Studies of hepatic latency in human ovale malaria

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Malaria in humans is caused by several species of parasite belonging to the Plasmodium group, which pass from infected mosquitoes into the person's liver, where after a period of incubation the infection emerges into the blood, causing the fevers and other symptoms we associate with malaria. One of the species causing malaria in humans is Plasmodium ovale, which was first discovered in 1922. It was not until 2010, however, that we were able to provide convincing evidence that these were actually two different parasites which could not be distinguished from each other just by looking down a microscope. We developed some simple DNA testing methods which allow health workers to tell which of these two species is present; using these it is now clear that this type of malaria is actually more widespread than had been thought. Although ovale malaria does not commonly cause a life-threatening form of malaria, two features make it hard to control, and a serious challenge for efforts to eliminate malaria altogether in some countries. Firstly, it is often present in people's blood in relatively small numbers at the same time as other malaria parasites which are more abundant, and so is under-recognised. Secondly, it shares with one other species, Plasmodium vivax, the ability to "hibernate" at the liver stage for months or years, being resistant to almost all known malaria drugs when it is in this resting phase. Efforts to study these "sleeping" forms in the liver for P. vivax malaria have not been very successful, and although we have some ideas about them, these "sleeping" stages remain largely a mystery of modern biology. As host institution for the UK Malaria Reference Laboratory, we receive blood samples from malaria cases across the UK, and each year there are more than fifty ovale cases among them. We thus expect approximately one per week, and therefore have sufficient numbers coming through to plan a new study of these parasites. We have developed a way to purify the parasites in patient blood away from human blood cells, and we will seek to feed these to mosquitoes, and then infect liver cells obtained from the ongoing research work of colleagues at UCL, nearby. If this is successful, we will have a new approach for studying liver-stage malaria, and in particular a new window into the mysterious world of the "sleepy" liver-stage parasites. This information should also help us to better understand these stages in P. vivax malaria, also.