Abstract

“Malaria is one of the most common infectious diseases, affects 300 million people each year, causes nearly 1 million deaths, primarily children. Its elimination is hampered by the lack of an effective vaccine, and the recurrent evolution of parasites resistant to frontline drugs. In the blood stage of malaria, one parasite (P. falciparum merozoite) invades a red blood cell (RBC), then grows by repeated clonal divisions over about 48 hours, subverting the normal metabolism of the RBC : digesting haemoglobin, the merozoites release toxic heme groups. The parasites crystallise the heme into hemozoin. The metabolism of haemoglobin, and the formation of hemozoin crystals, are specific to this family of parasites and essential to their survival, hence these have been the targets for most malaria drugs up to now; current research is turning the focus also on invasion. From typically a single infection, a merozoite multiplies over rounds of replication, with up to 20 parasites egressing into the bloodstream each generation. Here, the merozoites have a very short time (about a minute) to adhere and invade a new host cell, and start a new round of clonal growth. This process, repeated over weeks, leads to high fractions of infected RBC and huge numbers of parasites. This is at the root of most human symptoms (e.g. anaemia and haemorrhage) and mortality. A research project is allowing to develop low-cost microscopes in house, with similar optical specification to high end commercial units. Live single cell imaging is providing a new class of information which we and others refer to as “invasion phenotypes”.”