There have been important advances in the diagnosis and treatment of both the endemic and the opportunistic mycoses, in the delineation of the epidemiology of invasive pulmonary mould infections in immunocompromised patients and in the taxonomy of both yeasts and moulds that cause pulmonary infection. In the last decade, less well-known moulds, such as members of the Fusarium and Scedosporium genera, are increasingly found to cause invasive pulmonary infection. Newly described Aspergillus species that are pathogenic for humans are inherently more drug resistant, and acquired resistance is increasing among the usual species that cause human infection. Cryptococcus gattii has emerged in North America as a cause of pulmonary and central nervous system (CNS) infections. Understanding of many of these phenomena had to await the development of molecular methods that could be applied to fungal genomes.
Building on knowledge accrued in the last several decades regarding the cell wall composition of Aspergillus and the endemic fungi, Histoplasma capsulatum and Blastomyces dermatitidis, diagnostic tests for detecting these fungi have become a routine part of the approach to diagnosis. Antigen detection can be accomplished in urine, serum and body fluids, including respiratory samples obtained by bronchoalveolar lavage (BAL). Especially in immunocompromised patients, in whom antibody responses are notoriously poor, antigen detection has led to earlier diagnosis and improved outcomes.
In addition to improved diagnostic techniques, the introduction of new antifungal agents in the last decade has occurred because of studies detailing the synthesis of cell membranes and cell walls in yeasts and moulds. Armed with the knowledge of the action of fluconazole, voriconazole was synthesized specifically to allow more avid binding to the cell membrane of moulds, allowing an increase in the antifungal spectrum of activity. The new generation azole agents, voriconazole and posaconazole, have allowed safer and more effective treatment of many fungal infections, especially treatment of invasive mould infections in immunocompromised patients. Basic knowledge of cell wall synthesis in Aspergillus and Candida led to the development of the echinocandins, which target cell wall, rather than cell membrane components. By targeting a structure not shared with mammalian cells, the echinocandins, caspofungin, micafungin and anidulafungin are extremely safe agents for the treatment of invasive fungal infections.
This chapter will review new developments over the last decade in these areas in the context of the major fungal opportunists and endemic mycoses, and will focus on pulmonary aspects of infections with these fungi. The whole panoply of Aspergillus pulmonary infections can not be addressed in this review, but rather, the focus will be on invasive disease in immunocompromised hosts.