By Seema SinghWith the White House and President Bush hosting a first-of-its kind Malaria Summit on December 17, the disease has finally taken the center stage it deserves. India now joins the global fight against malaria with a new drug combination that has worked wonders in mice and will be tested in humans early 2007.

A group of Indian research institutions and hospitals are testing artemisinin, the most potent anti-malarial today, in combination with curcumin, which is a dietary compound derived from turmeric, an Indian spice used in curry. Researchers are hopeful as both artemisinin and curcumin are natural compounds, have been shown to be non-toxic in animal tests, and if successful, could solve many problems associated with the current artemisinin treatment, including limited supply and high cost.

Artemisinin is derived from wormwood bush and is the most-effective compound in treating drug-resistant malaria. It is, however, used in combination with synthetic compounds like amodiaquine, mefloquine, piperaquine, and lumefantrine because if used alone, artemisinin runs the risk of resistance development. Hence the World Health Organization has been hauling up drug companies that sell artemisinin as monotherapy.

“If we lose artemisinin, we will no longer have an effective cure for malaria,” said Dr. Arata Kochi, WHO’s malaria chief in January this year while urging 18 drug companies to halt improper marketing of the best anti-malarial. “It will take at least 10 years before another effective drug will become available.”

Today, the only WHO-approved artemisinin combination therapy (ACT) is being sold by Novartis as a two-in-one pill named Coartem, which combines artemisinin with lumefantrine. But at over $2 for a three-day treatment, it is still proving to be unaffordable for people who live in 107 malaria-prone countries including in Africa, Thailand, Burma, and Vietnam.

“Most of these combinations have side effects, pharmacokinetic mismatch and are not cost-effective,” said Govindarajan Padmanaban, principal researcher of the team from the Indian Institute of Science in Bangalore.

Moreover, since artemisinin is derived from plants, it is limited in supply. So, availability of the drug is proving to be detrimental in malaria control.

But artemisinin-curcumin combination may prove superior as both are from natural sources of long-term use and no resistance is known to curcumin. In fact, several global studies have recently shown curcumin to have anti-cancer, anti-Alzheimer, and anti-inflammatory properties.

“Curcumin is tolerated at very high doses and as much as 8 gram/day has been given for three months to cancer patients on trial without toxic side effects,” said Professor Padmanaban, who is also overseeing the human trials.

Global race for ACT

With an estimated 500 million cases in 2006, several groups around the world are testing various forms of artemisinin (artesunate, artemether, arteether) in combination with drugs and lower priced options could arrive soon.

International humanitarian organization Medecins Sans Frontieres’ (MSF) Drugs for Neglected Diseases Initiative (DNDi) is likely to introduce two new single-pill combination drugs in the next few months.

The first combination, artesunate-amodiaquine, is being manufactured by the French drug company Sanofi-Aventis and is expected to sell for just one dollar for a full regimen. The second combination, artesunate-mefloquine, is being produced by Brazil’s Far-Manguinhos, particularly for strains of malaria rampant in parts of Latin America and Southeast Asia.

An international group of clinicians, led by Nicholas White of MahidolUniversity in Bangkok and Francois Nostem of Shoklo Malaria Research Unit in Mae Sot in Thailand, is collaborating with non-profit Geneva-based Medicines for Malaria Venture to test a new combination of dihydroartemisinin and piperaquine. If all goes well, the new drug will be manufactured by a Chinese company Chongqing Holley Holding and might sell for about a dollar for the complete treatment.

Cost is undoubtedly one of the deciding factors in ACT and hence Indian researchers are cautiously optimistic about their new combination. Curcumin itself is a cheap compound. Researchers believe if their ACT result in animals is extrapolated to humans, there is a “potential to decrease the dose of artemisinin and further lower the cost of therapy”.

If things fall in place, the earliest that this new pill arrives on shelves will be 2009. But it still offers hope, as the anticipated cost is much less, $0.50 or lower. Not a bad proposition given the multi-million dollar global efforts to produce malaria vaccine is at least seven to eight years away and the incidence of malaria is projected to double by 2010.