For many 21st century Americans, malaria is a disease spread by mosquitoes that occurs across the globe.
But for John Adams, a professor at the University of South Florida’s College of Public Health, malaria is a world health threat he’s been working to eradicate for 12 years. Now, there is progress: New research at USF may help speed up the development of drugs to halt the disease.
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John H. Adams, Ph.D., Distinguished USF Health Professor and Dir., of Center for Global Health and Infectious Disease Research “The liver stage is the first stage of the infection. If you can block that,” Adams says, “you prevent any disease from developing.”
At USF's
College of Public Health, malaria research is led by Adams and Assistant Professor Rays Jiang. USF is at the forefront of the scientific effort, which involves teams of researchers globally. Among the university’s key partners are Walter Reed Army Institute of Research International Laboratory in Thailand, and the
Wellcome Sanger Institute, a premiere gene research facility in the United Kingdom.
The new research will now enable experimental liver study to be done in the lab, points out Adams, who earned his Ph.D. in Veterinary Medical Sciences from the University of Illinois.
“You can’t do those kinds of experiments on people, not the discovery part,” he explains.
Optimistically, news drugs and vaccines already in the pipeline can be developed within five or six years,” Adams says. It may take 10 years for those not yet in the mill.
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Jenna Oberstaller, a PhD doctoral fellow for malaria research at USF in Tampa.In addition to the liver research, the USF team has identified the set of genes associated with malaria parasite Plasmodium falciparum, which can help scientists determine which genes are critical to the parasite’s survival.
“When we know what keeps the parasite alive, that makes it a viable or possible drug target,” explains Jenna Oberstaller, a member of the team who holds a Ph.D. in Genetics from the University of Georgia.
What people say
Capt. Brian A. Vesely, Chief of Field Studies at the Walter Reed Army Institute of Research in Experimental Therapeutics Branch, is among those working on malaria drug development.
“We have been collaborating with USF to establish a reliable in vitro liver model that targets the hypnozoite; a difficult to treat stage that is responsible for relapsing malaria,” says Vesely, who earned his Ph.D. in Global Health at USF.
“This model allows us to evaluate drug candidates that can prevent or target the hypnozoite stage of the parasite earlier in the drug discovery process than was possible before. Finding drugs that can prevent or treat these stages are important for malaria elimination,” adds Vesely, whose next assignment is at the Armed Forces Research Institute of Medical Sciences in Bangkok.
Julian Rayner, Senior Group Leader at Wellcome Sanger Institute, has worked with USF on the gene research. “My lab uses large-scale approaches to identify and prioritize new malaria drug and vaccine targets,” he says. “This research, along with work we are doing in other parasite systems, is an important element in identifying which genes are the most important for the parasites, and therefore which ones are the best targets for future drug and vaccine development.”
Word about research spreads
The liver-related research is outlined in a
Nature Communications article by Allison Roth, a graduate research associate who recently earned her Ph.D. in Global Communicable Diseases at USF, along with Adams and others.
Science Magazine published an update on the gene research authored by USF team members Min Zhang, Chengqi Wang, Oberstaller and others.
Other publications have carried reports of the malaria research as well. Through Bioworld by
Clarivate Analytics, which carried a report on the gene research datelined Hong Kong, to Insights, Altmetric, the
NIH Director’s Blog, and the
USF website, word about the research is spreading.
At USF, new students can begin working with these methods. “We already have people here that we want to help further the technologies,” Roth says.
About the disease
Malaria develops after an individual is bitten by a female mosquito carrying a malaria parasite. “The parasite then transfers to the human where it goes into the bloodstream and makes its way to the liver,” Roth explains. “You become infected, but clinically there are no symptoms.”
It takes about a week for symptoms to appear. At that point, the malaria is harder to defeat.
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Courtney Herman, a senior biological scientist, looks at liver cell cultures of blood infected with malaria with Alison Roth, a research associate, both at USF.The disease is more prevalent in Africa, south of the Sahara, and in places like Papua New Guinea in the southwest Pacific Ocean, according to the U.S. Centers for Disease Control and Prevention. The most susceptible are children under age 5, and pregnant women.
Malaria has been eradicated in the United States, although about 1,700 cases occur annually, usually among travelers and immigrants from countries where the disease is spread.
Malaria can cause fever, chills, and other flu-like symptoms, resulting in complications and death if left untreated. There is no effective vaccine.
In 2016, about 445,000 people died of the disease, the CDC says. The victims were primarily children in Africa. An estimated 216 million suffered worldwide that year.
What’s the best way to reduce your chances of contracting malaria when traveling to areas where the disease is active? Captain Paul Arguin, M.D., CDC’s Acting Malaria Branch Chief in Atlanta, advises travelers to visit a doctor beforehand and get a prescription to avoid problems.
They also should use mosquito repellents to discourage bites, especially at nighttime when the insects are more active.
“People who have never been infected by malaria before are going to be the most vulnerable. There’s absolutely no immune response,” he points out.
Increasing the odds
Though there are drugs to fight the disease, physicians need extra ones that are potent and easy to use.
“Resistance develops eventually. Even though we still have a good handful, I want more,” Arguin says.
It would be great to have a vaccine that is safe, easy to administer, and long-lasting, he adds.
“There are still way too many people that get sick, that die of malaria every year,” he says. “I would like to bring those numbers down.”
A long struggle
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Swamy Adapa, a biological scientist, performs data analysis for malaria studies. While DDT has killed mosquitoes and brought temporary victories, the mosquitoes -- and the deaths -- have returned.
“There’s been a lot of programs in terms of reducing the deaths,” Adams says. “The irony of it is, as you begin to control routine exposure to just occasional exposures, deaths may go up.”
When exposure is ongoing, the body’s immune system builds up its own defenses which offer protection. “As immunity decreases, the protection against disease decreases,” Adams says.
So the long and arduous battle against malaria continues. It requires travel to places where the disease is, to be more “efficient,” says Adams, who recently returned from Bangkok, where he was teaching an intensive training workshop at Mahidol University on advanced methods of malaria research.
“You don’t work on malaria because it’s fun. It is an interesting disease, but it also is one of the most significant diseases globally -- and has been for a long time,” he explains. “In many countries, this is the major cause of death.”
Some $21 million in funding from the Gates Foundation, the National Institutes of Health, and USF, has been pumped into the effort since 2007. Inroads have been made, but drug resistance is hampering efforts. The mosquitoes are even becoming resistant to the insecticides used in bed nets, Adams says.
Adams has stepped up the research and brought together skilled researchers. A Florida Malaria Research Network is coordinating the efforts of several state universities. Two meetings have been held at USF.
“With infectious diseases, if you ignore them they come back to bite you,” Adams says. “In Florida, we’re particularly aware of that threat.”
Understanding the biology of the parasite is a “huge leap forward,” Oberstaller says.
“Once we know more about the enemy, we can do more to fight it,” she adds.