News, Science & Research

Laboratory strives to develop vaccine against malaria

Lab studies malarial resistance in children in Kenya, Tanzania to identify antibodies

By
Senior Staff Writer
Thursday, September 20, 2018

Jonathan Kurtis ’89 PhD’95 MD’96, professor of pathology and laboratory medicine, did not first develop an interest in malaria behind a lab bench or as a training physician in a clinical setting. Instead, Kurtis’ bout with the disease during his junior year abroad in Kenya gave him a first-hand look at one of the world’s deadliest diseases and began his research aspirations to prevent it.

His story began on a night train from Nairobi to Mombasa, where his project on coral reef ecology was set to begin. Far from home and with no way to contact his family, he met Americans in the dining car and stayed up all night talking and drinking with them, bonding over their shared nationality. After waking up sick in the morning, Kurtis arrived in Mombasa. “I actually paid a guy to carry my rucksack, which was insane because I was broke,” he recalled. Finally, he reached the mud hut that he had rented for the project, took the malaria pills he had brought with him and passed out. Three days later, he awoke with no recollection of what had happened since his arrival. He didn’t even remember taking the pills, but fortunately, he had — he later found out that they saved his life. It was clear that what he had contracted was cerebral malaria.

After recovering from the harsh disease, Kurtis was able to carry on his coral reef project and thoroughly enjoyed it. At the same time, however, he grew witness and subject to the reality of what “an important thumb malaria is pressing down on the world’s populations.”

Upon graduating with a bachelor’s degrees in Geology and Biology from the University, Kurtis entered Alpert Medical School. He often met with the travel physician who had prescribed the medication that he took abroad, G. Richard Olds, who served as professor of medicine, pediatrics, molecular, cell and development biology at the time. Olds had become a mentor to Kurtis in the time since he had returned from Kenya. At one point during his tenure as a medical student, Kurtis considered dropping out of medical school. As Kurtis remembers, Olds inspired him to instead pursue research in conjunction with medicine, pushing him toward a doctoral program in his laboratory. Under Olds’s direction, Kurtis completed his PhD on schistosomiasis, a tropical disease caused by parasitic worms.

Jennifer Friedman ’92 MD’96, director of clinical studies for Lifespan’s Center for International Health Research and a professor of epidemiology and pediatrics at the Med School, similarly developed an interest in the disease upon working in Kenya. She was a Fulbright scholar there in between completing medical school and starting residency. “I was inspired by the enormous burden of disease despite good drugs and, as later identified as part of work I was involved that year with CDC, insecticide-treated bed nets,” she wrote in an email to The Herald. Alongside Kurtis, she has researched malaria and other parasitic diseases for years, pulling upon her expertise in pediatrics to advance their work.

Now, Kurtis serves as the director of Lifespan’s Center for International Health Research, which has a team of twenty investigators studying not only malaria, but other diseases including helminth infections, a soil-transmitted infection and Friedman’s current research focus. Many of the current investigators started as graduate students or postdoctoral researchers at the center before rising through the ranks to their current positions.

In concept, a malaria vaccine has existed in a lab setting for nearly five decades. “No mouse need live in fear; we can protect rodents without any challenge at all. The problem is (the vaccination method) hasn’t generalized into humans,” Kurtis said. Mice are often used in scientific research as an earlier step before moving into more advanced models or human trials. But “in malaria, mice lie,” Kurtis said — the form of malaria the mice develop does not simulate the human form well.

As a result, Kurtis’ team has taken a different approach. They spend time in Kenya and Tanzania, and study malaria resistance in children there. In the lab, the group tries to identify antibodies that occur naturally in people who are malaria-resistant. The team aims to detect the target of these antibodies and then, through a vaccine, expose children to this target so they make the antibodies against it.

Currently, their vaccine work is being tested on monkeys since the animals can actually contract the same type of malaria as humans do. “Before we (begin trials on) children, we’ve got to make sure (the vaccine) is safe and effective, and the only way to do that at the moment is in non-human primates,” Kurtis said, highlighting the current necessity of research on animals in the field. With additional studies and sufficient funding, their hope is to start a phase one clinical trial in humans within two to three years.

Other researchers at the University are enthralled in understanding and potentially vaccinating against malaria as well. Dipak Raj, assistant professor of pathology and laboratory medicine at the Med School, has worked with Kurtis in the past to develop a malaria vaccine candidate. He started looking at possible vaccine mechanisms for malaria during his doctoral program in India, he said, before leaving for the United States and working at the National Institutes of Health before moving to the University. At the NIH, he helped identify a drug, Ketotifen, that has possible applications for malaria treatment.

In tandem with his research, Kurtis has worked directly with malaria patients. Currently, he is involved in a study of children living in Kisumu, a city near Lake Victoria in Western Kenya. The region is plagued with malaria and has one of the highest rates of transmission of the disease in the world, said Kurtis. He added that in Kisumu every child, every day, gets an infected mosquito bite; one out of four children don’t make it to their fifth birthday. Kids between the ages of two and seven were enrolled in the study, and within a month, half had developed clinical episodes of malaria. The team has done extensive follow-ups on these kids, and six months into the study, zero fatalities have occurred, Kurtis said. He added that despite medical care and this intense follow-up, the heart-wrenching truth is that they expect five percent of the children to die within the four years of the study. “How does it feel? It sucks. It absolutely sucks,” Kurtis reflected.