Evaluation of environmental factors related to Aspergillus fumigatus azole resistance in the Netherlands

Emergence of azole-resistant Aspergillus fumigatus represents a concern for public health worldwide. Here we applied a spatial analysis to a large number of records on A. fumigatus azole resistance in the Netherlands to evaluate the relationship of a set of environmental factors with the emergence of resistant isolates and to identify the potential risk areas. A total of 1850 aspergillosis cases were included in the analysis: 1559 caused by wild-type (WT) and 291 by azole-resistant (RES) strains. High-resolution maps containing environmental variables (climate, crop cultivations) were used as layers for spatial analysis. QGIS software was used for transformation and calculation of layers, and visualizing maps, whereas MaxEnt software was used to perform spatial analysis. A separate distribution map for WT and RES was generated using each layer, then the ratio between RES and WT suitability was calculated, and a new map was generated showing the areas where suitability of RES was higher than WT (ratio > 1). Layers presenting areas with a ratio > 1 were then used for a further analysis including all these layers together to generate a final risk map, to identify the most contributing environmental variables, and to estimate the number of people potentially exposed to the risk. Results showed that the areas with the highest RES/WT ratio were associated with the following variables: legume cultivations ratio 1.5-2.7; fruit tree plantations, ratio 2.1; dump sites and artificial sites, ratio 2.3-2.7; spring minimum and mean temperatures, ratio 1.6-1.8. Areas with medium, high, and very high risk covered a surface of about 2330 km2 and people exposed were >319,000, with Zeeland and Noord-Holland being the provinces with the highest risk. All together these results suggest that azole-resistance emergence is a complex phenomenon depending on a multitude of environmental variables that are not yet been fully explored.