A study by scientists in the United Kingdom suggests at least 40% of antifungal-resistant Aspergillus infections in UK patients are linked to environmental exposure, according to findings published today in Science Advances.

For the study, a team led by researchers with Imperial College London recruited citizen scientists to collect airborne spores of Aspergillus fumigatus, a widespread environmental fungus that's found in vegetation and soils and produces spores that can be inhaled. Inhalation of A fumigatus spores can cause severe lung infections in at-risk populations, such as cystic fibrosis patients and organ transplant recipients. The aim of the study was to assess human exposure to antifungal-resistant A fumigatus, which has been rising in recent years, in part due to azole-based fungicides used in plant agriculture.

From June 2018 through April 2019, 1,894 samples were collected, 919 of which yielded A fumigatus colonies. Screening of the isolates revealed that 111 (4.7%) were resistant to the agricultural fungicide tebuconazole, and further testing of 99 of those isolates found high resistance to azoles used for clinical infections, including itraconazole (86%), voriconazole (64%), and isavuconazole (83%). In addition, 51% of the A fumigatus isolates were resistant to three medical azoles, and 14% were resistant to all tested medical azoles.

It is imperative that we determine sources of azole-resistant A. fumigatus to reduce treatment failure in patients with aspergillosis.

After conducting whole-genome sequencing of the environmental isolates and comparing them to the genomes of clinical A fumigatus isolates from UK patients, which showed shared resistance mutations, the researchers concluded that roughly 40% of antifungal-resistant A fumigatus infections in the United Kingdom are acquired from environmental exposure. They estimate a per capita cumulative annual exposure of 21 days.

"Because of the ubiquity of this measured exposure, it is imperative that we determine sources of azole-resistant A. fumigatus to reduce treatment failure in patients with aspergillosis," the study authors write.

A series of reports published yesterday by the Africa Centres for Disease Control and Prevention on antimicrobial resistance (AMR) in 14 countries highlights a lack of capacity for bacteriologic testing and limited access to antibiotics.

The project, by the Mapping Antimicrobial Resistance and Antimicrobial Use Partnership (MAAP), reviewed 819,584 AMR records collected from 205 laboratories and data from 327 hospital and community pharmacies and 16 national-level antimicrobial consumption data sets covering 2016 through 2019. The countries involved in the project were Burkina Faso, Cameroon, Eswatini, Gabon, Ghana, Kenya, Malawi, Nigeria, Senegal, Sierra Leone, Tanzania, Uganda, Zambia, and Zimbabwe. Africa has the highest mortality rate from AMR infections in the world, but most available AMR data from these countries to date have been based on statistical modeling.

While the project produced 14 individual reports for each country, among the key findings overall were that only 1.3% of the biology laboratories across the 14 countries perform bacteriologic testing, 80% perform fewer than 1,000 antimicrobial susceptibility tests a year, and testing was consistently conducted for only 5 of the World Health Organization's 15 antibiotic-resistant priority pathogens. In 8 of the 14 countries, more than half of the population is out of reach of a bacteriology laboratory.

The study also found that, of 187,000 clinical samples tested for AMR, 88% had no information on patients' clinical profiles, including the diagnosis and origin of infection, which makes it difficult to understand what's driving AMR.

Analysis of antimicrobial consumption data indicated that only four antibiotics accounted for more than 67% of antibiotic used in healthcare settings in the 14 countries, and that access to broader-spectrum antibiotics for resistant infections was limited. Up to 34 uncategorized antibiotics were found to be in circulation.

The project is supported by a grant from the Fleming Fund.

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