The Fungi (Medical Mycology)

Lecture 04 [Notes]
There are more than 100,000 species of identified fungi. Of these, between 50 to 100 are know to be pathogenic to humans. Only about 20 species cause fatal infections. Diseases caused by fungal agents are called MYCOSES and can be divided into four major subdivisions based on the site of infection. These groups are: the SUPERFICIAL, the CUTANEOUS, the SUBCUTANEOUS, and the SYSTEMIC mycoses. A fifth group is also included. They are known as the OPPORTUNISTIC mycoses and are seen in a compromised host.*
(see also: The Emerging Fungal Threat, Science, Vol.266, pp. 1632-1634, December 9, 1994)

Asexual Spores Formed by Fungi**

Conidia - This term is sometimes used generically for all asexual spores. It may be used specifi- cally for spores borne singly or in clusters along the sides or at the tips of hyphae or of specialized hyphal branches called conidi- ophores. They are highly diversified in shape size, color and septation. Large (usually multinucleate) and small usually uninucleate, conidia are called macro- and microconidia respectively. Examples of genera forming this type of spore: Aspergillus, Penicillium, Cephalosporium, Microsporum, Trichophyton

Arthrospores - These are cylindrical cells formed by a double septation of hyphae. Individual cells called spores are released by fragmentation. Examples: Coccidioides, Trichophyton

Blastospores - Buds that arise from yeast or yeast-like cells. Examples: Candida, Saccharomyces

Chlamydospores - Thick-walled, round spores formed from terminal or intercalated hyphal cells. Examples: Candida

Sporangiospores - Spores formed within sac-like structures called sporangia at the end of hyphal stalks or on special hyphal branches called sporan- giophores. Examples: Coccidioides, Rhizopus

1. The Dermatophytes (Cutaneous Mycoses)

The dermatophytes are a closely related group of fungi which cause specific infections of humans and animals. The diseases they cause are referred to as DERMATOPHYTOSES, RINGWORM, or TINEA. They invade only the superficial keratinized areas of the body such as the skin, hair, and nails. They do not cause systemic infections and rarely, if ever, invade the subcutaneous tissues.

Cutaneous mycoses represent the most common fungal diseases in humans and are important health problems in countries where over-crowding and lack of simple hygiene exist. There are three genera of dermatophytes that cause infection: Trichophyton, Microsporum, Epidermophyton. Cutaneous diseases can be treated by oral admini-stration of Griseofulvin, an antibiotic which has an affinity for keratinized tissues. Topical ointments such as Tolnaftate (Tinactin), Haloprogrin, and Miconazole are effective but require prolonged administration. Other ointments sometimes used are Desenex and Whitfield's.

a. Genus Trichophyton

Microscopically, microconidia are the prominent spore forms. Various species are responsible for ringworm of the scalp (tinea capitis) and body (tinea corporis). Some species are common causes of "athlete's foot" (tinea pedis). Other species may cause tinea unguium, tinea barbae, and tinea cruris. The hair and nails may also be invaded.

b. Genus Epidermophyton

Microscopically, only broad to oval macroconidia are produced. This genus is represented by a single species, E. floccosum, and is found only in man. It grows in epidermis (especially in intertriginous areas, as between the toes), but the hair is not invaded. It is usually responsible for either tinea cruris or tinea pedis.

c. Genus Microsporum

Microscopically, large, spindle-shaped, multi-celled, rough, thick-walled macroconidial spores are numerous and characteristic. Most species infect the hair of children, domesticated and wild animals. Children commonly acquire the infection from dogs and cats. One specie, M. audouini, used to be the most frequent cause of ringworm of the scalp in children in the U.S. but now shares equal billing with Trichophyton tonsurans. The genus may cause tinea corporis, or tinea capitis.

2. Subcutaneous Mycoses

Subcutaneous mycotic infections are usually initiated by penetration of the skin with contaminated splinters, thorns, or soil. Once established, these infections tend to remain localized in subcutaneous tissues and tend to be extremely persistent. Treatment may sometimes require surgery plus antifungal agents such as Amphotericin-B. Potassium iodide may be used topically.

a. Sporothrix schenkii

This organism is single-celled, cigar-shaped and Gram +. It is found within macrophages or polymorphonuclear cells of lesions or exudates from humans and animals. The disease it causes is known as sporotrichosis. The disease is characterized by an ulcerated lesion at the site of inoculation. Multiple nodules and abscesses occur along the superficial draining lymphatics. The disease is usually sporadic among farmers and gardeners. A few industrial outbreaks have occurred among workers exposed to batches of heavily infected timbers or plants. The spores can also be inhaled. The organism is found in North, Central, and South America as well as Africa. In the United States, it is found along the Mississippi and Missouri valleys and throughout the Northeast.

b. Hormodendrum (Fonsecaea) pedrosoi

This fungus, with at least two others, Hormodendrum F. compacta and Phialophora verrucosa, produce the disease known as chromoblastomycosis. Infection arises from penetration of the skin by contaminated splinters or soil. The infection is most common in the tropics although its distribution is worldwide. The infection is seen on the legs of bare-legged laborers and lesions appear as warty, ulcerating, cauliflower-like growths.

3. Systemic Mycoses (Diseases Involving the Internal Organs)

These infections can penetrate the epithelial tissues and become disseminated throughout the body. Infections arise most frequently from inhalation of spores found in the soil. If the infective dose is sufficient, disease can result. Infection usually starts by development of lung lesions which may resolve themselves with no further damage. Some diseases may become chronic and the symptoms often mimic tuberculosis. If the fungal agents become disseminated into the bloodstream, other internal organs may become infected.
The treatment of systemic mycoses include Amphotericin-B alone or in combination with 5-fluorocytosine. More recently Ketoconazole has shown significant control and relief.

a. Cryptococcus neoformans

This yeast-like, non-sporulating, non-mycelial, budding fungus is characterized by the development of a wide capsule in tissue and culture. It has an attraction for the central nervous system and is often considered the most dangerous of the systemic mycoses. The disease is called cryptococcosis. Inhalation of the cells is assumed to initiate pulmonary infection, with subsequent spread to other viscera and the CNS by way of the bloodstream. Minor infections are common. Amphotericin-B is usually effective.

In the severe, chronic, and disseminated form of the disease, the brain, meninges, lungs, and other viscera, skin, and bones are involved to varying extents in different patients. Chronic meningitis is the most frequent and mimics tubercular meningitis. The lesions may simulate brain abscesses or brain tumors. Pulmonary lesions are usually inapparent. The disease appears sporadically and in essentially all parts of the world. The organism has been isolated from soil, particularly when enriched with pigeon droppings. Since the fungus remains viable in dried materials for many months, contaminated materials are a potent source of airborne infections. The organism is also opportunistic in the compromised patient.

b. Blastomyces dermatitidis

This organism is spherical, thick-walled, budding, and yeast-like in tissues, exudates, and cultures at 370 C. It produces a granular infection of the skin and internal organs which appears very similar clinically and histologically to tuberculosis. Infection apparently begins in the lungs and spreads, by means of the circulatory and lymphatic systems, to the bones, skin, prostate (in males) and other viscera. The gastrointestinal tract is normally spared. The skin lesions are often quite conspicuous. The disease is largely confined to Canada and the United States, particularly in the Mississippi Valley and east to the Carolinas. Once again, pigeon droppings provide a rich growth medium.

c. Histoplasma capsulatum

This organism is a small, oval, yeast-like fungus in tissues and cultures. In infected tissues, it is usually localized in macrophages and reticulo- endothelial cells. The organism is present in soil and inhalation of spores leads to pulmonary infection. Miliary (seedlike) nodules and lesions appear through-out the lung parenchyma and hilar lymph nodes become enlarge. The initial infection is mild and may pass unnoticed. In a small number of infected individuals the infection becomes progressive and widely disseminated, with lesions in practically all tissues and organs. Fever, wasting, and enlargement of liver, spleen, and lymph nodes occur and the disease may closely simulate tuberculosis. The disease is known as histoplasmosis or Darling's disease. In some parts of the country it is so prevalent that it is called "summer flu." It is localized in areas that have been enriched with bird excreta, especially from birds such as starlings, chickens, crows (but not pigeons), as well as bats. It is endemic in the Mississippi River Valley and it is estimated that over 30 million people in the U.S. have been infected.

d. Coccidioides immitis

A spherical, thick-walled endospore filled organism occurs in tissue and exudates. The disease, known as coccidioidomycosis, is highly infectious as arthrospores are easily spread. It is the most virulent of the systemic mycoses. It may produce an acute, benign, primary, self-limited respiratory infection or a chronic, malignant, secondary, progressive, disseminated infection usually referred to coccidioidal granuloma. The organism grows as a saprobe in desert soils of the southwestern United States and northern Mexico. It is sometimes known as Valley Fever. Infection is established by inhalation of airborne spores.
Of the 52 reportable diseases, this is the only fungal disease organism that is reportable.

e. Candida albicans

This oval, budding, yeast-like fungus produces blastospores and pseudo- mycelia in tissues and exudates. Its exact etiologic significance in any disease process is difficult to establish since it is often present in the mouth and intestinal tract of healthy individuals. It is often a secondary contaminant in other recognized diseases. It may truly be considered an opportunistic organism because it may cause cutaneous, subcutaneous, mucocutaneous, or systemic infections. When Candida becomes invasive it establishes a variety of acute or chronic, localized or widely disseminated lesions. Dependent upon body site infected, Nystatin or Candicidin may be used as well as previously mentioned drugs.

A number of fungi are not pathogenic in healthy humans, but may become virulent pathogens in those suffering from a variety of disorders, and in those treated intensively with broad-spectrum antibacterial drugs or with immunosuppressive measures.

Fungal diseases are the exception and not the rule. The fungal agent often induces a cell-mediated immune response in which there is inflammation and a walling off of the agent in a fibrous, calcified deposit.

The two most important factors that determine ones susceptibility to disease are the number of organisms to which the host is exposed (infective dose) and the general state of health of the host at the time of exposure. Allergic reactions in some individuals are not surprising since spores are frequently inhaled.

* modified from General Microbiology, Boyd, p. 691
** modified from Microbiology, Davis, Dulbecco,, p. 972
summary chart - Fundamentals of Microbiology, Alcamo, pp. 456-457

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