Invasive mould infections in solid organ transplant patients: modifiers and indicators of disease and treatment response

Abstract

Purpose Invasive mould infections, in particular invasive aspergillosis (IA), are comparatively frequent complications of immunosuppression in patients undergoing solid organ transplantation (SOT). Guidelines provide recommendations as to the procedures to be carried out to diagnose and treat IA, but only limited advice for SOT recipients. Methods Literature review and expert consensus summarising the existing evidence related to prophylaxis, diagnosis, treatment and assessment of response to IA and infections by Mucorales in SOT patients Results Response to therapy should be assessed early and at regular intervals. No indications of improvement should lead to a prompt change of the antifungal treatment, to account for possible infections by Mucorales or other moulds such as Scedosporium. Imaging techniques, especially CT scan and possibly angiography carried out at regular intervals during early and long-term follow-up and coupled with a careful clinical diagnostic workout, should be evaluated as diagnostic tools and outcome predictors, and standardised to improve therapy monitoring. The role of biomarkers such as the galactomannan test and PCR, as well as selected inflammation parameters, has not yet been definitively assessed in the SOT population and needs to be studied further. The therapeutic workup should consider a reduction of immunosuppressive therapy. Conclusions The role of immunosuppression and immune tolerance mechanisms in the response to invasive fungal infection treatment is an important factor in the SOT population and should not be underestimated. The choice of the antifungal should consider not only their toxicity but also their effects on the immune system, two features that are intertwined.

Epidemiology and Prognosis of Invasive Fungal Disease in Chinese Lung Transplant Recipients

“…In the present study, 1-year all-cause mortality was significantly higher in the IFD group (47.6%) than in the NIFD group (25.2%). Previous investigations have reported mortality rates ranging from 19 to 72% (4,6,23,(32)(33)(34). Since IFD often develops in patients with a more serious disease, it is difficult to establish whether IFD per se contributes to the poor outcome in LTRs.…”

Update on invasive fungal infections in the Middle Eastern and North African region

“…IFIs are an important cause of morbidity and mortality among high-risk groups including solid organ transplantation (SOT) recipients and hematological malignancy patients. For instance, mortality rates were the highest for IA (67-82%) as well as cerebral forms of mucormycosis (73.5%) [6].…”

The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?

“…Although graft-associated cells, EVs, and/or soluble antigens migrate into the recipients’ lymphatic system to alter the activities of the recipient’s immuno-competent cells, in most human Txs, these events fail to promote tolerance. The failure could be due to ( 1 ): the inflammation induced cyto- and chemokines ( 2 ), the allograft’s failure to generate more cells and their derivatives (EVs, antigens) ( 3 ), the intensity of preoperative or post-surgical inflammation in the microenvironment of the allograft ( 4 ), the immunosuppressive therapies, and/or ( 5 ) the immunosuppressive properties HLA-polyreactive antibodies generated by HLA OCs ( 93 , 198 – 200 ).…”