Genetic Markers Associated With Failure of Anti-malarial Drugs Identified

Highlights

• Malaria is a life-threating disease caused by a Plasmodium parasite
• Two genetic markers that are resistant to malaria treatment have been found
• Anti-malarial drugs are losing its efficacy to treat the disease due to the rapid spread of drug-resistance parasites

Two genetic markers that are associated with the malaria parasites’ that have the ability to resist piperaquine have been identified. Piperaquine is a powerful anti-malarial drug that combines dihydroartemisinin to treat malaria. The combination of these two drugs is losing power in Cambodia due to the rapid spread of drug-resistant parasites. //National Institutes of Health researchers and their colleagues carried out a genome-wide association study on 297 parasites isolated from Cambodian malaria patients to a reference malaria parasite genome, and the team identified two genetic markers that are linked to piperaquine resistance.

A simple test was carried out on blood of a patient with malaria. The blood was collected with a finger pinprick test. The test could show whether the patient has parasite with the genetic marker. If so, the anti-malarial drug dihydroartemisinin-piperaquine will not be effective, say the study authors. Thus, an alternative drug combination (artesunate-mefloquine) should be used.

The research team at Wellcome Trust Sanger Institute (WTSI), UK, identified the first genetic marker with a mutation in one of the subunit in a gene on the parasite’s chromosome 13. This genetic change makes the parasite resistant to piperaquine than parasites without it. However, this marker does not play a functional role in enabling parasites to resist piperaquine.

In contrast, scientists found that the second genetic marker had an increased number of copies of genes encoding two proteins of the family called Plasmepsin ( plasmepsin II and plasmepsin III) were linked to piperaquine resistant. Malaria parasites use plasmepsin that helps them digest human blood, while the exact mechanism of action of piperaquine is unknown. Parasites react to piperaquine by increasing plasmepsin production. Parasites with extra copies of the plasmepsin II, and III genes will be able to withstand piperaquine treatment. A parasite with higher piperaquine drug resistance has increased susceptibility to the malaria drug mefloquine. This observation gives a clue to develop malaria treatment regimens that combine three or more drugs to exploit opposing resistance-susceptibility attributes.

By studying the genome of the malaria parasites, researchers say that it helps to use genetic markers to monitor the spread of the drug-resistant malaria and also understand the biology and evolution of the malaria parasite better.

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Source-Medindia