American Foundation for AIDS Research, October 2004
Olivia Weisser

August 2004 — After years of complacency bred widespread resistance to its most accessible treatments, malaria has reappeared on the Western world’s radar screens. When researchers discovered the drug chloroquine in the 1950s, they hailed it as a cheap solution to the disease. For decades it was widely distributed; some nations even added it to salt supplies. Now the parasite is resistant to the drug. According to clinical trials, up to 64% of East Africans taking chloroquine fail their treatment. And the parasite developed similar resistance to second-line regimens.

Last January, a group of clinicians and researchers attacked the World Health Organization (WHO) in response to rising malaria-related death rates. The group accused the WHO of “medical malpractice” for failing to promote newer, pricier medicine and outlined its failure to alter its malaria policy despite prevailing chloroquine resistance (Lancet 2004;363:237–40).

But in 2001, the WHO did officially recommend the most potent treatment, called artemisinin-based combination therapy (ACT), as the first-line regimen for malaria in endemic areas. Today, the WHO’s top four recommended treatments for malaria are ACTs. The organization asserts that responsibility for choosing specific drug policies rests with individual countries — not the WHO.

Amir Attaran, the lead author on the editorial, and 13 others argued that African countries fail to adopt newer drugs because donating governments, specifically the US and Great Britain, discourage ACT due to cost. Novartis Pharmaceuticals sells ACT for 90 cents to $2.40, compared with a mere 10 cents for chloroquine.

The editorial also censured the Global Fund to Fight AIDS, Tuberculosis, and Malaria — the largest financial supporter of ACT — for funding proposals that require using dated drugs. But in May, the WHO and the Global Fund altered their procedures and allowed countries to change their drug policies without reapplying for grants. And due to attention over the editorial, the Global Fund’s Technical Review Panel also changed existing grants to promote ACT. “According to my understanding, the board has endorsed all the recommendations, which is good,” said Allan Schapira, coordinator of malaria policy at the WHO.

Almost 40% of the world’s population is at risk of contracting malaria. The disease occurs in over 100 countries and is endemic to mostly tropical, rural, and marginalized areas. In Africa, about 90% to 100% of the population is at risk, compared with 5% to 15% of those living in Asia and the Americas. A red blood cell infection transmitted by mosquitoes, malaria results from a parasite that lives in blood. While there are four types of parasites, Plasmodium falciparum causes most malaria-related deaths in Africa, Asia, and Latin America. Insecticide-treated nets are a simple form of protection from malaria-laden mosquitoes.

People living in endemic areas are repeatedly infected from mosquitoes, and over time develop mechanisms to kill the parasite or prevent it from replicating. Because children have not yet developed this immunity, they are at highest risk for infection and death. Due to their lowered immunity, pregnant women comprise the second highest risk group. Malaria increases the risk of stillbirth and low birth weight. HIV-infected people are also more susceptible to malaria, though few studies exist within the coinfected population. Some new research presented at the XV International AIDS Conference in Bangkok indicates that coinfected pregnant women are more likely to transmit HIV to their babies (see “HIV and Malaria: A Malefic Mix” in the October 2004 issue).

Strategies for treating malaria vary depending on factors such as available drugs, the type of malaria, and the parasite’s resistance patterns. The relatively new artemisinin class, a component of ACT, originates from sweet wormwood, a 2,000-year-old traditional Chinese remedy for fever. The plant-based drug is combined with at least one other antimalarial to knock out the parasite. Artemisinins act quickly, while the second drug remains active longer and can destroy remaining parasites.

Artemisinin-based drugs are not approved for treating malaria in the US, since sales would scarcely cover the cost of approval. Only one ACT, the Novartis drug, is available as a single pill. This fixed-dose combination contains lumefantrine and artemether, a synthetic derivative of artemisinin; the WHO preapproved it to treat malaria in developing countries. Other drug combinations in development are several years away from approval.

Now, Where Is the Money?

Despite the victory for Attaran and his colleagues, activists persist in fighting for more money. The move to incorporate ACT into existing grants at the WHO and Global Fund will cost an estimated $1 billion over the next 5 years. Countries with existing grants will also spend their allocated money more quickly than planned on the newer, costlier medicine.

Still, Schapira remains optimistic: “Increased allocations are going to the Global Fund, and the share going to malaria proposals is higher than before.” In 1998, the Global Fund allotted $60 million to malaria. This swelled to over $200 million in 2003. In addition, financing for ACT has flowed from Roll Back Malaria partnerships, United Nations organizations, and nongovernmental organizations such as Médicins Sans Frontières (Doctors Without Borders). Although the Global Fund provides assistance for all three epidemics in its name, Schapira claims that to his knowledge, the malaria epidemic is not diverting money from HIV.

But everyone — disgruntled scientists and Schapira alike — acknowledges that the money required to curb malaria-related mortality is severely lacking. “The money for the Global Fund is far from sufficient to cover the needs,” Schapira admits. “Most of the countries in Africa with the worst artemisinin drug situations are requesting support [for] using ACT,” he added. But available money cannot meet this demand. The WHO estimates that by 2005, the need for ACT will grow from 20 million to as many as 220 million treatments per year. “Right now there is well below 50% coverage for real needs, both in terms of treatment and prevention,” Schapira warned.

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