Are We There Yet? Recent Progress in the Molecular Diagnosis and Novel Antifungal Targeting of Aspergillus fumigatus and Invasive Aspergillosis

Are we there yet? Every parent has heard this inexorable question, but it is especially wrenching to hear it from a patient with a fatal illness. When someone, or someone's child, is diagnosed with invasive aspergillosis (IA) caused by Aspergillus fumigatus, the outcome has historically been bleak. In 2013, the field is erupting with exciting advances on multiple scientific fronts. But whether those research findings will improve clinical outcomes is still unclear—does your spouse, child, or neighbor now live or die with this disease? Medical breakthroughs over the last few decades surrounding cancer and transplantation, the main underlying conditions of those afflicted with IA, have been nothing short of astonishing. However, this revolution has also spawned a plethora of immunocompromised patients to inhale fungal spores and develop IA. For many patients with an absent immune system, the second leading cause of death, just behind cancer remission or transplant failure, is infection. The leading infectious cause of death is invasive fungal infections, and the most common mortal fungal infection is A. fumigatus. So have we sufficiently advanced scientifically for today's clinical needs in order to diagnose and treat IA—are we there yet? A. fumigatus is both a beautiful and frustrating fungus. The beauty lies in the pathogen's ability to readily adapt its niche based on the host. The same fungus that lives in compost piles can shear pulmonary blood vessels in immunosuppressed patients, masquerade as an allergic trigger in an ectopic individual, or hide as a saprophyte and slowly sap the strength from an unsuspecting normal host. The frustration with this fungus is the current difficulty in early and accurate diagnosis, a limited number of effective antifungal treatments coupled with the growing emergence of antifungal resistance, and some persistent basic mechanistic questions surrounding its growth and regulation.