Tracking Malaria’s Emerging Drug Resistance

A microarray analysis of Southeast Asian malaria patients has revealed the factors driving the growing resistance to the drug Artemisin.

AsianScientist (Dec. 16, 2014) – Scientists from Nanyang Technological University (NTU) have discovered exactly how the malaria parasite is developing resistance towards the most important front-line drugs used to treat the disease. Their results have been published in Science.

Malaria is a mosquito-borne disease which affects over 60 million people worldwide and in serious cases, can be fatal. There is currently no viable vaccine for malaria while antimalarial drugs and prophylaxis are losing its efficacy with increasing drug resistance.

Artemisinin is derived from Artemisia annua (also known as sweet wormwood), a plant that traditionally has been used in Chinese medicine to treat fever. In combination with other anti-malaria drugs, artemisinin typically eliminates the malaria parasite Plasmodium falciparum from the blood of patients with acute malaria within two to three days. In contrast, clearance of resistant parasites from the blood takes up to five days, and occasionally the treatment shows no effect at all.

NTU Associate Professor Zbynek Bozdech, who led an international research team from ten different countries, said knowing how the malaria parasite is developing drug resistance will help healthcare workers better treat patients suffering from malaria infections.

The researchers analyzed over 1,000 blood samples from infected patients from a variety of regions where Artemisinin resistance was either already well established (regions in Cambodia and Vietnam), emerging (regions in Myanmar) or presently not detected (regions in Bangladesh and Democratic Republic of the Congo).

“To find out exactly what the parasite is doing to protect itself against the drug, we used functional genomics techniques to analyze the gene expression patterns of parasites isolated from patient blood and correlated the results with the clinical and geographical data,” said Bozdech.

The analysis showed that artemisinin resistance is associated with increased expression of a cellular pathway—the so-called unfolded protein response pathway—that is involved in the repair of damaged proteins.

Artemisinin-resistant parasites also showed delayed development from younger to older stages of their life cycle, a possible second survival strategy. Transitioning to a new stage is a big metabolic effort for the parasite and includes the production of many new proteins, making it potentially more vulnerable to the protein-damaging effect of artemisinin. Thus, remaining in a younger stage for longer might help P. falciparum to avoid or reduce damages.

“Firstly, the malaria parasite increases its capacity to repair the damage caused by artemisinin, which gives it a higher chance of survival,” said the study’s first author Dr. Sachel Mok, a research fellow at NTU.

“And secondly, because the drug is more effective against the parasite during the second half of its developmental cycle, the parasite slows down its growth and delays its maturation, which also increases its chance of survival,” she added.

Bozdech, the Associate Chair for Research at NTU’s School of Biological Sciences, said understanding the mechanisms of P. falciparum’s resistance to artemisinin is key in the development of new strategies to counter the rapid spread of resistance that threatens recent advances in global malaria control and elimination.

The article can be found at: Mok et al. (2014) Population Transcriptomics of Human Malaria Parasites Reveals the Mechanism of Artemisinin Resistance.


Copyright: Asian Scientist Magazine; Photo: Nanyang Technological University.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Nicola Wittekindt received a PhD in Molecular Toxicology from the Federal Institutes of Technology (ETH) Zürich, Switzerland, and a MSc in Biology from the University of Konstanz, Germany. She is currently a science writer at the Nanyang Technological University in Singapore.

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