“More than 300 million worldwide are sickened by malaria each year, and about one million die,” said Dr. Steven Maher, a post-doctoral researcher at the USF College of Public Health. “For most people, the disease causes the individual to be bed stricken for days or weeks and the symptoms are very unpleasant.”
Dr. Maher, an alumnus who earned his PhD in global communicable diseases from the department of global health in 2014, has been working on malaria research since his time as a PhD student and decided to continue his research at the COPH as a post-doctoral researcher.
He contributed to the $5.45 million dollar grant USF received from the Bill and Melinda Gates Foundation, to create devices mimicking the human liver in order to analyze the life cycle of the malaria parasite and examine new drugs or vaccines for the Plasmodium vivax and Plasmodium falciparum forms of malaria.
The research team has received an additional four years of funding to continue this research.
“I didn’t want to leave the work unfinished, and it was just starting to get to a level where it could make an international impact,” he said.
In humans, the malaria parasite grows and multiplies first in the liver cells and then in the red cells of the blood, according to the Centers for Disease Control.
Maher and colleagues have become one of the first labs to create a simple, robust liver cell culture system built with a plastic molding technique that they invented and patented.
At present the only way to completely remove all Plasmodium vivax from an individual is to treat with the drug Primaquine, the only approved drug to remove dormant parasites from the liver, according to Maher.
However, Dr. Maher notes that Primaquine is toxic to many individuals.
“Future chemoprotection of populations from malaria is dependent on identification of new compounds that kill the dormant parasites,” Dr. Maher said. “To find these new compounds, we must use in vitro liver culture techniques, but liver culture is notoriously difficult.”
Infecting the liver cultures with Plasmodium vivax and then screening drugs to test if they kill the liver forms of malaria, Maher said his team is on the forefront of this research and is being noticed by the antimalarial drug community.
“We are now beginning to screen potential new drugs provided by both USF and outside developers,” Dr. Maher said. “Prior to these advances, drug developers were dependent on rodent animal models to screen for liver stage activity, but rodent models do not accurately predict results in humans.”
Dr. Maher and colleagues have also become the first lab to fully troubleshoot the four-week protocol required to perform Plasmodium vivax studies, making it available and practical for other labs to emulate.
The lab is also the first to demonstrate reactivation of Plasmodium vivax dormant forms in in-vitro culture.
Operating out of the Center for Drug Discovery and Innovation (CDDI) and conducting site visits to Thailand, he credits the resources of the COPH with providing him the opportunity to continue advancing his research in this area.
“The CDDI has everything you would want for a drug screening facility, including advanced robotics and imaging systems,” he said. “CDDI has the chemists to provide compounds for antimalarial drug screening, the engineers to help build our screening protocols and systems, and the biological resources, such as access to a well-maintained insectary providing mosquitoes, all in one place to efficiently perform antimalarial research.”
Mr. Maher said that drug screening is process-development dependent and that he has found joy in this type of problem solving.
“I want to make a difference,” Dr. Maher said. “I appreciate basic research but I would love to retire knowing that the people I meet in endemic countries may one day be aided by our research.”
Going global in the battle against malaria
For Ms. Alison Roth, a first year PhD student in the department of global health, her passion for engaging in malaria research grew even more after traveling to Thailand.
“In Thailand, we work with collaborators both at the Armed Forces Research Institute of Medical Sciences and Shokolo Malaria Research Unit who show extreme motivation and dedication to eliminate the burden of those infected,” she said.
“Here in the U.S. those who are doing malaria-associated research are so removed from the disease that it can be easy to forget what exactly your impact can be,” Ms. Roth said. “For me, it is very rewarding to be a part of a project that has capability to greatly influence the discovery of an effective vaccine and ultimately lead to the eradication of this complex disease.”
She is focusing her research on highlighting the use of novel functional assays that are more realistic to what the malaria parasite encounters upon initial entry into the human host.
“We utilize new methodologies to recapitulate the pivotal period of sporozoite transmission from mosquito to human through modifying the in vitro culture microenvironment physically and by exposure to specific biological stimulatory factors; albumin, glucose, calcium, amino acids,” she said. “In collaboration with Dr. Steven Maher and Dr. Dennis Kyle [Distinguished University Health Professor in the department of global health at COPH], I have applied their novel in vitro human liver model based in micro-device platform to evaluate liver stage development of these conditioned sporozoites.”
Sporozoite is the term used to describe the stage the malarial parasite is in when it lives inside the salivary glands of the mosquito host.
When a mosquito bites a human host, it injects sporozoites at the site and causes the initial infection.
Ms. Roth said she is focusing her research on the use of novel functional assays to simulate key development and transition phases to evaluate potential pre-erythrocytic vaccine candidates.
She is able to screen potential vaccines that target the sporozoite stage of the parasite.
Ms. Roth earned her MPH in global communicable diseases from the COPH and said the research exposure she received as an MPH student, as well as the collaborative nature of the COPH affirmed her decision to continue her research efforts here.
“The Global Health Department in the COPH is filled with research labs offering modern technologies and imaging systems that are essential to facilitate my research efforts,” Roth said. “We have access to an Operetta high-imaging content system, Perkin Elmer, which allows for high-throughput processing with precise imaging. Additionally, our location in the IDRB [Interdisciplinary Research Building] building houses multiple core facilities through the CDDI which offer a wide range of services from diverse fields including biology, bioengineering, and chemistry.”
She said her current research findings will also assist to advance future vaccine design and drug discovery.
“We are applying the recent advancements in next generation sequencing to the Plasmodium sporozoite which will be beneficial for future vaccine design and drug discovery,” she said.
The World Health Organization estimates 3.2 billion people, predominantly in Africa and southeast Asia, are at risk of malaria, a fact that resonates with Ms. Roth.
“Malaria is an important public health issue due to the increase of drug resistance to the top used anti-malarials and no vaccine currently available making the eradication of malaria a difficult task,” she said. “Parasites are a fascinating field and I find the complex life cycle of malaria parasite very intriguing.”
Story by Ms. Anna Mayor, USF College of Public Health