Malaria prevention and eradication has long been a goal of health officials around the world. New research shows promise: a compound with the potential to simultaneously treat and prevent malaria infections. The research, published in Science Translational Medicine, is a big step in the fight against malaria given the challenges of increasing global drug resistance.
The development of this drug, known as ELQ-300, was carried out by the Swiss non-profit organization, Medicines for Malaria Venture, University of South Florida, Drexel University, Monash University, the Portland Veteran Affairs Medical Center, and the Oregon Health and Science University.
Malaria is a disease caused by a parasite species called Plasmodium. This parasite is carried by female Anopheles mosquitoes, which transmit the parasites to humans through bites, or taking blood meals. Plasmodium has three stages in its life cycle. First, it lives in the liver. It then moves to the bloodstream where it is active and causes symptoms such as fever, chills, nausea and body aches. It then reproduces in the blood and can be transmitted to another person via the bite of a mosquito.
The new antimalarial drug works by interrupting the lifecycle of Plasmodium. ELQ-300 attacks the parasite by disabling the mitochondria (or the cell’s power source) of Plasmodium cells. The parasite is destroyed, and a person does not experience symptoms. This drug also prevents transmission since a person who has taken ELQ-300 no longer has active Plasmodium in their bloodstream.
According to reporting from Voice of America, ELQ-300 has been shown to be thirty times more effective at curing malaria in mice than a common antimalarial drug currently in use, atovaquone. The new drug has been relatively so successful for two key reasons.
First, ELQ-300 is able to kill the parasite in all three stages of its life cycle. Dr. Dennis Kyle, a professor at USF and co-leader on this project, said that this is “one of the first drugs ever” to do this. In order to kill the parasite in all three stages, the drug maintains its potency over an extended time period. However, researchers had to balance this potency against the risk of side effects. ELQ-300 is strong enough to disable the mitochondria of Plasmodium parasites without affecting human cells.
Research so far has also shown that ELQ-300 is less likely to cause the development of drug resistance in malaria parasites. Drug resistance occurs through the evolution of pathogens and is aided by misuse of antimicrobials. For example, some diseases require several doses of a drug to be treated. If a patient skips or forgets a dose, the pathogen continues to survive and acquires resistance to the drug in use. Drug resistance has made the fight against malaria a race to create effective drugs against evolving parasites. For instance, in recent years, resistance to the malaria drug artemisin has made malaria treatment more and more difficult in southeast Asia.
Testing of ELQ-300 on mice has not resulted in the evolution of any drug-resistant parasites so far. The researchers believe that this could be due to the dosage and potency of the drug over a longer time period. Because the single required dose works for a longer time, there is a greater chance that it will destroy all the Plasmodium cells before they can develop resistance.
The new drug has also been praised because it can be given in much lower doses than existing antimalarials drugs. These smaller doses mean smaller pills, good for patients, and lower costs, good for funders and governments.
Dr. Michael Riscoe a co-leader of this project at Oregon Health and Science University was optimistic about the lack of resistance. “These findings suggest that if the drug is eventually developed for human use, then it could enjoy a long, useful clinical life before resistance emerges in the field.”
However, some experts believe that resistance will inevitably develop. Roland Cooper, a pharmacologist at Dominican University of California countered, “No matter how good the drug looks at this point, most likely the parasite will figure out how to become resistant to it.”
Still, given the fact that current antimalarial drugs are becoming less and less effective due to drug resistance, another solution is needed to address malaria in the near future.
ELQ-300 will next move to testing in clinical trials to make sure it is safe and effective in people. If approved, the drug would be available in several years.
This new drug is just one of many efforts over thousands of years to prevent and control malaria. Past projects have included everything from malaria predictor models to genetically engineered mosquitoes to vaccines. In the end, a combination of these tools will likely be most successful in controlling malaria.