Malaria mortality rate in Africa and Asia could double in a few decades as the drug used most frequently is rendered useless

Within the next five years, international organizations and world leaders should begin collectively to contribute $300 million to $500 million annually to create a global subsidy that would make new combination malaria treatments available to the world's poor for as little as 10 cents per treatment course, says a new report from the Institute of Medicine of the National Academies.

Without significant investments in these new treatments -- called "artemisinin-based combination therapies" (ACTs) -- the malaria mortality rate in Africa and Asia could double in a few decades as the drug now used most frequently is rendered useless by rapidly spreading resistance.

A centralized procurement agency should be established to buy ACTs from drug manufacturers at competitive prices using the subsidy funds and then resell them at substantially lower prices to public and private distribution organizations within countries where malaria occurs. The procurement agency could be either a new entity or a branch within an established organization, but initially procurement should be done by an existing organization with sufficient capacity, such as UNICEF. Conditions for participation should be placed on countries and drug manufacturers to ensure that the subsidized price actually reaches consumers and that use of single-drug therapies is discouraged. Combination therapies that contain both an artemisinin and one of several other antimalarial drugs should replace monotherapies as the first-line treatment for malaria, which is a leading killer of the poor, particularly in Africa, the report emphasizes.

"The widely used drug chloroquine likely will be useless within a relatively short time, making it all the more urgent that the global community provide significant subsidies to get ACTs into widespread use everywhere that malaria is endemic," said Kenneth J. Arrow, professor of economics, Stanford University, Stanford, Calif., and chair of the committee that wrote the report. "Artemisinins are extremely effective and apparently safe, and so far the malaria parasites have not developed resistance to them. No other currently available therapy has all the advantages of these drugs. Worldwide use of ACTs will enable us to halt and even reverse the rising death toll from malaria, while development of new and perhaps more effective remedies continues. But until ACTs are as affordable as chloroquine, impoverished people will continue to rely on cheaper, less effective drugs and on single-drug therapies. It is crucial that the world switches to combination therapies to prolong each individual drug's effectiveness and delay resistance."

The Case for a Global Subsidy

Over more than 50 years, low-cost chloroquine has saved millions of lives and cured billions of debilitating infections. Even in the poorest nations -- including many in Africa, where individuals frequently purchase their medicines themselves rather than receive them through public programs -- most people can afford chloroquine at its retail price of 10 cents per course of treatment. But because of rampant chloroquine resistance among the parasites that cause the disease, the death rates from malaria are increasing in Africa for the first time in decades. In sub-Saharan Africa alone, about 1 million children die from malaria each year.

Artemisinins, which are derived from a plant used in Chinese herbal medicine, have proved highly effective in treating malaria in Asia over the last 25 years, and resistance to these new drugs has not appeared so far, the report notes. In addition to quickly curing patients, artemisinins have reduced malaria transmission where they have been widely used. However, ACTs currently cost about $2 per treatment course, which is beyond the financial reach of many developing nations and impoverished people, especially families of poor rural children, who are most likely to die from malaria.

The recommended $300 million to $500 million annual subsidy should put the price of ACTs in the range of 10 cents to 20 cents per course, providing enough medicine for several hundred million people around the world. The cost of ACTs should be no higher than the least expensive single-drug therapy, the report says; otherwise, individuals who buy their own medications will choose the cheaper option and perpetuate drug-resistance problems. Even at the subsidized prices, however, the poorest members of many societies still will need additional help to access the drugs.

Not all of the money for ACT subsidies would have to be "new," the report notes. For example, some of it could come from funds that organizations such as the World Bank's International Development Association already have earmarked for activities such as global health, poverty reduction, or other developmental programs, but have yet to spend. At the same time, money for subsidies should not be diverted from budgets for national or local initiatives to control the mosquitoes that transmit malaria.

The committee's proposed centralized procurement system would help keep prices low and production high by tapping multiple manufacturers. By creating a reliable market, the subsidy would spur more drug makers to begin producing ACTs. In addition, the procurement agency should monitor quality control in the drug-production process; create incentives for countries to follow prudent malaria-treatment policies; and provide technical assistance, such as helping countries to set up monitoring and evaluation systems and train regulators.

The procurement system should discourage use of single-drug therapies by requiring participating countries and drug distributors to avoid production of artemisinin-only treatments or any other single-drug treatment involving drugs that are or could be used in combination with artemisinins. The parasites that cause malaria eventually will develop resistance to any single therapy, even highly effective artemisinins, but they are much less likely to survive if a second effective antimalarial drug is simultaneously used. The use of artemisinins alone in the treatment of malaria is common in parts of Asia. If resistance to this class of drugs develops, mutated strains of malaria parasites will likely spread across national borders. Officials from the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria also have embraced the combination approach in malaria control programs.

Evaluation and Research

Under the committee's proposal, countries that receive subsidized antimalarials through the procurement system would be expected to monitor how well public and private drug-distribution channels deliver the drugs to the people who need them. Information should be collected on such things as retail prices and whether products are in the original packaging when they reach consumers. Countries also should be required to track the emergence of drug resistance, the report says. And nations that receive subsidized ACTs should be expected to educate the public about the new drugs and their proper use. To encourage ongoing development of new antimalarials, the committee added, governments and other organizations that support malaria-control activities should offer financial assistance to major research initiatives in this area -- such as the Medicines for Malaria Venture (MMV), WHO's Special Programme for Research and Training in Tropical Diseases, and the efforts of the Walter Reed Army Institute of Research (WRAIR). The global investment in research and development for new antimalarial agents should rise quickly to $60 million to $80 million a year, half of which should be provided by the U.S. government to WRAIR and its partners; the other half should go to MMV from its regular funders.

Combining effective antimalarial treatment with other malaria-control measures in well-designed programs can reduce sickness and deaths from the disease. For example, insecticide-treated bed netting can substantially reduce child mortality from malaria. Countries should carry out intensive, integrated programs of malaria control in areas where transmission can be dramatically reduced or eliminated within a few years.