FROM SCIENCE
A recently evolved strain of Mycobacterium is circulating in hospitals worldwide, causing nearly impossible-to-treat lung infections among patients with cystic fibrosis.
A genome-wide study has determined that Mycobacterium abscessus is not transmitted through soil and water, as once thought, but is a nosocomial infection transmitted person to person through droplet and surface contamination, Andres Floto, MD , reported in Science ( 2016 Nov 11;354[6313]:751-7 ).
“The bug initially seems to have entered the patient population from the environment, but we think it has recently evolved to become capable of jumping from patient to patient, getting more virulent as it does so,” Dr. Floto of the University of Cambridge, England, wrote in a press statement.
The path of global transmission is not yet entirely clear, the authors noted. But since it first appeared, around 1978, M. abscessus has spread globally, strongly suggesting that asymptomatic carriers may be one source of transmission.
“We found no evidence of cystic fibrosis patients or of equipment moving between centers in different countries, indicating that the global spread of M. abscessus may be driven by alternative human, zoonotic, or environmental vectors of transmission,” the researchers wrote.
The team conducted whole-genome sequencing on 1,080 samples of M. abscessus obtained from 517 cystic fibrosis patients in clinics and hospitals within the United States, the United Kingdom, Europe, and Australia. They identified three subspecies, some of which contained nearly genetically identical strains, “suggesting widespread transmission of circulating clones within the global cystic fibrosis patient community.”
Most patients (74%) were infected with these genetically identical strains despite their diverse geographic locations. The isolates were amazingly similar, the authors noted: 90% differed by less than 20 single nucleotide polymorphisms.
Using these strains, the researchers were able to construct several possible transmission chains in most of the cystic fibrosis centers included in the study. The three dominant circulating clones were all observed in the United States, European, and Australian samples, indicating transcontinental transmission.
“We also detected numerous examples of identical or near-identical isolates infecting groups of patients in different cystic fibrosis centers and, indeed, across different countries, indicating the recent global spread of M. abscessus clones throughout the international cystic fibrosis patient community.”
The team also determined that the common ancestor of these strains probably emerged around 1978.
Another sequencing series tracked specific isolates among individual patients. This strongly suggests person-to-person transmission. Adding this to their previous work on M. abscessus transmission, the authors postulated that spread was probably by surface contamination by droplet contamination and by cough aerosol from infected patients.
The team then looked at clinical outcomes associated with the bacteria and treatment with amikacin and macrolides – antibiotics typically used to fight this very-challenging infection. “We did observe increased rates of chronic infection in individuals,” infected with the clones, which were resistant to both those medications, they said.
In immunodeficient mice, the strains were more likely to cause granulomatous and inflammatory lung changes. And the bacteria tended to survive even after being consumed by macrophages, “suggesting that the establishment of transmission chains may have permitted multiple rounds of within-host genetic adaptation to allow M. abscessus to evolve from an environmental organism to a true lung pathogen.”
The research was funded by the Wellcome Trust and the Cystic Fibrosis Trust in the United Kingdom. There were no financial disclosures.
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