Emerging Malaria Drug Resistance to be Investigated by Gene Chip

A "gene chip" may help identify malaria drug resistance and help combat the devastating disease. The chip has been developed by developed by researchers from the University of Notre Dame's Eck Institute for Global Health.

The team of researchers includes Notre Dame's Michael Ferdig, associate professor of biological sciences and doctoral student Becky Miller along with John Tan, managing director of the Genomics Core Facility, in collaboration with Tim Anderson of Texas Biomedical Research Institute and Francois Nosten, M.D., the Shoklo Malaria Unit in Thailand.

Malaria - Causes, Symptoms, Diagnosis, Prevention, Treatment
Malaria is caused by a parasite that enters blood through the bite of an infected mosquito. It is characterized by fever, vomiting, shivering, sweating and other symptoms.

"Malaria has tormented humans forever and continues to thwart comprehensive control efforts," Ferdig said.

"Resistance eventually emerges to every drug tried and vaccines are always 'on the horizon' but have not yet materialized," he explained.

Artemisinin, a natural product from a plant used in China for centuries, is the latest candidate drug to combat multi-drug resistant malaria. However, this last line of defense against malaria worldwide is increasingly falling victim to the problem of malaria drug-resistance. The loss of the drug would be devastating to malaria control efforts.

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Mosquito-borne diseases, like malaria, filaria, dengue, etc are common in places conducive of mosquito breeding. Swamps, ponds and stagnated drainage provide optimal breeding ground for mosquitoes.

"For past drugs, most notably chloroquine, discovery of mutations causing resistance and an understanding of how resistance arose and spread has been 'retrospective': too late to do any good, after the drug has already failed," Ferdig said.

"We can use our novel method to see resistance as it is emerging, respond in real-time and modify strategies to save a drug, such as protecting it with new formulations and combinations tailored to the specific location of emergence," he stated.

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The Notre Dame team, working with the project leaders at Texas Biomedical, used the new genomics and bioinformatics approaches to investigate malaria drug-resistance.

Tan of Notre Dame's Genomics and Bioinformatics Core Facility, working with Miller and other members of the Ferdig team was instrumental in developing the gene chip to perform detailed genetic analysis of malaria patient samples.

This chip can analyze 7,000 informative "SNPs" (single nucleotide polymorphisms) spaced evenly throughout the parasite genome.

"This gives researchers the ability to 'see' how the genome is changing under drug selection. This is especially valuable in Southeast Asia because it is a hotspot for anti-malarial drug resistance," Tan said.

Resistance has been confirmed in Cambodia and is emerging in Thailand. There has been no concerted use of artemisinin in Laos. These conditions enabled researchers to identify genome regions showing signatures of emerging drug resistance. The Texas group then zeroes in on these regions in more than 700 patients to find candidate genes that could be the cause of resistance.

"We now have markers for emerging resistance and new hypotheses that we will use to track down the resistance mechanism," Ferdig said.

"Together these will indicate new ways to adjust the use of artemisinin (most notably to modify the combinations of partner drugs) and to regulate the pace of resistance," he added.

The new discovery is described in a paper appearing in the latest early online edition of the journal Science.

Source-ANI