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Malaria resistance: ground zero

March 2011
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The best drug against falciparum malaria used to be chloroquine, but over a 30-year period it was rendered largely ineffective as the parasites became increasingly resistant to it. The next drug was defeated in half the time."
Here in western Cambodia, migrant workers come and go to work the fields and build roads. While their labor is needed they’re also contributing to the transmission and spread of malaria. Many of them don’t sleep under bednets at night, when the mosquitoes bite, and their access to treatment is limited.

That’s in stark contrast to the resident population, which has been targeted in a major government campaign to control malaria.

Villagers here in the Pailin area are being given bednets that are doused with slow-release insecticide. If used properly, they should be able to kill mosquitoes for several years. They’ve proven to be effective but they’re not a silver bullet against the disease.

Making matters worse is an even greater threat: There’s increasing evidence that parasites carrying the most deadly strain of malaria, called Plasmodium falciparum, are developing drug resistance.

Scientists from around the world have come here to determine how and why this is happening.

Dr Mark Fakuda led one of the studies, which was performed by a US military research unit called AFRIMS. He’s examining a local teacher who is typical of the findings. Like at least a third of the patients in the study, he’s still positive for malaria after four days of treatment.

Fakuda says it may not sound like much, but it is significant. “One would expect parasites to clear in perhaps two days to 48 hours or so,” he says. “What we’re noticing at this site in particular, is that the mean time for parasite clearance is between 60 and 65 hours. We’re concerned that this is a harbinger for early resistance that might later translate into the drugs being ineffective to achieve a cure.”

This is a serious concern because it’s happened before.

The best drug against falciparum malaria used to be chloroquine, but over a 30-year period it was rendered largely ineffective as the parasites became increasingly resistant to it. The next drug was defeated in half that time.

In both cases, the resistance began here in western Cambodia and spread as far as Africa, where 90% of malaria’s victims live.

Now the drugs being used are called ACTs: combination therapies based on the compound artemisinin. As good as they are, the threat of resistance is causing great concern in the global health community.

Dr Larry Slutsker, chief of the malaria branch at the US Centers for Disease Control and Prevention (CDC) is extremely worried. “It would just be a disaster if we lost ACTs as our primary treatment line against falciparum malaria,” he says. “It would be a disaster in terms of morbidity, in terms of mortality, in terms of increasing transmission and sort of a feedback cycle making malaria very much worse, particularly in Africa where transmission is highest.”

To combat the spread of resistance in Cambodia, the government is implementing a containment project.

Mass screening has taken place in the area and at least one volunteer per village has been trained to conduct free tests for anyone with a fever.

Dong Socheat, Cambodia’s top malaria official, says they’re making progress. “There is very active detection. And we work with the laboratory in order to detect the last parasite standing.”

Key to its success is finding out how and why the parasites are developing a tolerance to the ACTs. A trip to the local market provides clues.

Shoppers come here not only for fruit and vegetables but also for medication from private pharmacies that have been here for years.

We accompanied Dr Prudence Hamade of the UK-based Malaria Consortium, which is one of the non-governmental organizations working in the area, to see how anti-malarial pills are being prescribed.

Hamade entered one of the small pharmacies and didn’t like what she found. “This is very interesting talking to this private medicine seller. He has two varieties of medicine for malaria, for falciparum malaria. One is Malarine which is social marketed by Population Services International.” She says this drug has clear instructions, “but it’s possible that the patients already cut it up and only take it until they’re feeling better.”

Then Hamade comes across another option. “The second drug he’s selling is artesunate monotherapy,” she says. “The normal way to take artesunate is to take it once a day for seven days if you want to get a complete cure. He’s selling it to take twice a day for three days.”

“This is the whole problem that we find in the private sector,” says Hamade. “Patients are not getting the correct dose, not getting the correct combination, and this is going to lead to drug resistance developing very rapidly unless it can be controlled.”

The Cambodian government is aware of the problems in the marketplace. It has tried to educate people about the correct medications to take and has banned the sale of monotherapies: single drugs that are easy for parasites to adapt to.

But even if these efforts are largely successful, any resistant strains that slip through the net could grow into a major problem.

Worst of all, if resistance to ACTs does become widespread, malaria victims could be left defenseless.

Larry Slutsker of the CDC says “Unfortunately there are no drugs on the market, or waiting to be introduced, that can replace these ACTs. The next class of drugs are probably at least 10 years away, so we are relying very heavily on these ACTs for the next decade or so to keep us with an effective therapy for malaria.”

The World Health Organization warns that if there is no effective therapy, and resistance spreads to Africa, the results could be catastrophic. This with a disease that already kills one child every 30 seconds.
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