Each year, malaria parasites infect up to half a billion people and kill at least one million, most of them in sub-Saharan Africa, most of them children under the age of five. Nearly 3,000 children die each day. Before dying, they suffer severe anemia and recurring bouts of high fever, as the microbes invade red blood cells, reproduce, and escape, exploding the cells and releasing a devastating toxin. Fluid accumulates in the lungs, the blood turns acidic, the kidneys fail, and the brain can become inflamed, causing dizziness, seizures, and even personality changes.

And that doesn’t even fully describe the horror of the disease. “It’s not just the deaths,” says Filip Dubovsky, the scientific director of the Malaria Vaccine Initiative, a program funded by the Bill and Melinda Gates Foundation. “It’s the farmer who’s too sick to get to his work, to feed his family. It’s the loss of a fetus to a mother who’s expecting a baby. The thing is, people are used to it-and that’s one of the biggest tragedies.”

For decades, public-health groups have combatted malaria by trying to control infective-mosquito populations with insecticides and treating as many of the ill as possible with antimalarial drugs. But problems with parasite resistance to the drugs and mosquito resistance to the poisons-not to mention distribution costs and logistics-mean that far too often these strategies fail. Essential to the battle is finding a way to prevent the disease despite infective bites. “A vaccine is really badly needed,” says Marcel Tanner, director of the Swiss Tropical Institute in Basel. An effective vaccine could be cheaply and easily integrated into existing programs to immunize infants in malaria-infested regions against common childhood diseases. And in fact, researchers are working on almost 90 different versions of a malaria vaccine, 17 of which have started human testing (see “Sampling of Malaria Vaccines in Human Testing,” below).

Despite decades of effort, however, scientists have yet to produce a vaccine that works. “There has been a lot of technical failure,” says Marie-Paule Kieny, who coordinates the World Health Organization’s funding of malaria vaccine research. The main reason is that the parasites make slippery targets, routinely changing their appearance as they mature and spending much of their lives inside human blood cells, where the immune system has a hard time tracking them down. Since most vaccines work by training the immune system to fight invaders directly, the malaria microbes’ exceptional elusiveness has made vaccine development maddeningly frustrating.

But new hope is emerging from an unlikely source: the sugar responsible for the disease’s devastation. Instead of prompting the immune system to find and kill the malaria parasites, a new vaccine seeks to prime the immune system to attack the toxin that causes the most lethal aspects of the disease. The result of a collaboration between immunologist Louis Schofield of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and chemist Peter Seeberger of the Swiss Federal Institute of Technology in Zrich, the vaccine consists of a synthetic version of the malaria toxin-a sugar molecule that Schofield first identified in the late 1980s. So far, tests of the vaccine have yielded promising results in animals.

To commercialize the vaccine, Seeberger and Schofield have helped start up a company, Ancora Pharmaceuticals in Cambridge, MA. With the right funding, Seeberger says, the team could be ready to start human tests by the end of the year; but that funding has yet to materialize. The problem is in many ways endemic to malaria research. And the cause is simple: the disease afflicts mainly poor countries that have little political or financial clout. “One of the toughest things with malaria is going to be getting a way to finance the work,” says biotech entrepreneur Carmichael Roberts, Ancora’s cofounder. Seeberger is blunter. “Hell would break loose if 40,000 people died in the U.S. in a month,” he says, as has happened in some malaria-ridden regions of Africa.

Many experts doubt that the sugar-based vaccine will be the sole answer to malaria, but if it works, it could be a vital piece of the strategy for combatting the disease. Because the vaccine comprises a sugar, it has advantages over other vaccines being tested: it does not require refrigeration, and it could be more robust against parasite resistance. And that could help it save lives and ultimately boost the economies in many developing nations. “If we could reduce malaria by 10 percent, that would be enough for me,” Seeberger says. “You’re talking about millions of people.”