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Genomic Data Helps Explain Yaws Re-emergence, Antibiotic Resistance in Papua New Guinea

NEW YORK – Using genome sequencing, an international team has tracked the consequences of an antibiotic campaign on the bacterial subspecies behind yaws — a neglected tropical disease that involves disfiguring skin, bone, and joint infections.

"The results from this study are influencing the next steps and approaches we take to eradicate this disease," co-senior author Oriol Mitjà, a researcher affiliated with Papua New Guinea's Lihir Medical Center, the University of Papua New Guinea, and the University of Barcelona, said in a statement.

For a paper published in the October issue of Lancet Microbe, researchers from Papua New Guinea, the UK, and elsewhere attempted to sequence the genomes of Treponema pallidum subspecies pertenue isolates from more than three dozen yaws-related skin lesions from individuals on Papua New Guinea's Lihir Island between the spring of 2013 and late 2016.

Based on genome sequence and phylogenetic clues for 20 successfully sequenced isolates of the yaw-causing bacteria, the team was able to get a look at the consequences of a World Health Organization "mass drug administration" program, which aimed to dial down yaws cases with the widespread use of an antibiotic called azithromycin.

"The resolution afforded by genome sequencing to track agents of infectious diseases is vital for our efforts," co-senior author Nicholas Thomson, a researcher affiliated with the Wellcome Sanger Institute and the London School of Hygiene and Tropical Medicine, said in a statement.

While past work suggested that the antibiotics-based attempts to control yaws had whittled the population of T. p. pertenue, the latest findings offered a look at the re-emergence patterns associated with a remaining T. p. pertenue sequence type known as JG8, which itself appears to encompass at least three different lineages that cropped up in different parts of the island over time.

The work also offered a look at the genetic shifts that are helping the bacterial subspecies dodge the antibiotic. For example, the team tracked down a handful of cases involving macrolide-resistant forms of T. p. pertenue, and genome sequences available for three of those antibiotic-resistant cases were similar to one another.

By bringing in deep amplicon sequencing analyses, the researchers were able to identify pre-treatment forms of the resistant bugs that had been antibiotic-sensitive. Despite the multiple re-emergence events at play in the area, those results suggested that azithromycin resistance may arise relatively rarely, since their sequence data pointed to the same fixed, post-treatment antibiotic-resistance genotype in an apparent index case of yaws and in several cases that were in contact with that individual.

"The development of antibiotic resistance is worrying, but the fact that it only occurred once after a mass drug administration is positive news," first author Mathew Beale, a researcher at the Sanger Institute, said in a statement. "We still need to be very concerned about resistance, but it may be possible to manage it."

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