The epidemiology of invasive fungal infections in transplant recipients

Abstract

Transplant patients, including solid-organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are exposed to various types of complications, particularly rejection. To prevent these outcomes, transplant recipients commonly receive long-term immunosuppressive regimens that in turn make them more susceptible to a wide array of infectious diseases, notably those caused by opportunistic pathogens. Among these, invasive fungal infections (IFIs) remain a major cause of mortality and morbidity in both SOT and HSCT recipients. Despite the continuing improvement in early diagnostics and treatments of IFIs, the management of these infections in transplant patients is still complicated. Here, we provide an overview concerning the most recent trends in the epidemiology of IFIs in SOT and HSCT recipients by describing the prominent yeast and mold species involved, the timing of post-transplant IFIs and the risk factors associated with their occurrence in these particularly weak populations. We also give special emphasis into basic research advances in the field that recently suggested a role of the global and long-term prophylactic regimen in orchestrating various biological disturbances in the organism and conditioning the emergence of the most adapted fungal strains to the particular physiological profiles of transplant patients.

Fig. 1

Epidemiology of invasive fungal infections (IFIs) in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Pathogens are represented based on their prevalence in SOT and HSCT. Invasive candidiasis are the most common IFIs in SOT recipients, followed by invasive aspergillosis, non-Aspergillus molds infections, cryptococcosis and finally Pneumocystis jirovecii pneumonia (PCP). Liver, small bowel and pancreas transplant recipients have the highest rates of Candida infection. The highest incidence of aspergillosis is observed among lung and heart transplant recipients. Non-Aspergillus mold infections and PCP are mainly observed in lung transplants. Kidney and liver transplant recipients have the highest rates of cryptococcosis. Invasive aspergillosis are the most common IFIs in HSCT recipients, followed by invasive candidiasis, mucormycosis, other mold infections and finally PCP.

Fig. 2

Timing of invasive fungal infections (IFIs) after solid organ (SOT) and hematopoietic stem cell (HSCT) transplantations.

Fig. 3

A schematic overview of the factors influencing the pathogenesis of invasive fungal infections in transplant recipients. Primary fungal infections following transplantation may be due to microorganism inhalation from an environmental source such as soil or hospital environment (e.g. Mucorales, Cryptococcus spp., Aspergillus spp. Pneumocystis jirovecii), a previously quiescent infection reactivation (e.g. Cryptococcus spp.), infected donor organs and tissue grafts (e.g. Cryptococcus spp., Scedosporium apiospermum) or from an endogenous source with the patient's flora (e.g. Candida spp.). Several clinical and biological parameters have been described as risk factors for IFIs after SOT and HSCT. Predisposing factors include fungal virulence traits and host characteristics. Another major determinant factor is the use of immunosuppressive and antimicrobial drugs. These molecules interfere with the patient's flora and antifungal immune response which impact the type of IFI and its time of onset. GVHD: Graft-vs-host-disease; HLA: Human leukocyte antigen; CMV: Cytomegalovirus; MPA: mycophenolic acid.