Essentials

The mycoses are disorders caused by fungi, which are saprophytic or parasitic organisms found in every continent and environment. Many are common commensals in nature, but others cause agricultural disease. The mycoses that are human infections include diseases ranging from those that are worldwide and common, such as dermatophytosis and candida infections, to those that are rare and often potentially life threatening, e.g. histoplasmosis. In humans, fungi usually adopt one of two morphologies: (1) the yeast form—where individual cells produce daughter cells by a process of budding and subsequently separate; or (2) the hyphal form—where cells do not separate but multiply to produce chains of cells joined end to end.

Diagnosis

Mycological diagnosis is often complex because many fungi are also commensals or transiently carried in humans, hence it is necessary to show both that the organisms are present and that they are causing disease, which is particularly difficult in the context of opportunistic fungal infection. The main laboratory diagnostic tests involve (1) visualization of fungi in tissue—by direct microscopy or histopathology; (2) culture—often using a glucose peptone agar (Sabouraud’s agar); (3) detection of antibody, fungal antigens or DNA fragments—assimilation of genetic tests such as PCR-based methods into routine diagnosis has been slow, and they are offered by few laboratories.

Superficial infections

Superficial fungal infections may reach prevalence rates of 15 to 25% in some communities, with the common infections being dermatophytosis or ringworm, pityriasis versicolor, and superficial candidosis.

Dermatophytoses—otherwise known as tinea infections—commonly affect the feet (tinea pedis), the body (tinea corporis), the scalp (tinea capitis) and the finger and toe nails (onychomycosis). They occur in all climates and usually present in primary care as scaly rashes. Diagnosis is made by direct microscopy of skin scales mounted in potassium hydroxide (20%) to demonstrate hyphae, and by culture.

Pityriasis versicolor—caused by a skin surface commensal, Malassezia globosa,and often triggered by sun exposure. Presentation is with hypo– or hyperpigmented scaling on the trunk. Laboratory diagnosis (if required) is by demonstration of the yeasts and hyphae in skin scales removed by scraping.

Superficial candidosis (candidiasis)—these infections affect the mouth, vagina, and body folds, often in the context of some form of predisposition, e.g. recent antibiotic therapy or, in the case or severe oral infection, immunosuppression including that associated with HIV/AIDS. Infections are diagnosed by microscopy and culture, the latter being particularly important where non-albicans Candida species may be involved.

Treatment—the main treatments for superficial mycoses are topical agents that include imidazole preparations (e.g. ketoconazole, clotrimazole), but for widespread infections or those involving hair or nails, oral imidazoles (e.g. itraconazole, fluconazole) or the allylamine, terbinafine, are employed.

Subcutaneous mycoses

Subcutaneous fungal infections, e.g. mycetoma (Madura foot), chromoblastomycosis and sporotrichosis, are not common and usually restricted to the tropics and subtropics. They may present in immigrants from tropical areas, sometimes years after the person has left the tropics, and hence cause diagnostic confusion. Diagnosis is by histological examination of affected tissues or culture. Treatment is often difficult, with only partial responses being achieved, but oral imidazole drugs or terbinafine are helpful in some cases.

Systemic mycoses

Systemic mycoses are deep and often disseminated infections that involve many different sites, including the blood and bone marrow. They may be caused by organisms which invade normal hosts (endemic mycoses) and those which only cause disease in compromised patients (opportunistic mycoses).

Endemic mycoses—these include histoplasmosis, coccidioidomycosis and infections due to Penicillium marneffei, all of which may occur in healthy people, although many are also common complications of HIV/AIDS. Initial manifestations are as respiratory infections, but they can spread haematogenously to other sites, e.g. skin, liver, and brain. Diagnosis is made on culture or biopsy of affected areas.

Opportunistic mycoses—these occur in those who are immunocompromised, e.g. patients with neutropenia secondary to cancer. The routes of fungal entry into the body are very variable, e.g. skin, gastrointestinal tract, lung. Infections include systemic candidosis, aspergillosis, and zygomycosis, but in severely compromised patients, e.g. those with profound neutropenia, many organisms not usually associated with human disease can cause invasive infections, e.g. Fusarium species. Cryptococcus neoformans, a yeast that can invade the lungs, often presents with meningitis or other signs of intracranial infection.

Prognosis and treatment—the endemic mycoses are often fatal if untreated, and even with treatment the mortality of opportunistic fungal infection can be high, e.g. over 40% for the severely neutropenic patient with aspergillosis. Aside from supportive care, oral or parenteral agents such as amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin are the treatments of choice, but detecting the organisms and successfully treating the infections remains a challenge.

Introduction

Fungi are saprophytic or parasitic organisms that are normally assigned to a distinct kingdom. As eukaryotes, they have the complex subcellular organization and highly organized genetic material seen in both animal and plant cells. The cell wall is a distinctive feature of fungi and has a complex cytoskeleton based on mannan, glucan, or chitin subunits. The arrangement and reproduction of individual cells is also characteristic. Most fungi form new cells terminally, which remain connected to form long, branching filaments or hyphae (the mould fungi). Some reproduce in a similar manner but each new cell separates from the parent by a process of budding (the yeast fungi). It is a feature of certain fungi to be yeast-like during one phase of their life history but hyphal at another, a phenomenon known as dimorphism. In culture, mould fungi usually form a cottony growth on laboratory media while yeasts normally have a smooth, shiny appearance.

Fungi adversely affect humans in a number of ways. They cause disease indirectly by spoilage and destruction of food crops, with subsequent malnutrition and starvation. Many of the common moulds produce and release spores, which may act as airborne allergens to produce asthma or hypersensitivity pneumonitis. Fungi elaborate complex metabolic by-products, some of which are useful to humans, such as the penicillins. However, others are toxic. Disease caused by the ingestion of fungal toxins includes both poisoning by eating certain mushrooms (mycetism) and damage caused by the ingestion of minute quantities of toxin (mycotoxicosis), e.g. in contaminated grain. The contribution of the latter mechanism to human disease remains largely unexplored, as does the question of whether inhalation of toxic fungal spores may cause pathology. Finally, fungi may invade human tissue. Medical mycology is largely concerned with this last group. Invasive fungal diseases are normally divided into three groups: the superficial, subcutaneous, and deep mycoses. In superficial infections, such as ringworm or thrush, fungi are confined to the skin and mucous membranes. Extension deeper than the surface epithelium is rare. Subcutaneous infections are usually tropical: the main site of involvement is within subcutaneous tissue, although secondary invasion of adjacent structures such as bone or skin may occur. In deep or systemic infections, deep organs such as the lung, spleen, or brain are invaded. This classification of mycoses is based on the main ‘sphere of involvement’ by the causal organisms, but there are exceptions. For instance, brain involvement has been recorded in patients with chromoblastomycosis, which is normally a subcutaneous infection.

The fungi causing systemic mycoses are often classified in two groups: the opportunists and the endemic pathogens. The former cause disease in overtly compromised individuals. These contrast with the true pathogens, which cause infection in all subjects inhaling airborne spores.