PerspectiveInfectious Disease

Toward a chemical vaccine for malaria

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Science  07 Dec 2018:
Vol. 362, Issue 6419, pp. 1112-1113
DOI: 10.1126/science.aav7479

Summary

Despite considerable progress in combating malaria, it remains one of the world's most important infectious diseases, with 50% of the world population at risk of developing the disease and a mortality rate of ∼0.5 million annually (1). The lack of an effective vaccine and the relentless ability of the Plasmodium parasite responsible for malaria to develop drug resistance has contributed to the continuing disease burden (24). Artemisinin-combination therapies (ACTs) are the mainstay of current treatment regimens, but decreased effectiveness, particularly in Southeast Asia, threatens our ability to control this disease. A global effort to develop new drugs for the treatment and prevention of malaria is under way but not guaranteed to succeed (3, 5, 6). These efforts include a systematic attempt to target all life-cycle stages of the parasite to allow combination therapies to be developed, which are also likely to reduce the development of resistance. High-throughput screens (HTSs) designed to identify small drug-like molecules that prevent growth of blood-stage parasites (7, 8) and target-based approaches have identified new compounds that are currently in preclinical development and/or various stages of human clinical trials for treatment of malaria (3). Missing from these efforts has been a high-throughput technology to find liver stage–specific chemotypes. On page 1129 of this issue, Antonova-Koch et al. (9) report an HTS effort that has filled this gap. They identify a substantial number of new chemical starting points with potent liver-stage antimalarial activity, promising a new capacity to feed compounds through the drug development pipeline for chemoprotection.