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The rise of resistance

August 2011
Nyanza Province, Kenya and Pailin, CambodiaWant to embed this video?
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ACTs are the gold standard for anti-malarials, but as good as they are, there’s a crack in the armor."
Many developing countries have made tremendous strides in the fight against malaria in recent years with the introduction of bednets treated with insecticide, wider public awareness campaigns and greater access to medication.

But still, the parasitic disease transmitted by mosquitoes is one of the most feared, sickening 200 million people every year and claiming around 800,000 lives, most of them children in Africa.

Indeed on many pediatric wards in Africa a large percentage of the children are likely to have malaria. Here in western Kenya the disease accounts for about one in three deaths of those under five years old.

And the misery extends to those who survive. Vulnerable children can catch malaria repeatedly, sometimes three or four times every year. That’s tough, not just for the child, but also the parents and guardians who must look after them.

When diagnosed with malaria, the best treatment is with drugs known as ACTs. They’re combination therapies based on the compound artemisinin.

ACTs are the gold standard for anti-malarials, but as good as they are, there’s a crack in the armor.

There’s increasing evidence that parasites carrying the most deadly strain of malaria, called Plasmodium falciparum, are developing drug resistance.

Strangely though, the warning signs are not in Africa, but in a small pocket of Southeast Asia.

Researchers have descended on the area in western Cambodia, near the border with Thailand, to study the phenomenon.

Dr Mark Fakuda led a study in 2009 that was performed by a U.S. military research unit called AFRIMS. He came across numerous patients that were still positive for malaria after four days of treatment with ACTs.

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 in western Cambodia and spread as far as Africa, where 90% of malaria’s victims live.

Now the threat of resistance to ACTs is causing great concern in the global health community.

Dr Larry Slutsker, chief of the malaria branch at the 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.

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 which have been here for years.

Some of the pharmacists can be found selling sub-standard or counterfeit drugs, or partial doses of approved medications.

Inadequate treatment like this often kills weaker parasites, but the strong ones survive, and can develop resistance.

The Cambodian government is trying to combat this by banning monotherapies, which are single drugs that are easy for parasites to fight.

The government has also conducted mass screenings in the area and trained at least one volunteer in each village to conduct free malaria tests for anyone with a fever.

But even if those strategies succeed in Asia, the recipe for disaster still exists in Africa.

People here, like in Asia, sometimes fail to take the full dose of anti-malarials.

Counterfeit drugs are also a problem.

Meghna Desai, who is with the CDC’s malaria branch in Kenya, says governments must ensure people are getting the right medications. “I cannot stress the importance of that and I don’t think all countries in Africa have succeeded in doing that.”

If they fail, and resistance becomes 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 45 seconds.
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