Malaria Strain Resists Drugs, May Threaten Millions, Study Says

By Simeon Bennett


July 30 (Bloomberg) -- Malaria is becoming resistant to the most powerful drugs available in Southeast Asia, as the World Health Organization races to stop the spread of the strain that could be “disastrous” for global malaria control.

Treatments derived from artemisinin, the basis of the most effective anti-malaria drugs, took almost twice as long to clear the parasites that cause the disease in patients in western Cambodia as in patients in northwestern Thailand, according to a study published today in the New England Journal of Medicine.

The delay in parasite clearance times shows the drugs are losing their power against the disease in Cambodia, the study said. The failure of artemisinin-based treatments would be “disastrous” for global efforts aimed at curbing the death and disease wrought by the malady, said Arjen Dondorp, who led the study at the Mahidol Oxford Research Unit in Bangkok.

“There is no question that this is resistance to artemisinin,” Carlos Campbell, a malaria expert with the Seattle-based Program for Appropriate Technology in Health, or PATH, wrote in an editorial accompanying the study. “History warns us that it will intensify and spread unless containment steps are taken.”

Scientists have known for decades that Pailin, near Cambodia’s border with Thailand, is a breeding ground for drug- resistant malaria. Chloroquine and Roche Holding AG’s Fansidar started to fail there in the 1950s and 1960s, before becoming ineffective elsewhere, according to the study. The WHO, with $23 million from the Bill & Melinda Gates Foundation, is coordinating efforts to prevent artemisinin-resistant malaria from spreading to Africa, which has 90 percent of the world’s cases of the disease.

Delayed Clearance

Delayed parasite clearance times have been observed in southern Cambodia since the study’s completion, a sign the resistant strain has already spread within the country, Dondorp said in a phone interview. Dondorp and colleagues treated 40 people in Pailin and another 40 in Wang Pha in Thailand, with artesunate, a form of artemisinin.
In Pailin, the drug took a median of 84 hours to clear the parasite from patients’ blood, compared with 48 hours, the standard, in Wang Pha, according to the study. After three days, artesunate failed to clear the parasite in 55 percent of patients in Pailin, compared with 8 percent in Wang Pha.

Widespread artemisinin resistance “would cause millions of deaths, without exaggeration,” Dondorp said in an interview in January.

Deadly Disease

Malaria strikes about 250 million people each year and kills more than 880,000, mostly children under 5, according to the WHO. It’s the world’s third-deadliest infectious disease, behind AIDS, which results in about 2 million deaths each year, and tuberculosis, which kills 1.6 million people annually, the Geneva-based WHO said.

Malaria is caused by a tiny parasite called Plasmodium, carried in the saliva of female mosquitoes. When an infected insect bites a person, the bugs travel to the liver, multiply and enter the bloodstream. There they invade red cells, leading to fever, chills, nausea and diarrhea. Unchecked, they cause red cells to stick to the walls of capillaries, slowing blood flow. Sufferers can die from organ failure without treatment.

The latest findings confirm those of earlier, inconclusive studies that suggested artesunate was losing potency in the region. Until now, researchers weren’t sure whether slowing cure rates were due to the failure of artesunate or another less powerful drug, mefloquine, that’s usually given with it.

No Alternative

Campbell noted that there isn’t an alternative class of malaria drugs to replace artemisinin derivatives. Artemisinin- based medications work by giving malaria a short, sharp shock, clearing most of the parasites from the blood within hours. The drawback is they don’t remain in the body. The WHO’s guidelines recommend combining the drug with one of several less-powerful, longer-lasting medicines that eradicate stragglers.

Those other drugs, such as mefloquine, may cause adverse effects including nausea, vomiting and nightmares. When the two drugs are sold side by side, rather than combined in a single pill, some patients take only the artemisinin to avoid unpleasant symptoms, paving the way for relapses and drug resistance.

Counterfeit drugs containing suboptimal amounts of artesunate may also have contributed to the development of the resistant strain, Dondorp said.