New Anti-Malarial Treatment Provides Hope in Battle Against Drug Resistance

A female Anopheles stephensi feeding on human blood. The mosquito carries the parasite which causes malaria. Photograph: CDC / Phanie / Rex Features.Trials show new drug could kill parasite and prevent the spread of malaria, which kills over half a million a year, and would cost around $1 per treatment.A new malaria treatment has been developed by scientists, and could help turn the tide against rapidly emerging drug-resistant strains of a disease which kills over half a million people a year.The new compound rapidly kills the parasite in mice, and also appears capable of stopping the transmission of malaria - a crucial step in the bigger battle to eradicate the disease entirely.The need for new malarial drugs is becoming increasingly urgent as new resilient strains of the malaria parasite have emerged, threatening to leave existing drugs powerless against the infection.Existing frontline treatments help patients recover, but fail to prevent them passing the infection back to mosquitoes, meaning the spread of the disease continues unabated.Professor Ian Gilbert, a medicinal chemist at the University of Dundee, who led the research, said: “There’s increasing concern about the growing level of resistance. There’s also a desire to have drugs that, as well as treating the infection, stop people from getting malaria in the first place and stop the spread.”The new drug could combat both these problems simultaneously, he said – assuming the results are replicated in people. The human version of the therapy, developed by the pharmaceutical company Merck, is expected to enter clinical trials within a year.There were around 200 million cases of malaria in 2013 and 584,000 deaths, mostly pregnant women and children under five in sub-Saharan Africa, according to World Health Organisation figures.However, scientists predict that the number of deaths could rise dramatically with the emergence of resistance to existing drugs, including the most widely used treatment, artemisinin.Artemisinin-resistant strains of malaria are already in circulation around the Burma-India border, with patients taking up to a week to respond to treatment compared to the usual couple of days. Current predictions suggest resistance could take around three years to reach Bangladesh and India and scientists are racing to find new treatments before this scenario plays out.Dr Michael Chew of the Wellcome Trust, which provided funding for the project, said: “The need for new antimalarial drugs is more urgent than every before, with emerging strains of the parasite now showing resistance against the best available drugs. If [these strains] spread to Africa, where populations are most at risk of malaria, it would be a disaster of global proportions.”Professor Dominic Kwiatkowski, director of the Centre for Genomics and Global Health at the University of Oxford agreed: “If artemisinin resistance becomes established in Africa it could have disastrous effects on child mortality.”People are infected by the malaria parasite when they are bitten by a mosquito carrying the parasite, Plasmodium falciparum. The single-celled organism begins by invading liver cells and then the red blood cells, at which point the person will develop flu-like symptoms including a fever, headache and vomiting. In its final phase, the parasite reproduces in the blood, turning into a form that can be picked up again by mosquitoes, continuing the spread of disease.Most existing drugs target the parasite at the red blood cell stage – the point at which symptoms are caused - but leave parasites that have already moved on to the transmission phase intact.The new compound appears to improve on this by killing the parasite at its liver, red blood cell and transmission phases. It works by blocking the production of a protein that is important across the parasite’s lifecycle.“It’s very exciting that it can hit all three phases,” said Gilbert.The scientists tested the compound, called DDD107498, against parasites taken from blood samples of Indonesian patients living in an area with some of the most resilient strains of malaria in circulation.The results, published in the journal Nature, found the compound was not toxic to human cells, even at high concentrations, and that it has a long wash-out period from the blood, meaning that the treatment could potentially be given as a single dose.The compound was identified by Dundee’s Drug Discovery Unit, in a project that screened a total of 4,700 drug candidates before pinpointing this one.“This is a particularly exciting prospect as it kills multiple life cycle stages, is long lasting and has a new mode of action,” said Chew.The scientists estimate that the drug would cost around $1 per treatment, meaning it could be made available to patients living in poverty.The crucial test will be whether the impressive results are repeated in human trials. The prospects of results being replicated are better for malaria, which depends mostly on destroying the parasite, than for many complex human diseases, the authors said.“There’s good evidence to suggest that what happens in mice would translate to patients,” said Gilbert. “There’s no guarantee, but it’s quite rare to get to this stage and then fail.”“One of the major challenges for the field is to have an active pipeline of potential new treatments,” said Kwiatkowski. “This discovery is therefore welcome news.”