An online report in Malaria Journal reveals that scientists have discovered genetic mutations in the deadliest malaria parasite in Africa that makes them resistant to one of the most powerful anti-malarial drugs. The researchers point out that the finding is a stark reminder that even the best weapons against malaria could become obsolete.
The most effective and commonly used malaria treatments belong to the artemisinin group of drugs, the most powerful drugs that have the lowest risk of becoming resistant to the malaria parasite when used in combination with other drugs, as for instance artemisinin-based combination therapies (ACTs). The new study, however, confirms earlier suggestions, stating that mutations in one of the key parts of the parasite can provide resistance to artemether, which is one of the two most effective artemisinins.
The St George's team, from the University of London, discovered that 11 of the 28 samples from malaria-infected study participants were resistant to artemether, and that the drug's efficacy was on average reduced to half. They also established that each of the parasites had identical genetic mutations.
The study participants contracted malaria whilst traveling abroad, with the highest malaria risk being in sub-Saharan Africa, where 90% of the 1 million people malaria fatalities worldwide occur each year.
Professor Sanjeev Krishna, who led the study, said:
"Artemether and ACTs are still very effective, but this study confirms our fears of how the parasite is mutating to develop resistance. Drug resistance could eventually become a devastating problem in Africa, and not just in Southeast Asia where most of the world is watching for resistance. Effective alternative treatments are currently unaffordable for most suffering from malaria. Finding new drugs is, therefore, crucial."
The researchers analyzed samples from patients who were infected with the Plasmodium falciparum parasite, i.e. the deadliest form of malaria, which is responsible for 9 out of 10 malaria deaths, and assessed the parasite's sensitivity to four artemisinins, i.e. artemisinin itself, artemether, dihydroartemisinin and artesunate.
They found that the 11 parasites that demonstrated a resistance towards artemether shared the same genetic mutations in an internal system, i.e. the calcium pump, which is used to transport calcium; vital for the parasite to function. They already demonstrated that the calcium pump had the potential to develop artemisinin resistance in one of their studies in 2003. The study showed that artemether resistance was strongest in several incidents in which a separate mutation occurred in another transport system, i.e. a protein called pfmdr1. This protein has already been linked to drug resistance.
The mutations had no considerable impact on the other artemisinins, which could be due to the fact that they were able to work on other transport systems in the parasite, and therefore compensated for the effects of resistance mutations in the calcium pump.
Professor Krishna wrote:
"At the moment, we do not know if the other artemisinins will follow suit, but given the shared chemistry they have with artemether it is tempting to think that they would."
He remarked that resistance could have developed due to the increasing use of ACTs, given that 300 million doses of ACTs were dispensed worldwide in 2011, and greater use could provide the parasites with more opportunities to develop genetic mutations that make them resistant.
The researchers highlight that this could lead to exactly the same resistance problem as was previously experienced with pre-artemisinin medicines like chloroquine. This process could be pushed along by incorrect use of malaria prophylaxis, examples include not completing the treatment course or by taking sub-standard drugs.
Professor Krishna concludes:
"New drug development is paramount, but it is vital that we also learn more about how artemisinins work so we can tailor ACT treatments to be effective for as long as possible."
Written by Petra Rattue