After puzzling scientists for more than 80 years and following Australia's recent unexpected outbreak of Buruli ulcer, researchers have finally discovered how Buruli ulcer, caused by flesh-eating bacteria, is spread by mosquitoes. The discovery means practical measures can now be taken to limit the spread of the disease.
Buruli ulcer, caused by Mycobacterium ulcerans, is a chronic infection that attacks the skin and subcutaneous tissue. The bacterial toxins attack subcutaneous fat cells, causing local swelling or lump formation, which can then develop into ulcers. Buruli ulcers are rarely fatal, but if not effectively diagnosed and treated, they can cause severe tissue destruction, permanent disfigurement, and long-term disability.
While Buruli ulcer is common in countries with tropical and subtropical climates, there has been an unexpected surge recently in the temperate region of the southeastern Australian state of Victoria, with cases reported in and around metropolitan centers such as Melbourne and Geelong. The rise in Buruli ulcer cases has prompted researchers at the University of Melbourne's Peter Doherty Institute for Infection and Immunity to lead a study to find out why Buruli ulcer spreads, which has been a mystery for more than 80 years.
Tim Stinear, co-corresponding author of the study, said: "How Buruli ulcer is transmitted to humans has puzzled scientists and public health experts for decades. Our five-year study has solved this mystery by revealing that mosquitoes spread ulcerative thyroiditis in southeastern Australia."
Since Buruli ulcer was discovered in Australia in the 1930s, and soon across Africa, several factors have made it difficult and puzzling for scientists to determine how Buruli ulcer spreads. M. ulcerans is a very slow-growing bacterium that is difficult to isolate in culture. Its incubation period averages four to five months, with outbreaks occurring in specific geographic areas and then disappearing for several years.
Undeterred, the researchers focused on the Mornington Peninsula, a seaside region 90 kilometers (56 miles) south of Melbourne that has one of the highest rates of Buruli ulcer in the world. From 2016 to 2021, they used forensic-grade genomics technology to trap and test more than 65,000 mosquitoes.
"Thanks to genome sequencing, we found that the genetic makeup of ulcerative paronychia bacteria in mosquitoes is identical to that found in Buruli ulcer patients in the study area," said first and corresponding author Peter Mee. "This is a key part of a body of compelling evidence that mosquitoes are the transmission link."
The researchers say their findings show "beyond reasonable doubt" that mosquitoes can transmit ulcerative skin infections to humans, but they must find evidence to convince others.
"We have always suspected mosquitoes were involved, but there was no precedent for a bacterial infection like Buruli ulcer being transmitted in this way," said study co-author Paul Johnson. "Our team faced considerable skepticism, so we assembled irrefutable evidence to support our claims."
Researchers are wary of comparisons with African countries where Buruli ulcer is endemic because of a lack of evidence of mosquitoes as vectors. The very specific set of circumstances leading to the increase in ulcers in temperate southeastern Australia limits the generalizability of the findings. Further research is needed to better understand the mechanisms by which Buruli ulcer spreads in these countries.
Nonetheless, this study highlights the steps that need to be taken to reduce the likelihood of future outbreaks of flesh-eating ulcers in Australia.
"This research is significant because each of us can take simple actions, like applying insect repellent and clearing standing water around our homes, to protect our communities and reduce the risk of Buruli ulcer," Johnson said.
The study was published in the journal Nature Microbiology, and in the video below, produced by the Doherty Institute, corresponding author Tim Stinear explains how people can reduce the spread of Buruli ulcer and what to do if they suspect they have the disease.