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She says there is great potential to “exploit the discoveries to control trypanosome infection,” either by blocking the parasite’s reproduction in the tsetse fly or by altering the surface coat in a way that would spur an effective defense by the human host’s immune system.
Because not all surface proteins are involved directly in antigenic variation—some are transporters that acquire nutrients or enzymes that break them down, others appear to be environmental sensors—such proteins might represent potential drug targets. For example, a drug might disrupt the growth of the parasite by interfering with its ability to bind host factors; alternatively, small molecules might bind the pathogen directly and deliver spurious signals. Other approaches include hijacking nutrient transporters to introduce harmful drugs into a parasite or inhibiting the activity of certain enzymes.
Working with researcher Reto Brun of the Swiss Tropical and Public Health Institute, Roditi’s lab is now trying to develop a technique to trick trypanosomes into prematurely moving on to the next stage of their life cycle—that is, to become insect forms in their mammalian host. If parasites were to shed their VSG coat and cover themselves with a procyclin coat, the thinking goes, they would be vulnerable to destruction in the human bloodstream.
Despite the promise of finding new drugs to attack the African trypanosome, there is far less potential for developing an effective vaccine, Navarro says, because it would be so difficult to cover all 1,500 possible surface variants of the pathogen. But researchers are optimistic that they will find more effective ways to target trypanosomes and ease the burden of African sleeping sickness, which infects more than 50,000 people a year in sub-Saharan Africa and is fatal if not treated.
If scientists can make more progress in slowing the parasite’s surface-protein switching, Cross believes, “the immune response can control a trypanosome infection.” Reflecting similar optimism, Navarro hopes that “we may be able to block the mechanism that allows the parasite to escape the host immune response.”
By weakening the surface-protein armor of trypanosomes, researchers are making them vulnerable and giving hope that the age-old African threat of sleeping sickness eventually will become a bad dream of the past.