5 years ago

Predicting invasive aspergillosis in haematology patients by combining clinical and genetic risk factors with early diagnostic biomarkers.

Rosemary A Barnes, P Lewis White, Christian Parr
The incidence of invasive aspergillosis (IA) in high risk haematology populations, is relatively low (<10%), despite unavoidable exposure Aspergillus in patients with potentially similar clinical risk. Non-clinical variables including genetic mutations that increase susceptibility to IA could explain why only certain patients develop disease. This study aimed to screen for mutations in 322 haematology patients classified according to IA status, and to develop a predictive model based on genetic risk, established clinical risk factors and diagnostic biomarkers.Genetic markers were determined by real-time PCR, and with clinical risk factors and Aspergillus PCR results were analysed by multi-logistic regression analysis to identify a best-fit model for predicting IA. Probability of IA was calculated and an optimal threshold determined.Mutations in Dectin-1 (rs7309123) and DC-SIGN (rs11465384 and rs7248637), allogeneic stem cell transplantation, respiratory virus infection and Aspergillus PCR positivity were all significant risk factors for developing IA and combined in a predictive model. An optimal threshold requiring three positive factors generated a mean sensitivity/specificity of 70.4%/89.2%, and a probability of developing IA of 56.7%. In patients with no risk factors the probability of developing IA was 2.4%, compared to >79.1% in patients with four or more factors. Using a risk threshold of 50%, pre-emptive therapy would have been prescribed in 8.4% of the population.

Publisher URL: http://doi.org/10.1128/JCM.01122-17

DOI: 10.1128/JCM.01122-17

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