Immunotherapy for invasive fungal infections in transplant patients: back to the future?

In the past decade, we have witnessed striking advances in the diagnosis and therapy of invasive fungal infections in immunocompromised patients. Similar to the quantum leap in HIV medicine about 15 years ago, this progress resulted from the synergy of new diagnostic assays (galactomannan antigen, beta-glucan, (pan-)fungal polymerase chain reaction), with new and better antifungal drugs such as azoles (voriconazole, posaconazole) and echinocandins (caspofungin, micafungin, anidulafungin) as well as testing of drug susceptibility and drug level monitoring. As a consequence, therapeutic, preemptive and prophylactic use of new antifungals has significantly reduced fungusrelated morbidity and mortality in high-risk patients such as those after allogenic hematopoietic stem cell transplantation. Fortunately, this emerging bonanza is chaperoned by international expert consensus defining microbiological, radiological and clinical criteria for diagnosis as well as for treatment response (1). Meanwhile, these antifungal strategies have also invaded the management of other immunosuppressed populations including solid organ transplantation (SOT) patients. In the recent surveillance data of the TRANSNET covering 23 US transplant centers, kidney transplant recipients had the lowest 1-year cumulative incidence rates of invasive fungal infections of 1.5% as compared to lung (8.6%), liver (4.7%) or heart (3.4%) transplant recipients (2). No increase in invasive fungal infections had been recorded among kidney transplant recipients as yet (2), but there is, fueled by case reports, a growing impression that these formerly rare disseminated fungal infections are more frequently encountered in the current era. Besides transplant tourism, the increasing intensity and duration of immunosuppression in the recent decade is among the key suspects. Thus, alemtuzumab induction was significantly associated with an increased risk of disseminated fungal infections as compared to the use of basiliximab (3). Also, fungal infections were increased in rituximab-treated kidney transplants and an independent risk factor for death (4). Apparently, the improved antifungal arsenal can be failing, even when withdrawing immunosuppressive treatment and thereby risking loss of the renal allograft.