General Description of Zygomycetes and Zygomycosis

The class Zygomycetes is a large group of fungi that comprise two orders of medical interest, the Mucorales and the Entomophthorales. Zygomycoses caused by Entomophthorales are generally chronic infections seen in immunocompetent patients, mostly in tropical areas (Dromer & McGinnis, 2002). General description of Entomophthorales and associated diseases have been reviewed recently (Prabhu & Patel, 2004; Ribes et al., 2000) and as no major advancement has been made recently in the knowledge and management of entomophthoromycosis, these fungi will not be detailed in this chapter. Human pathogens belonging to the order Mucorales are grouped into six families (Table 7.1) and comprise approximately 20 species in approximately 10 genera. The most frequent species responsible for zygomycosis are Rhizopus spp., Mucor spp., Rhizomucor spp., and Absidia spp. (Ribes et al., 2000). Other species such as Cunninghamella bertholletiae, Apophysomyces elegans, and Saksaenea vasiformis have been less frequently reported as etiological agents of zygomycosis.

Mucorales are hyaline fungi growing easily on standard culture media. Macroscopically, mycelium is expanding with a woolly appearance. Microscopically, these fungi are characterized by large, rarely septated hyphae. Mucorales can reproduce both by production of asexual sporiangiospores or by sexual zygospores. Sexual reproduction is seldom observed in culture as most of the pathogenic mucorales are heterothallic (i.e. production of zygospores need confrontation of two strains of opposite mating type). Identification of the species in culture then mainly relies on the presence of asexual spore-bearing structures. For some species, these structures are sufficiently characteristic for an easy identification. Nevertheless, for the most frequent species (i.e. Rhizopus spp., Mucor spp., Absidia spp., and Rhizomucor spp.) the overall morphology is similar and identification is based on detailed observation of presence, location, and morphological characteristics of specific structures (Figure 7.1). For this reason, a precise identification to the species level can only be performed by specialized laboratories. Beside macroscopic

K. Kavanagh (ed.), New Insights in Medical Mycology. © Springer 2007

Table 7.1 Zygomycetes species that have been described as human pathogens

Class

Order

Family

Genus

Species

Zygomycetes Mucorales

Mucoraceae

Mortierellales

Absidia

Apophysomyces

Chlamydoabsidia

Mucor

Thamnidiaceae

Cunninghamellaceae

Syncephalastraceae

Saksenaeaceae

Mortierellaceae

Rhizomucor

Rhizopus

Cokeromyces

Cunninghamella

Syncephalastrum

Saksenaea

Mortierella

A. coerulea A. corymbifera A. elegans C. padenii M. amphibiorum M. circinelloides M. hiemalis M. indicus M. racemosus M. ramosissimus R. miehei R. pusillus R. variabilis R. azygosporus R. microsporus R. oryzae R. schipperae R. stolonifer* C. recurvatus C. bertollethiae S. racemosum S. vasiformis M. polycephala* M. wolfii*

* The true pathogenic role R. stolonifer and Mortierellales in humans has not been definitely proven.

and microscopic morphology, few other identification criteria could be used such as maximum growth temperature or scanning electronic microscopy (de Hoog & Guarro, 2000; Scholer et al., 1983). Specific physiological tests have been used for discriminative identification between some closely related species (Vagvölgyi et al., 1996; Vastag et al., 1998; Ribes et al., 2000; Scholer et al., 1983), but no extensive studies have been performed on a sufficient number of isolates to date.

Clinical manifestations of zygomycosis can be grouped in five major entities: rhinocerebral, pulmonary, cutaneous, gastrointestinal, and disseminated infections (Dromer & McGinnis, 2002; Kwon-Chung & Bennett, 1992; Spellberg et al., 2005a). Common characteristics of these infections are the rapidity of progression and angioinvasion leading to vascular thrombosis and subsequently to tissue necrosis. Rhino-cerebral zygomycosis is one of the most frequent forms. It initially presents as acute sinusitis with rapid spread of infection to contiguous tissues of the orbit, skin, palate, and to the central nervous system. The main symptoms in patients with pulmonary zygomycosis include fever, cough, and chest pain. There are no specific clinical or radiological signs and this form of zygomycosis can easily be misdiagnosed for another filamentous fungal infection such as pulmonary

Figure 7.1 Microscopical characteristics of different species of zygomycetes. Some species can be easily identified such as Absidia corymbifera (A), Saksenaea vasiformis (B), or Cunninghamella bertholletiae (C). By contrast, other species share similar morphological traits making the pheno-typic identification more complex such as Rhizopus oryzae (D) and Rhizopus microsporus (E), or Mucor circinelloides (F) and Rhizomucor pusillus (G)

Figure 7.1 Microscopical characteristics of different species of zygomycetes. Some species can be easily identified such as Absidia corymbifera (A), Saksenaea vasiformis (B), or Cunninghamella bertholletiae (C). By contrast, other species share similar morphological traits making the pheno-typic identification more complex such as Rhizopus oryzae (D) and Rhizopus microsporus (E), or Mucor circinelloides (F) and Rhizomucor pusillus (G)

invasive aspergillosis. Cutaneous zygomycosis is mainly acquired in a patient with altered skin barrier. Typical cases are traumatic injuries with contamination by soil but can also occur in patients with extensive burns or following traumatic implantation of the fungi at injection site. Gastrointestinal mucormycosis is a rare infection but generally acute and rapidly fatal. Symptoms are nonspecific and variable depending on the gastrointestinal tract site involved. Disseminated zygomycosis occurs after hematogenous spread of the infection from any primary site and is generally fatal. The brain is the most common site of dissemination but many other organs can be involved.

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