Continuous Surveillance of Invasive Fungal Infection: A Realistic Goal for the Near Future

To the Editor—Using the Prospective Antifungal Therapy (PATH) Alliance registry, Neofytos et al. [1] investigated the epidemiology and outcome of invasive fungal infections (IFIs) in hematopoietic stem cell transplant (HSCT) recipients. Because use of Web-based registries is pivotal for progress in understanding IFIs, the Italian Hema e-Chart Group is also engaged in a prospective, multicenter, observational study designed to analyze all febrile events in patients with hematological malignancies (L.P., M.C., and A.N., unpublished data). Hema e-chart prospectively collects high-quality data derived from clinical experience and provides information on epidemiology and prophylactic and/or therapeutic drug use for IFIs. Distribution of investigating centers across Italy and a potentially large patient cohort facilitate the study of IFIs and the identification of appropriate subgroups for diverse research interests. Starting in March 2007, each patient who has a newly diagnosed malignancy and all those who undergo HSCT are censored to assess IFI epidemiology. In December 2008, 25 centers were active, 4403 patients were enrolled (3243 patients who received new diagnoses and 1160 HSCT recipients), and 1173 febrile events had been registered. Interim analysis of HSCT recipients shows a 43% incidence of febrile events per population (34% and 65% in autologous and allogeneic HSCT recipients, respectively), a 5% incidence of fungal infection per population, and a 13% incidence of fungal infection per event (5% and 23% in autologous and allogeneic HSCT recipients, respectively). Our current fungal mortality rate is 35%. These findings are different from those of the PATH Alliance, but because that study lacked a denominator, such as Hema e-chart’s pool of censored patients, the authors only counted the number of infectious episodes. They admitted that the incidence of IFI could not be calculated because the total number of transplants performed at each center was not recorded, but they concluded that invasive aspergillosis was stable, a downward trend emerged in invasive candidiasis, and Zygomycoses infections were increasing. Because no details were given on antifungal prophylaxis and treatments, it is hard to concur with the authors that the good response rate to antifungal therapy was a result of voriconazole use, because other antifungal drugs and combinations thereof were also administered. The PATH Alliance investigation had the merit of trying to monitor IFIs prospectively but reported only outcomes of invasive aspergillosis after bone marrow or peripheral blood transplantation. Cord blood transplantation and IFIs due to other fungi were excluded. Although the study was defined as being multicenter, 147 of the 234 patients were enrolled by 2 centers, and almost 50% of allogeneic HSCTs and 68.5% of autologous HSCTs were performed by single centers, which the authors stated “may have skewed the presented outcomes and created further biases” [1, p. 271]. Unlike other epidemiological analyses, no difference emerged at 6 weeks after transplantation in IFI incidence or outcomes, regardless of whether the stem cell source was allogeneic or autologous [2, 3]. Intervals from HSCT to IFI were similar, but some IFIs were reported as late as 6 years after autologous transplantation. We do not know whether CD34 cells were selected for autologous grafts, implying extensive T cell depletion, or why 75.3% of autologous HSCT recipients received steroids. Only neutrophil counts were monitored, and no information was given on lymphocyte reconstitution. Whether changes in physicians’ attitudes or changes in IFI epidemiology are responsible for these unexpected results is unclear.