Ironically, compliance suffers because ACTs are so effective—they act so quickly that many patients don't bother to finish
the three-day treatment course because they feel better. "With SP, it was one drug in one pill in one shop, over and out,"
says Marcel Tanner, director of the Swiss Tropical Institute. "A three-day combination is a difficult conceptual sell in any
The Global-Warming Link
But when patients don't comply, resistance is sure to follow. Scientists from the Pasteur Institute Network recently documented
resistance to artemisinin in Senegal and in French Guiana.
"Allowing ACTs more or less wanton use in the most peripheral areas is dangerous in the long run," says Ronald Waldman, a
professor of clinical population and family health for Columbia's Mailman School of Public Health. "In the countries where
I've worked, they don't want community-level health workers to use ACTs. That means everyone suspected of malaria is referred
to a health facility, which in some cases, is just not feasible."
However, efforts to get subsidized malaria treatments distributed in the community—rather than just in public hospitals—are
accelerating. Last year, WHO backed use of ACTs in home-based management of malaria. Meantime, public health experts are exploring
new approaches to responsible access. For example, WHO is partly funding a pilot project in 39 villages in Burkina Faso that
provides subsidized Coartem. Volunteers are trained to manage sales and administration of the drug, and the surrounding area
will be monitored for resistant strains.
The Need for New Treatments and Big Pharma
Several new drugs emerging from the pipeline will add to the ACT stockpile. This spring, the Drugs for Neglected Diseases
Institute (DNDi), a drug development nonprofit, will launch two fixed-dose ACTs, artesunate/amodiaquine (AS/AQ) and artesunate/mefloquine
(AS/MQ), says Robert Sebbag, vice president, access to medicine, Sanofi-Aventis, which partners with DNDi on AS/AQ. (See "Many
Possibilities, Few Certainties".)
Developing new malaria drugs shouldn't be hard, at least in theory, according to MMV's Hentschel. While the disease lacks
the market luster that drives pharma to develop most drugs, he says, it does have other things going for it. Current treatments
already exist, as does extensive knowledge about the parasite. There are also good, predictive animal models and the ability
to run small, comparatively cheap clinical trials. Finally, compared with TB and HIV, fewer drugs are needed to create an
effective combo therapy.
"Still," says Hentschel, "easier does not mean easy." Case in point: Researchers were dealt a major blow over the recent failure
of Ranbaxy and MMV's Phase II compound RBx11160, intended to be the first synthetic antimalarial—which would have been quick
and easy to produce. Right now, while other non-ACTs are in the works, it's far from clear what the next "type" of drug will
be, or when it will come to the market. "Although there are a lot of promising research projects in the early discovery phases,"
says Tanner, who assisted in the biological screening of RBX1160, "we have no projects in the preclinical development that
That's why it's so important for groups like MMV to extend their reach into pharma companies. According to the Malaria R&D
Alliance, $323 million was invested in malaria R&D in 2004 (the most recent year for which numbers are available). Of that,
industry kicked in only 12 percent.
MMV is accelerating its partnership efforts. One of the newest is a partnership with the Novartis Institute for Tropical Diseases
(NITD). Effective this January, NITD will include malaria in its research portfolio. Originally, says Paul Herrling, MMV and
the Wellcome Trust had approached Novartis, offering to pay for half of a new basic research program in malaria.
"We had to say no," says Herrling. "The dengue and TB program had grown, and we had to dedicate our resources there."