Malaria claims nearly half-a-million lives worldwide each year — and yet we still know so little about the immunology of the disease that has plagued humanity for centuries.

There were 216 million cases in 2016, according to the World Health Organization. Sub-Saharan Africa carries 80 percent of the global burden of the mosquito-borne infectious disease which devastates families, disrupts education, and promotes the vicious cycle of poverty.

It is particularly brutal to pregnant women, who are three times more likely to suffer from a severe form of the disease, leading to lower birthweight among their newborns and higher rates of miscarriage, premature and stillborn deliveries.

“Pregnant women and their unborn children are more susceptible to the adverse consequences of malaria, so we are working to investigate new strategies and even lay the foundation for a vaccine to prevent malaria in pregnancy,” said Prasanna Jagannathan, MD, an assistant professor of medicine who is this year’s recipient of the Rosenkranz Prize.

Jagannathan, an infectious disease physician who is also a member of Stanford’s Child Health Research Institute, said the $100,000 stipend that comes with the prize will allow his lab members to ramp up their research in Uganda. A member of the nonprofit Infectious Disease Research Collaboration in Kampala, his team is particularly interested in how strategies that prevent malaria might actually alter the development of natural immunity to malaria.

“With support from the Rosenkranz Prize, we hope to identify maternal immune characteristics and immunologic targets that are associated with protection of malaria in pregnancy and infancy,” Jagannathan said.

The Dr. George Rosenkranz Prize for Health Care Research in Developing Countries is awarded each year by the Freeman Spogli Institute for International Studies and Stanford Health Policy to a young Stanford researcher who is trying to improve health care in underserved countries. It was established in 2009 by the family or Dr. George Rosenkranz, a chemist who first synthesized cortisone in 1951, and later progesterone, the active ingredient in oral birth control pills.

“My father has held a lifelong commitment to scientific research as a way to improve the lives and well-being of communities around the world,” said Ricardo T. Rosenkranz, MD. “In particular, he has always sought to improve the health of at-risk populations. Dr. Jagannathan’s work offers the very sort of innovative ingenuity that characterized my father’s early research, as well as his vision towards the future.”

Jagannathan and his collaborators at UCSF and in Uganda are currently conducting a randomized control trial of 782 Ugandan women who are receiving intermittent preventive treatment with a fixed dose of dihydroartemisinin-piperaquine(or IPTp-DP), a medication that has dramatically reduced the risk of maternal parasitemia, anemia, and placental malaria. Their preliminary data suggests that among 684 infants born to these women, maternal receipt of IPTp-DP may lead to a reduced incidence of malaria in the first year of life.

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“Having the discretionary support of the Rosenkranz Prize will allow us to generate some preliminary ideas from this trial that could lead to larger studies, to push this agenda further along,” Jagannathan said.

That agenda is to create a vaccine that targets pregnant women to prevent malaria both during pregnancy — but also potentially preventing malaria in infants, giving them a better start in life.

“We’re not the first ones to think of this, but we have the opportunity to test these hypotheses in incredibly unique settings, with really well-studied cohorts that have real-world implications in terms of what we find,” Jagannathan said. “I’m hopeful that the data that’s generated over the new few years will allow us to keep moving forward.”

Jagannathan has been traveling to Uganda for a decade to study malaria. He’s seen firsthand the relentless, gnawing impact the disease has on daily life.

“Before I went to Uganda I really didn’t understand the burden that malaria causes in communities — and it’s just incredible,” he said. His first study was on children aged 5 and under who had on average six episodes of malaria a year.

“They just get it over and over again, and the toll on society is enormous,” he said. The clinics are overwhelmed and a parent or sibling must miss work or school to stay home with that child.

Yet, in highly endemic settings, children eventually develop an immunity that protects against the adverse outcomes from malaria. If he and his colleagues can understand how pregnant women and children develop this clinical immunity to malaria, it could lead to better treatments and preventative strategies.

“If we understand the mechanisms that underlie naturally acquired immunity, that would offer some clues as to how we can develop a vaccine that actually allows either that immunity to occur more quickly or prevents us from developing immunity that allows for the parasite to persist without symptoms,” he said.

There is currently a malaria vaccine undergoing testing in Africa. The vaccine, known as RTS,S, was developed by GlaxoSmithKline and the PATH Malaria Vaccine Initiative, with support from the Bill and Melinda Gates Foundation. Decades in the making, four doses of the vaccine are required to reduce malaria infection in humans.

“It’s a remarkable vaccine in that it’s effective in the beginning, but the problem is that the efficacy wanes very rapidly,” Jagannathan said, noting that some studies show that beyond three years, the effectiveness drops to 15-20 percent.

“That’s the big issue and why people are really interested in trying to find new strategies and new approaches for a next-generation malarial vaccine,” he said. “That’s the overarching aspect of what motivates my work.”

Dr. David Relman investigates the secrets of the life sciences to help build a safer world.

The Stanford microbiologist and professor of infectious diseases has been named the next co-director of the university’s Center for International Security and Cooperation (CISAC). An adviser to the federal government on emerging biological threats, Relman believes his new role at CISAC will strengthen its core mission of making the world a safer place.

“There is a strong link between microbiology, infectious diseases and international security,” Relman said. “It is increasingly clear that the destabilizing effects of human population growth and displacement, environmental degradation and climate change are all mediated in part through the emergence and spread of infectious diseases. In addition, rapidly evolving capabilities of individuals in the life sciences around the globe make it increasingly likely that this science will be used to cause harm.”

Relman, the Thomas C. and Joan M. Merigan Professor at Stanford and chief of infectious diseases at the VA Palo Alto Healthcare System, has advised the U.S. government about pathogen diversity, biosecurity and the future of the life sciences landscape. He is a member of the National Science Advisory Board for Biosecurity (NSABB), chairs the Forum on Microbial Threats at the Institute of Medicine in Washington, D.C. and has participated in a number of studies for the National Academies of Science.

"David Relman is one of the nation’s top scientists exploring the mysteries of infectious disease, a thoughtful adviser to policymakers, and an extraordinary colleague,” said Tino Cuéllar, a Stanford Law School professor and the center’s co-director. “He will make tremendous contributions to CISAC's leadership as we expand our activities on public health and biosecurity while continuing our work on arms control and nuclear security."

Founded nearly three decades ago, CISAC’s mission is to produce cutting-edge research and spread knowledge to build a safer world. Now a part of the Freeman Spogli Institute for International Studies (FSI), the center has a tradition of appointing co-directors – one from the social sciences and the other from the natural sciences – to advance the center’s interdisciplinary mission.

Relman will take up the post in January, when Siegfried Hecker’s term concludes after having served as co-director since 2007. Hecker, a nuclear scientist and director emeritus of the Los Alamos National Laboratory, is one of the world’s foremost experts on plutonium, nuclear weapons and nonproliferation. He will remain at CISAC and continue to teach in the department of Management Science and Engineering.

“It has been a personal pleasure to work with Sig,” said Cuéllar. “He has been an enormous asset to CISAC.  He will continue to be a visionary leader on nuclear security and arms control issues throughout the world.”

Relman joined Paul Keim, acting chair of the NSABB, to address a CISAC seminar in March about their work in advising the government on the potential dangers of laboratory-engineered H5N1 avian influenza.

The advisory board had been asked to review two manuscripts that described the deliberate modification of the H5N1 avian influenza virus so as to be transmissible for the first time from mammal to mammal via a respiratory route. This provoked a debate in the scientific community about the risks of such work and whether the details of these experiments should be published – details that would enable anyone skilled in the art of virology and molecular biology to recreate these highly virulent and transmissible viruses. Some argued that the research could end up in the wrong hands. The board eventually recommended in a split decision that this research should be published.

“Life scientists need to be involved in discussions about the oversight of risky science and the responsible conduct of science, so that the potential benefits can be realized while the risks are minimized,” Relman said.

Relman will continue to run his research lab at the Stanford University School of Medicine and the VA Hospital in Palo Alto, where his focus is on the beneficial communities of microbes in the human body. He is president-elect of the Infectious Diseases Society of America and a member of the Institute of Medicine at the National Academies of Science. He received his S.B. in biology from MIT in 1977 and an M.D. from Harvard Medical School in 1982. He completed his clinical training in internal medicine and infectious diseases at Massachusetts General Hospital in Boston.

“The appointment of a life scientist who focuses on infectious diseases and biosecurity is an innovative step for our work in international security and cooperation,” said Gerhard Casper, president emeritus of Stanford University and director of the Freeman Spogli Institute for International Studies.

Relman tells a story that illustrates his passion for scientific discovery. On a routine visit to his dentist about 15 years ago, he brought along his own test tube. He asked the dentist to give him some plaque that he had scraped off Relman’s teeth. He wanted to study his own bacteria.

“As a clinician, I can tell you my colleagues were not looking for new microbes to worry about,” Relman said. “Some of them believed there might well be some really weird new microbes in soil or in the ocean, but that the human microbial ecosystem was something that we understood quite well. Of course – that was wrong.”

Using DNA sequencing technology, he has since discovered hundreds of new bacteria in the human body.

“Our ability to predict the next important technical or conceptual advance in the life sciences is miserable, as is our ability to anticipate how these advances will be used,” Relman said. “But we can at least hope to engage the scientific community and the general public in discussions about our goals and our understanding of risks – and how best to mitigate them.”