Tackling antimicrobial resistance in Aspergillus fumigatus in South East Asia

Pulmonary aspergillosis is a severe lung infection due to a green mould called Aspergillus fumigatus. We all inhale between 100 and 1000 Aspergillus spores daily, which can cause infections with mortality of around 40%, mostly in people with chronic lung diseases or weakened immune systems. There are estimated to be 4 million cases of pulmonary aspergillosis globally per annum, but very little is known about rates in South-East Asia. Antifungal resistance to the main class of drugs used to treat these infections, the triazoles, is rising. Environmental resistance rates of up to 90% have been detected in Vietnam, and 30% in Thailand. Resistance has been shown to double mortality. Work in Europe has shown that the increase in resistance is due to dual-use effects of triazole fungicides used in agriculture, as fungi are major crop pathogens. Resistant strains of Aspergillus fumigatus are emerging in the environment and causing infections in patients. As a consequence, the pharmaceutical industry is developing novel antifungal classes, however equivalent fungicides with the same mechanism of action are now being developed, and cross-resistance has been shown to occur experimentally. Fungicide usage is rapidly escalating in South-East Asia, but whilst composting has been identified as a major amplifier of azole-resistant Aspergillus fumigatus (ARAf) in Europe, composting is not routinely performed in South East Asia. However the higher temperatures in this region mean that amplification may occur independently of compost. Therefore understanding the agricultural drivers and hotspots for amplification of Aspergillus resistance and the impact on human health in South East Asia is urgently required. This will allow us to develop rational interventions to mitigate the risk of high mortality pulmonary aspergillosis infections whilst ensuring that food security is not compromised. Aims 1: Develop novel point-of-care technologies to enable field testing for fungicide concentrations and levels of ARAf in South East Asia We will use low-cost “Delta Traps to sample air and “eco sensors” to capture water samples from soil. Fungicides will be detected using innovative point-of-care tests and ARAf identified using portable DNA tests. Techniques will be validated using Mass Spectrometry and Metabarcoding. 2: Field studies in Thailand, Vietnam and Laos to determine the extent of antifungal usage in the environment and the relationship to ARAf. Capacity building in local laboratories at specific hub sites in Bangkok, Hanoi and Vientiane to enable field testing and accurate diagnosis of pulmonary aspergillosis. We will then undertake field studies across one health aimed at understanding the extent of rural and urban anfungal use in the environment, the relationship to ARAf in the environment, the burden of pulmonary aspergillosis and the degree of resistant infections 3: Develop an appropriate interventional strategies to try to mitigate the risk of ARAf. We will assess local practices for fungicide use, undertake further experimental work to better understand the safe levels of fungicide usage in the environment. The evidence we generate will enable us to engage the agricultural industry, end-users, and policy makers to develop just interventions to mitigate the risk of ARAf. Together, these studies will deliver training and capacity building for South East Asian partners to be able to track Aspergillus resistance, identify its underlying causes, and be able to determine the impact of resistant Aspergillus infections on human health. A international framework will be developed to tackle the underlying causes.