An international research partnership from Tunisia, the United States and France has led to a new and safe treatment for patients with cutaneous leishmaniasis (CL) with an investigational antibiotic cream, first identified at the Walter Reed Army Institute of Research (WRAIR). CL is a parasitic disease that causes scarring lesions and affects 1.5 million people worldwide every year, especially in the developing world and in children. The results of the study conducted by the US Army Medical Research and Materiel Command (USAMRMC), WRAIR researchers, the Institut Pasteur de Tunis, and the Institut Pasteur (Paris) was published on Feb 7 in the New England Journal of Medicine.
Study investigators evaluated WR 279,396, a combination of two antibiotics (15 percent paromomycin-0.5 percent gentamicin). In the trial, WR 279,396 cured the initial lesions in 81 percent of the patients who participated in the clinical trial. Curing the disease was defined as the shrinking of the lesion, growth of normal skin and absence of relapse. Adverse events were reported in less than 5 percent of all study groups and were primarily reported as minor reactions at the application site.
A cream with paromomycin alone (15 percent paromomycin) had a similar cure rate of 82 percent. In the study, only 58 percent of the patients who received a placebo saw the lesions cured.
Researchers expected that both single and combination therapies would be equally effective, treating CL caused by L. major, a parasitic species common in the Mahgreb and the Middle East. However, the combination therapy holds additional promise for global use since early research shows that the combination therapy may be more effective against the parasitic species found in Central, North and South America.
Current CL treatments are toxic heavy metals called antimonial salts that must be administered either intravenously or injected directly into the lesion. Because of toxicity, many health care providers are hesitant to use them to treat the disease. People who have CL must leave home and work to undergo the standard 20-day course of treatment at a medical center. Public health workers in the developing world see patients resort to home treatments like burning their lesions with battery acid or red-hot machetes, rather than seek out painful and expensive medical treatments. These home remedies can compound the severity of scarring.
WR 279,396 has the potential to become a first-line treatment patients could apply themselves.
“CL is not a killing disease, so it’s received very little attention from the research community,” said Professor Hechmi Louzir, Director of the Institut Pasteur de Tunis. “Yet, the effects of CL are lasting. The scarring means many patients face lifelong social stigma at work, school and in social settings, and it is particularly devastating to women and children who are just starting their lives.”
WRAIR and Institut Pasteur researchers formed a partnership 10 years ago around their common need for better CL treatments. Thousands of US Service Members became infected with CL in Iraq. Future deployments to the Middle East and elsewhere may expose US military personnel to infections in the future. In Tunisia, where the Phase III clinical trial was conducted, up to 10,000 new cases are reported each year and more than half of those cases are in children. The disease also affects immigrants and travelers in Europe.
The U.S. Food and Drug Administration has designated WR 279,396 as eligible for fast-track review, since CL is a neglected disease. The Fast Track program of the FDA is a process designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Additional research is being planned in Latin America to explore the use of the topical cream for leishmaniasis.