Unprecedented Prevalence of Azole-Resistant <i>Aspergillus fumigatus</i> Identified in the Environment of Vietnam, with Marked Variability by Land Use Type

Abstract

Background: Azole-resistant Aspergillus fumigatus (ARAF) presents a threat to global public health, particularly where prior tuberculosis or underlying lung disease is prevalent. Southeast Asia is estimated to have a large burden of Aspergillus disease yet mycology diagnostic laboratory capacity is limited and systematic surveillance for drug resistance is absent. ARAF’s threat is thus poorly understood in this populous region. Methods: We conducted environmental surveillance in southern Vietnam, collecting air and ground samples across land-use types including cultivated land, urban residential land, and national park. We determined susceptibilities of A. fumigatus and non-fumigatus Aspergillus section Fumigati (ASF) isolates using EUCAST methodology, and measured residual agricultural azole concentrations in soil using liquid chromatography / tandem mass spectrometry. Findings: 95·2% of A. fumigatus isolates (59/62) were azole-resistant (31·6% for non- fumigatus ASF isolates (18/57)). Of all 119 ASF isolates, 55% were resistant or non-wild type to itraconazole, 65% to posaconazole and 50% to voriconazole. Both resistant isolates and agricultural azole residues were over-represented in cultivated land. The odds ratio for azole-resistance being detected, compared to national park sites, was ranged from 3·15-7·16 in cultivated lands types, and was highest in urban residential sites (9·31, p=0.0002). cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus isolates carried known resistance mutations, with TR34/L98H most frequent (34/38). Interpretation: Our data demonstrate alarmingly high levels of azole-resistant A. fumigatus in this region, which challenge the reliance of existing treatment guidelines on empiric azole therapy. Funding Statement: This project received internal funding from the University of Sydney. Declaration of Interests: None of the authors have any financial and personal potential conflicts of interest. Ethics Approval Statement: National Lung Hospital, Hanoi, Vietnam provided ethical approval for the study.