Pummelling parasites

Pummelling parasites

Maeve Haldane | Two weeks ago, Greg Matlashewski was hiking around the highlands of Peru. Sounds like the sort of trip an adventurer would take, but the chair of the Department of Microbiology and Immunology wasn't there to check out the breathtaking vistas.

	Professor Greg Matlashewski PHOTO: Owen Egan

Cutaneous leishmaniasis, not Incan ruins, was his focus. Matlashewski was following up on his trial experiments for treating the ravaging disease.

Cutaneous leishmaniasis is spread by sandfly bites, turning into sores on the skin that can develop into the more serious mucocutaneous leishmaniasis, a form of leprosy that leaves people horribly disfigured. The parasitic disease eats away at the face and has been around a long time. Even old Incan pottery depicts its effects.

Children are particularly at risk, due to their less-developed immune systems. "It's devastating and terrifying to the people there." Matlashewski says. "You see kids, maybe 17 years old, holding a scarf over their face to hide." They are marginalized and others worry that it's contagious.

Traditionally, infected villagers travel to Lima for 20 days' worth of glucantime injections. Sometimes treatment takes place in the villages, but there may not be enough glucantime for a full course for everyone, or days may be skipped because people have to work. Predictably, this results in greater resistance to the drug.

Together with vaccine immunologist Dr. Brian Ward of McGill's Centre for the Study of Host Resistance, Matlashewski devised a trial method of a combination treatment to try in Peru on patients who hadn't responded to the glucantime alone.

Matlashewski and Ward have coupled the course of injections with treating the lesions with applications of aldara, a drug made by 3M used to treat human papillomavirus (HPV) infections.

Matlashewski, who is also working on HPV, learned that aldara stimulates the immune system, causing macrophages (immune cells that eat bacteria, etc.) to attack viruses and protozoas within. Since leishmaniasis is a protozoa which multiplies in macrophages, it seemed likely that aldara would cause macrophages to kill leishmaniasis, and it does.

Geneticist Danuta Radzioch, of the Centre for Host Resistance, is also currently collaborating with Mat-lashewski in the lab on studies looking at the use of aldara in treating mycobacteria infections, a bacteria which also resides in macrophages and causes tuberculosis.

"Tuberculosis is a huge problem throughout the developing world, and is spreading in the developed world," Matlashewski says.

Because drugs are so expensive to develop, scientists are keen to find more uses for an existing one. For example, Merck developed ivermectin whose primary use is to treat heartworm in dogs and other domestic animals. It turns out that it can also cure other parasitic disease such as human river blindness in Africa. Aldara may turn out to be such a drug, useful to treat a number of important infectious diseases.

Matlashewski's treks to Peru are showing that the experiment is going well. Six months after treatment, 15 trial patients are rid of the infection and Matlashewski expects more success stories to come.

During his follow-up visits, he keeps an eye out for other cases of leishmaniasis to enrol in the study, and he's accompanied by several Peruvian doctors working on a variety of infectious diseases.

Although leishmaniasis in Peru is virulent enough to require a combination treatment, future tests might demonstrate that aldara could be used alone on milder types of leishmaniasis. "We can't solve the problem, but we can help a lot of people. There are a lot of children we can treat who won't suffer the horrendous effects of leishmaniasis," Matlashewski says.

But a vaccine could offer another solution. Visceral leishmaniasis, another form of this disease, quickly attacks the internal organs and is often a fatal infection through parts of India, Brazil and Northern Africa.

"This infection has moved up from North Africa and is now entrenched in Southern Europe," says Matlashewski. It's also a leading cause of death in AIDS patients in the south of France.

Dogs are the major animal reservoir for this variant, and Matlashewski is working on a vaccine to be tested intially in dogs in France and Brazil. In about a year, the researchers will be able to tell if it works, then they can start work on a vaccination for people.

They hope to generate an income from the veterinary vaccinations, which could then go towards funding vaccine trials in humans in developing countries.

"Universities have the opportunity to work on diseases where pharmaceutical companies can't. It's not the responsibility of universities to generate profits from their research," says Matlashewski.

"We can work and do research for the sake of people in developing countries and this is particularly important when it comes to infectious diseases. Universities are in a position to take the lead in this area but they must also encourage and foster collaborations with pharmaceutical companies who are sensitive to the needs of the developing world.

"I think pharmaceutical companies have gotten a bad rap in some cases. There are a number of instances where pharmaceutical companies provide drugs free of charge, financial support, and technical expertise with little expectation for return." Matlashewski adds, "3M has been very helpful to us in this regard."

Although there are a lot of interesting micro-organisms in the developing world, Matlashewski isn't just in this for the sake of research. "I don't want to just write papers, I want to make an impact on people."