The origins of malaria: there are more things in heaven and earth …

SUMMARY Malaria remains one of the most significant global public health burdens, with nearly half of the world's population at risk of infection. Malaria is not however a monolithic disease - it can be caused by multiple different parasite species of the Plasmodium genus, each of which can induce different symptoms and pathology, and which pose quite different challenges for control. Furthermore, malaria is in no way restricted to humans. There are Plasmodium species that have adapted to infect most warm-blooded vertebrate species, and the genus as a whole is both highly successful and highly diverse. How, where and when human malaria parasites originated from within this diversity has long been a subject of fascination and sometimes also controversy. The past decade has seen the publication of a number of important discoveries about malaria parasite origins, all based on the application of molecular diagnostic tools to new sources of samples. This review summarizes some of those recent discoveries and discusses their implication for our current understanding of the origin and evolution of the Plasmodium genus. The nature of these discoveries and the manner in which they are made are then used to lay out a series of opportunities and challenges for the next wave of parasite hunters.