MALARIA has existed since the days of the Roman Empire — in fact, the disease was so widespread throughout the empire that one of its monikers was “Roman fever.” More than a millennium later, malaria remains a significant health concern in many parts of the world, especially warm, humid regions that encourage the breeding of mosquitoes, which transmit the disease to humans.
Although malaria can be caused by several parasites from the Plasmodium genus, both P. falciparum and P. vivax top the list of clinical importance, owing to the high mortality and morbidity rates they cause. But the two species are polar opposites when it comes to how easy they are to grow in the lab; P. falciparum does well in in vitro cultures but P. vivax does not.
The primary challenge, explained Pablo Bifani, Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN), is that how P. vivax invades cells is not known. Furthermore, the parasites selectively invade a minute population in the blood, known as the reticulocytes, rendering them difficult to culture in the laboratory. To get around this problem, Bifani and collaborators at the University of Otago, New Zealand, developed an in vitro culture system for studying P. cynomolgi, the simian malaria that most closely resembles P. vivax.
“We found that P. cynomolgi in culture shares several morphological and phenotypic features with P. vivax, such as the display of caveolae structures, tightly attached rosettes, and most notably, similar patterns in drug susceptibility profiles which sometimes differ from those observed in P. falciparum,” he highlighted.
“With the model that we established, we now have for the first time an opportunity to study the development of P. vivax-like malaria at each stage of their life cycle,” Bifani said. “Previously, we could only study P. vivax-like malaria by either obtaining blood samples from infected patients or laboratory monkeys.”
Together with SIgN colleague Adeline Chua and international collaborators, Bifani and his team are now using their P. cynomolgi culture system as a platform to understand how P. vivax develops resistance to drugs and to screen for novel antimalarials. “Both are of particular importance due to the rise in drug-resistant P. vivax in the region,” he said.
Their work has now been shared with more than 16 labs worldwide, thanks to support from the Medicine for Malaria Venture and the Bill and Melinda Gates Foundation. “Some of our collaborators are in-vestigating gene expression at the different stages of the life cycle; others are studying the mechanism of invasion and development. We hope our findings will help to refine the drug discovery process in P. vivax,” he concluded.