The Next Opportunity in Anti-Malaria Drug Discovery: The Liver Stage

Malaria afflicts 350–500 million people annually, and this debilitating and deadly infectious disease exacts a heavy toll on susceptible populations around the globe. Efforts to find effective, safe, and low-cost drugs for malaria have sharply increased in recent years. Almost all of these efforts have focused on the cyclic blood stage of the disease, partly because the parasites can be easily maintained in culture through addition of human red blood cells to the growth medium, and partly because blood stage infection causes malaria's characteristic symptoms. However, the asymptomatic liver stage, which the parasite goes through only once in its life history, presents the best opportunity for developing drugs that both hit new targets and also could be used in highly desirable eradication campaigns. Recent research, especially on the frequency of differentially expressed genes in blood and liver stage parasites, supports the feasibility of discovering stage-specific drugs. Discovering these drugs will require a high-throughput liver stage phenotypic screen comparable to the existing blood stage screens, and the basic tools for such a screen have recently been created.