease, but most cases of human infection are caused by mem- Introduction bers of the Mucoraceae. This includes the genera , , , and . Two additional pathogenic The is composed of a group of lower families are the and the Saksenaceae. fungi whose thalli are generally aseptate (coenocytic) and Many different organisms have been implicated in human ill- that produce after fusion of isogamic organs ness, but the commonest cause of human infection is Rhizopus (gametangia). Three orders contain clinically relevant , oryzae (arrhizus). Other less frequent aetiological agents

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases CMI Richardson Ecology of the Zygomycetes and its impact 3

include Absidia corymbifera, elegans, Cunningha- grow in many ecological niches, the infrequency of disease mella bertholletiae, , and vasiformis. caused by zygomycetes attests to their low potential for vir- All of these moulds cause similar diseases in humans, and the ulence in the human host [9]. In contrast to the supposed diagnostic and therapeutic approaches are similar. widespread distribution of these fungi, disease in humans is Most members of the Entomophthorales are of limited to people who are severely compromised, those with insects and other invertebrates, but many species can also diabetes mellitus, or those who have experienced trauma. be found in the soil and on dung. The order is characterized These infections are worldwide in distribution. by the presence of forcibly discharged propagules. The clini- Most commonly, agents of zygomycosis gain entry to the cally important species are and Conidio- body through the respiratory tract. Sporangiospores are pre- bolus coronatus. sumably deposited in the nasal turbinates, and may be inhaled into the pulmonary alveoli. In the case of primary Taxonomy of the Zygomycota cutaneous mucormycosis, sporangiospores are introduced The classification of the Zygomycota is in a state of flux, and directly into abraded or occluded skin. They then proliferate the reader is referred to recent reviews of the phylogeny and can disseminate. of the phylum based on nuclear ribosomal sequence data Nosocomial outbreaks of mucormycosis are not as com- [2,3], and to a recent summary by Dannaoui and Garcia- mon as hospital-related infections, but have some- Hermoso [4]. The phylum Zygomycota is an ecologically het- times been linked to construction or renovation work, as erogeneous assemblage of non-zoosporic fungi composed of well as to contaminated ventilation systems. Nosocomial two classes, the Zygomycetes and the Trichomycetes. Phylo- clusters of cutaneous infections with Rhizopus rhizopodiformis genetic analyses have suggested that the phylum is polyphy- and have been traced to contaminated letic. White et al. have suggested that the phylum biomedical devices, or associated with the use of non-sterile Zygomycota is paraphyletic [5]. Although 12 clades were surgical dressings and splints. However, most cases of mucor- identified, only some of these corresponded to the nine in hospitalized patients are sporadic in nature, and it orders of Zygomycota currently recognized. Hibbett et al. [6] is much more difficult to determine whether these infections have presented a comprehensive phylogenetic classfication of are acquired inside or outside the hospital setting. the Fungi based on recent molecular phylogenetic analyses. The most dramatic shifts in the classification relative The Biology of the Zygomycetes to previous work concern the groups that have been tradi- tionally included in the and Zygomycota. Taxa traditionally placed in the Zygomycota are distributed Mucorales are fast-growing, and sporulate quickly and abun- among the and several subphyla incertae se- dantly [10]. They are oligotrophic to mesotrophic, and pri- dis, including the [6]. This group includes mary or secondary colonizers of substrates rich in simple the order Mucorales, which is the core group of the tradi- carbohydrates. Their physiological characteristics and bio- tional Zygomycota. Monophyly of the traditional Zygomycota chemical properties, e.g. production of chitinolytic , (including the Mucorales and Entomophthorales) was sug- make them successful competitors among fungi and common gested by a recent study by Liu et al. [7], using Rpb1 and inhabitants of soil and organic debris. Absidia, Fennellomyces, Rpb2 (the RNAPII core , which drives the transcrip- , Mucor, Umbelopsis and Zygorhynchus are the most tion of most messenger RNAs in eukaryotic cells, is com- common genera in agricultural and forest soils of the tem- posed of 12 polypeptides, Rpb1 being the largest subunit). perate zone, where they constitute almost 100% of zygo- However, this finding conflicts with results of analyses that mycetes. Species of Rhizopus are rarely found in these areas. have included additional loci and taxa, and that suggest that Mucorales are thermotolerant moulds that are ubiquitous the traditional phylum Zygomycota is polyphyletic [6,8]. in nature and are widely found on organic substrates, includ- ing bread, decaying fruits, vegetable matter, crop debris, nor- Epidemiology mal soils between growing seasons, compost piles, and The term mucormycosis (zygomycosis) is used to refer to animal excreta. The optimum environmental conditions for infections due to moulds belonging to the order Mucorales. the growth and sporulation of zygomycetes on these sub- These organisms can cause rhinocerebral, pulmonary, gastro- strates are 27C and high humidity. There are some thermo- intestinal, cutaneous or disseminated infection in predisposed philic species, most of which have been isolated from individuals, the different clinical forms often being associated composting materials. An understanding of the nutri- with particular underlying disorders. Even though these fungi tional requirements of zygomycetes will help to indicate on

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15 (Suppl. 5), 2–9 4 Clinical Microbiology and Infection, Volume 15, Supplement 5, October 2009 CMI

which substrates these fungi may be found. is the especially flies. However, there are very few data concerning main carbon source for growth. Like other fungi, zygomyetes the levels of zygomycete sporangiospores in outdoor and have a requirement for proteins and a range of organic and indoor air, especially in geographical areas where zygomyco- inorganic substances. The pH of a particular environment sis is particularly prevalent. The numbers of airborne zyg- can markedly affect the rate of extension, growth, and spor- omycete sporangiospores appear to depend on the presence ulation. Another factor that may influence the quality of of climatic conditions that favour growth and dispersal. growth is light. These properties of wide ecological distribu- A survey of indoor and outdoor air in and around 17 tion, rapid growth and thermotolerance are of particular homes in Cincinnati, Ohio, USA, using mould-specific quanti- importance in causing human disease. tative PCR, failed to detect any pathogenic mucorales [11]. During a 2-year air-sampling survey in Barcelona, Spain, the following genera were found, in decreasing order: Aureobasi- Dispersal Mechanisms in the Zygomycetes dum, Rhizopus, Mucor, Arthinium, Phoma, , Trichoderma and Botrytis [12]. A 1-year aeromycological study was con- In the Zygomycetes, the unit of dispersal is normally a sporan- ducted in the area of Zagreb, in order to establish seasonal giospore from within a . Typically, a sporangium variations in the composition and concentration of aeromy- may contain up to 100 000 spores. Smaller sporangia may cota [13]. Sampling was carried out at three locations at reg- contain only a few hundred spores. Some mucorales exhibit ular intervals using the Mas 100 Eco Air-sampler with xerophytism. Generally, mucoraceous moulds can produce Sabouraud-dextrose agar. The quantities of airborne fungi aerial growth only when the surrounding air is extremely peaked during spring and summer (110–284 CFU/m3), and damp. However, some mucorales can form sporangiospores lower levels were detected in autumn and winter at each of in dry air. In most mucorales, the wall of the sporangium the sampling sites (6–128 CFU/m3). In contrast to Cladospori- eventually dissolves. Not only does the wall, except for a um, Pencillium and Alternaria, very low levels of Mucor and Rhi- small collar around the base of the columella, break down, zopus were found. but water passes into the -mass through the columella. In what appears to be the largest study of airborne indoor The result is that a ‘sporangial drop’ is formed; this is consid- and outdoor fungal species and concentrations to date, Shel- erably larger than the original sporangium, and its spores are ton et al. [14] examined 12 026 fungal air samples (9619 dispersed by splash dispersal. Other species form dry, pow- indoor samples and 2407 outdoor samples) from 1717 build- dery spores. The sporangiospores dehisce, and the released ings located across the USA; these samples were collected sporangiospores can be dispersed by low-speed winds. The during investigations performed from 1996 most familiar example of a mucoraceous producing dry to 1998 [15]. For all buildings, both indoor and outdoor air sporangiospores is the common ‘bread mould’ Rhizopus. samples were collected with an Andersen N6 sampler. The culturable airborne fungal concentrations in indoor air were lower than those in outdoor air. The fungal levels were high- Where are Zygomycetes Found? est in the autumn and summer, and lowest in the winter and spring. Geographically, the highest fungal levels were found The environmental microbiology literature provides limited in the southwest, far west, and southeast. The most com- insights into how common zygomycetes are in the environ- mon culturable airborne fungi, both indoors and outdoors ment, and provides a few clues about which ecological niches and in all seasons and regions, were Cladosporium, , these fungi are found in. In particular, examination of air- non-sporulating fungi, and Aspergillus. Stachybotrys chartarum sampling surveys in indoor and outdoor environments might was identified in the indoor air in 6% of the buildings studied indicate the level of exposure or help explain the apparent and in the outdoor air of 1% of the buildings studied. Mucor seasonality of zygomycosis. Similiar analyses of other (species not specified), Rhizopus (species not specified) and environments might reveal specific point sources of fungal (species not specified) were detected in communities. indoor air more than in outdoor air, although this varied from one geographical area of the USA to another. How- Indoor and outdoor environments ever, agents of mucomycosis were not included in the cate- Sporangiospores released by the Mucorales range from 3 to gory of ‘common fungal types’. 11 lm in diameter, are easily aerosolized, and are readily A comparison of populations of mould species in homes dispersed throughout the environment. This is the major in the UK and USA using mould-specific quantitative PCR mode of transmission. Spores can also be carried by insects, did not detect any appreciable level of mucorales in dust

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15 (Suppl. 5), 2–9 CMI Richardson Ecology of the Zygomycetes and its impact 5

samples [15]. Zygomycetes do not appear to be common in time. Fungi, including and zygomycetes, buildings [16], suggesting that the various building materials play an important role in the decomposition of cellulose, lig- used in house construction do not support the growth of nin, and other more resistant materials, despite being con- these fungi, as compared with the wide profile of deutero- fined primarily to the outer layers and becoming active only mycetes found on damp substrates. A significant proportion during the latter part of the composting period [10]. of private residences, offices and workplaces are known to Many opportunistic mucorales are typical inhabitants of be damp, and estimates range from 20–50%. Numerous pub- natural composts, tropical soils, and other heated materials. lications have reported the moisture levels required for Indoor sites particularly associated with these fungi, there- growth of fungi on construction, finishing or furnishing mate- fore, may be those where humid organic material is exposed rials. Rhizopus species have a high moisture requirement for to heat, most notably within poorly maintained heating ducts growth, and are classified as hydrophilic. Members of the and attached humidifier structures, in soils of potted Mucorales are non-cellulolytic microorganisms, and do not (especially those placed in warm locations), and in indoor have any enzymatic activity, even against the most susceptible composts [8]. forms of cellulose, and so are not very likely to be found on R. oryzae and A. corymbifera have been found in potted building materials. All of these observations suggest that plant soil in a haematology unit where a leukaemia patient house residents are not generally exposed to zygomycetes in developed invasive mucormycosis [1]. They were also abun- their home environment, apart from mould-contaminated dantly represented in bird dung accumulating in an aviary [1]. food items such as bread and fruit. This notion is supported In hospitals, wooden materials such as tongue depressors by the absence of zygomycetes in indoor air-sampling surveys have repeatedly been found to be a source of Rhizopus inoc- [14]. ulum [1]. R. oryzae has been isolated from grains, onions, var- ious nuts, and stored seed potatoes [1]. Soil and composting vegetation Multiple studies mention soil contamination of soft tissue The simplistic view is that the agents of zygomycosis are damage followed by zygomycosis, apparently in immunocom- found in the soil, in composting vegetation, on rotting fruit, petent patients [17]. Traumatic inoculation of spores can in dust, during heavy excavation and construction, and in air- lead to extensive necrotic cutaneous infections. Cutaneous conditioning filters. The elevated temperatures found in mucormycosis is an aggressive disease. It can lead to necro- composting vegetation are selective for thermophilic species, tizing fasciitis or to widespread disseminated infection. such as some species of Absidia, Mucor, Rhizopus, and Rhizo- This form of disease is most often seen in patients with mucor. In general, these fungi are unable to utilize cellulose burns and other forms of local trauma, such as traumatic and lignin. They are characterized by rapid . implantation of sporangiospores via soil, needlestick injuries, Some species are found growing on dung. illicit drug injection sites, tattooing, and insect bites and There are currently c. 3300 species of currently known stings. Disruption of the cutaneous barrier seems to be a soil fungi. Very few studies have identified members of the prerequisite for the acquisition of cutaneous zygomycosis, Mucorales at particular sites where cases of zygomycosis with region-specific zygomycetes being isolated from soil at have been reported from. For many years, there has been the geographical site of trauma as well as from the patient. the view that most soil fungi are cosmopolitan and that spe- An illustrative case is where a patient who, while attempting cies at a particular site are only selected by various soil to extinguish burning clothes, rolled in moist soil that was parameters. It has also been the view that most fungal spe- found to be contaminated with Apophysomyces elegans [18]. cies potentially spend part of their in the soil. This view Apophysomyces elegans was first isolated from soil samples has now been modified considerably, as many plant-parasitic collected from a mango orchard in northern India [19]. In species are never isolated from the soil. This is particularly diabetic or immunosuppressed patients, cutaneous lesions pertinent when considering the Mucorales. may arise at an insulin injection site or a catheter insertion In general, composting is considered to be an aerobic pro- site. cess, suggesting high biological activity. It has been clearly Biological soil crusts are the community of organisms liv- demonstrated that the rise in temperature and the decom- ing at the surface of desert soils. Major components are cy- position of composting plant materials is brought about by anobacteria, , , , liverworts, and thermophilic microorganisms, including fungi [10]. Tempera- lichens. Zygomycetes do not appear to survive in this envi- ture and changes in the available food supply probably exert ronment. Species of zygomycetes have been cultured from the greatest influence in determining the species of organism geothermal soils in Yellowstone National Park, including comprising the population in a compost stack at any one species of Absidia and Cunninghamella, especially in close

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proximity to the perennial plant Dichanthelium langinosum, non-dermatophytic moulds, including species of zygomycetes the hot springs panic grass [20]. [24]. From 238 samples (skin scrapings, feathers, and soil), 258 fungi belonging to 21 genera were isolated. Rhizopus, Mu- Natural disasters cor and Absidia were isolated from skin scapings and soil but Natural disasters have also revealed specific environmental not from feathers. niches of zygomycetes. This was illustrated particularly by the Asian tsunami. Most of the tsunami survivors who expe- Exposure through colonization of nasal mucus. Because of rapid rienced near-drowning events remained in unclean and trau- growth and prolific spore production, inhalation of sporan- matic conditions without receiving any immediate medical giospores must be a daily occurrence [9]. It is known that the care. Patients lay for several hours or days in warm and stag- sporangiospores of some zygomycetes in indoor environ- nant water; normally poorly virulent environmental , ments have a very low settling rate and remain airborne for a fungi, and amoebae found ideal conditions for the coloniza- long time. Airborne fungal spores are almost ubiquitous, and tion of open wounds and bone fractures, and dissemination can be found on all human surfaces in contact with air, espe- to other body sites. Many survivors presented with necrotiz- cially on the upper and lower airway mucosa. Fifteen thousand ing fasciitis, a soft tissue infection associated with infarction to 170 000 spores are inhaled over a 24-h period by an adult of the dermis and subcutaneous tissue. The cause of this person, depending on environmental, climatic and regional fac- condition is usually polymicrobial, but cutaneous mucormy- tors. Fungal spores in the mucus of airway mucosa are cleared cosis is recognized as a cause of , as by mucociliary transport. Surprisingly, members of the Muco- agents of mucormycosis exhibit vasculotropism, which is rales are very rarely found in nasal mucus. Nasal mucus is pro- important in the pathophysiology of this condition, with the duced by the nasal mucosa, and mucus lining the airways endpoint being ischaemic necrosis of the affected tissue [21]. (trachea, bronchus, and bronchioles) is produced by special- The following case is illustrative [21]. A survivor of the ized airway epithelial cells (goblet cells) and submucosal Asian tsunami with soft tissue injuries and bilateral displaced glands. Small particles such as dust, particulate pollutants, and fractures of the inferior and superior pubic rami was found to , as well as infectious agents such as bacteria, become be infected with Apophysomyces elegans. Liposomal amphoteri- caught in the viscous nasal or airway mucus. cin B was commenced, and a course of 42 days was adminis- Do mycological studies of the biodiversity of the nasal tered. After surgical debridement, topical negative-pressure mucus help? The nose is a very efficient air sampler, and anal- dressings, nursing care, and antifungal therapy, split skin graft- ysis of the nasal mucosa should reflect the air spora of the ing was utilized to cover the resulting defect, with good environment where a patient has been residing and working. results. It was assumed that the affected areas had become In one study conducted in Austria, samples of nasal mucus infected with the fungus in contaminated water or soil. from patients suffering from chronic rhinosinusitis and from healthy persons were monitored over 28 months [25]. Sam- Other sources of zygomycetes ples of mucus were obtained by flushing the noses of patients Even though many previous reviews on the epidemiology of with saline or by endoscopic sinus surgery. Fungi from mucus zygomycosis have highlighted the growth and isolation of were cultured, and identification was performed microscopi- mucorales on intact and rotting fruit, bread and other food cally and by PCR, with subsequent sequencing of the ribo- items [1] there are very few systematic surveys. It is apparent somal internal transcribed spacer region. Altogether, 619 from the recent literature, at least, that mucorales do not con- strains of fungi were cultivated from 233 subjects. Eighty-one stitute a major part of the mycoflora of food-handling facilities. species were identified, with a maximum of nine different spe- When sampling the air in a fruit market, Kakde et al. [22] cies per person. The most prevalent isolates belonged to the found that Aspergillus was the most frequent and predomi- genera Penicillium, Aspergillus, Cladosporium, Alternaria, and Aure- nant detected. Cladosporium, Penicillium and Alternaria obasidium. Zygomycetes were found in only two subjects, spores were also fairly abundant. However, only one genus R. oryzae in one, and C. bertholletiae in another. Based on this of zygomycota was isolated, i.e. Cunninghamella, representing study it appears that analysis of nasal mucous does not reflect 0.3% of the spectrum of the moulds isolated. exposure to zygomycetes. When the faeces of rodents living in a stored-grain facility Zygomycetes are found occasionally in water-damaged in the Czech Republic were cultured, R. oryzae represented buildings, as demonstrated by air sampling, and analysis of 10% of the fungi isolated [23]. Sampling of skin scrapings settled dust by quantitative PCR. Outbreaks of rhinocerebral from infected poultry and the surrounding soil in the poultry or pulmonary zygomycosis have been linked to inhalation of facility revealed a very diverse profile of dermatophytic and sporangiospores in dust as a result of excavation, construction,

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15 (Suppl. 5), 2–9 CMI Richardson Ecology of the Zygomycetes and its impact 7

or contaminated air-conditioning filters. Some reports suggest very often in response to outbreaks of cases of nosocomial that the lower airways are colonized with agents of zygomyco- pulmonary . These studies provide an insight into sis [26]. Nevertheless, in patients with appropriate underlying the spectrum of fungal species in different hospital settings. conditions, isolation of zygomycetes, even from non-sterile Rainer et al. [30] reported the monitoring of the air in a spe- samples, is generally regarded as potentially significant [27]. cial-care unit of their hospital over a 6-month period. A total of 98 fungal species were identified, among them Aspergillus Exposure through the gastrointestinal tract. Ingestion of contam- fumigatus and , as well as 48 other species inated food materials, such as fermented milk, fermented considered to be potential pathogens, including species of porridge, and herbal/homeopathic remedies, and the use of Mucor and Rhizopus, but at very low levels (0.2–1.3 CFU/ ) contaminated tongue depressors, are recognized exposure m 3). The presence of these fungi suggests that air may be a risks for gastrointestinal mucormycosis. Gastrointestinal mu- discrete environmental source of nosocomial infection, per- cormycosis is a rare condition that has usually been encoun- haps most importantly for profoundly immunocompromised tered in malnourished infants or children. Persistent patients. ingestion of non-nutritional substances, gastric ulcers, severe A number of reports suggest that air-conditioning units in systemic illness, age extremes and systemic immunosuppres- hospital environments may constitute an environmental risk sion are additional predisposing conditions for gastrointesti- factor for mucormycosis. An illustrative report describes nal tract mucormycosis. two patients with rhino-orbital-cerebral mucormycosis occurring within a 3-week period caused by airborne trans- Contaminated medical devices. Whereas most zygomycete mission of R. oryzae, which was cultured from an air-condi- infections are community-acquired, nosocomial acquisition, tioner filter [31]. Rosen and Sternberg [32] reported a sporadic cases and pseudo-outbreaks have been linked with decrease in the numbers of rhinocerebral mucormycosis contaminated bandages, needles, and tongue depressors used diagnoses in post-mortem examinations associated with an to construct splints for intravenous and arterial cannulation improved ventilation system being installed in their institu- sites in preterm infants [1]. Percutaneous routes of exposure tion. In the patient series reported by Talmi et al. [33], there are very important in causing zygomycete infections. Trau- was no shared close environmental setting. matic implantation of spores via soil has been seen in many An unusual exposure to Rhizomucor pusillus in a hospital patients. Needlestick exposures have been implicated in setting was described by del Palacio Hernanz et al. [34]. zygomycotic infections occurring at the site of medicine Three patients suffering from acute leukaemia were treated injection, catheter insertion sites, injection sites for illicit with cytotoxic agents and broad-spectrum antibiotics, and drug use, and tatooing. Insect bites or stings have also been received blood transfusion and nasal packing for severe epi- implicated in disease transmission in cases of cutaneous and staxis. All developed necrosis of nasal and facial tissues, with subcutaneous zygomycosis. The development of wound zygo- facial swelling and oedema; two biopsy specimens showed mycosis has been seen with a variety of adhesive products typical mucorales , and Rhizomucor pusillus was used in the hospital setting. grown from one biopsy specimen. Air and surfaces in the unit and the air intake and exhaust ducts were all heavily col- , birds and insects as sources of zygomycetes. A study of onized by Rhizomucor pusillus and other zygomycetes. The dog skin biota demonstrated a peak prevalence of Rhizopus authors suggested that Rhizomucor pusillus spores from the species spores in summer, and of Mucor species in autumn, air invaded the tissues because of the local conditions pro- but at much lower concentrations than those of agents of moted by the nasal packing in their patients. dermatomycoses [28]. There is an interesting case report of an immunocompetent patient who developed a necrotizing Is zygomycosis (Mucormycosis) a Seasonal soft tissue infection after being pecked by a magpie. S. vasifor- Disease? mis was isolated from the cellulitic lesion [29]. Agents of zygo- mycosis have also been transmitted by insect and spider bites. Zygomycosis has not previously been regarded as having a seasonal pattern. Seasonal variations in the atmospheric con- Zygomycetes in Hospital Environments centrations of fungal spores for some moulds in several geo- graphical locations have been reported. In the USA, the A number of studies have looked at the biodiversity and highest levels were found in the autumn and summer, and concentration of airborne fungi in hospital environments, the lowest in the winter and spring, but agents of

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15 (Suppl. 5), 2–9 8 Clinical Microbiology and Infection, Volume 15, Supplement 5, October 2009 CMI

mucormycosis were not commonly found [14]. Seasonal dormancy of these spores in the sinuses. In conclusion, as peaks of Aspergillus conidia and other moulds have been we have little understanding of how and when patients are reported from Europe and the USA, but few data exist on exposed to agents of zygomycosis, there are no means of the seasonal frequency of the Mucorales or the seasonal preventing this infection. prevalence of mucormycosis. Only one study, by Talmi et al. [33], reported dates of onset of symptoms, for 19 patients Transparency Declaration in Israel with rhino-orbital and rhino-orbito-cerebral muco- rmycosis. The dates appeared to vary seasonally, but the var- iation did not reach statistical significance. A more recent M. Richardson has acted as a paid consultant to Gilead Sci- study from Lebanon suggested a clustering of onset of muco- ences (Europe) Ltd and has received honoraria from Gilead rmycosis at the end of a dry, warm period that lasted from Sciences, Pfizer and MSD. May to October [35]. References Sources of Entomophthorales

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