Gates Fights China Fakes, Drug Failure to Stem Malaria Disaster

By Simeon Bennett


Saron Samnith, 14, slouches in the doorway of his family’s thatched hut off a dusty track near Pailin, a city in western Cambodia. He has chills, diarrhea and a three-day-old headache -- signs of malaria.

The bout of the mosquito-borne disease, for which he tested positive, is his second in a month. The first left him comatose and in danger of dying, before medicines curbed the attack. Coursing through Saron’s veins may be the strain so dangerous that health officials --and the billionaire Bill Gates -- are racing to stop it from spreading before it kills millions.

In Pailin, a flood of counterfeit pills from China and elsewhere is helping to breed a superbug that resists even the most-effective medicine. The development threatens to unleash a global malaria “disaster” and undo decades of work to reduce illness, destitution and death, said Arjen Dondorp, a Thailand- based researcher.

“It’s a time bomb,” said Dondorp, the deputy director of the Wellcome Trust-Mahidol University Oxford Tropical Medicine Research Programme, with headquarters in Bangkok.

The World Health Organization plans to defuse the bomb with a screening and treatment program to contain and eliminate the resistant strain. The effort, in and near Pailin, may begin next month. The program is backed by $23 million from the Bill & Melinda Gates Foundation, based in Seattle.

“There’s more money put into baldness drugs than is put into malaria,” Gates told an audience in February, in Long Beach, California. “Because the disease is only in the poor countries, it doesn’t get much investment. You can’t get the economies in these areas going because it just holds things back so much.”

Doom Scenario

The risk of failure raises what Dorndop calls a “doom scenario.” In that sequence of events, migrant workers would first carry the bug to Thailand, Myanmar and India. Later the strain would spread to Africa, which already has 90 percent of the world’s malaria cases.

“We rang the warning bell in 2005 and nobody believed us,” said Pascal Ringwald, the Geneva-based WHO’s leading specialist in the malaria parasite’s ability to resist drugs. “Many people were skeptical.”

The doom scenario may be a decade away from materializing, giving the world time to prevent it, said Charles Delacollette, the head of WHO’s Mekong Malaria Programme, which covers Cambodia, Laos, Myanmar, Thailand, Vietnam and part of China.

“We don’t have many alternatives” to the antimalarial drug artemisinin, to which the parasite is becoming resistant in western Cambodia, Delacollette said in an interview in Bangkok. “That drug should be protected.”

Interpol Operations

Interpol, the international police organization based in Lyon, France, traced counterfeit drugs in Southeast Asia to China in 2006 as part of an investigation called Operation Jupiter. Last year, under Operation Storm, Interpol arrested 27 people in raids across Asia and seized more than 16 million fake pills valued at almost $7 million.

Chemical analysis of pills bought in Cambodia, Laos, Myanmar, Thailand and Vietnam found several other pharmaceutical ingredients, charcoal, and a precursor of the illicit drug ecstasy, according to an account of Operation Jupiter published in the journal Public Library of Science Medicine. Also present were spores and pollen from trees common in southern China, suggesting that at least some of the drugs were made there, the authors said.

“The evidence we have at the moment suggests China and India are sources of fake medicines, including in the case of China, fake anti-malarials,” said Paul Newton, a University of Oxford researcher who monitors counterfeit malaria drugs from an office in Vientiane, Laos.

Market Forecast

Interpol’s actions hardly dented the global market for counterfeit pharmaceuticals, which may reach $75 billion in 2010, an increase of more than 90 percent from 2005, according to estimates by the Center for Medicine in the Public Interest, a nonprofit organization based in New York. WHO says fakes, typically cheaper than real drugs, may account for as much as 30 percent of all medicines in developing nations.

“We’re talking about sophisticated, big syndicates, people who are very well organized,” said Aline Plancon, the Interpol officer who coordinated the operations. “It’s just insane. They’re making too much money, they’re betting too much on the health of people. We’ll do it again and again.”

Deadly Disease

Malaria strikes about 250 million people each year and kills more than 880,000, making it the world’s most lethal mosquito-borne disease, according to WHO.

The malady is caused by a microscopic parasite called Plasmodium, which is carried in the saliva of female mosquitoes. When an infected insect bites a person, the parasites multiply in the liver before entering the bloodstream. There they invade red cells, causing fever, chills, nausea and diarrhea. Unchecked, the bugs cause red cells to stick to the walls of capillaries, slowing blood flow. Without treatment, sufferers can die from organ failure.

The most-effective modern drugs against malaria are based on artemisinin, an ancient Chinese remedy derived from the leaves of the sweet wormwood tree. So-called artemisinin derivatives include artesunate and artemether, the key ingredients respectively in Sanofi-Aventis SA’s Coarsucam and Novartis AG’s Coartem.

Breeding Ground

While Cambodia accounts for only about 0.4 percent of the world’s malaria cases, the country is a breeding ground for strains that withstand medicines. Since the 1970s, at least three once-potent malaria drugs have failed in western Cambodia before becoming useless elsewhere in the world, according to WHO: first chloroquine and Roche Holding AG’s Fansidar, then mefloquine.

Now Dondorp and other researchers say the same thing is happening to artemisinin. In a study carried out last year and yet to be published, artesunate failed to clear malaria parasites within two days from the blood of about 70 percent of patients in Pailin compared with 7 percent in western Thailand.

For now, the drugs still clear the parasites, only more slowly -- a sign that resistance to artemisinin-based treatments is building. While Novartis, GlaxoSmithKlinePLC, Genzyme Corp. and Ranbaxy Laboratories Ltd. are developing new drugs and vaccines against malaria, those products are in the early stages of development and won’t be available for years.

Malaria ‘Disaster’

“If we lose the artemisinins at this stage, just now when we dare to mention the word ‘eradication’ again, it would be a disaster for malaria control,” said Dondorp, who led the study. “It would cause millions of deaths, without exaggeration.”

WHO aims to eliminate malaria from western Cambodia through the program backed by the Gates Foundation, the world’s biggest charity. The agency, an arm of the United Nations, plans to screen and treat about 25,000 people in the area next month, possibly expanding tests and treatment to hundreds of thousands later this year.

Those who test positive will probably be treated with Glaxo’s Malarone because it doesn’t contain artemisinin and will take the pressure off drugs that do, said Eva-Maria Christophel, a WHO medical officer implementing the plan.

In and around Pailin, Cambodia also plans to start treating patients with Chongqing Holley Pharmaceutical Co.’s Duo-Cotecxin instead of artemisinin-based drugs, said Duong Socheat, director of the nation’s malaria control program, by phone from Phnom Penh.

Fakes Abound

Fake pharmaceuticals abound in Pailin. At the city’s dusty, fly-blown Samaki Market, untrained vendors hawk cheap pills without a prescription at drugstores opposite stalls offering fried locusts. Shoppers on motorbikes squeeze through the busy, narrow lanes. The traffic moves past a woman sitting by a pile of dried fish, waving away flies with a swat made from a stick and plastic bags.

Anti-malaria pills bought by Bloomberg News at two Samaki market stalls for $5 were sold loose in clear plastic bags, with no labeling or printed information about what they contained or how to take them. Even if the drugs are genuine, taking too few of them may not cure patients and may contribute to drug- resistance, Oxford’s Newton said.

Counterfeiters have learned to fool the on-the-spot dye tests used to identify fakes by including small amounts of real medicine in the illegal copies, Newton said.

Murder

“If you make a medicine that contains no active ingredient for a disease you know can be fatal, at best that is manslaughter and at worst it is murder,” Newton said. As many as half of all artesunate pills available at shops in Southeast Asia may be fake, according to studies he has led.
While pills devoid of active ingredients won’t heal patients, those containing small amounts wipe out only the weakest parasites, enabling the hardiest to survive and spread resistance to genuine drugs.

A bigger contributor to drug resistance than counterfeiters is patients who don’t take medicines properly, according to WHO scientists.

So-called artemisinin-derivatives work by giving malaria a short, sharp shock, clearing most of the parasites from the blood within hours. The drawback is that the drugs don’t stick around in the body and, according to WHO guidelines, must be given with one of several less-powerful, longer-lasting partner medicines that mop up stragglers.

Adverse Effects

The problem is that those other drugs, such as mefloquine, an older product, cause adverse effects, including nausea, vomiting and nightmares. When the two drugs are sold side by side rather than in a single pill, some patients take only the artemisinin, paving the way for relapses and resistance.

“If you want to get rid of these resistant parasites, you in fact have to eradicate malaria from western Cambodia,” Dondorp said. “In the effort to reduce it, the last man standing will be the most resistant parasite.”

Apart from artemisinin-based drugs, there are few effective treatments for the disease. Some that do work, such as Glaxo’s Malarone, are too expensive for patients in developing countries, Dondorp said.

Insecticide-treated bed nets, credited with slashing cases and deaths in Africa, aren’t so effective in Southeast Asia, where the Anopheles diris mosquito that spreads the disease bites earlier in the evening, before its victims have taken shelter for the night.

In Pailin, Saron’s mother, Bot Yom, has lost faith in Western pharmaceuticals. She plans to rub a coin against her son’s skin until it becomes red. If the disease renders artemisinin-based drugs as useless as their predecessors, the folk remedy might be just as effective.

To contact the reporter on this story: Simeon Bennett in Singapore at sbennett9@bloomberg.net