A new and innovative laboratory technique, published this week in Nature Communications, will radically improve the way scientists can study liver-stage malaria outside the human body (in vitro). A team of USF researchers, in collaboration with groups from the Walter Reed Army Institute of Research International Laboratory in Thailand, the University of Georgia and others, developed a process to culture human liver cells, called hepatocytes, and more efficiently infect them with the malaria parasite. The technique allows researchers to overcome major resource limitations to study this parasite stage and more rapidly discover new therapies in the fight against malaria.
“This is one of the last frontiers of malaria research and it’s become critically important because this is the place where the infection starts in the human body,” said Dr. John Adams, a USF distinguished professor in the University of South Florida College of Public Health and the lead researcher on the project.
Nearly half of the world’s population is at risk of contracting malaria. In 2016, the parasite infected an estimated 216 million people, causing nearly half a million deaths.
Malaria, most severe in sub-Saharan Africa and South Asia, is one of the worst global health burdens. Humans are infected through contact with parasite-laden mosquitos and once bitten, the parasite enters the circulatory system and goes directly to liver to infect hepatocytes. When inside these cells, the parasite can lay dormant for a period of time or immediately move into the blood-stage. While it’s the blood-stage that causes the clinical disease, the earlier liver stage is a critical bottleneck in the early infection process and provides an opportunity for significant advancement in both drug and vaccine development to prevent malaria.
“Almost all of the current strategies are focused the blood-stage of malaria – after the person has already become infected. But, in order to eradicate this disease, you need to block the cycle of reinfection and the most efficient way to do that is by blocking the parasite from coming into the person,” Dr. Adams said. “This has not been possible previously because the methods of studying the liver stage have just not been there. Our technique makes that work possible.”
The current liver-stage treatment was developed in the 1950s and is very toxic for some patients, according to Dr. Adams. Researchers say this new technique represents a fundamental breakthrough in the fight against malaria by allowing new liver stage therapies to be explored.
Dr. Alison Roth, a researcher at USF and lead co-author of the article, says the new method, which can be used to study the two most prominent types of the malaria parasite, P. falciparum and P. vivax, uses standard format 384-well plates, allowing scientists to scale up their discovery process with existing high throughput screening technologies and screen preclinical drugs and vaccines more quickly. Using the 384-well format, researchers surpassed the current liver stage in vitro methods by improving long-term cultivation of primary human hepatocytes and enhancing parasite development rates. The technique, while very innovative and more efficient, is actually much simpler than current methods, allowing researchers around the world the chance to employ it in their work.
“Some of the other methods for researching liver stage malaria are very expensive with large biomaterial requirements. Our method reduces the cost and biomaterials, which makes it much more accessible,” Dr. Roth said. “It’s exciting to know that the model we’ve developed can be easily adapted to other labs and even used in endemic countries.”
USF researchers have already begun using their new method in their USF lab and with their Walter Reed collaborators to evaluate new drugs and validate new vaccines. Dr. Roth says they’re working to develop vaccines to prevent the parasite from infecting hepatocytes and also hope to develop drugs to kill the parasite after it’s entered the human body. It’s a breakthrough developed at USF that will have an impact around the world, and one day, save lives.