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Chapter 22

Pathogenic Fungi

Medical Mycology

• Field of medicine concerned with the diagnosis, management, and prevention of fungal diseases, or mycoses

• Mycoses are among the most difficult human diseases to diagnose and treat

• Signs of mycoses are often missed or misinterpreted

• Fungi are often resistant to antifungal agents

Epidemiology of Mycoses

• Fungi and their spores are almost everywhere in the environment

• Because they are widespread, most people will experience a mycosis at some time

• Typically acquired via inhalation, trauma, or ingestion

• Spread from person to person is infrequent

• Most mycoses are not contagious

• Dermatophytes, fungi found on the skin, are the major exception

Epidemiology of Mycoses

• Epidemics result from mass exposure to some environmental source of fungi

• Mycoses are generally not reportable and thus adequate information on their occurrence and spread is often lacking

Categories of Fungal Agents

• Only four fungi are usually considered true pathogens

• Have the ability to actively attack and invade tissues

• Exhibit dimorphism

• Based on differences in temperature

• In the environment they have mycelia thalli composed of hyphae and within the body they exist as yeast thalli

• Yeast forms are invasive due to the production of various enzymes and proteins that allow their survival within the body

• Endemic to certain regions, primarily in the Americas

Categories of Fungal Agents

• Opportunistic fungi account for the remaining diseases in humans

• Often commensals that take advantage of a weakness in a host’s defenses

• Distributed throughout the world

• Dermatophytes are considered in this group because they often occur in individuals susceptible to opportunistic fungi

• Four factors increase an individual’s risk for acquiring an opportunistic mycoses

Clinical Manifestations of Fungal Disease

• Fungal diseases are grouped in three categories of clinical manifestation

• Fungal infections

• Most common mycoses

• Caused by the presence in the body of either true pathogens or opportunists

• Toxicoses

• Acquired through ingestion

• Occurs when poisonous mushrooms are eaten

Clinical Manifestations of Fungal Disease

• Allergies

• Most often result from the inhalation of fungal spores

Diagnosis of Fungal Infections

• A patient’s history is critical for diagnosis of most mycoses

• Definitive diagnosis often requires isolation, laboratory culture, and morphological analysis of the fungus involved

• Sabouraud dextrose agar is used to culture fungi collected from patients

• This medium favors fungal growth over bacterial growth

• Various techniques are used to detect fungal cells in patient specimens

Diagnosis of Fungal Infections

• Immunological tests are not always useful for fungi

• Due to the prevalence of fungi in the environment it is often hard to distinguish between an infection and simple exposure

• Opportunistic infections are particularly difficult to diagnose

• Fungal types can be confused with one another as well as with other diseases

• Fungi can display abnormal morphology in tissues where infection wouldn’t normally occur

Antifungal Therapies

• Mycoses are among the most difficult diseases to heal

• Fungi can often resist the oxidative damage of T cells during cell-mediated immune responses

• As eukaryotes, fungi are similar to human cells and antifungal drugs can harm human tissues

• Fungi have ergosterol in their membranes rather than cholesterol and it is often a target for antifungal treatment

• Side effects can still result, especially with long-term use

Antifungal Therapies

• Amphoterecin B is the ‘gold standard” of antifungal agents but also the most toxic

• Other antifungal agents include various azole drugs, fluorocytosine, and griseofulvin

• Opportunistic infections treatment requires two steps

• High-dose treatment to eliminate or reduce the fungal pathogens

• Long-term maintenance therapy to control and prevent reinfection

Systemic Mycoses Caused by Pathogenic Fungi

• Infections spread throughout the body

• Caused by one of the four pathogenic, dimorphic fungi of the division Ascomycota

• Blastomyces, Coccidioides, Histoplasma, and Paracoccidioides

• Acquired through inhalation

• Begin as a generalized pulmonary infection that disseminates to the rest of the body

• Individuals working with dimorphic fungi in the laboratory must take multiple precautions to avoid exposure to spores

Systemic Mycoses Caused by Opportunistic Fungi

• Opportunistic mycoses don’t typically affect healthy humans

• Infections usually limited to people with poorly functioning immune systems

• Becoming more important as the number of immunocompromised individuals rises

• Can be difficult to identify because their symptoms are often atypical

• The five genera routinely encountered are considered “classical” opportunists

• Aspergillus, Candida, Cryptococcus, Pneumosystis, and Mucor

Zygomycoses

• Infections caused by various genera of fungi in the division Zygomycota

• Common in the environment with worldwide distribution

• Seen in individuals with uncontrolled diabetes, people who inject illegal drugs, in some cancer patients, and is some patients receiving antimicrobial drugs

• Infections usually develop in the face and head area

Emergence of Fungal Opportunists in Immunosuppressed Individuals

• AIDS patients have permanent immune dysfunction making a full cure of opportunistic infections unlikely

• Mycoses account for most deaths associated with AIDS

• Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans are so common in HIV-positive individuals their mycoses partly define end-stage AIDS

• Emergence of new fungal opportunists can result from the increase in immunocompromised individuals and fungi resistant to antifungal drugs

• Three emerging fungal diseases are particularly problematic

• Fusarium species cause respiratory distress, disseminated infections, and fungemia

• Penicillium marneffei causes pulmonary disease upon inhalation

• Trichosporon beigelii can cause a disseminated and drug-resistant infection in AIDS patients that is often fatal

Superficial, Cutaneous, and Subcutaneous Mycoses

• Are the most commonly reported fungal disease

• Mycoses are localized at the sites at or near the surface of the body

• Can be acquired by healthy individuals via person-to-person contact or through environmental exposure

• Diseases are usually not life threatening but can be chronic or recurring infections

Superficial Mycoses

• Are the most common fungal infections

• Usually acquired by direct contact with the fungus

• Confined to the outer, dead layers of the skin, nails or hair

Black Piedra and White Piedra

• Superficial infection that forms nodules on the hair shaft

• Transmission is often mediated by shared hair brushes or combs

• Several members of a family are usually infected at the same time

• Infected areas must often be shaved to remove the fungi

Dermatophytoses

• Fungal infections of the skin or nails caused by dermatophytes

• Infections were previously called ringworms because they resemble a worm lying below the surface of the skin

• Result from fungi that use keratin as a nutrient source and thus colonize only dead layers of skin, nails, and hair

• No living tissues are infected

• Dermatophytoses show a variety of clinical manifestations

• Treatment is with topical antifungal agents

Common Dermatophytoses

Malassezia furfur

• Normal inhabitant of the skin surfaces

• Causes various superficial infections that tend to be chronic

• Skin infected with M.furfur fluoresces pale green providing a rapid diagnostic method

• Infections are treated topically but oral therapy may be needed in more severe cases

Cutaneous and Subcutaneous Mycoses

• Fungi are commonly found in the soil

• Infections are rare

• Requires traumatic introduction of the fungal elements beneath the outer, dead layers of skin

• Most lesions remain localized to the subepidermal tissues in the skin

Sporotrichosis

• Sporothrix schenckii is the causative agent

• Causes a subcutaneous infection that is usually limited to the arms and legs

• Individuals who work with natural plant material are at the highest risk for infection

• Fixed cutaneous sporotrichosis

• Produces nodular lesions around the infection site

• Secondary lesions can occur on the skin along the course of lymphatic vessels

• Effectively treated with topical agents

Fungal Intoxications and Allergies

• Some fungi cause allergies or produce toxins that cause toxicosis

• 2 types of toxicosis

• Mycotoxicosis

• Caused by eating foods contaminated with fungal toxins

• Possible inhalation by Stachybotros

• Mycetismus

• Mushroom poisoning from eating a fungus

• Fungal allergens can elicit a hypersensitivity response in sensitive individuals

• Result from inhalation, ingestion, or other contact

Mycotoxicoses

• Mycotoxins are produced by fungi during normal metabolic activities but are poisonous to animals and humans

• Mycotoxins are often consumed in contaminated food crops

• Long term ingestion of mycotoxins can cause liver and kidney damage, gastrointestinal or gynecological disturbances, or cancers

• Aflatoxins are the most well-known mycotoxins

• Fatal to many vertebrates and carcinogenic at low levels when consumed continually

• Prevalent in the tropics

Mycotoxicoses

• Some mycotoxins, such as the ergot alkaloids, are used to make drugs

Mycetismus

• Most mushrooms are not toxic

• Mushrooms that produce poisons can cause neurological dysfunction or hallucinations organ damage, or even death

• Poisoning typically occurs when untrained individuals pick and eat wild mushrooms

• The deadliest mushroom toxin is produced by the “death cap” mushroom

Allergies to Fungi

• Fungal allergens are common both indoors and out

• Determining the specific cause can be difficult because of their presence in the environment

• Fungal allergens usually cause type I hypersensitivity reactions that can result in asthma, eczema, and hay fever

• Type II and III hypersensitivity reactions can occur but much less frequently

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