While rates of malaria death have declined in recent years, the parasitic microorganism still kills between 500,000 to 1 million people each year. Anywhere from 300-600 million people suffer from malaria, and over 40 percent of the world's population live in areas easily affected by it. A team of researchers from MIT could help greatly reduce those numbers.
For the first time ever, a group of MIT bioengineers have successfully grown the dormant form of malaria in engineered human liver tissue.
Dormant malaria remains one of medicine's most frustrating form of the parasite. It's resistant to nearly all antimalarial drugs and can frequently send people into relapse.
Scientists have struggled for years to figure out this type of malaria, and the team from MIT is no different. Professor Sangeeta Bhatia said the process took over a decade.
"After 10 years of hard work, we were able to grow the organism, show it had all the functional hallmarks, perform a drug screen against it, and report the first transcriptome of this elusive form."
"After 10 years of hard work, we were able to grow the organism, show it had all the functional hallmarks, perform a drug screen against it, and report the first transcriptome of this elusive form. I’m really excited because I believe it will open the door to both the basic biology of dormancy as well as the possibility of better medicines," Bhatia said.
Malaria in humans typically comes from one of two parasite types, either Plasmodium falciparum or Plasmodium vivax. It's the latter version of malaria that produces the deadly dormant forms called "hypnozoites," named that for their 'hypnotic' state.
"This dormant form has been seen as the critical barrier to eradication,” Bhatia says. “You can treat the symptoms of vivax malaria by killing all the parasites in the blood, but if hypnozoites linger in someone’s liver, these forms can reactivate and reinfect the blood of a patient. If a mosquito comes along and takes a blood meal, the cycle starts all over again. So, if we want to eradicate malaria, we have to eradicate the hypnozoite."
It's important to note that a drug does exist to combat these hypnozoites, the researchers pointed out. However, the drug called primaquine can't be used on a wide scale because it can cause certain blood cells to rupture in particular patients.
That frustration was what spurred Bhatia and the team to action in 2008 shortly after the Bill and Melinda Gates Foundation made it part of their yearly challenges. At the time, Bhatia was working on micropatterned surfaces to regrow liver cells and human liver tissue. This form of bio-nano engineering would make it easier for researchers to study the effects of certain diseases on the liver.
After seeing the need for better malaria research, Bhatia began culturing strains of Plasmodium falciparum to see if those parasites followed the same life cycle as they would in a typical human. The project was a success. Bhatia and the malaria team quickly started working with Plasmodium vivax. The hardest part of the study? Bringing the infected mosquitoes into the United States. Thus, team members had to travel to Thailand to get more samples from infected patients and often had to conduct research there.
“This is a very exciting study,” says Maria Mota, executive director of the Institute for Molecular Medicine at the University of Lisbon. “It provides not only the first transcriptional comparative characterization of replicating schizonts and hypnozoites of P. vivax, but most importantly demonstrates the feasibility of an in vitro platform to study hypnozoites without the need to use animals.”
Bhatia and her team want to continue testing out as many potential cures against this deadly "sleeping" parasite to find a solution as quickly as possible.