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Originally published September 9, 2010 at 8:28 PM | Page modified September 9, 2010 at 10:07 PM

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Gates Foundation shakes up science with goal to end malaria

After revitalizing research into the long-neglected disease malaria, the Bill & Melinda Gates Foundation is now revamping the scientific agenda to focus on the controversial goal it set three years ago: driving malaria to extinction.

Seattle Times science reporter

Imagine a vaccine that wouldn't keep you from getting sick, but could protect your neighbors from falling prey to one of the world's biggest killers. Then ask yourself: Would you get the shot?

The Bill & Melinda Gates Foundation is betting people in Africa will say yes when it comes to malaria.

After revitalizing research into the long-neglected disease, the Microsoft co-founder and his wife are revamping the scientific agenda with their eyes on the controversial goal they set three years ago: driving malaria to extinction.

Chief among the new priorities is a vaccine that would prevent mosquitoes from spreading the disease. People who are inoculated could still get malaria, but mosquitoes that bite them would not be able to infect anyone else.

Another tool sought is a pill that would not only cure malaria but also block its spread. And since global eradication means all malaria would be wiped out, more attention is going to the form of the disease common in Asia and South America — which can hide in the body and cause recurring bouts of fever.

"We came to the conclusion, which is widely shared, that the tools we currently have are not sufficient to eradicate malaria," said Dr. David Brandling-Bennett, leader of the foundation's malaria programs.

Eradication may be as much as 40 years away, but it's important to start work now on drugs and vaccines that can take a decade or more to bring to the field, he said in an interview monitored by a Gates Foundation public-relations representative.

As the world's richest — and perhaps most influential — philanthropy, the Gates Foundation has the power to sway both science and governments. Some experts fear its emphasis on eradication will divert too much money and energy away from efforts to treat the disease and toward a far-off goal.

Reports are due soon from a group of leading scientists funded by the foundation to draw up a research plan with eradication as the end game. The foundation is already shifting its priorities — and scientists around the world are taking note.

"It's not radical, but it is changing the emphasis," said Dr. Brian Greenwood, of the London School of Hygiene and Tropical Medicine.

The increased focus on the future means the Gates Foundation is ending its support for some efforts to lessen the disease's current toll. Those include research to improve treatment of the severe infections that strike children and pregnant women, and that are responsible for most of the estimated 850,000 annual deaths from malaria.

"In a general sense, we are focusing on prevention rather than treatment," Brandling-Bennett said in an e-mail.

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That concerns some experts, including Greenwood.

"We have to be careful not to put all our eggs in that basket," he said.

An outlandish goal?

When the Gateses issued their call for malaria eradication at a Seattle conference in 2007, the room was filled with "the sound of 300 people breathing in sharply at the same time," recalled Dr. Rob Newman, director of malaria programs for the World Health Organization (WHO).

To many malaria veterans, the notion seemed outlandish in the face of earlier failures. Though the disease was eliminated in many wealthy nations, a global-eradication push launched in 1955 faltered and malaria roared back across Africa and parts of Asia and South America. Only one disease — smallpox — has been eradicated. Efforts to stamp out polio have dragged on for decades.

But optimism is high that at least some victories are possible against malaria.

Researchers are gaining greater insight into the parasite that causes the disease and its diabolically complex life cycle. "Over the past five years, we have probably learned more about malaria than in any other time period in history," said malaria researcher Stefan Kappe, of Seattle BioMed, a nonprofit lab focused on diseases of the developing world.

Several African nations have slashed malaria's toll through use of insecticide-treated bed nets, indoor spraying and improved treatment for those who get sick.

But those efforts are costly and must be maintained indefinitely — which is one of the arguments for eradication. "Unless we can chart a way to get to a final solution, the concern is that malaria-control programs are going to run out of money and support a long time before we run out of malaria," said Dr. Kent Campbell, director of malaria programs for the Seattle nonprofit PATH, which tackles health problems in poor countries.

The disease continues to rampage across populous countries like Nigeria and the Democratic Republic of Congo, where transmission rates are intense and health systems shattered. WHO estimates there are nearly 250 million cases of malaria worldwide each year, mostly in Africa.

On the margins of malaria's range, it may be possible to stop local transmission through diligent use of nets and other simple control measures. But in the heart of malaria territory, where people are exposed to 500 infectious bites a year, nets will never be enough to eliminate the disease.

"If your arm falls out of the bed net for a night, that makes the bed net useless," said Kappe, in an interview monitored by a Seattle BioMed public-relations representative. "I don't think we will be able to eradicate malaria from these areas without a vaccine."

Breaking the cycle

The ideal role for a vaccine is to perform mop-up duty, after nets, spraying and treatment have driven malaria levels down, said Ashley Birkett, of the Gates-funded PATH Malaria Vaccine Initiative (MVI).

But not just any vaccine will work.

Malaria involves an intricate dance between people, the parasites and the mosquitoes that transmit them. After being injected by mosquito bite into a person's bloodstream, the parasite goes through stages that include hiding from the immune system then bursting out to destroy blood cells — and making the person feel miserable.

To complete its life cycle, the parasite has to get back into a mosquito. So it forms a stage that circulates in its human host's blood, where a mosquito bite can pluck it out and start the cycle again.

A vaccine that prevents illness but doesn't clear all those parasites from the blood stream would leave a reservoir of symptomless carriers. Mosquitoes that bite those carriers could transmit the disease to others.

What's needed is a vaccine that breaks the cycle, Birkett said.

But so-called transmission-blocking vaccines have always been problematic. Research has languished because it's not clear whether people would take a shot for the greater good. The technical hurdles are also formidable. A vaccine would have to be highly effective, safe and suitable for all ages so it could be given to entire communities.

Now, with Gates' interest in eradication, money is starting to flow to a few labs with promising candidates. MVI is devoting 17 percent of its research budget to transmission-blocking vaccines, and the total is expected to rise.

The general approach is to elicit antibody production in the inoculated person. When a biting mosquito sucks up the antibodies, they block parasite reproduction inside the insect.

Researcher Rhoel Dinglasan, at Johns Hopkins Malaria Research Institute in Baltimore, has an experimental vaccine that prevents the parasite from entering the mosquito gut. Tests show the approach has the added benefit of working against both the dominant African parasite and the one more common in Asia and South America.

Double-duty vaccine

It may also be possible to develop a double-duty vaccine: one that protects individuals from illness while also blocking its spread.

From his lab in Seattle's South Lake Union neighborhood, Kappe is starting the first human trials on a vaccine made up of whole parasites that have been genetically crippled so they can't cause the disease. The Gates-funded vaccine was 100 percent effective at blocking malaria's development in mice. That means the animals didn't get sick — and the parasites never got into their bloodstream, where a mosquito bite could pass them on to others.

As the research landscape shifts, the future has ironically become more uncertain for the vaccine that is likely to be first out of the chute. Called RTS,S, it's been backed with more than $400 million from the Gates Foundation and drugmaker GlaxoSmithKline. In preliminary trials in Africa, it protected about half of the children vaccinated. Final trials are under way, and the vaccine could be ready to market within a couple of years.

But because it would leave a large chunk of the population unprotected and capable of spreading malaria, a partially effective vaccine will never eradicate the disease.

What it could do, though, is save a lot of lives. But with simpler, cheaper measures like bed nets proving so effective, it might make more economic sense for countries to scale up those programs rather than spend money on a new vaccine that doesn't provide much more protection.

If RTS,S gains approval, there will be places where it makes sense, Birkett stressed. And scientists are already at work on a more effective version, which might someday be combined with a transmission-blocking vaccine to protect both individuals and communities.

Drugs used to treat malaria infections can be powerful tools to aid in eradication, if they also block the disease's transmission. Another Gates-funded program, Medicines for Malaria Venture, is stepping up the search for drugs that kill the stage of the parasite that passes from humans to mosquitoes, at the same time as easing the patient's symptoms, Brandling-Bennett said.

The emergence of drug- and insecticide-resistant parasites makes the search for new treatments and bug killers particularly urgent, he added.

Some skepticism

The Gates eradication call was quickly taken up by WHO and other international groups. "It's wonderful to have ... everyone marching to the same drummer, trying to achieve the same goal," said Newman, the WHO malaria chief.

The zeal is not universal, though, and some worry that skeptical scientists will be frozen out.

"They've made it pretty clear," said one malaria expert who asked not to be named. "If you're not part of that agenda ... you're not going to be grantees of theirs."

Dr. Robert Snow, head of the Malaria Public Health and Epidemiology Group in Kenya, argues that some of the African nations that have made malaria elimination a priority are setting up unrealistic expectations and may siphon money from more pressing health needs.

"There are some realities that people haven't grappled with," he said.

For Dinglasan, the 38-year-old Johns Hopkins vaccine researcher, the call for eradication was galvanizing — a view he shares with a group of under-40 malaria scientists that brainstorm and share data.

"The last time they tried to eradicate malaria, many of us were not even born yet," he said. "Now there's a chance to contribute and make an impact, and that's very cool for my generation."

Sandi Doughton: 206-464-2491 or sdoughton@seattletimes.com

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