By Geoff Barnett

Freelance Medical Writer and Editor

Not so long ago it was all very simple: living things belonged to one of two kingdoms - plant and animal; at least that's what I was taught. But as our biological knowledge expanded, it became increasingly difficult to rationally place some living things into either kingdom. Now most biologists recognise five kingdoms; plants, animals, fungi and two others. Discover their names and read summaries of the main characteristics of all five at Five Kingdom Classification System.

Fungi, which include yeasts, moulds, smuts and mushrooms, are responsible for causing four types of mycotic disease:

1. Hypersensitivity - an allergic reaction to moulds and spores;

2. Mycotoxicosis - poisoning by food products contaminated by fungi;

3. Mycetismus - the ingestion of preformed toxin (toadstool poisoning)

4. Infection - the subject of this Tour.

Depending on how they are classified there are between 100,000 and 200,000 species of fungi. Only a few hundred are pathogenic to man and Pathogenic Fungi gives an overview of their general characteristics and the diseases they cause. Fungal infections (mycoses) may be categorised in a number of ways, the most appropriate for our Tour being the clinical taxonomy method which classifies mycoses according to the degree of tissue involvement and mode of entry into the host:

- Superficial - localised to the skin, hair and nails

- Subcutaneous - infection confined to the dermis, subcutaneous tissue or adjacent structures

- Systemic - deep infection of the internal organs

- Opportunistic - infection in the immunocompromised patient

Fungi responsible for superficial mycoses are known as dermatophytes and are capable of hydrolysing keratin - a protein present in skin, hair and nails. Included in this group of diseases are some of the most common skin infections, notably tinea (ringworm), a generic term that embraces a variety of skin and scalp lesions such as tinea pedis (athlete's foot), tinea cruris (jock itch) and tinea unguium (ringworm of the nails). The word 'tinea' has an interesting origin, deriving from the similarity of the rounded lesions seen on the skin of many patients to the circular holes in fabrics caused by the larvae of moths of the genus Tinea. 'Ringworm' refers to the characteristic central clearing that often occurs in dermatophyte infections of the skin. Microbiology and Immunology On-line, written in the form of lecture notes, covers clinical manifestations, ecology, aetiological agents and therapy. For a wider selection of images than those shown on this site, click on Dermatomycoses.

As a superficial mycosis, candidiasis typically infects the mouth and vagina, and the term 'thrush' is generally applied to both, though some authorities restrict its use to the former. The location of the infection reflects the fact that Candida albicans, the fungus largely responsible, is a commensal of the gastrointestinal tract and vagina. Oropharyngeal Candidiasis part of the strangely titled but hugely impressive and exhaustive 'doctorfungus' site, is a 12-page account of all aspects of the condition. Although the article itself is illustrated, don't ignore the extensive collection of slides accessible from the 'Image Bank' link on the left-hand margin. The clinical features, diagnosis and management of vaginal candidiasis are described in note form at 2001 National Guidelines on the Management of Vulvovaginal Candidiasis.

Most superficial mycoses are easily diagnosed, readily amenable to treatment and rarely life-threatening; the same cannot be said for systemic and opportunistic fungal infections where medicine faces a major challenge. In the 1970s and '80s gram-negative bacterial sepsis was the chief nosocomial infection of concern; then in the 1990's infection with gram-positive bacteria came increasingly to the fore. Now, in many centres, Candida has become the fourth leading cause of nosocomial sepsis, overtaking even Escherichia coli, and is associated with a mortality rate of up to 40%. A short article, The Importance of Thinking Fungus* provides alarming figures, while the appositely titled 'Living Petri Dishes' - Who is at Risk?* is an equally short article that discusses the factors that predispose to fungal infection and have led to this threatening increase in its incidence.

And there's more bad news: over the last 20 years the problem of invasive candidiasis has been compounded by a significant shift in the epidemiology of candidaemia due to different species of the fungus. In the 1960s and '70s C albicans accounted for up to 90% of cases of candidaemia, but a US study from 1988 to 1992 found that the incidence of non-albicans Candida had overtaken that of C albicans Read more at The Changing Epidemiology of Candidal Infections* For a detailed description of all aspects of the disease and its treatment go to Invasive Candidiasis Overview.

Aspergillus, about 20 species of which have been identified as causative agents of opportunistic infections in man, is the second most common fungus in opportunistic mycoses following Candida, and is responsible for aspergillosis, a large spectrum of diseases. Invasive aspergillosis carries a mortality rate of 50% to 100% despite current therapy. Go to Aspergillosis for a 4-page review that covers microbiology and epidemiology, clinical features and management.

Yet another area of concern is the growing emergence of fungi previously unrecognised as being pathogens. In the words of Dr Mitchell Cohen, head of fungal and bacterial diseases at the US Centers for Disease Control and Prevention, 'The kind of thing that used to grow on bread in the kitchen is now causing life-threatening illness.' Click on Emerging Fungal Pathogens* for a list of the fungi concerned and brief descriptions of the infections they cause.

Coupled with the disturbing escalation in the incidence of fungal infections are the limitations of current therapeutic options. Clinicians are currently limited to about four or five classes of antifungal drugs that in general fall well short of the profile of the ideal agent specified at An Overview of the New Antifungal Agents for Deep Mycoses*, namely, a broad spectrum of activity; fungicidal rather than fungistatic; be available in oral and injectable formulations; cause minimal drug interactions; be safe at efficacious doses; be cost-effective; and be stable to resistance. You'll have come across most of the available drugs when reading the Tour's links, but for a comprehensive list, including some under development, go to Medical . A click on any of the drug names elicits further well-presented information, much of it referenced.

Of particular interest are the three glucan synthesis inhibitors, also referred to as echinocandins - the first new class of antifungal drugs in many years. Their novel mechanism of action - the selective inhibition of the synthesis of an essential component of the cell wall of many fungi - have led to them being hailed as 'the penicillin for fungi'. The only licensed product in this class, Cancidas (caspofungin - Merck) was launched in the US and some other countries earlier this year and is indicated for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies. Peak annual sales between $300 million and $500 million are forecast.

With the introduction of the glucan synthesis inhibitors a new generation of antifungal treatments has surely begun to unfold. Certainly the progress in generating and implementing strategies for the development of new antifungal agents as disclosed in the pdf article New Potential Targets for Antifungal Development gives grounds for optimism and has led to one observer proclaiming it 'the golden age of mycology.'

* Medscape articles requiring free registration at www.medscape.com

Do you have any comments on this article? Please contact Geoff directly at geoff@healthcare-edit.demon.co.uk.

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