Access: Parasites Lost




Whether bisphosphonates will serve as a new treatment for tropical diseases remains to be seen, but Croft is encouraged. "We've been testing drugs for at least 20 years, so we have a good idea of what looks like a good drug. When you see something good, you get a little bit excited about it," he says. "One has got to be skeptical as a scientist. There's a long way to go yet, but this has got the smell of an interesting story."

A good drug is one that kills parasites at low concentrations while simultaneously requiring extremely high concentrations to kill mammalian cells, Croft says. Once it passes that hurdle, a drug must then show efficacy in animals and later in people. Because existing treatments are so often ineffective, bisphosphonates—if they prove successful—would be an important advance in treating tropical fevers. Croft also finds it especially encouraging that bisphosphonates inhibit not only the malaria parasite, but also the parasites that cause the less common tropical diseases. Unlike malaria, these other diseases are too rare to attract much heavy investment in research and development.

Trypanosoma brucei, the parasite that causes African sleeping sickness, in infected mouse blood. Photo courtesy of Sinclair Stammers for the World Health Organization Special Programme for Research and Training in Tropical Diseases.

Docampo notes that because bisphosphonates are already used in humans, if they work for parasitic diseases, they could be put into clinical use relatively quickly. "They have already passed all the toxicity tests. They are known not to be mutagenic or carcinogenic," he says.

Docampo cautions, however, that even under the best scenario, routine use of bisphosphonates for malaria in people is a ways off. "I think we need to do more animal studies to establish the dose-response and which are the best compounds, and then after that, human trials," he says.

This research is supported by the National Institutes of Health.