The study, conducted by an Ethiopian-led consortium including the Armauer Hansen Research Institute and international collaborators from the Drugs for Neglected Diseases initiative and Spain’s Instituto de Salud Carlos III, was a multicenter, randomized, controlled, open-label, adaptive Phase II/III trial. It compared a single session of thermotherapy, in which a heated device delivers 50 degrees Celsius to the lesion for 30 seconds, against the current standard of weekly injections of pentavalent sodium stibogluconate directly into the lesion, a regimen that must continue for four to six weeks. Participants were adults aged 18 to 60 years with parasitologically confirmed, uncomplicated localized cutaneous leishmaniasis, enrolled across Ethiopian treatment sites including ALERT Comprehensive Specialized Hospital, Boru Meda General Hospital, and Wacha Health Center.

The trial was designed with methodological rigor unusual for studies in this field. Prespecified futility and interim analyses guided progression through the trial phases, and an independent Data and Safety Monitoring Board oversaw the process, ultimately recommending that the final phase II analysis include 183 participants. Of these, 91 were randomized to thermotherapy and 92 to intralesional sodium stibogluconate. Most participants were men, 60.4 percent in the thermotherapy arm and 53.3 percent in the drug arm, and the median age was 27 years. Cure was assessed at two time points: initial cure evaluated at day 90 or 105, and final cure assessed at day 180, using both intention-to-treat and per-protocol analyses to capture different views of treatment effect.

The intention-to-treat results, which include every participant as randomized, showed that initial cure rates were 44.0 percent for thermotherapy and 52.2 percent for intralesional sodium stibogluconate, a difference that did not reach statistical significance (p = 0.266). Final cure rates at day 180 were similarly comparable in this analysis, at 34.1 percent versus 43.5 percent (p = 0.191). By contrast, the per-protocol analysis, restricted to participants who completed treatment as assigned, found a statistically significant advantage for the drug regimen, with final cure rates of 39.2 percent for thermotherapy versus 57.6 percent for intralesional sodium stibogluconate (p = 0.032). This divergence between analytic perspectives reflects an important practical reality: some participants in the drug arm did not complete the full multi-week injection course, whereas thermotherapy required only a single visit.

The safety findings were unambiguous. No serious adverse events were reported in either arm, and all observed adverse events were mild and resolved without complications. Health-related quality of life, measured with validated dermatological instruments, improved significantly in both treatment arms after cure, indicating that successful lesion healing translates into tangible benefits in patients’ daily lives regardless of which therapy achieved it.

From a technical standpoint, the trial’s design choices deserve attention. The thermotherapy protocol, a single application of 50 degrees Celsius for 30 seconds, exploits the thermal sensitivity of Leishmania parasites within skin lesions, inducing local parasite killing while sparing surrounding tissue. Intralesional sodium stibogluconate, by contrast, relies on pentavalent antimonial compounds delivered directly into the lesion over repeated weekly visits. The adherence advantage observed for thermotherapy is therefore not a minor convenience but a structurally meaningful difference: a treatment requiring one healthcare visit is far easier to complete than one demanding four to six weekly presentations, particularly for patients in rural Ethiopia who may travel long distances and bear significant opportunity costs for each clinic visit.

The authors argue that in resource-limited Ethiopian settings, where most cutaneous leishmaniasis cases go entirely untreated and patients risk lifelong disfigurement, thermotherapy provides a pragmatic, single-session alternative wherever access to intralesional sodium stibogluconate is constrained. The intention-to-treat equivalence, combined with superior adherence and an acceptable safety profile, supports this position, even as the per-protocol results caution that patients who can reliably complete the full drug course may achieve somewhat higher cure rates with the standard therapy. The nuance matters for policy: the best treatment is not only the most efficacious in ideal conditions but the one patients can actually finish.

The study also fills a glaring evidence gap. Ethiopian clinical practice for L. aethiopica infections has historically been informed by trials conducted in other regions with different parasite species, most commonly Leishmania major or Leishmania tropica, whose responses to heat and antimonials can differ. By generating species-specific, locally grounded data, the trial gives Ethiopian clinicians and national program managers the kind of evidence needed to tailor treatment guidelines to the parasite actually circulating in their highland foci.

Funding for the work came in part from the European and Developing Countries Clinical Trials Partnership (EDCTP2) programme supported by the European Union, with the study device and medications supplied by the Drugs for Neglected Diseases initiative and molecular work supported by the Armauer Hansen Research Institute and Instituto de Salud Carlos III. The trial was registered in the Pan African Clinical Trials Registry (PACTR202205775486864) on 30 May 2022, and the article was published open access in BMC Medicine on 19 September 2026, ensuring that the results are freely available to the health systems that most need them.

For the global community working on neglected tropical diseases, the trial’s message is twofold. First, heat-based therapy can credibly compete with injectable drug regimens for localized cutaneous leishmaniasis when adherence to prolonged treatment is unrealistic, making it a candidate for scale-up in endemic districts. Second, the divergence between intention-to-treat and per-protocol outcomes is a reminder that in real-world neglected disease care, the route and duration of treatment are as decisive as the drug itself. As Ethiopia and neighboring endemic countries weigh how to expand care for a disease that has long hidden in plain sight, a thirty-second burst of controlled heat, delivered in a single visit, may prove to be one of the most pragmatic tools at their disposal.

Subject of Research: A phase II randomized controlled trial comparing thermotherapy with intralesional sodium stibogluconate for Leishmania aethiopica cutaneous leishmaniasis in Ethiopia

Article Title: Thermotherapy compared with intralesional sodium stibogluconate for Leishmania aethiopica cutaneous Leishmaniasis in Ethiopia: A phase II randomized controlled trial

Article References: Thermotherapy compared with intralesional sodium stibogluconate for Leishmania aethiopica cutaneous Leishmaniasis in Ethiopia: A phase II randomized controlled trial. (n.d.). https://doi.org/10.1186/s12916-026-05244-6

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05244-6

Keywords: cutaneous leishmaniasis, Leishmania aethiopica, thermotherapy, intralesional sodium stibogluconate, randomized controlled trial, Ethiopia, treatment efficacy, neglected tropical diseases, phase II trial, adherence, BMC Medicine, public health