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Originally published in Science Mag. For full article, click here.

As efforts to eliminate malaria increase, the need for chemoprotective agents to protect vulnerable populations will also increase (3). The idea is to find a long-lasting agent to treat infections before they become symptomatic and to develop these into a chemical vaccine (that is, a drug that protects against disease). The best malaria stage of infection to target for this approach is the one in the liver. The malaria life cycle begins when an infected mosquito injects sporozoites into a person, some of which find their way to the liver to establish infection (10) (see the figure). After replication in hepatocytes, malaria parasites burst out and infect erythrocytes, setting up an amplifying intraerythrocytic cycle. From 101 sporozoites that reach the liver, up to 105 merozoites will emerge into the blood, and up to 1012 will then build up in the bloodstream during a severe infection. A drug that blocks parasite replication in the liver works on a much lower parasite burden and thus has a lower chance of encountering and selecting for a rare parasite with a resistance mutation than do blood stage–active compounds. This is particularly so if a compound does not have activity on both stages and therefore does not put selective pressure on a large blood-stage parasite load.