Malaria is transmitted among humans by mosquitoes carrying sporozoite forms of protozoan Plasmodium species. The sporozoites reproduce abundantly in the liver of an infected person, creating tens of thousands of merozoites in a structure called a schizont, which later ruptures, releasing the parasites into the bloodstream. Some parasites develop into gametocytes that, when ingested by another mosquito, progress through the stages of ookinete and oocyst before maturing into sporozoites and completing the protozoan life cycle.

Most antimalarial drugs currently in use are effective only against the blood stages of infection and are further beset by the emergence of resistant Plasmodium strains. To better address the prevention, treatment and eventual eradication of malaria, public health experts recommend the development of new antimalarial drugs that can target multiple life stages, that are active against drug-resistant Plasmodium strains and that are less likely to select for resistant mutations. The ideal medicines would also be suited to single-dose oral administration to help ensure treatment compliance and would have long half-lives to help prevent reinfection.

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It's a tall order, to be sure. But an international group of biochemists recently reported a promising new candidate for malaria treatment called ELQ-300. It belongs to a class of compounds called quinolone-3-diarylethers, modified from the quinolone drug endochin, which was first found to have antimalarial activity in the 1940s.

When administered to mice exposed to Plasmodium parasites, a single oral dose of ELQ-300 prevented infections from developing. In mice with existing malaria, four daily doses of ELQ-300 completely cured the infection (Sci. Transl. Med. 5, 177ra37; 2013). ELQ-300 targeted both the liver and blood stages of Plasmodium protozoa in hosts, as well as the life cycle stages involved in transmission via mosquito vectors (gametocytes, zygotes, ookinetes and oocysts). The drug was active against a Plasmodium falciparum strain that has a mutation associated with resistance to atovaquone, a currently used antimalarial medicine, and also boasted a much lower propensity to induce Plasmodium resistance. Combined with its high bioavailability, metabolic stability and oral efficacy, these characteristics make ELQ-300 an excellent candidate for further study. Michael K. Riscoe (Veterans Affairs Medical Center and Oregon Health & Science University, Portland, OR) and Roman Manetsch (University of South Florida, Tampa), who led the development team, are investigating drug formulations and planning preclinical safety and toxicity studies. They expect to proceed to clinical trials of ELQ-300 within a few years.