Mucormycosis: A Review on Environmental Fungal Spores and Seasonal Variation of Human Disease

doi:10.4236/aid.2012.23012

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Advances in Infectious Diseases, 2012, 2, 76-81

http://dx.doi.org/10.4236/aid.2012.23012 Published Online September 2012 (http://www.SciRP.org/journal/aid)

Mucormycosis: A Review on Environmental Fungal Spores

and Seasonal Variation of Human Disease

Rima I. El-Herte, Tania A. Baban, Souha S. Kanj*

Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

Email: *[email protected]

Received May 1st, 2012; revised June 3rd, 2012; accepted July 5th, 2012

ABSTRACT

Mucormycosis is on the rise especially among patients with immunosuppressive conditions. There seems to be more

cases seen at the end of summer and towards early autumn. Several studies have attempted to look at the seasonal varia-

tions of fungal pathogens in variou indoor and outdoor settings. Only two reports, both from the Middle East, have ad-

dressed the relationship of mucormycosis in human disease with climate conditions. In this paper we review, the rela-

tionship of indoor and outdoor fungal particulates to the weather conditions and the reported seasonal variation of hu-

man cases.

Keywords: Mucormycosis; Seasonal Variation; Fungal Air Particulate Concentration; Mucor; Rhizopus; Rhinocerebral

1. Introduction

Mucormycosis refers to infections caused by molds be-

longing to the order of Mucorales. Members of the fam-

ily Mucoraceae are the most common cause of mucor-

mycosis in humans. This includes the genera Absidia,

Mucor, Rhizomucor, and Rhizopus. Two additional patho-

genic families are the Cunninghamellaceae and the Sak-

senaceae. These are opportunistic fungi that are able to

cause acute, rapidly progressing fulminant infections in

compromised hosts. They can cause rhinocerebral, pul-

monary, gastrointestinal, cutaneous and disseminated in-

fections. Risk factors for such infections include diabetes,

ketoacidosis, lymphoma, leukemia, neutropenia, corti-

costeroid use, long term immunosuppressive therapy, de-

feroxamine therapy, and prior intake of fungal prophy-

laxis with voriconazole [1]. Such infections are fatal if no

adequate and rapid surgical and medical interventions are

initiated. Two reports suggested that the incidence of

mucormycosis increases in summer and early autumn

[2,3]. In this review, we present the available published

literature on the seasonal variation of the air concentration

of various spores of mucorale sp. and other fungi and the

seasonal variation of clinical mucormycosis.

2. Environment and Seasonality

Mucorales are thermotolerant. They are ubiquitous in na-

ture and widely found on organic substrates, including

bread, decaying fruits, vegetable matters, crop debris, soil,

compost piles, animal excreta, and on excavation and con-

struction sites. Sporangiospores are easily aerosolized, and

are readily dispersed throughout the environment making

inhalation the major mode of transmission. Published data

describing the levels of zygomycete sporangiospores in

outdoor and indoor air in relation to seasonal variation is

scarce.

2.1. Outdoor Concentration and Seasonal

Variation

Most of the studies addressing variations of fungal spores

in the air in relation to the season have been done in

European countries. The earliest study that considered

metereological conditions and airborne particulate con-

centration of fungi was done in Athens and showed that

during autumn and winter the number of suspended mi-

crofungi was twice as high as in spring and summer [4];

Mucor species were cultured during the months of June

through December excluding September. This result sug-

gested a positive correlation with humidity and a nega-

tive correlation with temperature. In a Spanish study

done in 1980 over a two-year survey on the airborne

fungi in the atmosphere of Barcelona, Rhizopus, and Mu-

cor were the second most commonly isolated fungi after

Aureobasidium [5]. In another study by Herrero in Pa-

lencia in 1992, air cultures revealed that Mucor sp. were

the most common pathogens (25%) followed by Asper-

gillus sp. (23%) and Penicillium sp. (16%). Thirty two

percent of the fungal colonies grew in autumn, while

*Corresponding author.

Mucormycosis: A Review on Environmental Fungal Spores and Seasonal Variation of Human Disease 77

28% during spring [6]. A study from Ankara, Turkey

failed to reveal mucoracae in air particulates but showed

a predominance of other fungi such as Cladosporium

(75.5%) followed by Alternaria (6.1%), Leptosphaeria

(2.2%) and others. The highest value of spore concentra-

tion was detected in July, and the lowest in January. This

was thought to be related to monthly mean temperatures,

wind velocity and humidity [7]. Soil and air samples

from seven different localities around a Turkish city were

sampled and revealed that the most isolated genus from

air samples was Alternaria (43.96%), followed by Clado-

sporium (25.52%) and Phoma (5.40%) [8]. Fusarium and

Penicillium occurred at very low concentrations in air

and no mucoracae were isolated. The highest airborne

spore concentration was found during autumn and the

lowest concentration during the summer. Aspergillus’ air

spore concentration was very low in all seasons during

the research period [8]. Another Turkish study meas-

uring the indoor and outdoor concentration of fungi in

Istanbul revealed that Cladosporium and Alternaria were

the most commonly recovered followed by Penicillium,

Aspergillus, Rhizopus, Aureobasidium, Mucor and Fusa-

rium at a lower concentration [9]. Oliveria et al. found

similar results in Porto, Portugal: Cladosporium being

the most common to recover (74.5%) throughout the year

followed by Alternaria, Aspergillus, Penicillium, Botry-

tis, Coprinus, Epicoccum, Fusarium, Ganoderma, Mucor ,

and Ustilago. The highest airborne spore concentrations

in Porto were observed during summer and late autumn

and the lowest during winter and were negatively corre-

lated with wind speed; while positively correlated with

temperature and relative humidity. Alternaria, Botrytis

and Ganoderma spore density peaked from summer to

autumn. Spore densities of Corynespora, Fusarium, Oid-

ium, Periconia and Rhizopus peaked in late spring [10].

Results were similar in studies done from Northeast

America where Cladosporium sp. was also dominant in

both indoor and outdoor air in summer, with not much

isolated mucoracae [11]. In another study done in the

USA in 2002, the median outdoor fungal concentrations

varied according to seasons and were highest in the fall

and summer and lowest in the spring and winter. Mostly

they were Cladosporium, Penicillium, Aspergillus; how-

ever, there was no available data concerning Mucor and

Rhizopus sp. [12]. The seasonal variation of fungal pro-

pagules in a fruit market environment in Nagpur, India

showed that Aspergillus was the most frequent and pre-

dominant genus detected, peaking in summer, followed

by Cladosporium, Penicillium and Alternaria peaking

during December-January [13]. Fungi related to animals

have also been studied. Rodents from a Czech study

showed that they harbor various species of Aspergillus,

Mucor and Penicilliu m ; R. oryzae represented 10% of the

fungi [14]. Studies on the fungal biota of the fur of dogs

in Spain yielded Alternaria, Aspergillus, Cladosporiurn,

Chrysosporium, Penicillium and Scopulariopsis. Mucor

(27.3%) peaked in autumn and Rhizopus (14.5%) in

summer [15]. Another study looking into the dermatomy-

cosis of the dogs revealed that Mucor sp. formed 1.5% of

the causative agents mostly in warm and humid climates

[16]. In an Indian study, fungi involved in skin infections

in poultry included Aspergillus, Pencillium, Alternaria,

Rhizopus, Chry sospor ium, Mucor , Scopulariopsis among

others and the soil tested in the vicinity revealed Chry-

sosporium, Alternaria, Aspergillus, Paecilomyces, Peni-

cillium, Mucor, and Rhizopus among various other gen-

era [17].

2.2. Indoor Concentration and Seasonal

Variation

The spore density of different fungi was measured in

different districts of Istanbul and the results showed that

Penicillium and Aspergillus were the most abundant fol-

lowed by Rhizopus, Mucor and Fusari um; Rhizopus was

found at a lower density outdoors than in indoor air [9].

In the US, the indoor fungal concentrations were founde

to be highest in the fall and summer and lowest in the

spring and winter. The most commonly recovered fungi

were Cladosporium, Penicillium, the nonsporulating fungi

and Aspergil lus. Mucor and Rhizopus sp. were detected

mostly in winter and summer [12]. Also indoor mycobiota

varied with the niche. Wooden and paper materials had

the highest median concentrations of fungi whereas min-

eral insulation, ceramic products, and paints and glues

had the lowest. The wooden materials harbored Penicil-

lium and yeasts, as well as Cladosporium and Stachybotrys.

Ceramic products, paints and glues seemed to favor

Acremonium and Aspergillus versicolor [18].

2.3. Seasonal Variation of Human Disease

Roden et al. analyzed 929 cases of mucormycosis with-

out shedding light on its seasonal variation [19]. Possible

seasonal variation of mucormycosis has been addressed

in 2 studies, both from the Middle East. Al-Ajam et al.

reported a series of 16 cases of invasive rhinocerebral,

cutaneous and pulmonary mucormycosis. He showed that

the onset of symptoms clustered at the end of a dry pe-

riod, which consistently extended from late May to Oc-

tober; i.e. early summer to end of autumn in 12 out of 16

patients with a statistically significant seasonal variation

(p = 0.007) which coincided with increasing rain levels

[2]. However, data is lacking on the mycobiota species

and their concentration in Beirut or any other cities in

Lebanon. A similar study from Israel analyzing 36 cases

of rhinocerebral mucomycosis showed that most of the

cases occurred between August and December with a

peak incidence in September. In this country, the weather

Mucormycosis: A Review on Environmental Fungal Spores and Seasonal Variation of Human Disease

is hot and humid from May till September. Rhizopus

oryzae was the most commonly isolated organism [3].

Infection with mucorales has also been reported to o-

ccur as a consequence of natural disasters such as vol-

canic eruptions [20] and tsunami [21,22]. In some reports,

the victims had multiple sites of necrotizing fasciitis due

to R. arrhizus, Apophysomyces elegans and others. Analy-

sis of the volcanic mud flow revealed Rhizopus arrhizus,

Mucor sp., Trichoderma sp., Penicillium sp., Fusarium sp.,

Aspergillus niger, Paecylomyces sp. and Candida sp.

Table 1 summarizes the various studies done correlat-

ing fungi, air particulate concentration with season and

climate.

3. Discussion

The various published reports show that Mucor and

Rhizopus sp. are not among the most commonly isolated

fungi from outdoors environment with highest outdoor

concentrations in spring and summer [13,15], whereas

indoor concentration of these fungi was highest during

winter and spring [13]. Other studies have failed to detect

any mucorales by PCR from indoor and outdoor air sam-

ples [23]. Hence a clear conclusion cannot be reached.

Sesonal variation of human mucormycosis seems to be

plausible. The 2 studies from the Middle East showed

that most cases of mucormycosis occurred in late sum-

mer, fall and early winter. In Lebanon, the cases clus-

tered between August and December when the weather

ranges from hot and dry to wet and cool. In Israel, the

weather is very similar to Lebanon and cases also had a

similar distribution according to the months of the year

(Figure 1). In both studies there was no attempt to iden-

tify the source of infection but infection was attributed to

airborne transmission from air conditioners. Two patients

of the latter study had infection with R. oryzae, which

was also cultured from the doctor’s office. This sug-

gested that improving the ventilation systems may de-

creases the incidence. Also no unusual precipitations or

temperature data were recorded from the Israeli study. It

is probable that infestation can build up in earlier months

and manifest in August and September. However, in both

studies there is no data about the fungal particulate air

concentration to correlate them to this type of fungal in-

fection. Other publications about invasive mucormycosis

infection did not mention any information about the sea-

son when these patients were diagnosed [19]. There re-

main many unanswered questions that need to be ad-

dressed in future studies. Particularly investigating whe-

ther the organisms have a true seasonal variation in out-

door and indoor settings and whether this correlates to

human diseases. Since both studies addressing seasonal

variations of human disease have been done in the Mid-

dle East in countries with similar weather and humidity

conditions, the results cannot be extrapolated to other

regions and countries. It will be of interest to study this

in various centers worldwide where there are increasing

numbers of immunosuppressed patients at risk for mu-

cormycosis such as oncology and transplant patients.

Knowledge about seasonal variation of this deadly fungal

infection might have important implications. Physicians

will have a lower threshold to consider such infections in

their immunocompromised hosts, better attention to air

filters in transplant units during peak seasons, and possi-

ble prophylaxis in outbreak situations, especially with the

availability of potent oral agents such as posaconazole

are to be considered [24]. Since mucormycosis is fatal in

most cases when therapy is delayed, more efforts should

be done by the medical community caring for immuno-

compromised patients to better understand its epidemic-

ology. The availability of advanced culture and molecu-

Figure 1. Distribution of mucormycosis cases versus month of year in Israel and Lebanon (with permission from author [2]).

Mucormycosis: A Review on Environmental Fungal Spores and Seasonal Variation of Human Disease 79

Table 1. The table shows each author’s publication, country, year time during which the highest concentration of fungi was

recovered, the fungi recovered and associated meteorological factors. High humidity, rain, low temperatures showed positive

correlation with increasing air particulates concentration; not all studies showed correlation with wind velocity.

Author/Country Year Time Molds Species Factors

Outdoor Bartzokas/Greece Autumn & Winter Aspergillus

Penicillium

Alternaria

Mucor

Low Temperature and

Increase Humidity

Calvo et al./Spain Aureobasidium

Rhizopus

Mucor

Arthrinium

Fusarium

Herrero/Spain Autumn & Spring Mucor

Aspergillus

Penicillium

Ceter et al./Turkey July Cladosporium

Alternaria

Leptosphaeria

Humidity

Temperature

Wind Speed

Asan et al./Turkey Autumn Alternaria

Cladosporium

Phoma

Çolakoğlu/Turkey Cladosporium

Alternaria

Penicillius

Aspergillus

Rhizopus

Aureobasidium

Mucor Fusarium

Oliveria et al./Portugal Summer & Late Autumn Cladosporium

Alternaria,

Aspergillus

Penicillium

Temperature Humidity

Ren et al./ Summer Cladosporium

Shelton et al./USA Summer & Autumn Cladosporium

Penicillium

Aspergillus

Kakde et al./India December-January/Summer Aspergillus

Cladosporiu

Penicillium

Alternaria

Stejskal et al./Czech Aspergillu,

Mucor

Penicillium

R. oryzae

Cabafies et al./Spain Summer & Autumn Alternaria,

Aspergillus

Cladosporiurn

Chrysosporim

Penicillium

Scopulariopsis

Mucor

Jand et al. Mucor Warmth and Humidity

Saidi et al./India Chrysosporium

Alternaria

Aspergillus

Paecilomyces

Penicillius Mucor

Rhizopus

Mucormycosis: A Review on Environmental Fungal Spores and Seasonal Variation of Human Disease

Continued

Indoor Çolakoğlu/Turkey Penicillium

Aspergillus

Rhizopus, Mucor

Fusarium

Rhizopus

Shelton et al. Fall & Summer

Winter & Summer Cladosporium,

Penicillium

Aspergillus

Mucor

Rhizopus sp.

Human Disease Al-Ajam et al./Lebanon May-October/Summer-Autumn Rain

Shpitzer et al./Israel August-December/Summer-Winter

lar techniques would help in correlating environmental

fungi to human diseases [25].

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