Fungi are a very diverse group but there are only three categories of medical importance, which are mycotoxicoses, hypersensitivity diseases and host colonisation and resulting disease state.

The metabolic diversity of fungi means they produce a number of specialised metabolites including alkaloids, toxins and psychotropic agents. Mycotoxicosis is often the result of accidental or recreational ingestion. A good clinical history is often required but the patient isn’t always able to provide it meaning the identification of the ingested substance is often difficult. Induced emesis is often the first line of treatment followed by supportive therapies like assisted breathing or fluids.

Epidemics eg St Anthony’s Fire occurred in the middle ages due to contamination of rye with Claviceps purpurea which produces ergot alkaloids. C. purpurea causes convulsions and gangrene due to vasoconstriction.

Fungi may be consumed for recreational purposes as they produce psychotropic agents eg psilocybin and psilocin. Lysergic Acid Diethylamide (LSD) is a semi synthetic derivative.

Aflatoxins have major economic impacts eg Turkey X disease. Turkey X disease occurs when poultry food is contaminated with Aspergillus flavus. It causes gross haemorrhage and necrosis of tissue in birds and can affect the human food chain as well. It has carcinogenic properties. Even if birds recover from Aspergillus they still can’t be used for human consumption.

There are high fungal spore counts in the air. We inhale large numbers every time we inhale. Antigenic stimulus is host dependent and hypersensitivity occurs as a result of immunoglobulin production and lymphocyte stimulation against spore proteins. Hypersensitivity pneumonitis → rhinitis, asthma and alveolitis. Fungal hypersensitivity diseases don’t require fungal growth. Skin tests are possible to help identify hypersensitivity.

Only around 50 fungal species cause significant human disease. However it’s likely that number will increase as there's many new species currently emerging. Many pathogenic fungi mainly affect immunocompromised individuals. Many pathogenic fungi are dimorphic, meaning they exist as either yeasts or in filamentous forms. Many filamentous species produce conidia or sexual spores. Spore morphology, alongside molecular and immunological tools, is important in identification and diagnosis. Diagnostic methods are still a lot more basic for fungi than for bacteria/viruses and fungi are often diagnosed by looking under a microscope.

Superficial mycosis, meaning the fungus only infects the surface layer of skin, hair or nails, are quite common. They’re usually treatable with topical antifungal creams or liquid aerosols eg miconazole nitrate or griseofulvin. Fungi which cause superficial mycoses are collectively known as dermatophytes. Superficial mycoses caused by Trichophyton species cause fungal infections of the feet and other moist skin surfaces. Transmission occurs by spores through flaking and itching skin.

Subcutaneous mycosis infect the deeper layer of the skin and are typically caused by different fungi than superficial infections. They’re mainly treated by topical drugs although oral drugs eg azole antifungal agents are taken in severe cases.

Sporotrichosis is caused by saprophyte Sporothrix schenckii and is an occupational hazard for people working in close contact with soil eg agriculture workers, miners and gardeners as spores can enter through cut skin.

Chromoblastomycosis is caused by several species eg Fonsecaea pedrosoi, Phialophora verrcucose and Cladosporium carrionii. Fungal growth is both subcutaneous and cutaneous, with crusty wart-like lesions forming on the hand and leg. Most common in tropical/subtropical conditions and occurs due to fungal infection from puncture wound.

Systemic mycosis is the most serious as the fungus infects internal organs. Systemic fungal pathogens usually live in the soil and infect humans via inhalation of airborne spores. The spores travel from the lungs to other organs and the skin. Chemotherapy is difficult due to toxicity issues. Systemic mycosis primarily affects the elderly and immunocompromised meaning they’re the diseases of opportunistic pathogens.

Primary mycosis = healthy individual infected. Secondary mycosis = predisposing conditions make individual more susceptible to infections

Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum. It’s one of the most widespread primary fungal infection. It’s airborne and common in rural areas in midwest USA. Inhaled spores germinate and grow in the lungs. Clinicians often overlook histoplasmosis thinking it’s a more common respiratory infection caused by bacteria or viruses.

Coccidiodomycosis is caused by dimorphic fungus Coccidioides immitis. It’s common in desert regions of SW America. It’s a saphrophyte found in soil which is airborne when it rains. The respiratory symptoms caused by C. immitis are often a cause of pneumonia.

Blastomycosis is caused by dimorphic fungus Blastomyces dermatitidis. It’s endemic to the Great Lakes of North America. The fungus lives in rotten wood and soil near bodies of water. It’s a very slow growing lung infection and if left untreated subcutaneous dermal lesions form.

Paracoccidioidomycosis is caused by Paracoccidioides brasiliensis. It’s primarily a subtropical disease found in South America although it’s also potentially aquatic. Paracoccidioidomycosis is initially pulmonary but leads to lesions forming on the face or other extremities. Treated with azoles.

Cryptococcosis is caused by the yeast form of Cryptococcus neoformans. It can occur in virtually any organ of the body and initially infects the lungs or a wound. It’s the 2nd most common opportunistic pathogen in HIV/AIDS patients.

Candida albicans is a dimorphic yeast often found as a minor component of the human normal flora. Diseases caused by C. albicans include mild to serious infections. Their genome is highly dynamic meaning they undergo chromosomal rearrangements as a means of generating genetic diversity. C. albicans forms biofilms in a medical setting which are difficult to treat with antifungal agents.

Pneomocytosis pneumonia is often caused by Pnemocytosis jirovecil. It’s an opportunistic infection associated with chemo/AIDS patients, premature/severely malnourished children, the elderly and infants with hyper IgM syndrome which is an X linked or autosomal recessive trait.

Fungi are problematic to treat when they infect eukaryotes as much of the fungal cellular machinery is the same in animals and humans. Few drugs target metabolic processes specific to fungi.

Polyenes bind ergosterol and disrupt fungal membrane integrity, however they also target cytosterol.

Azoles and allylamines inhibit ergosterol synthesis.

Griseofulvin disrupts microtubule aggregation in mitosis.

Polyoxins inhibit chitin synthesis. Echinocandins inhibit glucan synthesis.

5-flurocytosine is a nucleotide analog which inhibits nucleic acid synthesis. Targets Candida and Cryptococcus neoforman infections. Used in combination with amphotericin B and/or azoles. They have relatively weak antifungal effects and resistance develops quickly.

Ergosterol is an analogue of cholesterol found in fungal membranes. It provides stability and shape maintenance. The two main classes of ergosterol inhibitors are polyenes and azoles. They bind ergosterol, deplete in the membrane and cause toxic intermediates to accumulate, destabilising the fungal membranes so they leak cations and die.

Echinocandins are a relatively new class of antifungal drugs. They inhibit glucan synthesis by inhibiting 1,3-beta glucan synthase. Beta glucans are carbohydrate polymers cross-linked with other fungal cell wall components.