But the world can't wait another 25 years for the perfect malaria vaccine, says Ballou. Instead stakeholders need to seize whatever approaches work today.

On-the-Ground Approaches

What will it take to end malaria? It will certainly require relying on some old lessons, such as those learned when WHO backed off from its malaria-prevention efforts in the '70s. But even more, it will need new thinking, new tactics, and, especially, new money. Here are some ways it's being done.

"In essence, Zanzibar has turned into a proving ground," says MMV's Hentschel. "It has gone from a situation where malaria was the biggest cause of childhood mortality to something that is fairly rare in a very short time, just by using everything available."

Package of prevention The epidemics of malaria and HIV overlap in Africa and, some argue, should be treated together. One major barrier, says the CDC's Slutsker, is the lack of data to support how ACTs work in HIV-immnosuppressed people.

However, there's innovation to be had on the prevention side. Malaria and HIV act synergistically in pregnant women to contribute to adverse birth outcomes, such as low birth weight, says Slutsker. Therefore, in the reproductive health setting, women should receive a prevention package including counseling on prevention of mother-to-child transmission of HIV and an insecticide-treated bed net.

Cheaper drugs By working with growers, Novartis was able to drop the price of Coartem. But further innovations may come from the lab, not the land—as RBx11160 almost proved. Still, researchers from the University of California, the California Institute of Quantitative Biomedical Research, and Amyris Biotech are forging ahead by working on synthesizing artemisinin. "Once you have a synthetic product," says Columbia's Waldman, "malaria will become a 'solvable problem' like HIV" because manufacturing it will no longer depend on the costly and variable availability of sweet wormwood trees.

In addition, three Indian generic companies have recently submitted ACTs for WHO's prequalification program, according to Bosman. If these drugs are approved, ACTs may become a competitive market with lower prices for all.

Public health Phase IV The issue of malaria resistance has demanded that organizations pay more attention to adherence. One result has been the creation of a support infrastructure to conduct outcomes studies in real-world settings—which public health officials can rely on to make policy and treatment decisions.

"It's really the public health sector equivalent of pharma's Phase IV program, but for ACTs—and about establishing appropriate relationships so that it can serve a market it doesn't understand," says Thomas Kanyok, a scientist for WHO's special program for research and training in tropical diseases. "There is more interest in looking at larger issues like pharmacovigilance—there are no systems like that in Africa."

Basic research Malaria needs more research into the mechanism of the disease. A key recent breakthrough came from the Broad Institute, where researchers mapped the genetic diversity of the malaria parasite. "One of the immediate applications is to spot evidence of the emergence of resistance to drugs that are just now being deployed—a kind of early warning surveillance system," says Dyann Wirth, director of Harvard's malaria initiative. "This can help researchers track mutations and update the vaccine, the way it's done with the influenza vaccine."