What are the risk factors of IFD?

Here, we talk about the risk factors of IFD in immune-compromised hosts and how this can pose challenges for diagnostics. We start by explaining the importance of understanding where the risk factors sit on the scale of low, intermediate and high risk.

Who is high risk?

Patients experiencing chronic granulomatous disease, allogeneic transplant therapies, AML/MDS treatments for induction chemotherapy, prolonged Neutropenia and/or high dose steroids are at the highest risk of developing fungal disease. However, the intermediate risk category is expanding with additional risk factors such as in ICU patients with severe influenza and chronic lymphocytic leukaemia patients. Additionally, new therapies like CAR-T therapies and Checkpoint inhibitors are increasingly becoming potential breeding grounds of fungal disease.

The challenges

Opportunistic infections during CAR-T therapies have become an increasing challenge. These therapies use re-engineered T-cells which leads to directed immunological responses to tumour antigens but the patient will be immunosuppressed as a side effect. Initially, the patient will be at risk of fungal infection from Candida species, and later will be at risk from Aspergillus and non-aspergillus moulds, and Pneumocystis.

New definitions

There are now set definitions for Influenza-Associated Pulmonary Aspergillosis (IAPA) which take into account clinical criteria, such as persistent fever, Dyspnoea and Haemoptysis, radiological criteria, such as bilateral infiltrates on pulmonary imaging, and mycological criteria such as positive Aspergillus cultures from a bronchoalveolar lavage (BAL).

New risks

New risk factors, in the form of immuno-modulating drugs and cellular therapies, are leading to a further expansion in immuno-modulating drugs and cellular therapies. Current diagnostics for serum biomarkers are not validated in new risk settings, especially with CAR-T therapies, influenza A or SARS-CoV-2 viral related secondary invasive fungal diseases. Combined diagnostics including serum biomarkers & molecular assays (RT-PCR) are still considered useful in bronchial samples and may allow early rapid diagnosis of IA. However, prospective studies evaluating targeted diagnostics, prophylaxis strategies and optimal management are needed.