Fungi and Fungal Disease

Abstract

This chapter describes some of the biological features of key pathogenic fungi, their effect on their human host, and the changing face of fungal disease epidemiology in light of an increasing immunocompromised patient population. The status of treatment options and the clinical pharmacology of current and emerging antifungal agents are also described, together with future directions and new approaches for the discovery of new drugs. Over the last 50 years, diseases of fungal origin have become increasingly prevalent. This includes superficial mycoses of the skin, hair, and nails, but more dramatically and of great medical concern is the rapid increase in systemic and life-threatening mycoses due to the increase in the immunocompromised patient population. Ironically, this increase is largely due to progress in medical science that has led to treatments of cancer, transplants, corticosteroid use postsurgical intensive care, broad-spectrum antibiotic use, greater longevity (in particular in the presence of an underlying disease), and increased survival rates in neonates and trauma patients (e.g., burns). Such conditions and treatments often lead to neutropenia and leukopenia, which remove a formidable host defense to what are usually harmless or even commensal fungi, but under immunosuppression become life-threatening pathogens. The spread of HIV and AIDS has also greatly reduced the immune-based resistance of patients to opportunistic fungal pathogens, in particular Candida albicans and other Candida species. Increased worldwide travel has also contributed to the spread of mycotic disease from once-endemic regions. This emergence of fungi as an ever-increasing cause of morbidity and mortality has led researchers and medicinal chemists, in academia, medicine, and industry, toward the discovery and development of new antifungal drugs.