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Clues to Emerging Drug-Resistant Malaria

Child in a poor village in Thailand, where artemisinin-resistant malaria has begun to emerge.N. Durrell McKenna, Wellcome Images. All rights reserved by Wellcome Images.

Researchers report that a first-line treatment for malaria is losing its effectiveness in parts of Asia. They've also found regions of the parasite’s genome that seem to underlie its drug resistance. The findings may offer clues to help block the spread of hard-to-treat malaria.

Each year malaria kills more than a half million people and infects over 200 million worldwide, mostly in tropical regions. Drug combinations containing artemisinin, introduced more than a decade ago, have helped to reduce malaria death and disease. But health officials have been alarmed by emerging strains of artemisinin-resistant parasites found in Cambodia. Scattered but unconfirmed reports also describe artemisinin resistance in nearby countries such as Thailand and Myanmar (Burma). International efforts are under way to contain these drug-resistant strains.

To take a closer look at the evolution and spread of artemisinin-resistant malaria, an international team of scientists conducted 2 related studies. They drew on data collected from over 3,000 patients hospitalized in malaria clinics in northern Thailand between 2001 and 2010. Most of the patients came from the adjacent country of Myanmar. All the patients received artemisinin-based therapy. The research was funded in part by the Wellcome Trust and NIH’s National Institute of Allergy and Infectious Diseases (NIAID), along with other NIH components.

The researchers examined whether artemisinin resistance had indeed emerged along the Thailand-Myanmar border. As reported in the advance online edition of the Lancet on April 5, 2012, they measured how quickly treated patients cleared malaria parasites from their blood. Slower clearance indicates drug resistance.

The scientists found that the proportion of slow-clearing infections rose from 0.6% in 2001 to 20% in 2010. In 2001, it took patients an average of 2.6 hours to clear half of the parasites from their blood. By 2010, the average half-life clearance time had lengthened to 3.7 hours. The researchers tested a battery of genetic variations in the parasites and found 148 unique parasite genotypes, each infecting from 2 to 13 patients. Those infected with the same genotypes had similar clearance rates, suggesting that genetic variants play an important role in determining artemisinin resistance.

The other study compared parasites from the adjacent countries of Cambodia, Thailand and Laos. Artemisinin resistance is most common in Cambodia, apparently emerging in Thailand and absent from Laos. The findings were reported in the April 6, 2012, issue of Science.

The researchers identified 33 genome regions that differed greatly in parasites from the 3 countries. They then took a more detailed look at these regions in more than 700 parasites derived from the malaria patients treated in Thailand. The analysis found a small region of chromosome 13 that was strongly linked to slower artemisinin clearance rates. This discovery will help to narrow the search for genes that lead to artemisinin resistance.

“If we can identify the genetic determinants of artemisinin resistance, we should be able to confirm potential cases of resistance more rapidly,” says study leader Dr. Timothy Anderson of the Texas Biomedical Research Institute. “This could be critically important for limiting further spread of resistance.”

—by Vicki Contie