Risk assessment on the impact of environmental usage of triazoles on the development and spread of resistance to medical triazoles in Aspergillus species

Risk assessment Technical report

In recent years, triazole resistance in human Aspergillus diseases appears to have been increasing in several European countries. However, current data on the prevalence of resistance are based on a small number of studies which are only available from a few European countries. A thorough investigation of this emerging public health problem is needed to avoid the development and spread of resistance.
There is a suggestion the resistant fungus has an environmental origin. Azole fungicides are widely used for crop protection and material preservation in Europe. They protect crops from disease, ensure yields and prevent fungal contamination of produce. It has been proposed that triazole resistance has evolved in the environment and could be driven by the selective pressure of azole fungicides. However, although evidence supporting this hypothesis is growing, the link between the environmental use of azole fungicides and the development of triazole resistance in Aspergillus spp. is not yet proven.
This report examines current evidence for the environmental origin of resistance in Aspergillus spp. and makes recommendations for further steps to assess the risks and consequences of the environmental usage of azole derivatives.

Executive summary

In its risk assessment, ECDC examines current evidence for the environmental origin of resistance to medical triazoles in Aspergillus spp. and makes recommendations for further steps to assess the risks and consequences of the environmental usage of azole derivatives. The report was prepared with the support of European and US experts.

Aspergillosis refers to a group of diseases which can result from Aspergillus infection and includes allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, aspergilloma and the most severe form, invasive aspergillosis.

ECDC estimated that 2 100 000 patients may be suffering from allergic aspergillosis and 240 000 from chronic aspergillosis each year. In addition, an estimated 63 250 cases of invasive aspergillosis, annually complicates the management of other diseases including leukaemia, transplantation, chronic obstructive pulmonary disease (COPD) and medical intensive care.

Triazole therapy has become the established treatment for human Aspergillus diseases. However, triazole resistance in Aspergillus spp. isolates appears to have been increasing in several European countries in recent years. If present, such resistance can severely limit treatment options. The inability to treat patients with triazole antifungals due to resistance has a significant impact on patient management and associated health costs.

Results from published studies suggest that triazole resistance has evolved in the environment and could be driven by the selective pressure of azole fungicides, which are widely used for crop protection and material preservation in Europe. Although evidence supporting this hypothesis is growing, the link between the environmental use of azole fungicides and the development of triazole resistance in Aspergillus spp. is not yet proven.

The report concludes on the importance of improved surveillance and diagnosis of resistance in Aspergillus diseases, as well as the development of further environmental and laboratory studies to confirm the environmental hypothesis.

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