New Malaria Initiative Launched

Stephen DeAngelis

April 30, 2009

At a time when the world’s attention is captured by the imminent possibility that a swine flu pandemic is about to occur, one might think that there is only bad news to be seen on the health front. Fortunately, there is some encouraging news as well. I have written a number of posts either dealing with or touching on the challenges presented by malaria (see, for example, News About Malaria Continues to Improve, Mapping Africa, and The Rise of “Creative Capitalism”: Tackling Malaria). About a million children a year die from malaria. I wrote in one of my earlier posts, “Malaria not only kills children, it saps both emotional and physical strength from those who contract the disease as well as those who must watch loved ones suffer from it. Development has no hope of gaining purchase in areas with sick populations.” A number of different approaches for dealing with malaria continue to be used, including mosquito nets that have been impregnated with insecticide, spraying to kill mosquitoes, and prophylactic medicines. The problem with medicines is that the parasite becomes resistant to them. The only way to stop malaria from becoming drug-resistant is to eradicate the disease. That, of course, is easier said than done and may even prove to be impossible. The latest treatment is called artemisinin combination therapies, or ACTs. The malaria parasite has already begun to show resistance to artemisinin, a chemical found in sweet wormwood that grows in temperate parts of Africa and Asia. To try and maintain its effectiveness, health providers recommend that artemisinin be used in combination with other drugs. In the post that discusses creative capitalism, I focus on The Artemisinin Project, which is supported by the Bill and Melinda Gates Foundation. The Project is trying to bring the cost of ACTs down to a dollar a treatment.

A new initiative believes that even a dollar a treatment is too high and hopes to reduce the wholesale cost to a nickel [“Subsidy Plan Seeks to Cut Malaria Drug Cost,” by Donald G. McNeil, Jr., New York Times, 17 April 2009]. By reducing the wholesale cost of ACTs, proponents of the new initiative hope that treatments can be sold globally for around twenty cents. This initiative doesn’t replace The Artemisinin Project; rather, it complements it. The Artemisinin Project’s goal of bringing down the cost to a dollar a treatment still holds. The new initiative is trying to raise subsidy money that will cover 95 cents of manufacturing costs.

“The subsidy program, unveiled in Norway, will have an initial budget of $225 million and will be run by a new partnership called the Affordable Medicines Facility for Malaria. Malaria experts hailed the program as one of the most important recent advances in fighting the disease, which kills one million people a year, 90 percent of them children. Awa Coll-Seck, executive director of the Roll Back Malaria Partnership, called it ‘a triumph of international cooperation.’ But the United States, the world’s biggest donor to the war on malaria, is not supporting it yet. The goal of the program is to press the few drug companies that now make artemisinin combination drugs to lower their private-sector price to $1 per treatment from $4, and then use donor funds to pay 95 cents of that dollar so the drugs cost only a nickel wholesale. The hope is that when the drugs are sold at retail in villages in Africa and Asia, the marked-up price will still be low enough to drive out inexpensive but less effective alternatives.”

The reason that cost reduction is so critical is that most at-risk populations are extremely poor. Given the choice between a twenty-cent treatment and one that costs a dollar, the cheaper treatment always wins. As a result, old, cheaper, ineffective treatments, such as, chloroquine, are being used against malaria parasites that have developed resistance against them. Researchers believe they are in a race with time. Since no new anti-malaria treatments are on the horizon, they want to try and eradicate the drug before ACTs run their useful course.

“The program is a joint effort by the Global Fund to Fight AIDS, Tuberculosis and Malaria; the Roll Back Malaria Partnership; the governments of Norway, Britain and the Netherlands; and the Unitaid partnership of 30 countries raising money through airline ticket fees. Heavily subsidizing the private malaria medicine market was first proposed in 2004 by a committee of the American Academy of Sciences led by Kenneth Arrow, a winner of the in economics. The Bill and Melinda Gates Foundation and the Clinton Foundation backed the plan.”

According to McNeil, the program will be introduced in Cambodia and ten Africa countries. He reports that the program intends to get ACTs into even the most remote villages. Unlike other diseases ravaging developing countries, likes AIDS and tuberculosis (which develop slowly), malaria strikes quickly and can kill a child in as little as 24 hours. If treatments are immediately available, their usefulness is limited. The World Health Organization only approves cocktail malaria treatments like ACTs because complementary drugs that linger longer in the bloodstream are needed to mop up artemisinin-resistant parasites. Only three companies, McNeil notes, currently manufacture ACTS (Novartis, Sanofi-Aventis and Ajanta, an Indian generics company).

McNeil concludes his article noting that diagnosis must accompany treatment. Parents in malaria prone areas often treat their fevered children with anti-malaria drugs fearing the worst when only 10 percent of fevers are actually malaria related. If that pattern continues, subsidy plans like the one discussed would be prove “costly and wasteful.” McNeil refers to a program in Ethiopia where 30,000 village health workers are taught to use rapid test kits. Unfortunately, those kits “are not widely available in Africa yet.” The Ethiopian health workers do more than simply test for malaria. They also weigh babies, advise on breast-feeding, give shots, and hand out mosquito nets. A combination of affordable drugs and reliable diagnosis can go a long way towards dramatically reducing deaths from malaria.

An article in The Economist discusses the challenge of insecticides, which, like medicines, often lose their potency because mosquitoes develop resistance [“Resistance is useless,” 11 April 2009 print issue].

“The traditional first line of attack on malaria, killing the mosquitoes themselves, has yet to have a serious makeover. One reason is that time and again chemical insecticides have produced the same dreary pattern. They prove wonderfully effective at first, only to dwindle into uselessness. This is because evolution quickly throws up resistant strains. Indeed, spraying campaigns, which generally aim to kill mosquitoes before they can breed, might have been devised as textbook examples of how to provoke an evolutionary response. With their competitors all dead, the progeny of a mosquito carrying a mutation that can neutralise the insecticide in question have the world to themselves.”

Scientists are now trying to tackle the problem of resistance from a different angle. Often innovations emerge when those considering a problem tackle it from a different perspective. In this case, scientists are trying to discover an effective insecticide that doesn’t trigger an evolutionary response. Andrew Read and his colleagues at Pennsylvania State University believe they have made a breakthrough.

“Dr Read started from the observation that it is old, rather than young, mosquitoes that are infectious. Only females can transmit malaria (males suck plant juices, not blood) but they are not born with the parasites inside their bodies. They have instead to acquire them from humans already carrying the disease, and that takes time. Once a female does feed on infected blood, the parasites she ingests require a further 10 to 14 days to mature and migrate to her salivary glands, whence they can be transmitted to another host when she next feeds. In theory, then, killing only the oldest female mosquitoes—those at significant risk of being infectious—could stop the transmission of the disease. Since these females would have had plenty of time to reproduce before they died, the evolutionary pressure imposed by killing them would be much lower.”

So do you go about targeting older, female mosquitoes? In Read’s case, you begin by modeling the problem mathematically. Read and his colleagues created the model then “plugged in data, collected from malaria hotspots in Africa and Papua New Guinea, that describe the insect’s lifespan and egg-laying cycles in those parts of the world and the way that malaria parasites grow inside mosquitoes.” The results obtained from the model were dramatic.

“The model, which they have just published in the Public Library of Science, reveals that selectively killing elderly mosquitoes would reduce the number of infectious bites by 95% and that resistance to such a tactic would spread very slowly, if it spread at all, because mosquitoes vulnerable to a post-breeding insecticide would have had a chance to pass on their vulnerable genes to future generations.”

I’d love to report that the scientists were able to take the data and develop an insecticide that targets only older, female mosquitoes, but that hasn’t occurred. The article notes that one possibility is using watered-down concentrations of current insecticides. This might work, the article states, because older mosquitoes are more vulnerable to insecticides than younger ones. A more interesting approach, however, is one that uses a completely new agent — in this case, a fungus.

“The team are working with fungi that take 10 to 12 days to become lethal. That is short enough to kill parasite-infected insects before they become infectious, but long enough to allow them to breed. A trial of this idea, spraying fungal spores on to bednets and house walls in Tanzania, is being set up at the moment. If it works, it will be a good example of the value of thinking about biological problems from an evolutionary perspective. People will still get bitten, but the bites will merely be irritating, not life-threatening.”

For those who simply don’t want to be bothered by mosquitoes, other scientists are working on a laser that can zap the pesky insect at ranges up to 100 feet [“Rocket Scientists Shoot Down Mosquitoes With Lasers,” by Robert A. Guth, Wall Street Journal, 14 March 2009]. There is no resistance to death by laser. For people who don’t believe in killing mosquitoes, there is reportedly a scientist in Japan who is trying to develop a way to turn mosquitoes into flying syringes so that they can deliver a dose of vaccine with every bite. Other scientists are trying to develop a malaria-free strain of mosquito that is hardier than today’s species so that it will naturally overtake the space now filled by the deadlier variety. There is good reason for the world to be concerned about a swine flu pandemic. But there are also good reasons for the world to worry about malaria, which year after year kills a million people.