Wed., September 11, 2013 11:30am (EDT)

Fast Tests For Drug Resistance Bolster Malaria Fight
By Richard Knox
Updated: 11 months ago

A Cambodian boy gets tested for malaria at a clinic along the Thai-Cambodian border, July 2010. Three strains of drug-resistant malaria have emerged from this region over the past 50 years.
A Cambodian boy gets tested for malaria at a clinic along the Thai-Cambodian border, July 2010. Three strains of drug-resistant malaria have emerged from this region over the past 50 years.
Malaria researchers have developed what they consider a crucial advance: Simple and fast tests that can tell when parasites have become resistant to the front-line drug against malaria.

Taken together, these tests give humans a new tool to counter the malaria parasite's ability to outwit every drug that's ever been devised against it.

The tests will help scientists and health workers with several critical tasks, not possible before:

Quickly determine if a person has a form of malaria that's resistant to artemisinin, the most potent anti-malaria drug currently available.

Map the spread of resistant malaria parasites in entire communities and regions so that control of infected mosquitoes can be focused.

Pinpoint artemisinin-resistant malaria parasites so scientists can identify the responsible genes and develop new drugs to get ahead of resistance.

Tension has mounted recently as pockets of artemisinin-resistant malaria have developed and spread in Cambodia, Thailand and Myanmar. Many experts think it's only a matter of time before the problem spreads to Africa, where most of malaria's devastation is concentrated.

"For almost five years, there's been a recognition that artemisinin was losing its punch in Southeast Asia," says Dr. Carol Hopkins Sibley, of the University of Washington, who wasn't involved in the new research.

"The only way to measure that [drug-resistance] was to give the drug and then monitor patients' blood every six hours for two or three days," Sibley tells Shots. "That's very difficult to do. Patients hate it. It requires people to interpret many malaria slides. It's amazingly expensive and laborious."

Tracking the spread of artemisinin-resistant malaria across the landscape, using the previous method, was logistically impossible.

A group from the U.S. National Institutes of Health, the Institut Pasteur in France and the Cambodian National Malaria Center devised two different tests to simplify and accelerate the detection of artemisinin resistance. They published their findings Tuesday in The Lancet Infectious Diseases.

One test quickly determines how a malaria parasite from a specific patient responds to artemisinin. It involves taking a blood sample and treating it with artemisinin in a test tube for six hours. The tester washes out the drug, incubates the treated parasites for another 66 hours, then counts the number that have survived.

"It can't be done in a mud hut, but it can be done in a field-based setting where one can culture the parasites," says study author Rick Fairhurst of the National Institute of Allergies and Infectious Diseases. "You need a reliable electricity source and an incubator."

The second test is more elaborate. It's designed to isolate the malaria parasite at an early stage of its life cycle the so-called ring stage. At this stage, malaria parasites are uniquely susceptible to artemisinin. So the test can determine how these immature forms are becoming resistant to the drug.

To do that, researchers have to grow various stages of the parasite in test tubes for a couple of weeks. They take the most mature stages and use them to infect fresh human red blood cells. Within a few hours, they have newly hatched ring-stage parasites that can be exposed to artemisinin.

Those ring-stage parasites that become resistant can be studied to determine the genetic mechanisms that protect them against the drug. These early-stage resistant parasites will also be valuable in testing new anti-malaria drugs.

"When you pull out the parasites and test the ring stage, only then can you confidently say, 'This is a resistant parasite, and that isn't,' " Fairhurst tells Shots. "I've already had a lot of people very interested in obtaining truly resistant ring-stage parasites to test different drugs against."

It's been very difficult to identify genetic markers of malaria drug resistance, says Sibley, scientific director of a group called Worldwide Antimalarial Resistance Network. "There was no way to isolate the parasites in the lab and say, 'I know these are resistant,' " she explains. "Now we can see which molecular patterns relate to resistance."

Having genetic markers of artemisinin resistance, she says, will also make it much easier to track the spread of resistant parasites.

"You can stick somebody's finger, get some DNA from the parasites and look for resistance markers," Sibley says. "So you could do surveillance in Myanmar, where it appears these resistant parasites have been moving. Then you'd know how big an area we have to worry about."

Then health workers could start at the outside of the area and work inward, she says, to treat infected patients and eliminate parasite-carrying mosquitoes. That's the strategy that worked to eliminate smallpox, she says.

The new technology has already paid off in Cambodia. Researchers discovered a man who was carrying an artemesin-resistant malaria parasite in eastern Cambodia, where resistance hadn't been seen before.


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