Imperial College London has conducted a new study that found that drug-resistant moulds are spreading from the environment to infect susceptible people’s lungs.
The researchers discovered six cases infected by a drug resistant form of Aspergillus fumigatus fungi. They could be traced back from spores found in the environment. The researchers used samples from England, Wales and Scotland to make their findings. They published them in Nature Microbiology.
Aspergillus fumigatus is an environment mould that can cause fungal pulmonary disease. People with healthy lungs can remove inhaled spores easily, but people with weakened immune systems or lung conditions may not be able to do so. This can lead to an infection called aspergillosis. 10-20 million people around the world are affected by aspergillosis. Usually, the infection is treated with an antifungal medication. However, there have been reports of emerging resistance to these drugs.
The researchers believe that this resistance developed because of the widespread use of agricultural azole fungicides. Similar-acting azole drugs are the first-line treatment for Aspergillus fumigatus patients. Because the Aspergillus fumigatus fungus mold is resistant to many drugs, it is often resistant even before it encounters the people it infects.
Researchers call for increased surveillance of Aspergillus fumigatus in the environment as well as the clinic to better understand the risk.
Professor Matthew Fisher from Imperial’s School of Public Health is the senior author. He says: “Understanding both the environmental hotspots as well as genetic basis of evolving fungal drugs resistance must be urgently addressed, because resistance is compromising how we can prevent and treat this disease.”
He states that “the prevalence of drug-resistant Aspergillosis has increased from negligible levels prior to 1999 to up to 3-40% now across Europe.” Aspergillus fumigatus may also be more common in people who have received stem cell or solid organ transplants, are on immunosuppressive treatment, have lung conditions, or have severe viral respiratory infections.
The researchers collected 218 Aspergillus fumigatus samples from England, Wales and Scotland between 2005 and 2017. The study included 218 samples of Aspergillus fumigatus from across the UK, Wales, Scotland, and Ireland between 2005 and 2017.
Researchers extracted DNA from the mould samples and sequenced it to determine if there was crossover between resistant spores in the environment and some patients.
Six strains of Aspergillus fumigatus were found in the environment that had infected six patients. Researchers concluded that the genetic similarities between the six strains of Aspergillus fumigatus were indicative that the fungus had spread from its environment to the patient.
Dr Johanna Rhodes from Imperial’s MRC Centre for Global Disease Analysis, School of Public Health, is the lead author. She says: “Increasingly the cases of Aspergillosis seen here are resistant to first-line azole drug treatments. However, we don’t know how these infections are acquired. We don’t know if they develop in patients’ lungs or if the mouldspores that infect them become resistant to drug treatment. Both routes of infection can be found in our study. This confirms the concern that mould spores that are resistant to treatment are capable of entering and infecting people’s lungs, causing more difficult-to-treat diseases.
Nearly half (106) of the 218 samples tested were resistant at least to one of the first-line anti-azole drugs used in clinic. 48% (104 samples), 29% (64 sample) to voriconazole and 21% (21 samples) to posaconazole were all resistant. More than 10% (26 samples, 23 environmental samples, and 3 samples from patients) were resistant at least two azole drugs.
Researchers discovered 50 new genes in 218 samples that were associated with drug resistant genes. They also discovered five new combinations of single-digit DNA changes (called single nucleotide Polymorphisms or SNPs) which were associated with drug resistance. One of these was resistant to multiple drugs.
Researchers looked at the genes in Aspergillus fumigatus samples and found two distinct groups: group A (123 out of 218 samples) & group B (95 samples). About 80% of the samples in group A were resistant to drugs, while 85% of those in group B were not. While the two groups were quite distinct, researchers discovered signs that they had swapped genetic material and created new forms of drug resistant.
According to the researchers, these findings suggest that Aspergillus fumigatus’s full spectrum of azole-resistance is still not fully understood.
Dr Rhodes said: “Our findings highlight novel ways of resistant infections being passed to people, and show that we need a better understanding about where and how Aspergillus fumigus generates drug-resistant compounds.”
The Natural Environment Research Council and the Wellcome Trust funded the study. Gilead Sciences, the Medical Research Council, and Gilead Sciences also contributed to the funding. It included researchers from Imperial, King’s College University Hospital and Trinity College Dublin, University of Aberdeen and The University of Manchester.