Researchers Discover Way to Predict Treatment Success for Disfiguring Skin Disease

It’s commonly said that the cure can be worse than the disease. That’s the case with current treatments for cutaneous leishmaniasis, a devastating skin infection that strikes nearly 1 million people a year, mostly in Africa and South America, and can lead to debilitating disability and deep social stigma.

There is no vaccine and existing treatments are problematic: Patients may feel sick for weeks while being treated. Those who give up waiting for improvements may stop treatment or visit another doctor to repeat the process. And even if they are cured, they’re likely to bear scars forever.

A study published Friday in the journal Nature Communications could transform how health care providers approach treating this disfiguring disease, caused by the Leishmania parasite. A team of researchers from the University of Maryland and the Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) in Colombia discovered a way to predict whether patients will respond to the most common treatment, potentially saving them from months of expensive, ineffective and toxic medication.

UMD Professor of cell biology and molecular genetics Najib El-Sayed, co-lead author of the study, noted that the standard drug used to treat the disease, meglumine antimoniate, typically fails in about 40-70% of patients.

“This failure rate holds even when patients complete the full course of the treatment, which takes up to 14 weeks,” El-Sayed said. “Finding out how effective the medication will be on a patient early on is very important because it can prevent weeks or months of ineffective treatment and help patients access more suitable alternatives much sooner.”

The team found that patients who failed to respond to meglumine antimoniate showed a distinctive pattern in their immune system, a sustained inflammatory state called a type I interferon response. This response is usually a crucial part of the body’s early response system against viruses, helping cells detect a pathogen and recruiting resources to fight against it.

“While this response is essential for fighting some infections, we found that when it remains elevated for too long, it can interfere with the treatment and healing process in patients with cutaneous leishmaniasis,” El-Sayed explained. “This elevated type I interferon response was observed across several innate immune cell types we analyzed in patient blood samples. By tracking these changes throughout the treatment process, we identified a clear pattern that distinguishes patients who successfully recover from those who won’t respond to standard medication.”

The researchers also developed a sophisticated scoring system that can accurately predict treatment outcomes for newly diagnosed patients using advanced machine learning techniques. By analyzing the activity of just nine genes, they could predict whether the treatment would work on a cutaneous leishmaniasis patient with 90% accuracy.

“This is significant progress for health care providers and scientists working to improve outcomes for cutaneous leishmaniasis patients,” said Maria Adelaida Gomez, a microbiologist with CIDEIM and co-lead author of the study. “The disease is starting to move to new places such as the United States, which means we need these resources more than ever.”

While the current test requires sophisticated laboratory equipment, the team is already working to produce a more portable and user-friendly version of the technology for doctors to use in the field. The researchers hope their new findings, particularly regarding the type I interferon pathway, could be a promising avenue for developing new therapeutics for cutaneous leishmaniasis. Their conclusions represent a shift from more traditional approaches —which usually focus solely on eliminating the parasite—to treatment methods that also consider the patient’s natural immune responses.

“It’s really one of the first attempts to translate laboratory findings of this disease into practical applications,” El-Sayed said. “Understanding why some patients don’t respond to treatment has been a major challenge in managing this disease. This work opens the door to precision medicine and developing better strategies that can personalize treatment for a wide range of patients.”