This is where TAK-187 comes in, says Urbina. “It is a compound that blocks the synthesis of ergosterol in the parasite without affecting that of cholesterol in the hosts, and it penetrates into the deep tissues where the parasite thrives.”

The "kiss" of the parasite's vector has aptly been called the kiss of death.

His team infected mice with a strain of T. cruzi, waited until they showed symptoms in a model of the chronic form of human Chagas disease, and then treated the animals with benznidazole, TAK-187, or a placebo. The two drugs either suppressed the parasite load in the mouse blood and tissue or eliminated T. cruzi entirely. But TAK-187 did so at a tenth of the dose, and it worked as well when given every other day, whereas benznidazole had to be administered daily. Postmortem tissue analysis also showed that TAK-187 was more effective than benznidazole at preventing inflammation and damage in the heart and skeletal muscle of the mice.

The researchers, whose work was published in the April 2005 issue of Antimicrobial Agents and Chemotherapy , believe the greater efficacy of TAK-187 comes down to the fact that it strikes at the parasite’s ability to replicate and that it is more slowly metabolized by the host, allowing a sustained antipsitic action. Citing these “potentially interesting” findings together with the “urgent need for new drugs,” John M. Kelly of the London School of Hygiene and Tropical Medicine says that “this preliminary report should point the way to trials on human patients.”

In another promising advance against parasitic disease, HHMI international research scholars Alan F. Cowman of the Walter and Eliza Hall Institute of Medical Research, in Melbourne, Australia, and Brendan S. Crabb of the University of Melbourne have peered behind the invisible cloak of the malaria parasite Plasmodium falciparum. This parasite invades the host’s red blood cells, from which it exports proteins. Some are virulence factors, aiding the parasite’s spread and colonization of its host; others remodel the surface of the red blood cell, making it undetectable by the host’s immune system.

		Once in the human body, malarial parasites spread to the liver and multiply in red blood cells such as this one, misshapen and bulging from the malarial parasites within. Image: Dr. Gopal Murti/Photo Researchers, Inc.

In a paper published in the December 10, 2004, issue of Science, Cowman’s group identified the common mechanism by which the parasite exports all 400-plus proteins. That mechanism “provides an extremely good target for the development of new drugs,” he says.

In a follow-up paper published in the April 8, 2005, issue of Cell, the Cowman and Crabb groups looked specifically at the parasitic proteins that render the red blood cell invisible. The immune system eventually works out what the masking protein is, and it mounts an immune response. But the elusive P. falciparum then switches to another protein—and it has a repertoire of at least 50 to choose from. The researchers shed even more light on this trick by showing how the gene for the protein in question is activated while the others are silenced.

Photo: ©Dr. Gopal Murti / Photo Researchers, Inc.

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