MYCOLOGY - CHAPTER  FIVE  

FILAMENTOUS FUNGI  

A. CHROMOBLASTOMYCOSIS 

A chronic, localized infection infection of subcutaneous tissues caused by several species of dematiaceous fungi. The 3 most common agents are: 

1. Fonsecaea pedrosoi (figure 1)

2. Cladosporium carrionii (figure 2 and 4)

3. Phialophora verrucosa (figure 3)

These fungi, recognized by a variety of names, are saprobes located in soil and decaying vegetation. The route of entry is usually by trauma. The lesions are sub-cutaneous and the surface can be flat or verrucous. The lesions take several years to develop. These organisms are called dematiaceous fungi, because they have a black color in the mycelium cell wall (in culture and in tissue). In tissue these fungi form sclerotic bodies which are the reproductive forms dividing by fission. These organisms induce a granulomatous reaction. The etiologic agents of chromoblastomycosis are septate, mold-like, branching, darkly pigmented which produce asexual fruits called conidia. We identify these fungi in culture by the shape and formation of the conidia. The fungi have a world-wide distribution especially in warmer climates like the tropics or the southern U.S. The melanin in the pigment may be a virulence factor. These organisms are distributed world-wide. There is no really successful therapy. Excision and local heat have been used with some success. Flucytosine (5-FC), thiabendazole and itraconazole have also been used to treat (or control) this disease. There are no serological tests to aid in the diagnosis.

 Figure 6.
 Mycetoma with presence of geotrichum   © Bristol Biomedical Image Archive. Used with permission

Mycetomas (fungous tumors) are also chronic, subcutaneous infections (figure 5). These are called eumycotic mycetoma (tumors caused by the TRUE fungi as opposed to those caused by actinomycetes) (figure 6). These tumors frequently invade contiguous tissue, particularly the bone. A diagnosis of the etiologic agent is essential for patient management because the prognosis and therapy differs. Mycetoma characteristics:

1. tumefaction - swelling

2. granules - a variety of colors (white, brown, yellow, black)

3. draining sinus tracts

The three most common etiologic agents are:

1. Madurella mycetomatis (figure 7 and 8)

2. *Exophiala jeanselmei (figure 9)

3. *Pseudallescheria boydii (figure 10 and 11)

*The most common in the US. These organisms are associated with the soil, thus you see many infections in the feet and legs.

 Clinical specimens for diagnosis:

1. pus -  with granules

2. tissue -  for histological examination

The color, size and texture of the granules are an aid in the diagnosis of mycetomas. The agents of mycetoma are all filamentous fungi which require 7-10 days for visible growth on the culture media and then another several days for specific identification. These fungi are identified by the colonial morphology, conidia formation and biochemical reactions. The species of fungi cannot be distinguished in histopathological tissue sections. Treatment is very difficult, but ketoconazole and itraconazole have been used with some success.

Figure 12.
 Histopathologic changes seen in zygomycosis due to Rhizopus arrhizus using FA stain technique. Rhizopus arrhizus, the most common Rhizopus spp., is known to be the cause of zygomycosis, an angiotropic disease, which means that it tends to invade the blood vessels, thereby, facilitating its systemic dissemination.

Figure 13.
 Histopathologic changes seen in a heart valve due to zygomycosis caused by Mucor pusillus. Using methenamine silver stain, one can detect the presence of fungal elements associated with zygomycosis, including sparsely septate hyphae, amongst a mostly acute inflammatory process with some island of chronic granulomatous inflammation. CDC/Dr. Libero Ajello

C. ZYGOMYCOSIS 

Also known as mucormycosis and phycomycosis. Zygomycosis is an acute inflammation of soft tissue, usually with fungal invasion of the blood vessels. This rapidly fatal disease is caused by several different species in this class. The zygomycetes, like the Candida species, are ubiquitous and rarely cause disease in an immunocompetent host. Some characteristic underlying conditions which cause susceptibility are: diabetes, severe burns, immunosuppression or intravenous drug use. 

The three most common genera causing this clinical entity are:

1. Rhizopus species (figure 12)

2. Mucor species (figure 13)

3. Absidia species

Characteristics: world-wide distribution, commonly in soil, food, organic debris, seen on decaying vegetables in the refrigerator and on moldy bread. Rhinocerebral infections are common. This disease is frequently seen in the uncontrolled diabetic. Typical case: An uncontrolled diabetic patient comes to ER (may be comatose depending on the state of diabetes) and a cotton-like growth is observed on the roof of the mouth or in the nose. These are the hyphae of the organism. If untreated, the patient will die within a few hours or days. What do you do to help this patient first? Controlling the diabetic state is most important before administering amphotericin.

These fungi have a tendency to invade blood vessels (particularly arteries) and enter the brain via the blood vessels and by direct extension through the cribiform plate. This is why they cause death so quickly.

Culture: A rapid growing, loose, white mold which is visible in 24 to 48 hours. With age, and the formation of sporangia, the colony becomes dark gray. The sporangia contain the dark spores. The mycelium is, wide (10-15 microns), ribbon-like and non-septate (coenocytic). This same appearance is clear in tissue sections. The species are identified by the morphology in culture. 

Treatment consists of debridement and amphotericin

There is an immunodiffusion test available, but the physician cannot wait for these results before instituting rapid, vigorous intervention. The diagnosis and treatment must be immediate and based primarily on clinical observations.

This photomicrograph depicts the appearance of a conidiophore of the fungus Aspergillus flavus. Aspergillus spp. are filamentous, cosmopolitan and ubiquitous fungi found in nature, are commonly isolated from soil, plant debris, and indoor air environments, and are the most commonly isolated filamentous fungi in invasive infections. CDC/Dr. Libero Ajello

  This chest radiograph shows probable aspergillosis with an aspergilloma, or fungus ball in the upper lobe of the right lung. Lung diseases that damage a lung can cause cavities that can leave a person more susceptible to developing an aspergilloma, or fungus ball. The fungus can then begin secreting toxic and allergic products, which may make the person feel ill.  CDC/M. Renz

D. ASPERGILLOSIS 

Aspergilli produce a wide variety of diseases. Like the zygomycetes, they are ubiquitous in nature and play a significant role in the degradation of plant material as in composting. Similar to Candida and the Zygomycetes, they rarely infect a normal host. The organism is distributed world-wide and is commonly found in soil, food, paint, air vents. They can even grow in disinfectant. There are more than one hundred species of aspergilli The most common etiologic agents of aspergillosis in the United States:

1.  Aspergillus fumigatus

2.  Aspergillus niger

3.  Aspergillus flavus

There are three clinical types of pulmonary aspergillosis:

1. Allergic - hypersensitivity to the organism. Symptoms may vary from mild respiratory distress to alveolar fibrosis.

2. Aggressive tissue invasion. Primarily a pulmonary disease, but the aspergilli may disseminate to any organ. They may cause endocarditis, osteomyelitis, otomycosis and cutaneous lesions.

3. Fungus ball  which is characteristically seen in the old cavities of TB patients. This is easily recognized by x-ray, because the lesion (actually a colony of mold growing in the cavity) is shaped like a half-moon (semi-lunar growth). The patients may cough up the fungus elements because the organism frequently invades the bronchus. Chains of conidia can sometimes be seen in the sputum.

Culture: Aspergilli require 1-3 weeks for growth. the colony begins as a dense white mycelium which later assumes a variety of colors, according to species, based on the color of the conidia. The hyphae are branching and septate. Species differentiation is based on the formation of spores as well as their color, shape and texture. 

Histopathology: The septate hyphae are wide and form dichotomous branching, i.e., a single hypha branches into two even hyphae, and then the mycelium continues branching in this fashion.

Serology: There is an excellent serological test for aspergillosis which is an Immunodiffusion test. There may be 1 to 5 precipitin bands. Three or more bands usually indicate increasingly severity of the disease. i.e., tissue invasion.

Treatment: Itraconazole and Amphotericin B.