Deciphering cutaneous ulcers

Tropical ulcers are cutaneous lesions common in low-income countries of tropical regions. In remote rural communities, between 5% and 15% of children suffers from these injuries, which can be very painful and generate great stigma. To date, it was known that two specific bacteria were involved in 60% of the ulcers, but the cause of the remaining 40% was unknown. A recent study, carried out jointly by ISGlobal and the IrsiCaixa AIDS Research Institute, used innovative techniques based on analysis of the bacterial genome to identify three other bacteria that cause approximately one third of skin ulcers. The findings of that study, published in the journal Clinical Infectious Diseases, have opened the door to the development of more precise diagnostic and treatment tools.

“We are very close to understanding the full spectrum of bacteria related to a disease that affects thousands of children in rural villages and also travellers,” says Oriol Mitjà, doctor and researcher at ISGlobal, who works in Lihir island (Papua New Guinea, Oceania) to try to eradicate these lesions. Infectious cutaneous ulcers are a widespread health problem among the population of low-income countries in Africa and South Pacific region. They mainly affect children and young people, causing in the worst case deep injuries that destroy muscles and tendons and even affect the bones, causing life-long malformations. They also generate a very important stigma because children who suffer from them can not go to school or play with other children, to avoid transmission.

Microbial Diversity in Skin Ulcers

Mitjà’s team has been working in Lihir for the last 6 years for the eradication of yaws, a tropical disease that causes cutaneous ulcers caused by the Treponema pallidum pertenue bacterium. Together, Treponema pallidum pertenue and Haemophilus ducreyi bacterium account for 60% of skin ulcers in humans. However, researchers observed that in one-third of people with such ulcers neither of these bacteria were found. To fill the knowledge gap, ISGlobal and IrsiCaixa undertook a joint study to identify the other bacteria that cause skin ulcers. The team analysed 122 samples of ulcers collected from children in Lihir between 2013 and 2014. Using mass sequencing techniques, they detected hundreds of different bacterial species, demonstrating the great microbial diversity in skin ulcers.

Of the bacteria identified, Haemophilus ducreyi was the most abundant, occurring in 23% of the samples; Treponema pallidum pertenue was found in 16%; Streptococcus dysgalactiae in 12%; Arcanobacterium haemolyticum in 8%; and Corynebacterium diphtheriae in 8%.  “These findings confirm the complexity of the pathogenesis of tropical ulcers and provide us with information that will be important for the eradication of these infections,” explains Marc Noguera-Julián, one of the team of researchers in the Microbial Genomics Group at IrsiCaixa “They also evidence the fundamental role of mass sequencing techniques in the study of infectious diseases in the 21st century.”

Oriol Mitjà elaborates, “We are very close to identifying the entire spectrum of the bacteria that cause tropical ulcers in thousands of children living in rural areas and travellers to those areas.” The current lines of treatment being used in Papua New Guinea have shown that tropical ulcers can be treated effectively with amoxycillin. Since, amoxycillin is also effective against the three species of bacteria identified in the recent study, the current protocols are also appropriate for those lesions. Even so, identifying the pathogens that cause these lesions and gaining a better understanding of their role will facilitate the future development of more precise diagnostic methods and more effective treatments, thereby contributing to efforts to eradicate tropical ulcers worldwide.