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Yale scientists could come one step closer to finding an effective treatment for a disfiguring disease that strikes millions world-wide with a new $5.4 million grant.

Researchers at the Yale School of Public Health were recently awarded an International Collaboration in Infectious Disease Research grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health over the next four and a half years to fund research into cutaneous leishmaniasis, a parasitic disease. The money, the maximum possible under the type of grant awarded, will support both field work in Colombia and lab work in Colombia and at Yale.

The principal investigators for the grant are Diane McMahon-Pratt, professor of epidemiology of microbial diseases, and Leonard Munstermann, senior research scientist in the division of epidemiology and microbial diseases. They will be joined by four other Yale researchers, as well as four scientists at CIDEIM, a non-governmental organization based in Cali, Colombia that conducts infectious disease research.

Cutaneous leishmaniasis, a neglected tropical disease that is found in 88 countries and threatens 350 million people according to the World Health Organization, causes skin ulcers that can take years to heal. It is caused by a parasite that enters humans through the bites of female sand flies. The disease, though not fatal in the cutaneous form, is still a major problem facing developing countries, David Sacks, a researcher on the leishmania parasite at NIH, said.

“It’s a problem that’s getting out of hand in a lot of countries,” he said. “It’s an emerging infection in many places and there are many different types of it.”

The current treatment, which calls for doses of antimony or arsenic, is not always successful and can be more harmful than the disease itself, Munstermann said. While the grant sponsors a wide range of research activities, from clinical drug trials in Colombia to lab-based work in New Haven, McMahon-Pratt said the focus of each piece of the overall puzzle is the same — to find ways to control the disease’s spread.

The research will include a clinical trial in Colombia of miltefosine, an anti-cancer drug that is being considered to treat cutaneous leishmaniasis. Miltefosine will likely have fewer side effects than current treatments, McMahon-Pratt said. Its effectiveness has been examined in another study unrelated to this grant, but she said this study will be the first to examine its use in children.

As dangerous as using current treatments is for adults, the current stable of drugs proves even less effective in children, McMahon-Pratt said. Previously, this was not a problem because children rarely contracted the disease that was confined mostly to rainforests. But in recent years, Munstermann said, it has spread into more populated areas, though it is still mostly confined to rural areas in developing countries.

Munstermann said that he has about 15 years of experience working at the Colombian equivalent of NIH. As an entomologist, Munstermann, will focus on the insect vectors, the sand flies that carry the infectious parasite into human populations. Beyond medications, means of controlling the disease could include insecticides to target the insects that transmit the disease. But, he said, at least 40 different species of sand flies have been implicated, and often one species will only pose a problem in a specific geographic region. Complicating matters, at least a dozen species of the parasite itself are known to exist.

Some of the Yale researchers will travel to Colombia to carry out their research. Munstermann said he routinely goes to the country, and McMahon-Pratt will be leaving for Colombia in March. The field work will be supplemented by lab work by CIDEIM collaborators and others at Yale.

One of the Yale researchers is no stranger to field work, though he will not be taking part in it for this project. Dr. Richard Bucala ’79 GRD ’79, a professor of internal medicine, will be working in a lab focusing on a host-susceptibility gene that, when highly expressed, may increase the risk of contracting cutaneous leishmaniasis when exposed to the parasite.

A malaria researcher primarily, Bucala runs clinical studies in Zambia and has traveled there many times with students from the School of Public Health and Yale College. Though he will not be traveling to Colombia, he said students generally accompany researchers from the School of Public Health on trips overseas.

The grant lasts until August 2010, enough time to make some important progress, McMahon-Pratt said.

“The epidemiological studies should be successful [by 2010],” she said, referring to the drug trials. “I think that will have the most direct impact.”

But she cautioned that the lab-based component will not be complete by then due to the project’s breadth.

“We’ll be well-started with the immunologic and genetic studies,” she said, noting that they would likely not be completed. “I think they will be harder.”

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